bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the socio-ecological model to explore factors that influence the implementation of a diabetes structured education programme (EXTEND project) inLilongwe, Malawi and Maputo, Mozambique: a qualitative study
Authors: Bamuya C. , Correia J. C. , Brady E. M. , Beran D. , Harrington D. , Damasceno A. , Crampin A. M. , Magaia Ana , Levitt Naomi , Davies M. J. , Hadjiconstantinou M.
Published: July 2021

Background

Diabetes Self-Management Education and Support (DSMES) programmes are vital for type 2 diabetes mellitus (T2DM) management. However, they are limited in Sub-Saharan Africa (SSA). To address this gap, a DSMES, namedEXTEND was developed in Lilongwe (Malawi) and Maputo (Mozambique). This qualitative study aimed to explore factors that influence the implementation of DSMES in these settings.

Methods

The Socio-ecological model was applied to explore factors influencing the implementation of DSMES in SSA. Data was analysed using the Framework method and constant comparative techniques. Sixty-six people participated in the study: people with T2DM who participated in the EXTEND programme; healthcare professionals (HCPs), EXTEND educators, EXTEND trainers, and stakeholders.

Results

Our findings indicate that there is a need to develop an integrated and dedicated diabetes services in SSA healthcare systems, incorporating culturally adapted DSMES and tailored diabetes training to all professions involved in diabetes management. Traditional media and the involvement of community leaders were proposed as important elements to help engage and promote DSMES programmes in local communities. During the design and implementation of DSMES, it is important to consider individual and societal barriers to self-care.

Conclusion

Findings from this study suggest that multi-faceted factors play a significant role to the implementation of DSMES programmes in LICs. In the future, EXTEND could be incorporated in the development of diabetes training and dedicated diabetes services in SSA healthcare systems, acting as an educational tool for both people with T2DM and HCPs. This project was supported by the Medical Research Council GCRF NCDs Foundation Awards 2016 Development Pathway Funding.
Men’s perceptions of sexual and reproductive health education within the context of pregnancy and HIV in Zambia: a descriptive qualitative analysis
Authors: Matenga Tulani Francis L. , Zulu Joseph Mumba , Nkwemu Sharon , Shankalala Perfect , Hampanda Karen
Published: July 2021

Background

Although health care providers are beginning to focus on men’s roles as fathers and husbands, there is limited understanding of how men view their ability to promote sexual and reproductive health in families affected by HIV and their experiences with receiving education through antenatal care. This paper aims to explore men’s perceptions of the education they need regarding sexual and reproductive health within the family in the context of HIV.

Methods

We interviewed a convenience sample of 18 male partners of pregnant women living with HIV in Lusaka, Zambia. Atlas.ti was used to facilitate data management and content analysis.

Results

Men reported being the primary decision-makers regarding sexual and reproductive issues in the family; however, they admitted far-reaching unmet needs in terms of information on sexual and reproductive health in the context of HIV. Most men felt that antenatal care was not a conducive setting to fully educate men on sexual and reproductive health because it is a woman’s space where their health concerns were generally neglected. There was a strong desire for more education that was specific to men’s sexual and reproductive health, especially because all the couples were affected by HIV. Men especially requested education on sexual preparedness, safe sex, the use of condoms in sero-concordant and sero-discordant relationships and general health information. Although men stated they were the main decision-makers regarding sexual and reproductive issues such as pregnancy, most men were not confident in their ability to promote sexual and reproductive health in the family because of limited knowledge in this area.

Conclusion

There is need to change the environment and messaging of antenatal care, as well as offer relevant education opportunities outside health facility settings to empower men with essential information for meaningful involvement in sexual and reproductive health in the context of HIV.
Evaluating the relationship between clinical and demographic characteristics of insulin-using people with diabetes and their health outcomes: a cluster analysis application
Authors: Eby Elizabeth L. , Edwards Alison , Meadows Eric , Lipkovich Ilya , Benneyworth Brian D. , Snow Kenneth
Published: July 2021

Background

The aim of this study was to determine how clusters or subgroups of insulin-treated people with diabetes, based upon healthcare resource utilization, select social demographic and clinical characteristics, and diabetes management parameters, are related to health outcomes including acute care visits and hospital admissions.

Methods

This was a non-experimental, retrospective cluster analysis. We utilized Aetna administrative claims data to identify insulin-using people with diabetes with service dates from 01 January 2015 to 30 June 2018. The study included adults over the age of 18 years who had a diagnosis of type 1 (T1DM) or type 2 diabetes mellitus (T2DM) on insulin therapy and had Aetna medical and pharmacy coverage for at least 18 months (6 months prior and 12 months after their index date, defined as either their first insulin prescription fill date or their earliest date allowing for 6 months’ prior coverage). We used K-means clustering methods to identify relevant subgroups of people with diabetes based on 13 primary outcome variables.

Results

A total of 100,650 insulin-using people with diabetes were identified in the Aetna administrative claims database and met study criteria, including 11,826 (11.7%) with T1DM and 88,824 (88.3%) with T2DM. Of these 79,053 (78.5%) people were existing insulin users. Seven distinct clusters were identified with different characteristics and potential risks of diabetes complications. Overall, clusters were significantly associated with differences in healthcare utilization (emergency room visits, inpatient admissions, and total inpatient days) after multivariable adjustment.

Conclusions

This analysis of healthcare claims data using clustering methodologies identified meaningful subgroups of patients with diabetes using insulin. The subgroups differed in comorbidity burden, healthcare utilization, and demographic factors which could be used to identify higher risk patients and/or guide the management and treatment of diabetes.
A realist systematic review of evidence from low- and middle-income countries of interventions to improve immunization data use
Authors: Osterman Allison L. , Shearer Jessica C. , Salisbury Nicole A.
Published: July 2021

Background

The use of routine immunization data by health care professionals in low- and middle-income countries remains an underutilized resource in decision-making. Despite the significant resources invested in developing national health information systems, systematic reviews of the effectiveness of data use interventions are lacking. Applying a realist review methodology, this study synthesized evidence of effective interventions for improving data use in decision-making.

Methods

We searched PubMed, POPLINE, Centre for Agriculture and Biosciences International Global Health, and African Journals Online for published literature. Grey literature was obtained from conference, implementer, and technical agency websites and requested from implementing organizations. Articles were included if they reported on an intervention designed to improve routine data use or reported outcomes related to data use, and targeted health care professionals as the principal data users. We developed a theory of change a priori for how we expect data use interventions to influence data use. Evidence was then synthesized according to data use intervention type and level of the health system targeted by the intervention.

Results

The searches yielded 549 articles, of which 102 met our inclusion criteria, including 49 from peer-reviewed journals and 53 from grey literature. A total of 66 articles reported on immunization data use interventions and 36 articles reported on data use interventions for other health sectors. We categorized 68 articles as research evidence and 34 articles as promising strategies. We identified ten primary intervention categories, including electronic immunization registries, which were the most reported intervention type (n = 14). Among the research evidence from the immunization sector, 32 articles reported intermediate outcomes related to data quality and availability, data analysis, synthesis, interpretation, and review. Seventeen articles reported data-informed decision-making as an intervention outcome, which could be explained by the lack of consensus around how to define and measure data use.

Conclusions

Few immunization data use interventions have been rigorously studied or evaluated. The review highlights gaps in the evidence base, which future research and better measures for assessing data use should attempt to address.
Work-related stress and intention to leave among midwives working in Swiss maternity hospitals – a cross-sectional study
Authors: Peter Karin Anne , Meier-Kaeppeli Barbara , Pehlke-Milde Jessica , Grylka-Baeschlin Susanne
Published: July 2021

Background

Health systems around the globe are struggling to recruit qualified health professionals. Work-related stress plays an important role in why health professionals leave their profession prematurely. However, little is known about midwives’ working conditions and intentions to leave their profession, although this knowledge is key to work force retention. Therefore, we aimed to investigate work-related stress among midwives working in Swiss maternity hospitals, as well as differences between midwives and other health professionals and the stressors associated with midwives’ intention to leave the profession.

Methods

We conducted a data analysis of two cross-sectional studies encompassing midwives working in labour, postpartum and/or gynaecology wards of 12 public Swiss maternity hospitals. Data was collected by self-report questionnaire assessing potential stressors and long-term consequences of stress at work. Data were analysed using descriptive statistics, Kruskal Wallis tests and logistic regression modelling.

Results

A total of 98 midwives took part in the study and one in three midwives reported doing overtime sometimes-always. Also, the score for work-private life conflicts was significantly higher among midwives than among other health professionals, with the exception of physicians (M = 37.0 versus 50.2, p < .001). Midwives’ meaning of work score (M = 89.4) was significantly higher than that of other health professionals (e.g. nurses (M = 83.0, p < .001) or physicians (M = 82.5, p < .01)). Generation Y midwives showed a significantly higher intention to leave their organisation than did the baby boomers (Mean scores 29.3 versus 10.0, p < .01). Results of the regression model revealed that if midwives could compensate for their overtime in the same month, their intention to leave the profession was lower (OR = 0.23, p < .05). Additionally, the more midwives were affected by work-private life conflicts (OR = 3.01, p < .05) and thoughts about leaving their organisation (OR = 6.81, p < .05), the higher was their intention to leave their profession prematurely.

Conclusions

The comparison with other health professions and the higher intention to leave the profession of younger midwife generations are important findings for heads of institutions as well as policy makers, and should stimulate them to develop strategies for keeping midwives on their staff. More extensive studies should implement and test interventions for reducing work-related stress and increasing the job and occupational satisfaction of midwives.
Are Nepal’s water, sanitation and hygiene and menstrual hygiene policies and supporting documents inclusive of disability? A policy analysis
Authors: Wilbur Jane , Scherer Nathaniel , Mactaggart Islay , Shrestha Govind , Mahon Thérèse , Torondel Belen , Hameed Shaffa , Kuper Hannah
Published: July 2021

Purpose

This study assesses the inclusion of disability in Nepal’s policy and guidance relevant to water, sanitation and hygiene (WASH), and menstrual hygiene management (MHM) in comparison to gender. We investigated both policy formulation and implementation, using the Kavrepalanchok district as a case study.

Materials and methods

We used the EquiFrame framework, adapted for disability and gender, and focusing on WASH and MHM. Ten Nepali policies and guidance documents were reviewed and scored for quality against the framework, which included 21 core concepts of human rights. We also interviewed key informants to consider the inclusion of disability in the implementation of MHM interventions. We applied stratified purpose sampling to 12 government officials and service providers working in Kathmandu and the Kavrepalanchock district; conducted in-depth interviews and analysed data thematically using Nvivo 11.

Results

Disability was inadequately covered within the policy documents, and MHM policy commitments for disability were almost non-existent. Participation of people with disabilities in policy development was limited; within Kavrepalanchok, policy commitments were not implemented as intended and disability service providers were unable to allocate government resources. Inadequate data on disability and MHM resulted in limited professional understanding of the issues, as service providers had no training. A narrow WASH infrastructure approach to improving MHM for people with disabilities was prioritised. MHM interventions were delivered in schools; these failed to reach children with disabilities who are often out of school. Finally, there were indications that some caregivers seek sterilisation for people with disabilities who are unable to manage menstruation independently.

Conclusion

Though the Constitution of Nepal enshrines gender equality and disability inclusion, there are consistent gaps in attention to disability and MHM in policies and practice. These omit and exclude people with disabilities from MHM interventions. Investment is required to generate evidence on the MHM barriers faced by people with disabilities, which would then be drawn on to develop training on these issues for professionals to improve understanding. Subsequently, policy makers could include more concepts of human rights against disability in relevant policies and service providers could implement policy commitments as intended.
Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy
Authors: Wang Xiaoyan , Wu Ming , Zhang Xiaolong , Li Feida , Zeng Yongyi , Lin Xinyi , Liu Xiaolong , Liu Jingfeng
Published: July 2021

Background

Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy.

Results

The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo.

Conclusion

BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.

Graphic abstract
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

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

The 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

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

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

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

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

Background

In 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.

Results

We 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%.

Conclusion

We 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

Lung 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

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

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

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.
Effect of KCNQ1 rs2237892 polymorphism on the predisposition to type 2 diabetes mellitus: An updated meta-analysis
Authors: Jiang Hong-Liang , Du Han , Deng Ying-Jun , Liang Xue
Published: July 2021

Objectives

Previous studies have analyzed the potential effect ofKCNQ1rs2237892 polymorphism on the predisposition to type 2 diabetes mellitus, but the findings are inconclusive and the subject of debate. The purpose of our study was to provide further insight into the potential association betweenKCNQ1rs2237892 polymorphism and the risk of type 2 diabetes mellitus.

Methods

In total, 50 articles (60 studies) with 77,276 cases and 76,054 controls were utilized in our analysis. The pooled odds ratio (OR), 95% confidence interval (95% CI), andpvalue were used to evaluate the significance of our findings. Funnel plots and Beggar’s regression tests were utilized to determine the presence of publication bias.

Results

Our meta-analysis results indicated thatKCNQ1rs2237892 polymorphism could be correlated with the risk of type 2 diabetes mellitus under the C allelic, recessive, and dominant genetic models (OR = 1.25, 95% 1.19–1.32,p < 0.001; OR = 1.50, 95% CI 1.34–1.68,p < 0.001; OR = 1.26, 95% CI 1.14–1.40,p < 0.001, respectively). Additionally, ethnicity analysis revealed that the source of control, case size, and Hardy–Weinberg Equilibrium status were correlated to the polymorphism in the three genetic models.

Conclusions

Our meta-analysis demonstrated significant evidence to support the association betweenKCNQ1rs2237892 polymorphism and predisposition to type 2 diabetes mellitus.
Fixed point results for weak contractions in partially ordered b-metric space
Authors: Seshagiri Rao N. , Kalyani K. , Prasad K.
Published: July 2021

Objectives

We explore the existence of a fixed point as well as the uniqueness of a mapping in an ordered b-metric space using a generalized $$({\check{\psi }}, \hat{\eta })$$

(

ψ
ˇ

,

η
^

)

-weak contraction. In addition, some results are posed on a coincidence point and a coupled coincidence point of two mappings under the same contraction condition. These findings generalize and build on a few recent studies in the literature. At the end, we provided some examples to back up our findings.

Result

In partially ordered b-metric spaces, it is discussed how to obtain a fixed point and its uniqueness of a mapping, and also investigated the existence of a coincidence point and a coupled coincidence point for two mappings that satisfying generalized weak contraction conditions.
Sublingual immunotherapy tablet: a cost-minimizing alternative in the treatment of tree pollen-induced seasonal allergic rhinitis in Canada
Authors: Ellis Anne K. , Gagnon Rémi , Hammerby Eva , Shen Julia , Gosain Sheena
Published: July 2021

Background

A cost-minimization analysis (CMA) was performed to evaluate the economic implications of introducing the SQ Tree sublingual immunotherapy (SLIT)-tablets marketed as ITULATEK® (Health Canada regulatory approval in April 2020) for the treatment of pollen-induced (birch, alder and/or hazel) seasonal allergic rhinitis in Canada (Ontario and Quebec), where Tree Pollen subcutaneous immunotherapy (SCIT) is already an available treatment option.

Methods

A CMA was deemed appropriate and was based on the assumption that the SQ Tree SLIT-tablets have comparable efficacy to Tree Pollen SCIT. A societal perspective was adopted in the model, including relevant costs of medications, costs of health care services, and productivity losses. The time horizon in the model was three years, which corresponds to a minimal treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where available, and validated by Canadian specialist clinicians (allergists) in active practice in Ontario and in Quebec, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, scenario analyses were performed by testing alternative assumptions for selected parameters (e.g., Tree Pollen SCIT resource use, discount rates, number of injections, annual SCIT dosing with maintenance injections, and nurse time support), to evaluate their impact on the results of the analysis.

Results

The direct costs, including the drug costs, and physician services costs, for three years of treatment, were similar for both SQ Tree SLIT-tablets vs. Tree Pollen SCIT in both Ontario and Quebec ($2799.01 and $2838.70 vs. $2233.76 and $2266.05 respectively). However, when the indirect costs (including patient’s travel expenses and lost working hours) are included in the model, total savings for the treatment with SQ Tree SLIT-tablets of $1111.79 for Ontario and $1199.87 for Quebec were observed. Scenario analyses were conducted and showed that changes in assumptions continue to result in the savings of SQ Tree SLIT- tablets over Tree Pollen SCIT.

Conclusions

The CMA indicates that SQ Tree SLIT-tablets are a cost-minimizing alternative to Tree Pollen SCIT when considered from a societal perspective in Ontario and Quebec.
Autism-associated biomarkers: test–retest reliability and relationship to quantitative social trait variation in rhesus monkeys
Authors: Oztan Ozge , Talbot Catherine F. , Argilli Emanuela , Maness Alyssa C. , Simmons Sierra M. , Mohsin Noreen , Del Rosso Laura A. , Garner Joseph P. , Sherr Elliott H. , Capitanio John P. , Parker Karen J.
Published: July 2021

Background

Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1–3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores.

Methods

Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: “Case 2A” intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling.

Results

All biological measures (except AKT) showed significant test–retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects).

Conclusions

These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.