bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacist attitudes and provision of harm reduction services in North Carolina: an exploratory study
Authors: Parry Rachel A. , Zule William A. , Hurt Christopher B. , Evon Donna M. , Rhea Sarah K. , Carpenter Delesha M. 
Published: July 2021

Abstract
Background
Pharmacists are among the most accessible healthcare providers in the United States and uniquely positioned to provide harm reduction services. The availability of pharmacy-based harm reduction services and pharmacist attitudes toward delivering these services have been understudied to date. We examine North Carolina (NC) pharmacists’ experiences with and attitudes about harm reduction services and explore differences between rural and urban pharmacists.

Methods
A convenience sample of NC pharmacists participated in an anonymous, online survey regarding harm reduction services: non-prescription syringe sales; naloxone dispensing; and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) screening. Urban–rural differences were analyzed using Pearson’s chi-square or Fisher’s exact tests. Open-ended responses were analyzed thematically.

Results
Three hundred pharmacists responded to the survey; 68 (23%) practiced in rural counties. Dispensing non-prescription syringes and naloxone at least occasionally was reported by 77% (n = 231) and 88% (n = 263) pharmacists, respectively. Pharmacy-delivered HIV or HCV screening was rare. Urban pharmacists dispensed naloxone more frequently than rural pharmacies (p = 0.04). Only 52% of pharmacists agreed that persons who inject drugs should always be allowed to buy non-prescription syringes. Rural pharmacists’ attitudes toward harm reduction services for persons who inject drugs were statistically, though marginally, less supportive when compared to urban pharmacists’ attitudes. The most common barrier to non-prescription syringe access was requiring patients to provide proof of prescription injection medication use, which 21% of pharmacists reported was required by their pharmacy’s policy on non-prescription syringe sales.

Conclusions
Although most pharmacies distributed naloxone and sold non-prescription syringes, pharmacy store policies and personal beliefs inhibited naloxone and non-prescription syringe dispensing. NC community pharmacies infrequently offer HIV and HCV screening. Paired with disseminating the evidence of the positive impact of harm reduction on individual and public health outcomes to NC pharmacists, institutional and systems changes to practice and policy may be important to promote harm reduction service availability, particularly for rural NC residents.
Trial registration: N/A.
GSTP1 as a novel target in radiation induced lung injury
Authors: Lei Xiao , Du Lehui , Yu Wei , Wang Yao , Ma Na , Qu Baolin 
Published: July 2021

AbstractThe glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.
Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction
Authors: Oberman Klaske , Hovens Iris , de Haan Jacco , Falcao-Salles Joana , van Leeuwen Barbara , Schoemaker Regien 
Published: July 2021

Abstract
Background
Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model.

Methods
Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14.

Results
Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced.

Conclusion
A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.
How wearable sensors have been utilised to evaluate frailty in older adults: a systematic review
Authors: Vavasour Grainne , Giggins Oonagh M. , Doyle Julie , Kelly Daniel 
Published: July 2021

Abstract
Background
Globally the population of older adults is increasing. It is estimated that by 2050 the number of adults over the age of 60 will represent over 21% of the world’s population. Frailty is a clinical condition associated with ageing resulting in an increase in adverse outcomes. It is considered the greatest challenge facing an ageing population affecting an estimated 16% of community-dwelling populations worldwide.

Aim
The aim of this systematic review is to explore how wearable sensors have been used to assess frailty in older adults.

Method
Electronic databases Medline, Science Direct, Scopus, and CINAHL were systematically searched March 2020 and November 2020. A search constraint of articles published in English, between January 2010 and November 2020 was applied. Papers included were primary observational studies involving; older adults aged > 60 years, used a wearable sensor to provide quantitative measurements of physical activity (PA) or mobility and a measure of frailty. Studies were excluded if they used non-wearable sensors for outcome measurement or outlined an algorithm or application development exclusively. The methodological quality of the selected studies was assessed using the Appraisal Tool for Cross-sectional Studies (AXIS).

Results
Twenty-nine studies examining the use of wearable sensors to assess and discriminate between stages of frailty in older adults were included. Thirteen different body-worn sensors were used in eight different body-locations. Participants were community-dwelling older adults. Studies were performed in home, laboratory or hospital settings. Postural transitions, number of steps, percentage of time in PA and intensity of PA together were the most frequently measured parameters followed closely by gait speed. All but one study demonstrated an association between PA and level of frailty. All reports of gait speed indicate correlation with frailty.

Conclusions
Wearable sensors have been successfully used to evaluate frailty in older adults. Further research is needed to identify a feasible, user-friendly device and body-location that can be used to identify signs of pre-frailty in community-dwelling older adults. This would facilitate early identification and targeted intervention to reduce the burden of frailty in an ageing population.
Antiviral drugs arbidol and interferon alpha-1b contribute to reducing the severity of COVID-19 patients: a retrospective cohort study
Authors: Yin Peng , Meng Juan , Chen Jincheng , Gao Junxiao , Wang Dongqi , Liu Shuyan , Guo Qinglong , Zhu Muchun , Zhang Gengwei , Liu Yingxia , Li Ye , Zhang Guoliang 
Published: July 2021

Abstract
Objectives
The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia.

Methods
This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People’s Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir–ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness.

Results
Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084–0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15–0.58, p =  0.0005). The use of lopinavir–itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of − 5.2 days (IQR − 3.0 to − 7.5, p = 4e−06) compared with the control group.

Conclusion
Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients’ recovery time.
Defending access to medicines in regional trade agreements: lessons from the Regional Comprehensive Economic Partnership – a qualitative study of policy actors’ views
Authors: Townsend Belinda 
Published: July 2021

Abstract
Background
The Regional Economic Partnership Agreement (RCEP) is a mega regional trade agreement signed by fifteen countries on 15 November 2020 after 8 years of negotiation. Signatories include the ten members of the Association of South East Asian Nations (ASEAN) plus China, New Zealand, Japan, South Korea and Australia. India was a negotiating party until it withdrew from the negotiations in November 2019. The RCEP negotiations were initially framed as focused on the needs of low income countries. Public health concerns emerged however when draft negotiating chapters were leaked online, revealing pressures on countries to agree to intellectual property and investment measures that could exacerbate issues of access to medicines and seeds, and protecting regulatory space for public health. A concerted Asia Pacific civil society campaign emerged in response to these concerns, and in 2019, media and government reporting suggested that several of these measures had been taken off the table, which was subsequently confirmed in the release of the signed text in November 2020.

Results
This paper examines civil society and health actors’ views of the conditions that successfully contributed to the removal of these measures in RCEP, with a focus on intellectual property and access to medicines. Drawing on twenty semi-structured qualitative interviews with civil society, government and legal and health experts from nine countries participating in the RCEP negotiations, the paper reports a matrix of ten conditions related to actor power, ideas, political context and specific health issues that appeared to support prioritisation of some public health concerns in the RCEP negotiations.

Conclusions
Conditions identified included strong low and middle income country leadership; strong civil society mobilisation, increased technical capacity of civil society and low and middle income negotiators; supportive public health norms; processes that somewhat opened up the negotiations to hear public health views; the use of evidence; domestic support for health issues; and supportive international public health legislation. Lessons from the RCEP can inform prioritisation of public health in future trade agreement negotiations.
Shape decomposition algorithms for laser capture microdissection
Authors: Selbach Leonie , Kowalski Tobias , Gerwert Klaus , Buchin Maike , Mosig Axel 
Published: July 2021

AbstractBackgroundIn the context of biomarker discovery and molecular characterization of diseases, laser capture microdissection is a highly effective approach to extract disease-specific regions from complex, heterogeneous tissue samples. For the extraction to be successful, these regions have to satisfy certain constraints in size and shape and thus have to be decomposed into feasible fragments.ResultsWe model this problem of constrained shape decomposition as the computation of optimal feasible decompositions of simple polygons. We use a skeleton-based approach and present an algorithmic framework that allows the implementation of various feasibility criteria as well as optimization goals. Motivated by our application, we consider different constraints and examine the resulting fragmentations. We evaluate our algorithm on lung tissue samples in comparison to a heuristic decomposition approach. Our method achieved a success rate of over 95% in the microdissection and tissue yield was increased by 10–30%.ConclusionWe present a novel approach for constrained shape decomposition by demonstrating its advantages for the application in the microdissection of tissue samples. In comparison to the previous decomposition approach, the proposed method considerably increases the amount of successfully dissected tissue.
Targeted therapy in advanced non-small cell lung cancer: current advances and future trends
Authors: Majeed Umair , Manochakian Rami , Zhao Yujie , Lou Yanyan 
Published: July 2021

AbstractLung cancer remains the leading cause of cancer-related mortality in both men and women in the US and worldwide. Non-small cell lung cancer is the most common variety accounting for 84% of the cases. For a subset of patients with actionable mutations, targeted therapy continues to provide durable responses. Advances in molecular and immunohistochemical techniques have made it possible to usher lung cancer into the era of personalized medicine, with the patient getting individualized treatment based on these markers. This review summarizes the recent advances in advanced NSCLC targeted therapy, focusing on first-in-human and early phase I/II clinical trials in patients with advanced disease. We have divided our discussion into different topics based on these agents' mechanisms of action. This article is aimed to be the most current review of available and upcoming targeted NSCLC treatment options. We will also summarize the currently available phase I/II clinical trial for NSCLC patients at the end of each section.
Lowering blood pressure by changing lifestyle through a motivational education program: a cluster randomized controlled trial study protocol
Authors: Islam Fakir M Amirul , Lambert Elisabeth A. , Islam Sheikh Mohammed Shariful , Islam M. Ariful , Biswas Dip , McDonald Rachael , Maddison Ralph , Thompson Bruce , Lambert Gavin W. 
Published: July 2021

Abstract
Background
High blood pressure is an independent risk factor of cardiovascular disease (CVD) and is a major cause of disability and death. Managing a healthy lifestyle has been shown to reduce blood pressure and improve health outcomes. We aim to investigate the effectiveness of a lifestyle modification intervention program for lowering blood pressure in a rural area of Bangladesh.

Methods
A single-center cluster randomized controlled trial (RCT). The study will be conducted for 6 months, a total of 300 participants of age 30 to 75 years with 150 adults in each of the intervention and the control arms. The intervention arm will involve the delivery of a blended learning education program on lifestyle changes for the management of high blood pressure. The education program comprises evidence-based information with pictures, fact sheets, and published literature about the effects of high blood pressure on CVD development, increased physical activity, and the role of a healthy diet in blood pressure management. The control group involves providing information booklets and general advice at the baseline data collection point. The primary outcome will be the absolute difference in clinic SBP and DBP. Secondary outcomes include the difference in the percentage of people adopting regular exercise habits, cessation of smoking and reducing sodium chloride intake, health literacy of all participants, and the perceived barriers and enablers to adopt behavior changes by collecting qualitative data. Analyses will include analysis of covariance to report the mean difference in blood pressure between the control and the intervention group and the difference in change in blood pressure due to the intervention.

Discussion
The study will assess the effects of physical activity and lifestyle modification in controlling high blood pressure. This study will develop new evidence as to whether a simple lifestyle program implemented in a rural region of a low- and middle-income country will improve blood pressure parameters for people with different chronic diseases by engaging community people.

Trial registration
ClinicalTrials.gov NCT04505150. Registered on 7 August 2020
Effects of traditional Chinese medicine combined with chemotherapy for extensive-stage small-cell lung cancer patients on improving oncologic survival: study protocol of a multicenter, randomized, single-blind, placebo-controlled trial
Authors: Chen Yuyi , Yu Mingwei , Liu Zishen , Zhang Yi , Li Qiwei , Yang Guowang 
Published: July 2021

Abstract
Background
Extensive-stage small-cell lung cancer (ES-SCLC) is characterized by extensive metastases, aggressive progression, and poor prognosis. Chemotherapy is applied as a preferred first-line regimen for ES-SCLC, but inadequate for improving its overall survival. Traditional Chinese medicine (TCM) is widely used in the clinical practice of ES-SCLC for its synergy with chemotherapy. However, there is still no substantial evidence to prove that TCM can effectively improve the long-term efficacy of ES-SCLC patients. The study intends to determine whether the TCM with chemotherapy can improve the overall survival (OS) in treating with ES-SCLC when compared with chemotherapy alone.

Method/design
A multicenter, randomized, single-blind, placebo-controlled clinical trial will be conducted to determine whether the TCM granules combined with chemotherapy can improve the OS of ES-SCLC. Two hundred seventy participants will randomly receive 4–6 cycles (21 days per cycle) of chemotherapy plus TCM granules or placebo. The primary outcome measure is OS. The secondary outcome measures includes progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and tumor markers. Visits will be performed at the end of each cycle during the treatment period and then every 3 months in the follow-up period until the patients’ death or study completion.

Discussion
The study’s result will provide a high-level evidence for TCM granules using with chemotherapy on the first-line treatment of ES-SCLC.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900022991. Registered on 6 May 2019 (prospective registration).
High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification
Authors: Olbrecht Siel , Busschaert Pieter , Qian Junbin , Vanderstichele Adriaan , Loverix Liselore , Van Gorp Toon , Van Nieuwenhuysen Els , Han Sileny , Van den Broeck Annick , Coosemans An , Van Rompuy Anne-Sophie , Lambrechts Diether , Vergote Ignace 
Published: July 2021

Abstract
Background
High-grade serous tubo-ovarian cancer (HGSTOC) is characterised by extensive inter- and intratumour heterogeneity, resulting in persistent therapeutic resistance and poor disease outcome. Molecular subtype classification based on bulk RNA sequencing facilitates a more accurate characterisation of this heterogeneity, but the lack of strong prognostic or predictive correlations with these subtypes currently hinders their clinical implementation. Stromal admixture profoundly affects the prognostic impact of the molecular subtypes, but the contribution of stromal cells to each subtype has poorly been characterised. Increasing the transcriptomic resolution of the molecular subtypes based on single-cell RNA sequencing (scRNA-seq) may provide insights in the prognostic and predictive relevance of these subtypes.

Methods
We performed scRNA-seq of 18,403 cells unbiasedly collected from 7 treatment-naive HGSTOC tumours. For each phenotypic cluster of tumour or stromal cells, we identified specific transcriptomic markers. We explored which phenotypic clusters correlated with overall survival based on expression of these transcriptomic markers in microarray data of 1467 tumours. By evaluating molecular subtype signatures in single cells, we assessed to what extent a phenotypic cluster of tumour or stromal cells contributes to each molecular subtype.

Results
We identified 11 cancer and 32 stromal cell phenotypes in HGSTOC tumours. Of these, the relative frequency of myofibroblasts, TGF-β-driven cancer-associated fibroblasts, mesothelial cells and lymphatic endothelial cells predicted poor outcome, while plasma cells correlated with more favourable outcome. Moreover, we identified a clear cell-like transcriptomic signature in cancer cells, which correlated with worse overall survival in HGSTOC patients. Stromal cell phenotypes differed substantially between molecular subtypes. For instance, the mesenchymal, immunoreactive and differentiated signatures were characterised by specific fibroblast, immune cell and myofibroblast/mesothelial cell phenotypes, respectively. Cell phenotypes correlating with poor outcome were enriched in molecular subtypes associated with poor outcome.

Conclusions
We used scRNA-seq to identify stromal cell phenotypes predicting overall survival in HGSTOC patients. These stromal features explain the association of the molecular subtypes with outcome but also the latter’s weakness of clinical implementation. Stratifying patients based on marker genes specific for these phenotypes represents a promising approach to predict prognosis or response to therapy.