bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
Authors: Glass Evan B. , Hoover Alyssa A. , Bullock Kennady K. , Madden Matthew Z. , Reinfeld Bradley I. , Harris Whitney , Parker Dominique , Hufnagel Demetra H. , Crispens Marta A. , Khabele Dineo , Rathmell W. Kimryn , Rathmell Jeffrey C. , Wilson Andrew J. , Giorgio Todd D. , Yull Fiona E. 
Published: May 2022

Abstract
Background
Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer.

Methods
We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models.

Results
Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model.

Conclusions
In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies.
Living with presbyopia: experiences from a virtual roundtable dialogue among impacted individuals and healthcare professionals
Authors: Brujic Mile , Kruger Paola , Todd Jeff , Barnes Elizabeth , Wuttke Mark , Perna Flavia , Aliò Jorge 
Published: May 2022

Abstract
Background
Presbyopia is a common progressive vision disorder characterised by an inability to focus on near objects. The emergence of newer treatment options in addition to spectacles or contact lenses highlights the importance of assessing patient/user preferences.

Methods
People with presbyopia and healthcare professionals (HCPs) took part in a moderated, structured discussion of specific questions on a virtual advisory-board platform. The objective was to better understand unmet needs and the experience of living with the condition. Closed and open questions were included.

Results
Nine individuals (age 40 to 70 years) with presbyopia participated, from Australia, China, France, Italy, Ireland, Japan and the US. One ophthalmologist and one optometrist represented the perspective of HCPs. Over two weeks, 621 posts were entered on the platform. There was widespread agreement that the often stated association between age and presbyopia was unfortunate. Some participants had developed presbyopia at 30–45 years of age. What is more, the association with age was seen as implying a natural process, reducing the incentive to treat. Instead there was a call for an action-oriented view of presbyopia as a condition which may be effectively treated in the future. All participants experienced dealing with presbyopia as burdensome, affecting quality of life to varying degrees. When considering new treatments, convenience was the most important factor. The option to administer drops when needed was considered favourable, but short-acting treatments may not reduce inconvenience compared with spectacles. Participants viewed a therapy that targets the underlying cause of the condition favourably compared with symptomatic treatment. Side effects would severely reduce the appeal of drops. For clinical trials in presbyopia, patient-reported outcomes should be mandatory and need adequately to capture quality of life. Studies in presbyopia must be designed to minimise the inconvenience to participants in order to counter the risk of high drop-out rates.

Conclusions
The interactive format provided insights into living with presbyopia, particularly the negative impact on quality of life, subjects’ openness to new therapies, and the need to move away from considering the condition an unavoidable and intractable consequence of ageing.
Unconditional cash transfers and maternal substance use: findings from a randomized control trial of low-income mothers with infants in the U.S.
Authors: Yoo Paul Y. , Duncan Greg J. , Magnuson Katherine , Fox Nathan A. , Yoshikawa Hirokazu , Halpern-Meekin Sarah , Noble Kimberly G. 
Published: May 2022

Abstract
Background
Policy debates over anti-poverty programs are often marked by pernicious stereotypes suggesting that direct cash transfers to people residing in poverty encourage health-risking behaviors such as smoking, drinking, and other substance use. Causal evidence on this issue is limited in the U.S. Given the prominent role of child allowances and other forms of cash assistance in the 2021 American Rescue Plan and proposed Build Back Better legislation, evidence on the extent to which a monthly unconditional cash gift changes substance use patterns among low-income mothers with infants warrants attention, particularly in the context of economic supports that can help improve early environments of children.

Method
We employ a multi-site, parallel-group, randomized control trial in which 1,000 low-income mothers in the U.S. with newborns were recruited from hospitals shortly after the infant’s birth and randomly assigned to receive either a substantial ($333) or a nominal ($20) monthly cash gift during the early years of the infant’s life. We estimate the effect of the unconditional cash transfer on self-report measures of maternal substance use (i.e., alcohol, cigarette, or opioid use) and household expenditures on alcohol and cigarettes after one year of cash gifts.

Results
The cash gift difference of $313 per month had small and statistically nonsignificant impacts on group differences in maternal reports of substance use and household expenditures on alcohol or cigarettes. Effect sizes ranged between − 0.067 standard deviations and + 0.072 standard deviations. The estimated share of the $313 group difference spent on alcohol and tobacco was less than 1%.

Conclusions
Our randomized control trial of monthly cash gifts to mothers with newborn infants finds that a cash gift difference of $313 per month did not significantly change maternal use of alcohol, cigarettes, or opioids or household expenditures on alcohol or cigarettes. Although the structure of our cash gifts differs somewhat from that of a government-provided child allowance, our null effect findings suggest that unconditional cash transfers aimed at families living in poverty are unlikely to induce large changes in substance use and expenditures by recipients.

Trial Registration
Registered on Clinical Trials.gov NCT03593356 in July of 2018.
Pregnant adolescents’ lived experiences and coping strategies in peri-urban district in Southern Ghana
Authors: Kotoh Agnes M. , Sena Amekudzie Bernice , Opoku-Mensah Kwabena , Baku Elizabeth Aku , Glozah Franklin N. 
Published: May 2022

Abstract
Background
Adolescence, a transition period from childhood to adulthood forms the foundation of health in later life. The adolescence period which should have been characterised by good health is often marred with life-threatening and irreparable consequences of public health concern. Teen pregnancy is problematic because it could jeopardise adolescents’ safe transition to adulthood which does not only affect adolescents, but also their families, babies and society. There is ample evidence about the determinants and effects of teen pregnancy, but it is fragmented and incomplete, especially in Sub-Sahara Africa. This study presents pregnant adolescents’ voices to explain significant gaps in understanding their lived experiences and coping strategies.

Methods
This narrative inquiry, involved in-depth interviews with 16 pregnant adolescents, who were recruited from a peri-urban district in Southern Ghana using purposive and snowball techniques in health facilities and communities respectively. The audio recorded interviews were transcribed verbatim and analysed manually using content analysis.

Results
Many pregnant adolescents are silent victims of a hash socio-economic environment, in which they experience significant financial deprivation, parental neglect and sexual abuse. Also, negative experiences of some adolescent girls such as scolding, flogging by parents, stigmatisation and rejection by peers and neighbors result in grieve, stress and contemplation of abortion and or suicide. However, adolescents did not consider abortion as the best option with regard to their pregnancy. Rather, family members provided adolescents with critical support as they devise strategies such as avoiding people, depending on God and praying to cope with their pregnancy.

Conclusion
Adolescent pregnancy occurred through consensual sex, transactional sex and sexual abuse. While parents provide support, pregnant adolescents self-isolate, depend on God and pray to cope with pregnancy and drop out of school. We recommend that the Ministries of Education and Health, and law enforcement agencies should engage community leaders and members, religious groups, non-governmental organisations and other key stakeholders to develop interventions aimed at supporting girls to complete at least Senior High School. While doing this, it is also important to provide support to victims of sexual abuse and punish perpetrators accordingly.
Primary care patients’ perspectives on the use of non-pharmacological home remedies in Geneva: a cross-sectional study
Authors: Winkler Neria E. , Sebo Paul , Haller Dagmar M. , Maisonneuve Hubert 
Published: May 2022

Abstract
Background
Home remedies are anchored in patients’ everyday life, but their use in Western cultures remains scarcely explored. Our objectives were to investigate primary care patients’ perspectives and use of non-pharmacological home remedies in Geneva (Switzerland).

Methods
In spring 2020, we conducted a cross-sectional survey among adult primary care patients in randomly selected general practices (N = 15). Patients were recruited in the waiting rooms and asked to complete a questionnaire about their sociodemographic characteristics, their home remedy use, and their expectations and reasons for using (or not using) home remedies. We employed descriptive statistics to summarise the data and logistic regression adjusted for clustering within practices to explore associations between home remedy use and participants’ sociodemographic characteristics.

Results
Three hundred fourteen of three hundred ninety patients agreed to participate in the study (participation rate 80.5%). Home remedies were used by 64.4% of patients. The main reasons given were for preventive purposes (55.3%), self-care (41.0%), as an alternative to conventional medicine (40.5%) and to avoid or delay a medical consultation (38.5%). One-third of patients considered that it was the GP’s role to spontaneously inform them about home remedies (36.4%), another third considered that it was the GP’s role to inform them, but only upon specific request (32.3%), and the last third of patients declared that it was not the GP’s role to provide information about home remedies (30.3%). Patients living in an urban zone (adjusted OR 2.1; 95%CI 1.0–4.4; p 0.05) and those with a tertiary education background (adjusted OR 1.9; 95%CI 1.0–3.6; p 0.05) believed that it was their GP’s role to inform them about home remedies.

Conclusions
Home remedies are used by a majority of primary care patients in Geneva. For a comprehensive and safe healthcare management in the context of patient-oriented medicine, more evidence-based research on efficacy and safety of home remedies as well as their place in primary care consultation is required.
Hybrid versus distance learning environment for a paediatric dentistry course and its influence on students’ satisfaction: a cross-sectional study
Authors: Yousry Yasmin Mohamed , Azab Maha Moussa 
Published: May 2022

Abstract
Background
During the novel COVID-19 pandemic, many universities adopted distance and hybrid learning as a modification to their teaching methods to ensure continuity of education, abiding by the worldwide recommendations of social distancing.

Aim
To compare learning environments created through hybrid learning versus distance learning, to deliver paediatric dentistry course, and to assess the correlation between the created learning environment and students’ satisfaction.

Method
In this cross-sectional study, students enrolled in a hybrid paediatric dentistry course were asked to participate in an electronic survey. The learning environment was assessed using Distance Educational Learning Environment Survey (DELES), students’ satisfaction was assessed using Satisfaction Scale (SS). Retrospective data for distance learning course was used for comparison. Ordinal data were compared using Mann-Whitney U test. Spearman’s rank order correlation coefficient was used to correlate students’ satisfaction with DELES. Multiple regression analysis was used to predict satisfaction.

Results
A total of 376 students’ data were considered in the study. Hybrid learning had significantly higher scores than distance learning in 3 DELES scales. There was a statistically significant weak positive correlation between satisfaction and DELES. Multiple regression analysis model was statistically significant and accounted for (22.8%) of the variance in students’ satisfaction. Only “Instructor support” (p = 0.001) and “Student autonomy” (p < 0.001) had a significant effect on satisfaction.

Conclusion
This study supports the superiority of a hybrid learning environment over a complete distance learning environment, it also shows that satisfaction is correlated and can be predicted by the created learning environment.

Trial registration
This study has been registered on clinicaltrials.gov on 21 May 2020 with an identifier: NCT04401371.
Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies
Authors: Perez-Cornago Aurora , Dunneram Yashvee , Watts Eleanor L. , Key Timothy J. , Travis Ruth C. 
Published: May 2022

Abstract
Background
The association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity relates to fatal prostate cancer and described the cross-sectional associations of commonly used adiposity measurements with adiposity estimated by imaging in UK Biobank. We also conducted a dose-response meta-analysis to integrate the new data with existing prospective evidence.

Methods
218,237 men from UK Biobank who were free from cancer at baseline were included. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis.

Results
In UK Biobank, 661 men died from prostate cancer over a mean follow-up of 11.6 years. In the subsample of participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI, body fat percentage and WC were strongly associated with imaging estimates of total and central adiposity (e.g. visceral fat, trunk fat). The hazard ratios (HR) for prostate cancer death were 1.07 (95% confidence interval = 0.97–1.17) per 5 kg/m2 higher BMI, 1.00 (0.94–1.08) per 5% increase in total body fat percentage, 1.06 (0.99–1.14) per 10 cm increase in WC and 1.07 (1.01–1.14) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 19,633 prostate cancer deaths for BMI, 670 for body fat percentage, 3181 for WC and 1639 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.07–1.12), 1.03 (0.96–1.11), 1.07 (1.03–1.11), and 1.06 (1.01–1.10), respectively.

Conclusion
Overall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven and/or due to differences in detection. In either case, these findings support the benefit for men of maintaining a healthy body weight.
Effectiveness of oral care interventions on malodour in dogs
Authors: Croft Julie M. , Patel Krusha V. , Inui Taichi , Ruparell Avika , Staunton Ruth , Holcombe Lucy J. 
Published: May 2022

AbstractBackgroundOral malodour is identified by pet owners as an unpleasant inconvenience, but they may not recognise this likely indicates underlying disease. The primary cause of oral malodour relates to the presence of bacteria in the oral cavity often associated with gingivitis and periodontitis. The purpose of this study was to determine the effect of feeding two oral care chews with different textural properties on oral malodour and the proportion of bacterial species involved in the production of volatile sulphur compounds (VSCs).MethodsFourteen dogs (9 Petit Basset Griffon Vendéen (PBGV) and 5 Beagle dogs)participated in the randomised cross-over study for a total of 14 weeks. The cohort was divided into four groups with each exposed to a different intervention per week: chew A, chew B, tooth brushing control or a no intervention control. An induced malodour method was used to assess VSCs in breath samples using a portable gas chromatograph (OralChroma™). Microbiological samples (supragingival plaque and tongue coating scrapes) were analysed for VSC-producing bacteria using Oral Hydrogen Sulfide agar with lead acetate.ResultsVSCs were detected in the dogs’ breath samples and levels of hydrogen sulphide and methyl mercaptan were found to be reduced following an intervention. Chew B significantly reduced the levels of both hydrogen sulphide (p < 0.001) and methyl mercaptan (p < 0.05) compared to no intervention. Reductions in methyl mercaptan were also observed for chew A and tooth brushing but these were not statistically significant. When compared to no intervention, all interventions significantly reduced the total bacterial load and VSC producing bacterial load in plaque (p < 0.001). For tongue samples, only chew B significantly reduced the total bacterial load and VSC-producing bacterial load (p < 0.001) compared to no intervention.ConclusionsBy inducing oral malodour and subsequently applying the one-time interventions, significant reductions in the levels of VSCs were observed. The use of oral care chews texturally designed to deliver a deep, all-round cleaning action can be particularly effective at managing oral malodour in dogs, likely through an enhanced ability to remove bacteria.
Baseline T-lymphocyte and cytokine indices in sheep peripheral blood
Authors: Yang Jihui , Lv Yongxue , Zhu Yazhou , Li Shasha , Tao Jia , Chang Liangliang , Zhu Mingxing , Zhao Jiaqing , Wang Yana , Wu Changyou , Zhao Wei 
Published: May 2022

Abstract
Background
Sheep are an important livestock species worldwide and an essential large-animal model for animal husbandry and veterinary research. Understanding fundamental immune indicators, especially T-lymphocyte parameters, is necessary for research on sheep diseases and vaccines, to better understand the immune response to bacteria and viruses for reducing the use of antibiotics and improving the welfare of sheep. We randomly selected 36 sheep of similar ages to analyze cell-related immune indicators in peripheral blood mononuclear cells (PBMCs). The proportions of CD4+ and CD8+ T cells in PBMCs were detected by flow cytometry. We used Concanavalin A (Con A) and Phorbol-12-myristate-13-acetate (PMA)/Ionomycin to stimulate PBMCs, and measured the expression of IFN-γ, IL-4, and IL-17A using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISpot). Simultaneously, PMA/Ionomycin/brefeldin A (BFA) was added to PBMCs, then the expression of IFN-γ, IL-4, and IL-17A was detected by flow cytometry after 4 h of culturing. In addition, we observed the proliferation of PBMCs stimulated with Con A for 3, 4, and 5 days.

Results
The proportions of CD4+ T lymphocytes (18.70 ± 4.21%) and CD8+ T lymphocytes (8.70 ± 3.65%) were generally consistent among individuals, with a CD4/CD8 ratio of 2.40 ± 0.79. PBMCs produced high levels of IFN-γ, IL-4, and IL-17A after stimulation with PMA/Ionomycin and Con A. Furthermore, PMA/Ionomycin stimulation of PBMC yielded significantly higher cytokine levels than Con A stimulation. Flow cytometry showed that the level of IFN-γ (51.49 ± 11.54%) in CD8+ T lymphocytes was significantly (p < 0.001) higher than that in CD4+ T lymphocytes (14.29 ± 3.26%); IL-4 (16.13 ± 6.81%) in CD4+ T lymphocytes was significantly (p < 0.001) higher than that in CD8+ T lymphocytes (1.84 ± 1.33%), There was no difference in IL-17A between CD4+ (2.83 ± 0.98%) and CD8+ T lymphocytes (1.34 ± 0.67%). The proliferation of total lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes continued to increase between days 3 and 5; however, there were no significant differences in proliferation between the cell types during the stimulation period.

Conclusions
Evaluating primary sheep immune indicators, especially T lymphocytes, is significant for studying cellular immunity. This study provided valuable data and theoretical support for assessing the immune response of sheep to pathogens and improving sheep welfare.