bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chicken muscle hydrolysate reduces blood pressure in spontaneously hypertensive rats, upregulates ACE2, and ameliorates vascular inflammation, fibrosis, and oxidative stress
Authors: Fan Hongbing , Liao Wang , Spaans Floor , Pasha Mazhar , Davidge Sandra T. , Wu Jianping 
Published: February 2022

AbstractSpent hens are egg‐laying chicken reaching the end of their egg‐laying cycle and are seen as a by‐product to the egg industry. A spent hen muscle protein hydrolysate prepared by food‐grade thermoase PC10F (SPH‐T) has previously shown antihypertensive potential. In the present work, we further investigated its antihypertensive effect and underlying mechanisms in spontaneously hypertensive rats. There are three groups: untreated, low dose (250 mg SPH‐T/kg/day body weight), and high dose (1,000 mg SPH‐T/kg/day body weight). Oral administration of SPH‐T over a period of 20 days reduced systolic blood pressure by 25.7 mm Hg (p < 0.001) and 11.9 mm Hg (p < 0.05), respectively, for the high‐ and low‐dose groups. The high‐dose treatment decreased the circulating level of angiotensin II (from 25.0 to 5.7 pg/ml) while increased angiotensin‐converting enzyme 2 (ACE2) (from 1.3 to 3.3 IU/ml) and angiotensin (1–7) (from 37.0 to 70.1 pg/ml) significantly (p < 0.05). Furthermore, the high‐dose group doubled the aortic expression of ACE2 while reduced the expression of angiotensin (Ang) II type 1 receptor (by 35%). Circulating inflammatory cytokines including tumor necrosis factor alpha and monocyte chemoattractant protein‐1 as well as vascular inflammatory proteins including inducible nitric oxide synthase and vascular cell adhesion molecule‐1 were attenuated by ∼15%–50% by the treatment; nitrosative stress (35%) and type I collagen synthesis (50%) in the aorta were also attenuated significantly (p < 0.05). Moreover, SPH‐T possessed an umami taste (no obvious bitter taste) as analyzed by electronic tongue.Practical ApplicationHypertension is a global health concern, afflicting more than 20% of adults worldwide. Uncovering the antihypertensive effect of spent hen protein hydrolysate underpinned its functional food nutraceutical applications for the prevention and treatment of hypertension.
A systematic review of clinical practice guidelines for persons with osteoarthritis. A “Best Evidence for Rehabilitation” (be4rehab) paper to develop the WHO’s Package of Interventions for Rehabilitation
Authors: Oral Aydan , Arman Sina , Tarakci Ela , Patrini Michele , Arienti Chiara , Etemadi Yasaman , Rauch Alexandra , Negrini Stefano 
Published: February 2022

AbstractAimIdentifying existing interventions for rehabilitation and related evidence presents a crucial step in developing the World Health Organization's (WHO) Package of Interventions for Rehabilitation. This paper reports the results of a systematic search that aimed to identify clinical practice guidelines (CPGs) relevant to the rehabilitation of people with osteoarthritis and presents the CPG recommendations and the current state of evidence available for the interventions in the CPGs.MethodsThis paper is part of the “Best Evidence for Rehabilitation” (be4rehab) series, developed according to the methodology presented in the WHO's Package of Interventions for Rehabilitation introductory paper by Rauch et al, published in 2019. It is a systematic review of the existing CPGs on osteoarthritis published between 2009 and 2019. Identified CPGs were screened taking into consideration conflict of interest, the provision of information regarding the strength of recommendation(s), and quality to be selected. Quality of CPGs was assessed using the AGREE II tool.ResultsAfter title and abstract screening, 51 CPGs were identified. Considering the inclusion/exclusion criteria, 26 CPGs were selected. After checking for quality, comprehensiveness, multi‐professionality, and publication date, five CPGs were finally included in the review. The strong recommendations for people with knee and hip osteoarthritis consistently included in all the selected CPGs, sometimes called “core treatments”, were patient education, exercise training, and weight reduction if overweight or obese. Generally, recommendations overlap in the CPGs.ConclusionThe systematic search revealed high‐quality CPGs on osteoarthritis for the identification of “Best Evidence for Rehabilitation (be4rehab)” regarding interventions for rehabilitation of people with osteoarthritis.
Comparative effectiveness and safety of antipsychotic drugs in patients with schizophrenia initiating or reinitiating treatment: A Real‐World Observational Study
Authors: Brodeur Sébastien , Vanasse Alain , Courteau Josiane , Stip Emmanuel , Lesage Alain , Fleury Marie‐Josée , Courteau Mireille , Roy Marc‐André 
Published: February 2022

AbstractObjectiveTo compare the effectiveness and safety of various second‐generation antipsychotics (SGAs), newer oral and long‐acting injectable (LAI) SGAs, and first‐generation antipsychotics (FGAs) treatments in patients with schizophrenia or schizoaffective disorder (SCZ).MethodsThis retrospective cohort study included medical administrative information for patients with a diagnosis of SCZ living in Quebec (Canada), initiating or reinitiating at least one antipsychotic (AP) drug (with a clearance baseline period of 12 months without any APs). Effectiveness was defined by a reduced risk of hospitalization for mental disorder and discontinuation, and safety by a reduced risk of all‐cause death and hospitalization for non‐mental disorder, 2 years after AP initiation or reinitiation. Cox proportional hazard models were used to estimate the events associated with different antipsychotics compared with oral olanzapine.ResultsThe study cohort included 19,615 patients initiating or reinitiating an antipsychotic drug between January 2006 and December 2015. Results showed better effectiveness of clozapine (adjusted HR 0.36, 95% CI 0.30–0.42, p < 0.0001) and LAI SGAs (adjusted HR 0.56, 95% CI 0.51–0.61, p < 0.0001) compared with oral olanzapine when adding discontinuation to hospitalizations for mental disorder as a composite measure of effectiveness, as opposed to oral FGAs (adjusted HR 1.36, 95% CI 1.27–1.46, p < 0.0001) and LAI FGAs (adjusted HR 1.22, 95% CI 1.12–1.32, p < 0.0001). Most APs were as safe as oral olanzapine.ConclusionThe effectiveness of LAI SGAs and clozapine appears to justify their use and are as safe as a recognized treatment (oral olanzapine) in Quebec (Canada).
Psychotropic medication deprescribing in residential aged care facilities: An exploratory study of the knowledge and attitudes of family members of residents with dementia
Authors: Lai Rhoda , Withiel Toni Dianne , Angelone Melissa , Redpath Cameron , O’Connor Daniel W. , Plakiotis Christos 
Published: February 2022

AbstractObjectivesGeneral practitioners face many barriers to deprescribing psychotropic medications in people with dementia in nursing homes, including a lack of knowledge about their medication histories. This study explored the knowledge of family members about residents’ medications and their willingness to support deprescribing.MethodsSixty‐six family members of residents from seven residential aged care facilities participated in this cross‐sectional study. Participation involved nomination of recognised medications, rating their effectiveness and rating level of support for deprescribing.ResultsFifty‐five per cent of medications were recognised by family members; significantly fewer psychotropics were recognised than non‐psychotropic medications. Though rated as just as effective, support for deprescribing psychotropics was significantly higher. Most family members were agreeable to deprescribing with general practitioner support.ConclusionsAlthough there is a gap in family members’ knowledge about psychotropic medications, overall they are supportive of deprescribing. Findings emphasise the need for psychoeducation among family members. Providing family members with a list of prescribed medications, specifying the type of and reason for prescription and side effects of each, is recommended to facilitate their advocacy for deprescribing on behalf of nursing home residents.
What influences student situational engagement in smart classrooms: Perception of the learning environment and students' motivation
Authors: Lu Guoqing , Xie Kui , Liu Qingtang 
Published: February 2022

AbstractSituational engagement plays a critical role in promoting students' academic performance. In a smart classroom environment, this study collected longitudinal real‐time data for 105 college students at a university in central China to investigate the relationship among situational engagement, personal characteristics and learning environment perceptions. Hierarchical linear modelling showed that environmental perception and students' personal factors have different effects on situational engagement. Specifically, (1) social support perceptions, autonomous motivation and controlled motivation have a significant impact on behavioural engagement; (2) perceptions of social and media support, autonomous motivation and controlled motivation have a significant impact on shallow cognitive engagement; and (3) perceptions of teacher and social support, self‐efficacy and autonomous motivation significantly predict deep cognitive and emotional engagement. This study suggests that the effect of the perception regarding advanced technology‐supported learning environments on students' situational engagement is limited, and instructors should pay more attention to improving students' perceptions of teacher and social support, self‐efficacy and autonomous motivation to promote students' situational deep cognitive engagement in smart classrooms.
Practitioner notesWhat is already known about this topic

Compared with overall engagement, situational engagement fluctuates and changes with time and context.
Situational engagement is a product of environmental and personal factors.
Few studies have focused on the nature of situational engagement and how environmental and personal factors influence situational engagement in smart classrooms.
What the paper adds

This study contributes to the existing literature by investigating the critical factors that predict situational engagement, using the experience sampling method in a smart classroom at a Chinese university.
Environmental perception, self‐efficacy and students' motivation factors have different effects on situational engagement in a smart classroom.
Perceptions of teacher and social support, self‐efficacy and autonomous motivation significantly predict deep cognitive and emotional engagement, while perceptions of media support only have a significant impact on shallow cognitive engagement.
Personal factors (controlled and autonomous motivation) moderate the relationship between environmental perception factors and situational engagement.
Implications for practice and/or policy

Rather than only providing external technology‐rich conditions, instructors should focus more on improving students' perceptions of teacher and social support, self‐efficacy and autonomous motivation in the smart classroom environment.
Instructors should promote students' perception of teacher support and their autonomous motivation to enhance their deep cognitive engagement.
Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019
Authors: Swan Dawn , Hayden Patrick J. , Eikema Dirk‐Jan , Koster Linda , Sauer Sandra , Blaise Didier , Nicholson Emma , Rabin Neil , Touzeau Cyrille , Byrne Jennifer , Huynh Anne , Cornelissen Jan J. , Potter Victoria , Forcade Edouard , Parrish Christopher , Gribben John , Chretien Marie‐Lorraine , Mielke Stephan , Gedde‐Dahl Tobias , Reményi Péter , Tsirigotis Panagiotis , Garcia Guiñón Antoni , Beksac Meral , Schönland Stefan , Yakoub‐Agha Ibrahim 
Published: February 2022

SummaryMultiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy‐based induction fell significantly, being largely replaced by bortezomib‐based regimens. The two‐year complete response rate increased from 22% to 42%. The five‐year progression‐free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
Astrocytes expressing Vitamin D‐activating enzyme identify Parkinson’s disease
Authors: Mazzetti Samanta , Barichella Michela , Giampietro Federica , Giana Angelica , Calogero Alessandra M , Amadeo Alida , Palazzi Nicola , Comincini Alessandro , Giaccone Giorgio , Bramerio Manuela , Caronni Serena , Cereda Viviana , Cereda Emanuele , Cappelletti Graziella , Rolando Chiara , Pezzoli Gianni 
Published: February 2022

AbstractIntroductionAstrocytes are involved in Parkinson's disease (PD) where they could contribute to α‐Synuclein pathology but also to neuroprotection via α‐Synuclein clearance. The molecular signature underlying their dual role is still elusive. Given that vitamin D has been recently suggested to be protective in neurodegeneration, the aim of our study was to investigate astrocyte and neuron vitamin D pathway alterations and their correlation with α‐Synuclein aggregates (ie, oligomers and fibrils) in human brain obtained from PD patients.MethodsThe expression of vitamin D pathway components CYP27B1, CYP24A1, and VDR was examined in brains obtained from PD patients (Braak stage 6; n = 9) and control subjects (n = 4). We also exploited proximity ligation assay to identified toxic α‐Synuclein oligomers in human astrocytes.ResultsWe found that vitamin D‐activating enzyme CYP27B1 identified a subpopulation of astrocytes exclusively in PD patients. CYP27B1 positive astrocytes could display neuroprotective features as they sequester α‐Synuclein oligomers and are associated with Lewy body negative neurons.ConclusionThe presence of CYP27B1 astrocytes distinguishes PD patients and suggests their contribution to protect neurons and to ameliorate neuropathological traits.
Translating stem cell research into development of cellular drugs—a perspective from manufacture of stem cell products and CMC considerations
Authors: Zhang Yu Alex , Stacey Glyn N. 
Published: February 2022

AbstractThe development of human pluripotent stem cell (PSC)‐derived medicinal products has been gathering steam in recent years, but the translation of research protocols into GMP production remains a daunting task. The challenges not only reside with the nature of cellular therapeutics but are also rooted in the general inexperience in industry‐scale production of stem cell products. Manufacturers of PSC‐derived products should be aware of the technical nuances and take a holistic approach toward early planning and engagement with their academic partners. While not all issues will be readily resolved soon, the collective knowledge and consensus by the manufacturers and key stakeholders will help to guide rapid progression of the field.
Simultaneous effect of habitat remnancy, exotic species, and anthropogenic disturbance on orchid diversity in South Australia
Authors: Martín‐Forés Irene , Bywaters Samantha L. , Sparrow Ben , Guerin Greg R. 
Published: February 2022

AbstractOrchids are potentially useful as ecological indicators because of their sensitivity to habitat fragmentation and anthropogenic disturbance. While many studies explore the effect of single factors on orchid diversity, few investigate how the extent, configuration, and condition of surrounding habitat affect whole orchid communities. Here, we unravel the effect of biological invasions, anthropogenic disturbance (i.e., grazing pressure, ecological condition), and habitat fragmentation on an Australian orchid community. We sampled 39 plots across nine sites in the Mount Lofty Ranges, Australia. We recorded the number of orchid species and number of individuals per species in mid‐winter, early‐spring, and late‐spring to account for the effect of season on species visibility, with 115 surveys in total. We ranked grazing intensity and ecological condition, and estimated cover of exotic species. We analyzed the response of richness and diversity through generalized linear mixed models, and differences in species composition through non‐metric multidimensional scaling. Habitat configuration in the surrounding landscape had different effects at increasing radii, explaining 29%–87% of variance. Patch‐level orchid diversity was positively correlated with habitat edges in the immediate area, and with habitat cohesion at medium scales, whereas diversity was negatively correlated with increasing mean patch habitat area across larger surrounding areas. Orchids co‐existed with exotic species but were negatively affected once exotic cover exceeded 20%. Species composition was correlated with exotic cover. Our findings reveal a complex relationship between orchid communities and their surrounding environments suggesting orchids benefit from a somewhat disturbed environment at patch and landscape scales. These idiosyncratic responses suggest orchid diversity may be unreliable as early‐warning indicators of habitat disturbance.
Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes
Authors: Kahl Sabine , Ofstad Anne Pernille , Zinman Bernard , Wanner Christoph , Schüler Elke , Sattar Naveed , Inzucchi Silvio E. , Roden Michael 
Published: February 2022

AbstractAimsEmpagliflozin treatment reduced liver fat in small type 2 diabetes cohorts. This post‐hoc study evaluated effects of empagliflozin on risk for non‐alcoholic fatty liver disease‐related steatosis and fibrosis, as well as the relationship between risk categories and cardiorenal outcomes in the randomized, placebo‐controlled EMPA‐REG OUTCOME trial.Materials and methodsEMPA‐REG OUTCOME treated 7020 people with type 2 diabetes and cardiovascular disease with 10/25 mg/day empagliflozin or placebo. For this analysis, the Dallas steatosis index, hepatic steatosis index, non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score were calculated to assess steatosis and fibrosis risk. Changes from baseline in scores were examined by mixed model repeated measures and their associations with cardiorenal outcomes and mortality by Cox regression.ResultsAt baseline, 73% and 84% of participants had high steatosis risk by Dallas steatosis index and hepatic steatosis index, whereas 23% and 4% had a high risk of advanced fibrosis by non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score. Percentages of people at high steatosis risk slightly decreased with empagliflozin only, whereas empagliflozin did not improve percentages of individuals at high fibrosis risk over time compared with placebo. The high risk of advanced fibrosis at baseline related to higher risk for cardiovascular events. Effects of empagliflozin on cardiorenal and all‐cause mortality outcomes were consistent across all risk groups.ConclusionsEmpagliflozin may reduce steatosis but not fibrosis risk in individuals with type 2 diabetes and cardiovascular disease. The improvements in cardiorenal outcomes and mortality associated with empagliflozin therapy appear to be independent of steatosis and fibrosis risk.
Neurodevelopmental trajectories in children with cleft lip and palate: A longitudinal study based on the Japan Environment and Children's Study
Authors: Tsuchiya Shinobu , Tsuchiya Masahiro , Momma Haruki , Aida Jun , Nagatomi Ryoichi , Yaegashi Nobuo , Arima Takahiro , Igarashi Kaoru ,   the Japan Environment and Children's Study Group
Published: February 2022

AbstractCleft lip and/or palate (CL/P), the most prevalent congenital anomaly, is understood to negatively affect a wide range of child development. Since the concept remains controversial, because most published work is from cross‐sectional studies, we examined the neurodevelopmental trajectories in participants with CL/P through a longitudinal comparison with the general population during early childhood using data from a nationwide birth cohort study in Japan. The linear mixed models for each domain of the Ages and Stages Questionnaire, third edition (ASQ‐3), were used to detect differences in standardised mean scores between groups. The ASQ‐3 is a general neurodevelopmental screening tool comprising communication, gross motor, fine motor, problem‐solving, and personal‐social domains. Participants’ neurodevelopment was determined semi‐annually from 6 to 36 months of age. The trajectories of standardised mean scores in each domain showed several significant differences between the control and CL/P groups, with the maximum difference at 24 months of age in the communication domain. Indeed, CL/P was associated with significantly lower scores in the communication (coefficient: –3.31, 95% CI: –5.09 to –1.14), problem‐solving (coefficient: –3.13, 95% CI: –5.07 to –1.18), and personal‐social domains (coefficient: –1.99, 95% CI: –3.87 to –0.11). Trajectories of ASQ‐3 scores suggest neurodevelopmental delays in children with CL/P.
Epidemiology of exertional heat illness in Thoroughbred racehorses in temperate eastern Australia: The role of extrinsic (environmental) factors in disease causation
Authors: Brownlow M. , Mizzi J. X. 
Published: February 2022

Summary
A simple epidemiological model of disease causation is proposed for exertional heat illness (EHI) in Thoroughbred racehorses. The agent of disease causation that must be present for the condition to occur is strenuous exercise, producing substantial quantities of metabolic heat. This is stored during racing but must be dissipated rapidly in the post‐race period to prevent core body temperature rising to a critical level and causing the clinical manifestations of EHI. Environmental factors are next in the epidemiological triad, and it is a common misconception that these are the direct cause of EHI. In fact, environmental conditions enable EHI by either diminishing the evaporative capacity of the environment or promoting internal heat gain. This article deals with the specific effects of the four thermal elements, separately and in combination, on individual thermo‐effector mechanisms. The final component in the epidemiological triad is individual host factors. A critical premise of epidemiology is that conditions such as EHI may not occur randomly in a population but may be more likely to occur in some individuals due to the presence of certain factors that predispose them to the condition. For the purpose of assessing risk, it is not feasible to examine the balance between metabolic heat production and the intrinsic and extrinsic factors, which collectively determine each individual's heat stress response. Therefore, the measurement of environmental factors remains the only practical way of obtaining a credible risk assessment for EHI, so that effective countermeasures can be instigated and the welfare of our racehorses ensured.