bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer
Authors: Chen Jing , Wan Runlan , Li Qinqin , Rao Zhenghuan , Wang Yanlin , Zhang Lei , Teichmann Alexander Tobias 
Published: June 2021

AbstractDrug resistance is always a great obstacle in any endocrine therapy of breast cancer. Although the combination of endocrine therapy and targeted therapy has been shown to significantly improve prognosis, refractory endocrine resistance is still common. Dysregulation of the Hippo pathway is often related to the occurrence and the development of many tumors. Targeted therapies of this pathway have played important roles in the study of triple negative breast cancer (TNBC). Targeting the Hippo pathway in combination with chemotherapy or other targeted therapies has been shown to significantly improve specific antitumor effects and reduce cancer antidrug resistance. Further exploration has shown that the Hippo pathway is closely related to endocrine resistance, and it plays a “co-correlation point” role in numerous pathways involving endocrine resistance, including related pathways in breast cancer stem cells (BCSCs). Agents and miRNAs targeting the components of the Hippo pathway are expected to significantly enhance the sensitivity of breast cancer cells to endocrine therapy. This review initially explains the possible mechanism of the Hippo pathway in combating endocrine resistance, and it concludes by recommending endocrine therapy in combination with therapies targeting the Hippo pathway in the study of endocrine-resistant breast cancers.
CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression
Authors: Liu Yi , Chen Simin , Peng Gang , Liao Yiwei , Fan Xuegong , Zhang Zuping , Shen Chenfu 
Published: June 2021

Abstract
Background
An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma.

Methods
RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression.

Results
The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis.

Conclusions
CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.
Factors associated with access to health care among foreign residents living in Aichi Prefecture, Japan: secondary data analysis
Authors: Higuchi Michiyo , Endo Maki , Yoshino Asako 
Published: June 2021

AbstractBackgroundIn Japan, foreign residents, and particularly new arrivals in the country, experience barriers to health care and show poorer health outcomes when compared to Japanese nationals. The health-care-related situation for foreign residents in Japan has been characterized by drastic changes over time; thus, there is difficulty identifying individuals who are “left behind” by the system. In this study, we aimed to identify, among foreign residents who attended informal free medical consultations, factors associated with “being advised to visit a medical facility” and “being referred to a medical facility,” which represented hypothetical proxy indicators of barriers to health care.MethodsSecondary data analyses were conducted using the activity records of a non-governmental organization that provides free consultations targeting foreign residents in various locations in Aichi Prefecture, Japan. Participant characteristics, including insurance coverage, were determined. Bivariate and multi-variate analyses were performed to identify factors associated with having barriers to health care.ResultsAmong 608 extracted cases, 164 (27.5%) cases were advised to visit a medical facility, and 72 (11.8%) were referred to a medical facility during the consultations. Those who were not covered by public insurance showed a 1.56-time (95% confidence interval [CI]: 1.19–2.05) higher prevalence of being advised to visit a medical facility when compared to those who were covered by public insurance. Unemployed people and students were more likely to be referred to a medical facility than were professional workers; the prevalence ratios were 3.28 (95% CI: 1.64–6.57) and 2.77 (95% CI: 1.18–6.46), respectively.ConclusionsAlthough the majority were insured, almost 30% were advised to visit a medical facility, which implied that they had had limited access to the formal health-care system before availing of the free consultations. The findings highlight those uninsured, unemployed people and students, who are considered vulnerable to access to health care. It is vital to provide those who are vulnerable with the necessary support while updatinge evidence, so that no one is “left behind.”
Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy
Authors: Lu Dehua , Wang Yanpu , Zhang Ting , Wang Feng , Li Kui , Zhou Shixin , Zhu Hua , Yang Zhi , Liu Zhaofei 
Published: June 2021

Abstract
Background
Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies.

Methods
We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi).

Results
CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms.

Conclusion
These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens.

Graphic Abstract
High levels of used syringe use and unsafe sex among people who inject drugs in Kumasi, Ghana: an urgent call for a comprehensive harm reduction approach
Authors: Messersmith Lisa J. , Adjei Rose , Beard Jennifer , Bazzi Angela R. , Earlywine Joel J. , Darko Edwin , Agyarko-Poku Thomas , Asafo Mabel Kissiwah , Bempah Sherry Adoma , Adu-Sarkodie Yaw 
Published: June 2021

Abstract
Background
Drug use is a growing concern in Ghana. People who inject drugs (PWID) are highly vulnerable to HIV and other infectious diseases. Ghana’s National Strategic Plan for HIV/AIDS 2016–2020 identifies PWID as a key population, but efforts to address the needs of PWID have lagged behind those targeting sex workers and men who have sex with men. Lack of information about PWID is a critical barrier to implementing effective HIV prevention and treatment. We aimed to learn more about the vulnerability of the PWID population in order to inform much-needed harm reduction interventions.

Methods
From April to July 2018, we conducted a mixed methods study in Kumasi, Ghana, to identify all major drug using locations, count the numbers of PWID to obtain rough population size estimations, and administer anonymous surveys to 221 PWID regarding drug use and sexual behavior. We also tested for HIV, HCV, and HBV from syringes used by survey participants.

Results
Key informants identified five major drug using locations and estimated the total PWID population size to be between 600 and 2000. Enumerators counted between 35 and 61 individuals present at each of the five bases. Sharing syringes and reusing discarded syringes are common practices. Over half of survey participants (59%) reported past-month syringe sharing (34% used a used syringe and 52% gave away a used syringe). Individuals with higher injection frequency (≥ 21 times weekly) and who injected with four or more people had higher odds of syringe sharing. Of the survey participants reporting sex in the last month (23%), most reported having one partner, but only 12% used condoms. Nearly all women (11/13) reported exchanging sex for drugs and 6/13 reported exchanging sex for money in the last six months. Fifteen percent of participants (all men) reported paying for sex using drugs or money. Of the used syringes, prevalence estimates were 3% (HIV), 2% (HCV), and 9% (HBV).

Conclusions
Our findings confirm the urgent need to implement harm reduction interventions targeting PWID and to build a strong and enabling legal and policy environment in Ghana to support these efforts.
The relative importance and stability of disease burden causes over time: summarizing regional trends on disease burden for 290 causes over 28 years
Authors: Dyson Henry , Van Gestel Raf , van Doorslaer Eddy 
Published: June 2021

Abstract
Background
Since the Global Burden of Disease study (GBD) has become more comprehensive, data for hundreds of causes of disease burden, measured using Disability Adjusted Life Years (DALYs), have become increasingly available for almost every part of the world. However, undergoing any systematic comparative analysis of the trends can be challenging given the quantity of data that must be presented.

Methods
We use the GBD data to describe trends in cause-specific DALY rates for eight regions. We quantify the extent to which the importance of ‘major’ DALY causes changes relative to ‘minor’ DALY causes over time by decomposing changes in the Gini coefficient into ‘proportionality’ and ‘reranking’ indices.

Results
The fall in regional DALY rates since 1990 has been accompanied by generally positive proportionality indices and reranking indices of negligible magnitude. However, the rate at which DALY rates have been falling has slowed and, at the same time, proportionality indices have tended towards zero. These findings are clearest where the focus is exclusively upon non-communicable diseases. Notably, large and positive proportionality indices are recorded for sub-Saharan Africa over the last decade.

Conclusion
The positive proportionality indices show that disease burden has become less concentrated around the leading causes over time, and this trend has become less prominent as the DALY rate decline has slowed. The recent decline in disease burden in sub-Saharan Africa is disproportionally driven by improvements in DALY rates for HIV/AIDS, as well as for malaria, diarrheal diseases, and lower respiratory infections.
Geographic variation and associated factors of long-acting contraceptive use among reproductive-age women in Ethiopia: a multi-level and spatial analysis of Ethiopian Demographic and Health Survey 2016 data
Authors: Ebrahim Oumer Abdulkadir , Zeleke Ejigu Gebeye , Muluneh Atalay Goshu 
Published: June 2021

Abstract
Background
High fertility rates and unintended pregnancies are public health concerns of lower and middle income countries such as Ethiopia. Long acting contraceptives (LACs) take the lion’s share in reducing unintended pregnancies and high fertility rates. Despite their numerous advantages, the utilization of LACs remains low in Ethiopia. This study is aimed to explore the geographic variation and associated factors of long acting contraceptive use among reproductive-age women in Ethiopia.

Methods
This is a secondary data analysis of 2016 Ethiopian Demographic and Health Survey (EDHS) data. A total of weighted sample sizes of 10,439 reproductive-age women were included in the final analysis. To clean and analyze the none-spatial data Stata 14 was used while ArcGIS 10.6 and SaTScanTM version 9.6 software were used for spatial analysis. Multilevel Mixed-effect Logistic regression model was used to identify associated factors of LACs utilization. An Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was reported to identify significant variables.

Results
Long acting contraceptive utilization was non-random (Moran’s I: 0.30, p-value < 0.01). Statistically, clusters with significant low utilization of LACs were found in Somali, Afar, Gambela, northern Amhara, eastern Oromia and western part of Southern Nations Nationalities and Peoples (SNNP) regions. Adjusting for other factors such as being married (AOR = 2.51, 95% CI: 1.29–4.87), having one to two (AOR = 2.14, 95% CI: 1.43–3.22), and three to four children (AOR = 1.68, 95% CI: 1.02–2.76), urban (AOR = 1.59, 95% CI: 1.16–2.19), want no more children (AOR = 1.40, 95% CI: 1.08–1.83), working status of women (AOR = 1.33, 95% CI: 1.07–1.65) increased the odds of LACs utilization. While previous history of abortion (AOR = 0.56, 95% CI: 0.39–0.80), and living in the pastoralist community (AOR = 0.22, 95% CI: 0.14–0.35) reduced the odds of LACs utilization in Ethiopia

Conclusions
Significant geographic variation of LACs utilization was observed in Ethiopia. Spots with Low LACs utilization were found in the eastern, north eastern and western part of the country. Socio-demographic and pregnancy related factors were significant determinants of LACs utilization. Designing intervention programs targeting the identified hot spot clusters, and variables that can hinder the utilization of LACs is very important to increase the utilization.
Identification and characterization of lncRNA AP000253 in occult hepatitis B virus infection
Authors: Hao Qingqin , Wang Zheng , Wang Qinghui , Chen Bo , Qian Huizhong , Liu Xiao , Cao Hong , Xia Wei , Jiang Jian , Lu Zhonghua 
Published: June 2021

AbstractBackgroundRecent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear.MethodsThe plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines.ResultsAmong candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines.ConclusionsAP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.
Imaging side effects and complications of chemotherapy and radiation therapy: a pictorial review from head to toe
Authors: Albano Domenico , Benenati Massimo , Bruno Antonio , Bruno Federico , Calandri Marco , Caruso Damiano , Cozzi Diletta , De Robertis Riccardo , Gentili Francesco , Grazzini Irene , Micci Giuseppe , Palmisano Anna , Pessina Carlotta , Scalise Paola , Vernuccio Federica , Barile Antonio , Miele Vittorio , Grassi Roberto , Messina Carmelo ,   Young SIRM Working Group, Albano Domenico , Benenati Massimo , Bruno Antonio , Bruno Federico , Calandri Marco , Caruso Damiano , Cozzi Diletta , De Robertis Riccardo , Gentili Francesco , Grazzini Irene , Micci Giuseppe , Palmisano Anna , Pessina Carlotta , Scalise Paola , Vernuccio Federica , Messina Carmelo 
Published: June 2021

AbstractNewer biologic drugs and immunomodulatory agents, as well as more tolerated and effective radiation therapy schemes, have reduced treatment toxicity in oncology patients. However, although imaging assessment of tumor response is adapting to atypical responses like tumor flare, expected changes and complications of chemo/radiotherapy are still routinely encountered in post-treatment imaging examinations. Radiologists must be aware of old and newer therapeutic options and related side effects or complications to avoid a misinterpretation of imaging findings. Further, advancements in oncology research have increased life expectancy of patients as well as the frequency of long-term therapy-related side effects that once could not be observed. This pictorial will help radiologists tasked to detect therapy-related complications and to differentiate expected changes of normal tissues from tumor relapse.
Characterization of substantia nigra neurogenesis in homeostasis and dopaminergic degeneration: beneficial effects of the microneurotrophin BNN-20
Authors: Mourtzi Theodora , Dimitrakopoulos Dimitrios , Kakogiannis Dimitrios , Salodimitris Charalampos , Botsakis Konstantinos , Meri Danai Kassandra , Anesti Maria , Dimopoulou Aggeliki , Charalampopoulos Ioannis , Gravanis Achilleas , Matsokis Nikolaos , Angelatou Fevronia , Kazanis Ilias 
Published: June 2021

Abstract
Background
Loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) underlines much of the pathology of Parkinson’s disease (PD), but the existence of an endogenous neurogenic system that could be targeted as a therapeutic strategy has been controversial. BNN-20 is a synthetic, BDNF-mimicking, microneurotrophin that we previously showed to exhibit a pleiotropic neuroprotective effect on the dopaminergic neurons of the SNpc in the “weaver” mouse model of PD. Here, we assessed its potential effects on neurogenesis.

Methods
We quantified total numbers of dopaminergic neurons in the SNpc of wild-type and “weaver” mice, with or without administration of BNN-20, and we employed BrdU labelling and intracerebroventricular injections of DiI to evaluate the existence of dopaminergic neurogenesis in the SNpc and to assess the origin of newborn dopaminergic neurons. The in vivo experiments were complemented by in vitro proliferation/differentiation assays of adult neural stem cells (NSCs) isolated from the substantia nigra and the subependymal zone (SEZ) stem cell niche to further characterize the effects of BNN-20.

Results
Our analysis revealed the existence of a low-rate turnover of dopaminergic neurons in the normal SNpc and showed, using three independent lines of experiments (stereologic cell counts, BrdU and DiI tracing), that the administration of BNN-20 leads to increased neurogenesis in the SNpc and to partial reversal of dopaminergic cell loss. The newly born dopaminergic neurons, that are partially originated from the SEZ, follow the typical nigral maturation pathway, expressing the transcription factor FoxA2. Importantly, the pro-cytogenic effects of BNN-20 were very strong in the SNpc, but were absent in other brain areas such as the cortex or the stem cell niche of the hippocampus. Moreover, although the in vitro assays showed that BNN-20 enhances the differentiation of NSCs towards glia and neurons, its in vivo administration stimulated only neurogenesis.

Conclusions
Our results demonstrate the existence of a neurogenic system in the SNpc that can be manipulated in order to regenerate the depleted dopaminergic cell population in the “weaver” PD mouse model. Microneurotrophin BNN-20 emerges as an excellent candidate for future PD cell replacement therapies, due to its area-specific, pro-neurogenic effects.