bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost analysis of lurasidone for the treatment of schizophrenia in adolescents and adults within the United Kingdom
Authors: Dymond Amy , Afonso Daniela , Green Will 
Published: August 2022

Abstract
Background
Schizophrenia is a serious mental health condition characterised by distortions in thought processes, perception, mood, sense of self, and behaviour. Lurasidone, a second-generation atypical antipsychotic, represents an additional treatment option alongside existing antipsychotics for adolescents and adults with schizophrenia. An economic model was developed to evaluate the incremental costs of lurasidone as a first-line treatment option compared to existing antipsychotics.

Methods
A Markov model was developed to estimate the cost impact of lurasidone as a first-line treatment option for both adolescents and adults. The sequence-based model incorporated the following health states: stable (no relapse or discontinuation), discontinuation (due to adverse events or other reasons), and relapse. Data used to determine the movement of patients between health states were obtained from network meta-analyses (NMAs). The time horizon ranged from three to five years (depending on the patient population) and a six-weekly cycle length was used. Unit costs and resource use were reflective of the UK NHS and Personal Social Services and consisted of the following categories: outpatient, adverse events, primary and residential care. Extensive deterministic sensitivity analysis was undertaken to assess the level of uncertainty associated with the base case results.

Results
Lurasidone is demonstrated to be cost-saving as a first-line treatment within the adolescent and adult populations when compared to second-line and third-line respectively. Lurasidone is more expensive in terms of treatment costs, resource use (in the stable health state) and the treatment of adverse events. However, these costs are outweighed by the savings associated with the relapse health state. Lurasidone remains cost-saving when inputs are varied in sensitivity analysis and scenario analysis.

Conclusions
Lurasidone is a cost-saving first-line treatment for schizophrenia for both adolescents and adults.
A novel fatty acid metabolism-related signature identifies features of the tumor microenvironment and predicts clinical outcome in acute myeloid leukemia
Authors: Zhang Hai-Bin , Sun Zhuo-Kai , Zhong Fang-Min , Yao Fang-Yi , Liu Jing , Zhang Jing , Zhang Nan , Lin Jin , Li Shu-Qi , Li Mei-Yong , Jiang Jun-Yao , Cheng Ying , Xu Shuai , Cheng Xue-Xin , Huang Bo , Wang Xiao-Zhong 
Published: August 2022

Abstract
Background
Acute myeloid leukemia (AML) is the most common malignancy of the hematological system, and there are currently a number of studies regarding abnormal alterations in energy metabolism, but fewer reports related to fatty acid metabolism (FAM) in AML. We therefore analyze the association of FAM and AML tumor development to explore targets for clinical prognosis prediction and identify those with potential therapeutic value.

Methods
The identification of AML patients with different fatty acid metabolism characteristics was based on a consensus clustering algorithm. The CIBERSORT algorithm was used to calculate the proportion of infiltrating immune cells. We used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a signature for predicting the prognosis of AML patients. The Genomics of Drug Sensitivity in Cancer database was used to predict the sensitivity of patient samples in high- and low-risk score groups to different chemotherapy drugs.

Results
The consensus clustering approach identified three molecular subtypes of FAM that exhibited significant differences in genomic features such as immunity, metabolism, and inflammation, as well as patient prognosis. The risk-score model we constructed accurately predicted patient outcomes, with area under the receiver operating characteristic curve values of 0.870, 0.878, and 0.950 at 1, 3, and 5 years, respectively. The validation cohort also confirmed the prognostic evaluation performance of the risk score. In addition, higher risk scores were associated with stronger fatty acid metabolisms, significantly higher expression levels of immune checkpoints, and significantly increased infiltration of immunosuppressive cells. Immune functions, such as inflammation promotion, para-inflammation, and type I/II interferon responses, were also significantly activated. These results demonstrated that immunotherapy targeting immune checkpoints and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages, are more suitable for patients with high-risk scores. Finally, the prediction results of chemotherapeutic drugs showed that samples in the high-risk score group had greater treatment sensitivity to four chemotherapy drugs in vitro.

Conclusions
The analysis of the molecular patterns of FAM effectively predicted patient prognosis and revealed various tumor microenvironment (TME) characteristics.
“They're causing more harm than good”: a qualitative study exploring racism in harm reduction through the experiences of racialized people who use drugs
Authors: Godkhindi Parnika , Nussey Lisa , O’Shea Tim 
Published: August 2022

AbstractBackgroundIncreased opioid-related morbidity and mortality in racialized communities has highlighted the intersectional nature of the drug policy crisis. Given the racist evolution of the war on drugs and the harm reduction (HR) movement, the aim of this study is to explore racism within harm reduction services through the perspectives of our participants.MethodsWe conducted a qualitative descriptive study to explore the perspectives of racialized service users and providers on racism in the HR movement in the Greater Toronto and Hamilton Area (GTHA). Four racialized service users and four racialized service providers participated in semi-structured interviews that were audio-recorded, transcribed, and analysed thematically.ResultsFive themes related to racism in HR were generated: (1) whiteness of harm reduction as a barrier to accessing services, (2) diversifying HR workers as a step towards overcoming distrust, (3) drop-in spaces specific to Black, Indigenous, and people of colour are facilitators to accessing harm reduction, (4) lack of representation in HR-related promotional and educational campaigns, and (5) HR as a frontier for policing.ConclusionsOur findings suggest that structural and institutional racism are prevalent in HR services within the GTHA, in the form of colour-blind policies and practices that fail to address the intersectional nature of the drug policy crisis. There is a need for local HR organizations to critically reflect and act on their practices and policies, working with communities to become more equitable, inclusive, and accessible spaces for all people who use drugs.
The Janus-faced role of TRPM2-S in retroperitoneal liposarcoma via increasing ROS levels
Authors: Li Xiangji , Bu Fanqin , Ma Shixiang , Cananzi Ferdinando , Zhao Yu , Xiao Mengmeng , Min Li , Luo Chenghua 
Published: August 2022

Abstract
Background
Retroperitoneal liposarcoma (RPLS) is a specific soft tissue sarcoma with a high recurrence rate. The short isoform of transient receptor potential cation channel subfamily M member 2 (TRPM2-S) plays an important role in the regulation of reactive oxygen species (ROS). However, the association between TRPM2-S and RPLS and its underlying mechanisms remains unclear.

Methods
The expression of both TRPM2-S and TRPM2-L in RPLS tissues was verified by kimmunohistochemistry (IHC). The regulation on Ca2+ influx by TRPM2-S was evaluated by Fluo-4 AM staining. The effect of TRPM2-S on cell proliferation and apoptosis was tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining and Flow cytometry respectively. The level of cellular ROS was assessed by the DCFH-DA probe. Different concentrations of H2O2 were used to provide oxidative stress on RPLS cells. The underlying mechanisms were further explored by Western blotting.

Results
The IHC assays showed that TRPM2-S, but not TRPM2-L, was prognostic in RPLS. Low TRPM2-S level was associated with poor disease-free survival (DFS). Calcium influx signal intensity was significantly decreased under TRPM2-S overexpression, which resulted in a decrease in the levels of FOXO3a and PTEN. Correspondingly, the levels of pERK, pAKT, pP65, pGSK-3β, Bcl-2, and β-catenin were upregulated, and cellular ROS was gently increased under TRPM2-S overexpression. Moreover, TRPM2-S slightly promoted cell proliferation and inhibited apoptosis of RPLS cell lines under normoxia, but largely increased apoptosis rates under oxidative stress. The cleaved caspase3 was significantly upregulated by TRPM2-S overexpression under oxidative stress. N-Acetyl-l-cysteine (NAC), a small molecule antioxidant, could largely rescue RPLS cells from the apoptosis induced by H2O2.

Conclusion
TRPM2-S exerts Janus-faced effects in RPLS by increasing the ROS levels via inhibition on FOXO3a, which promotes cell proliferation under normoxia but induces apoptosis under oxidative stress.
What evidence exists on the effect of the main European lowland crop and grassland management practices on biodiversity indicator species groups? A systematic map protocol
Authors: Séchaud Robin , Van der Meer Markus , Fabian Yvonne , Jeanneret Philippe 
Published: August 2022

Abstract
Background
The intensification of the agricultural practices in Europe over the last decades has drastically transformed the agroecosystems. The simplification of the landscape, the loss of semi-natural habitats and the application of chemicals on crops are known to have led to biodiversity decline in agricultural landscapes, raising substantial concerns about the loss of essential ecosystem services, such as pollination or pest control. Depending on the location, the scale and the regional context, different indicator species groups (ISGs) are often surveyed to assess the state and trend of biodiversity changes in agroecosystems. Although the high diversity of these ISGs allows a broad overview of the biodiversity, it complicates the interpretation of the results and thus their application. In addition, species diversity metrics are various, from simple species counts to more complex measurements of diversity indices, sometimes with antagonistic responses. Here, to meet the pressing need for synthesis in this complex topic, we will follow a standardized systematic map protocol to collect and summarize the literature reporting the effects of the main European lowland agricultural management practices (AMPs) on a set of ISGs.

Methods
Following the systematic evidence synthesis standards, we developed the question to address in the systematic map using the PICO framework. We established a preliminary search string by combining search terms for the categories Population (ISGs), Intervention (AMPs) and Outcome (species diversity), as well as with two additional groups (Environment—to focus on lowland crop and grassland—and Location—to restrict the study area to Europe). We will conduct a comprehensive literature search of relevant peer-reviewed and grey literature using Web of Science and CABI platforms, Google Scholar, specialized websites and through our professional collaborator network. The comprehensiveness of the search will be assessed by comparing the literature collected to a test-list of ninety relevant articles. The repeatability of the literature screening process will be ensured by a list of inclusion/exclusion criteria and inter-reviewer consistency statistical tests. Data extraction will be organized in three complementary tables (article references, study characteristics, species diversity), on which we will perform queries to produce the tables, figures and maps that will compose the systematic map.
An investigation into oral fluency perceived by teachers and students—in a Vietnamese context of English education
Authors: Khau Anh Hoang , Huynh Van Thuy Mai 
Published: August 2022

AbstractThis study attempts to investigate how four groups of participants at Tra Vinh University perceive oral fluency. This study is conducted in the hope to obtain more perceptions of oral fluency so future rubrics can be developed based on such perceptions. The study used a set of items stating what oral fluency should be like, which was developed based on the Qualitative aspects of spoken language proposed by the Council of Europe (2019). To test if the items were accepted, the study invited 33 senior English-majored students, 20 English teachers with a BA, 22 English teachers with an MA, and 10 English teachers with a doctorate degree for the study. A five-point Likert scale questionnaire consisting of 18 closed-ended questions and an open-ended question was employed to collect the participants’ perceptions of oral fluency. The results showed that the participants with an MA and the participants with a doctorate degree tend to agree more with the items in the questionnaire while the other groups slightly agreed with most of the items. Furthermore, many of the participants provided the study with their own ideas about oral fluency, which were finally synthesized. Some limitations and recommendations of the study were also included.
Co-deposition of SOD1, TDP-43 and p62 proteinopathies in ALS: evidence for multifaceted pathways underlying neurodegeneration
Authors: Trist Benjamin G. , Fifita Jennifer A. , Hogan Alison , Grima Natalie , Smith Bradley , Troakes Claire , Vance Caroline , Shaw Christopher , Al-Sarraj Safa , Blair Ian P. , Double Kay L. 
Published: August 2022

AbstractMultiple neurotoxic proteinopathies co-exist within vulnerable neuronal populations in all major neurodegenerative diseases. Interactions between these pathologies may modulate disease progression, suggesting they may constitute targets for disease-modifying treatments aiming to slow or halt neurodegeneration. Pairwise interactions between superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43) and ubiquitin-binding protein 62/sequestosome 1 (p62) proteinopathies have been reported in multiple transgenic cellular and animal models of amyotrophic lateral sclerosis (ALS), however corresponding examination of these relationships in patient tissues is lacking. Further, the coalescence of all three proteinopathies has not been studied in vitro or in vivo to date. These data are essential to guide therapeutic development and enhance the translation of relevant therapies into the clinic. Our group recently profiled SOD1 proteinopathy in post-mortem spinal cord tissues from familial and sporadic ALS cases, demonstrating an abundance of structurally-disordered (dis)SOD1 conformers which become mislocalized within these vulnerable neurons compared with those of aged controls. To explore any relationships between this, and other, ALS-linked proteinopathies, we profiled TDP-43 and p62 within spinal cord motor neurons of the same post-mortem tissue cohort using multiplexed immunofluorescence and immunohistochemistry. We identified distinct patterns of SOD1, TDP43 and p62 co-deposition and subcellular mislocalization between motor neurons of familial and sporadic ALS cases, which we primarily attribute to SOD1 gene status. Our data demonstrate co-deposition of p62 with mutant and wild-type disSOD1 and phosphorylated TDP-43 in familial and sporadic ALS spinal cord motor neurons, consistent with attempts by p62 to mitigate SOD1 and TDP-43 deposition. Wild-type SOD1 and TDP-43 co-deposition was also frequently observed in ALS cases lacking SOD1 mutations. Finally, alterations to the subcellular localization of the three proteins were tightly correlated, suggesting close relationships between the regulatory mechanisms governing the subcellular compartmentalization of these proteins. Our study is the first to profile spatial relationships between SOD1, TDP-43 and p62 pathologies in post-mortem spinal cord motor neurons of ALS patients, previously only studied in vitro. Our findings suggest interactions between these three key ALS-linked proteins are likely to modulate the formation of their respective proteinopathies, and perhaps the rate of motor neuron degeneration, in ALS patients.
Barriers to Quality Perioperative Care Delivery in Low- and Middle-Income Countries: A Qualitative Rapid Appraisal Study
Authors: Bedwell Gillian J. , Dias Priyanthi , Hahnle Lina , Anaeli Amani , Baker Tim , Beane Abi , Biccard Bruce M. , Bulamba Fred , Delgado-Ramirez Martha B. , Dullewe Nilmini P. , Echeverri-Mallarino Veronica , Haniffa Rashan , Hewitt-Smith Adam , Hoyos Alejandra Sanin , Mboya Erick A. , Nanimambi Juliana , Pearse Rupert , Pratheepan Anton Premadas , Sunguya Bruno , Tolppa Timo , Uruthirakumar Powsiga , Vengadasalam Sutharshan , Vindrola-Padros Cecilia , Stephens Timothy J. 
Published: August 2022

BACKGROUND:
Provision of timely, safe, and affordable surgical care is an essential component of any high-quality health system. Increasingly, it is recognized that poor quality of care in the perioperative period (before, during, and after surgery) may contribute to significant excess mortality and morbidity. Therefore, improving access to surgical procedures alone will not address the disparities in surgical outcomes globally until the quality of perioperative care is addressed. We aimed to identify key barriers to quality perioperative care delivery for 3 “Bellwether” procedures (cesarean delivery, emergency laparotomy, and long-bone fracture fixation) in 5 low- and middle-income countries (LMICs).

METHODS:
Ten hospitals representing secondary and tertiary facilities from 5 LMICs were purposefully selected: 2 upper-middle income (Colombia and South Africa); 2 lower-middle income (Sri Lanka and Tanzania); and 1 lower income (Uganda). We used a rapid appraisal design (pathway mapping, ethnography, and interviews) to map out and explore the complexities of the perioperative pathway and care delivery for the Bellwether procedures. The framework approach was used for data analysis, with triangulation across different data sources to identify barriers in the country and pattern matching to identify common barriers across the 5 LMICs.

RESULTS:
We developed 25 pathway maps, undertook >30 periods of observation, and held >40 interviews with patients and clinical staff. Although the extent and impact of the barriers varied across the LMIC settings, 4 key common barriers to safe and effective perioperative care were identified: (1) the fragmented nature of the care pathways, (2) the limited human and structural resources available for the provision of care, (3) the direct and indirect costs of care for patients (even in health systems for which care is ostensibly free of charge), and (4) patients’ low expectations of care.

CONCLUSIONS:
We identified key barriers to effective perioperative care in LMICs. Addressing these barriers is important if LMIC health systems are to provide safe, timely, and affordable provision of the Bellwether procedures.
Plasticity of salmonfly (Pteronarcys californica) respiratory phenotypes in response to changes in temperature and oxygen
Authors: Malison Rachel L. , Frakes James I. , Andreas Amanda L. , Keller Priya R. , Hamant Emily , Shah Alisha A. , Woods H. Arthur 
Published: August 2022

ABSTRACT
Like all taxa, populations of aquatic insects may respond to climate change by evolving new physiologies or behaviors, shifting their range, exhibiting physiological and behavioral plasticity, or going extinct. We evaluated the importance of plasticity by measuring changes in growth, survival and respiratory phenotypes of salmonfly nymphs (the stonefly Pteronarcys californica) in response to experimental combinations of dissolved oxygen and temperature. Overall, smaller individuals grew more rapidly during the 6-week experimental period, and oxygen and temperature interacted to affect growth in complex ways. Survival was lower for the warm treatment, although only four mortalities occurred (91.6% versus 100%). Nymphs acclimated to warmer temperatures did not have higher critical thermal maxima (CTmax), but those acclimated to hypoxia had CTmax values (in normoxia) that were higher by approximately 1°C. These results suggest possible adaptive plasticity of systems for taking up or delivering oxygen. We examined these possibilities by measuring the oxygen sensitivity of metabolic rates and the morphologies of tracheal gill tufts located ventrally on thoracic segments. Mass-specific metabolic rates of individuals acclimated to warmer temperatures were higher in acute hypoxia but lower in normoxia, regardless of their recent history of oxygen exposure during acclimation. The morphology of gill filaments, however, changed in ways that appeared to depress rates of oxygen delivery in functional hypoxia. Our combined results from multiple performance metrics indicate that rising temperatures and hypoxia may interact to magnify the risks to aquatic insects, but that physiological plasticity in respiratory phenotypes may offset some of these risks.
Why did he say that? Teaching physicians-in-training how to recognize hidden emotions in end-of-life prognosis conversations: an autoethnography
Authors: Stonestreet John 
Published: August 2022

Background: This article begins with two unconscionable end-of-life prognosis-related quotes from best-selling physician-author, Atul Gawande, and an unnamed doctor, asking: “Why did he say that?” The article then proceeds to answer this question by showing how physicians’ most common end-of-life communication blunders are rooted in their unexplored emotions. Healthcare’s only widespread communication training focused on examining the role of hidden emotions in influencing the flow of conversation is found in Spiritual Care’s “Verbatim” education modules. While the need for physicians’ emotional self-awareness for improved end-of-life communication has been identified in the literature, no one has explored how this need might be met by custom-tailoring Spiritual Care’s “Verbatim” education modules for physicians-in-training. Methods: This article utilizes the qualitative research method of autoethnography to grant physicians access to the content and power of Spiritual Care’s “Verbatim” education modules for identifying hidden emotions in clinical communication. Results: Using a profound personal example from the author’s firsthand experience of the suggested training tool, the “Verbatim” module is shown to grant revelatory self-knowledge and invaluable emotional intelligence. The same model then illuminates the physician cases. Conclusion: Spiritual Care’s “Verbatim” education modules address universal issues of clinical communication and emotional self-awareness that are applicable to physician-patient/family conversations surrounding end-of-life decision-making. Customizing these communication modules for physicians-in-training may help to address physicians’ emotionally-triggered conversational miscues in end-of-life prognosis communication. Existing programs for complementary end-of-life communication training are noted, and it is claimed that a combination of each of these models, together with the proposed module, may be ideal. It is also admitted that no form of education or training can ensure ethical communication. Therefore the ultimate solution is to supplement communication training with real-time, third-party support and accountability. This can be achieved by the "Doctor Body Cam" intervention protocol, introduced here: https://aquila.usm.edu/ojhe/vol17/iss1/7/.