bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway monocyte modulation relates to tumour necrosis factor dysregulation in neutrophilic asthma
Authors: Niessen Natalie M. , Gibson Peter G. , Simpson Jodie L. , Scott Hayley A. , Baines Katherine J. , Fricker Michael
Published: June 2021

Background

Dysregulation of tumour necrosis factor-α (TNF-α) signalling is implicated in neutrophilic asthma. TNF-α signalling involves membrane-bound and soluble ligand (TNF-α) and receptors (TNFRs); however, little is known about how these proteins are altered in asthma. We hypothesised that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF dysregulation in neutrophilic asthma.

Methods

Measurements were made in 45 adults with asthma (36 non-neutrophilic, 9 neutrophilic) and 8 non-asthma controls. Soluble TNF-α, TNF receptor 1 (TNFR1) and TNFR2 were quantified in plasma and sputum supernatant by ELISA, and membrane-bound TNF-α/TNFR1/TNFR2 measured on eosinophils, neutrophils, monocytes, and macrophages in blood and sputum by flow cytometry. Marker expression was compared between inflammatory phenotypes and compartments, and relationship of membrane-bound and soluble TNF markers and immune cell numbers tested by correlation.

Results

Soluble sputum TNFR1 and TNFR2 were increased in neutrophilicversusnon-neutrophilic asthma (p=0.010 and p=0.029). Membrane-bound TNF-α expression was upregulated on sputumversusblood monocytes, while TNFR1 and TNFR2 levels were reduced on airwayversusblood monocytes and neutrophils. Soluble TNFR1 and TNFR2 in sputum significantly correlated with the number of airway monocytes (p=0.016, r=0.358 and p=0.029, r=0.327).

Conclusion

Our results imply that increased sputum soluble TNF receptor levels observed in neutrophilic asthma relate to the increased recruitment of monocytes and neutrophils into the airways and their subsequent receptor shedding. Monocytes also increase TNF-α ligand expression in the airways. These results suggest an important contribution of airway monocytes to the altered inflammatory milieu in neutrophilic asthma.
An adjusted and time-saving method to measure collateral ventilation with Chartis
Authors: Koster T. David , Klooster Karin , McNamara Hallie , Shargill Narinder S. , Radhakrishnan Sri , Olivera Ryan , Slebos Dirk-Jan
Published: June 2021

Introduction

Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the “volume trend for the previous 20 s” (VT20).

Methods

We retrospectively evaluated 249 Chartis assessments of patients scheduled for bronchoscopic lung volume reduction procedures. The VT20 was calculated, and several thresholds were compared between patients with collateral ventilation (CV positive) and without collateral ventilation (CV negative).

Results

100% of the CV negative patients reached a threshold of VT20 ≤6 mL, whereas all CV positive patients reached a VT20 ≥7 mL. The median “time saved” between VT20=6 mL and end of assessment was 60 s (range 5–354 s).

Conclusion

The threshold of VT20 ≤6 mL is a reliable method to exclude the presence of collateral ventilation when air flow rates are low and can therefore reduce bronchoscopic lung volume procedure times.
Seasonal variations of auxin and gibberellin A4 levels in cambial-region tissues of three conifers (Pinus elliottii, Chamaecyparis obtusa, and Cryptomeria japonica) with inherently different wood densities
Authors: Kijidani Yoshio , Tsuyama Taku , Takata Katsuhiko
Published: June 2021

We previously reported the species-specific annual ring formation characteristics of three conifers (slash pine (Pinus elliottii), hinoki (Japanese cypress, Chamaecyparis obtusa) and sugi (Japanese cedar, Cryptomeria japonica)) grown in the same stand over 2 years. We found that the species-specific annual ring formation characteristics affected the inherent difference in wood density among these conifers (slash pine > hinoki > sugi). Plant hormones in cambial-region tissues were believed to affect annual ring formation. However, seasonal variation of the amounts of plant hormones in cambial-region tissues had only been examined in a few tree species. In this study, as the first step to elucidating the role of plant hormones in annual ring formation in conifers, we report the seasonal variations of the auxin (indole acetic acid, IAA) and gibberellin A4 (GA4) levels in cambial-region tissues and their effects on annual ring formation in three conifers (slash pine, hinoki, and sugi) with inherently different wood densities.

Sugi (small wood density) had significantly higher levels of IAA and formed more tracheids in the early season than in the late season, although slash pine (large wood density) had higher levels of IAA and formed significantly more tracheids in the late season than in the early season. Hinoki (intermediate wood density) had constant IAA levels and formed a constant number of tracheids throughout the season. There were significant positive correlations between the levels of IAA in cambial-region tissues and the number of tracheids formed during late season in the two conifer species. A close relationship was observed between the seasonal ratio of the IAA levels (late/early season) and wood density. No consistent trend in the change in the level of IAA during the transition from earlywood to latewood formation was recognized among the three conifers. The IAA levels in slash pines were significantly higher than those in sugi and hinoki. The GA4 levels had no significant effect on number of tracheids formed in the three conifers. These results suggest that the species-specific seasonal variation patterns of the IAA levels might lead to the inherent differences in wood density among these three conifers through species-specific characteristics in the formation of annual rings.
Formation of autotriploid Carassius auratus and its fertility-related genes analysis
Authors: Wang Chongqing , Luo Xiang , Qin Huan , Zhao Chun , Yang Li , Yu Tingting , Zhang Yuxin , Huang Xu , Xu Xidan , Qin Qinbo , Liu Shaojun
Published: June 2021

Background

Formation of triploid organism is useful in genetics and breeding. In this study, autotriploidCarassius auratus(3nRR, 3n = 150) was generated fromCarassius auratusred var. (RCC, 2n = 100) (♀) and autotetraploidCarassius auratus(4nRR, 4n = 200) (♂). The female 3nRR produced haploid, diploid and triploid eggs, whereas the male 3nRR was infertile. The aim of the present study was to explore fertility of potential candidate genes of 3nRR.

Results

Gonadal transcriptome profiling of four groups (3 females RCC (FRCC), 3 males 4nRR (M4nRR), 3 males 3nRR (M3nRR) and 3 females 3nRR (F3nRR)) was performed using RNA-SEq. A total of 78.90 Gb of clean short reads and 24,262 differentially expressed transcripts (DETs), including 20,155 in F3nRR vs. FRCC and 4,107 in M3nRR vs. M4nRR were identified. A total of 106 enriched pathways were identified through KEGG enrichment analysis. Out of the enriched pathways, 44 and 62 signalling pathways were identified in F3nRR vs. FRCC and M3nRR vs. M4nRR, respectively. A total of 80 and 25 potential candidate genes for fertility-related in F3nRR and M3nRR were identified, respectively, through GO, KEGG analyses and the published literature. Moreover, protein-protein interaction (PPI) network construction of these fertility-associated genes were performed. Analysis of the PPI networks showed that 6 hub genes (MYC,SOX2,BMP4,GATA4,PTENandBMP2) were involved in female fertility of F3nRR, and 2 hub genes (TP53andFGF2) were involved in male sterility of M3nRR.

Conclusions

Establishment of autotriploid fish offers an ideal model to study reproductive traits of triploid fish. RNA-Seq data revealed 6 genes, namely,MYC,SOX2,BMP4,GATA4,PTENandBMP2, involved in the female fertility of the F3nRR. Moreover, 2 genes, namely,TP53andFGF2, were related to the male sterility of the M3nRR. These findings provide information on reproduction and breeding in triploid fish.
Evaluation of comprehensiveness and reliability of electronic health records concerning resuscitation efforts within academic intensive care units: a retrospective chart analysis
Authors: Dittmar Michael S. , Zimmermann Sabrina , Creutzenberg Marcus , Bele Sylvia , Bitzinger Diane , Lunz Dirk , Graf Bernhard M. , Kieninger Martin
Published: June 2021

Background

According to the literature, the validity and reliability of medical documentation concerning episodes of cardiopulmonary resuscitation (CPR) is suboptimal. However, little is known about documentation quality of CPR efforts during intensive care unit (ICU) stays in electronic patient data management systems (PDMS). This study analyses the reliability of CPR-related medical documentation within the ICU PDMS.

Methods

In a retrospective chart analysis, PDMS records of three ICUs of a single university hospital were searched over 5 y for CPR check marks. Respective datasets were analyzed concerning data completeness and data consistency by comparing the content of three documentation forms (physicians’ log, nurses’ log, and CPR incident form), as well as physiological and therapeutic information of individual cases, for missing data and plausibility of CPR starting time and duration. To compare data reliability and completeness, a quantitative measure, the Consentaneity Index (CI), is proposed.

Results

One hundred sixty-five datasets were included into the study. In 9% (n = 15) of cases, there was neither information on the time points of CPR initiation nor on CPR duration available in any data source. Data on CPR starting time and duration were available from at least two data sources in individual cases in 54% (n = 90) and 45% (n = 74), respectively. In these cases, the specifications of CPR starting time did differ by a median ± interquartile range of 10.0 ± 18.5 min, CPR duration by 5.0 ± 17.3 min. The CI as a marker of data reliability revealed a low consistency of CPR documentation in most cases, with more favorable results, if the time interval between the CPR episode and the time of documentation was short.

Conclusions

This study reveals relevant proportions of missing and inconsistent data in electronic CPR documentation in the ICU setting. The CI is suggested as a tool for documentation quality analysis and monitoring of improvements.
Factors related to retinal nerve fiber layer thickness in bipolar disorder patients and major depression patients
Authors: Liu Yanhong , Tong Yongsheng , Huang Lvzhen , Chen Jingxu , Yan Shaoxiao , Yang Fude
Published: June 2021

Background

We analyzed the correlation of the clinical data with retinal nerve fiber layer (RNFL) thickness and macular thickness in bipolar disorder patients and major depression patients. The aim of this study is to explore factors that affect RNFL thickness in bipolar disorder patients and major depression patients, with a view to providing a new diagnostic strategy.

Methods

Eighty-two bipolar disorder patients, 35 major depression patients and 274 people who were age and gender matched with the patients were enrolled. Demographic information and metabolic profile of all participants were collected. Best-corrected visual acuity of each eye, intraocular pressure (IOP), fundus examination was performed. RNFL and macular thickness were measured by optical coherence tomography (OCT). Correlations between RNFL and macular thickness and other data were analyzed.

Results

RNFL and macula lutea in bipolar dipolar patients and major depression patients are thinner than normal people. Triglyceride and UA levels are the highest in the bipolar disorder group, while alanine aminotransferase (ALT) and glutamic oxalacetic transaminase (AST) levels in the depression group are the highest. Age onset and ALT are positively while uric acid (UA) is negatively correlated with RNFL thickness in bipolar dipolar patients. Cholesterol level is positively correlated with RNFL thickness while the duration of illness is correlated with RNFL thickness of left eye in major depression patients.

Conclusions

RNFL and macula lutea in bipolar dipolar patients and major depression patients are thinner than normal people. In bipolar disorder patients, age-onset and ALT are potential protective factors in the progress of RNFL thinning, while UA is the pathological factor.
The effect of high blood pressure-health literacy, self-management behavior, self-efficacy and social support on the health-related quality of life of Kazakh hypertension patients in a low-income rural area of China: a structural equation model
Authors: Zhang Qinghua , Huang Feifei , Zhang Lei , Li Shasha , Zhang Jingping
Published: June 2021

Background

Health-Related Quality of Life (HRQoL) of hypertensive patients is not only affected by the disease itself but also by some subjective factors. Low health literacy is prevalent among ethnic minorities. Considering the Kazakh-Chinese people have the highest prevalence of hypertension in Xinjiang, and the High Blood Pressure-Health Literacy (HBP-HL) has not been included in the study of HRQoL. The synergistic effects and the potential mechanism HBP-HL, self-management behavior, therapeutic adherence, self-efficacy, social support on HRQoL remain unclear. This study aimed to introduce the HBP-HL, and develop a structural equation model (SEM) to identify the factors influencing of the HRQoL among Kazakh hypertensive patients.

Methods

The data was obtained by questionnaire survey and physical examination in 2015. Patients with hypertension were recruited through random cluster sampling in Kazakh settlements in Xinjiang. Firstly, the blood pressure was measured. Then the one-for-one household interviews were conducted by Kazakh investigators. The questionnaires regarding HBP-HL, HRQoL, self-management behavior, therapeutic adherence, self-efficacy, and social support were used to collect data. Finally, SEM was constructed, and p ≤ 0.05 was taken as significant.

Results

The data was analysed by SPSS18.0 and AMOS18.0 software. 516 Kazakh hypertension patients were recruited, and 94.4% of them had a relatively low HBP-HL score. The mean standardized scores of HRQoL, self-management, therapeutic adherence were poor; they were 63.5, 66.2, and 64.4, respectively. But 96.1% and 98.3% of the participants had high levels of self-efficacy and social support. The SEM of the HRQoL had a good overall fit (χ2/df = 2.078, AGFI = 0.944, GFI = 0.968, CFI = 0.947, IFI = 0.949, RMSEA = 0.046). The model indicated that the HBP-HL has the highest correlation with HRQoL, following with self-management behavior, social support, and self-efficacy.

Conclusions

Low HBP-HL is a major influenced factor of HRQoL among Kazakh hypertensive patients. Future programs should consider HBP-HL as the breakthrough point when designing targeting intervention strategies.
The use of coping strategies “shift-persist” mediates associations between physical activity and mental health problems in adolescents: a cross-sectional study
Authors: Dahlstrand Johan , Friberg Peter , Fridolfsson Jonatan , Börjesson Mats , Arvidsson Daniel , Ekblom Örjan , Chen Yun
Published: June 2021

Background

Self-perceived mental health problems among adolescents has had an upward trend. Concurrently, adolescents’ physical activity (PA) has been falling whilst sedentary time (SED) has increased. There is a lack of research using accelerometer measured PA and SED to study their relationships to perceived stress and psychosomatic symptoms, both frequently observed mental health problems among adolescents. Whether coping strategies is one of the mechanisms underlying such relationship is less clear.

Methods

A total of 2283 13-year olds were enrolled in the baseline examination of the STARS (STudy of Adolescence Resilience and Stress) study in Western Sweden. Light-, moderate-, vigorous-intensity PA (LPA, MPA and VPA) and SED were measured using hip-worn ActiGraph GT3X+ accelerometer. A total of 1284 adolescents provided valid accelerometer data (at least 4 days with ≥10 h per day). PA and SED during school-time and leisure-time were analysed separately. Surveys were utilized to monitor perceived stress, psychosomatic symptoms and the use of coping strategies “shift-persist”. Logistic regression and mediation analyses were performed adjusting for gender, ethnicity, socioeconomic status and puberty development.

Results

We observed that more time spent in PA was associated with less stress in adolescents. The associations were observed for LPA (Odds ratio for LPA per 60 min: 0.557 (95% CI 0.399–0.776), VPA (Odds ratio for VPA per 15 min: 0.688 (95% CI 0.588–0.806) and MVPA (Odds ratio for MVPA per 15 min: 0.795 (95%CI 0.718–0.879) during leisure time, but not during school time. Similar associations were observed between leisure time PA and psychosomatic symptoms. The associations remained statistically significant even after adjusting for the confounders. Further, our data showed that adolescents who engaged more time in PA during leisure time were more likely to adopt the coping strategies of “shift-persist”. Mediation analysis showed that the use of “shift-persist” mediated the associations between leisure time PA and stress/psychosomatic symptoms.

Conclusions

Leisure time physical activity, irrespective of intensity, may facilitate successful coping with stress and stress-related mental health problems in adolescents.
Geographic and demographic heterogeneity of SARS-CoV-2 diagnostic testing in Illinois, USA, March to December 2020
Authors: Holden Tobias M. , Richardson Reese A. K. , Arevalo Philip , Duffus Wayne A. , Runge Manuela , Whitney Elena , Wise Leslie , Ezike Ngozi O. , Patrick Sarah , Cobey Sarah , Gerardin Jaline
Published: June 2021

Background

Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread.

Methods

We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing.

Results

By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50–80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance.

Conclusions

Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission.
Synchronous bilateral Wilms’ tumor with liver metastasis
Authors: Sereke Senai Goitom , Sahal Abdirahman Omar , Mboizi Vincent , Bongomin Felix
Published: June 2021

Background

Wilms’ tumor (nephroblastoma) is mostly unilateral; however, bilateral Wilms’ tumors are seen in about 5–8% of patients. This can be synchronous or metachronous. It is uncommon to get liver metastasis from bilateral Wilms’ tumor.

Case presentation

An 8-year-old male Ugandan presented with a history of abdominal swelling and flank pains for 1 year. There was no history of hematuria. Both ultrasound and computed tomography of the abdomen demonstrated multiple solid lesions in both kidneys and a huge solid mass in segments V, VI, VII and VIII of the liver. Histological examination of renal biopsy specimen was favorable for chemotherapeutic regimens. However, following a multidisciplinary tumor board consensus, a nephron-sparing surgery was deemed unsuitable, and he was managed conservatively with chemotherapy (adriamycin and vincristine) with a palliative intent.

Conclusions

Metastatic bilateral Wilms’ tumor has a particularly poor prognosis. There are no clear evidence-based guidelines for the management of this rare presentation. This patient benefited from early palliative care and symptom management.
Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes
Authors: Seejore K. , Alavi S. A. , Pearson S. M. , Robins J. M. W. , Alromhain B. , Sheikh A. , Nix P. , Wilson T. , Orme S. M. , Tyagi A. , Phillips N. , Murray R. D.
Published: June 2021

Background

Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown.

Methods

Data from patients who underwent endoscopic TSS for a NFPMA (2009–2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes.

Results

Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004).

Conclusion

Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.
Approaching an undergraduate medical curriculum map: challenges and expectations
Authors: Chakrabarti Rima , Wardle Katie , Wright Tor , Bennie Taylor , Gishen Faye
Published: June 2021

Background

Feedback received from medical students at University College London Medical School (UCLMS) suggested a lack of clarity regarding the contents and subsequent assessment of the undergraduate curriculum. In order to address these issues, a specialist team was established with the aim of designing and implementing a Curriculum Map (CM), which have been recognised in their ability to provide a centralised, visual representation of the curriculum. While multiple perspectives from educators to stakeholders can be considered here, the need for the CM to remain student centred was identified as key at UCLMS. The aim of this study was therefore to understand the requirements of the CM prior to production from the perspective of the medical students.

Methods

A mixed-methods sequential study was conducted. The first stage involved gathering quantitative data using a primary online survey. This used 15 questions, rated by Likert scales and focussed around three domains: depiction of content, functionality and students’ likely engagement with a CM. There was a free-text question for additional comments. The second stage consisted of multiple student focus groups representing different years of the programme, conducted by trained facilitators following a predetermined scheme. Reflective Thematic Analysis (RTA) was used to synthesise the qualitative data, which was read independently by two researchers. All students at UCLMS were invited to participate in the study.

Results

There were 409 survey responses. 92% of students said they were ‘likely’ or ‘very likely’ to use a CM, with their key intended use being to monitor their learning progress and ensure preparedness for assessments. Five key themes emerged from the focus groups, namely that students wanted a CM to be: comprehensive; simple and intuitive; able to link content throughout the course; aligned with assessment; and useful to monitor students’ progress.

Conclusions

Through this study, valuable insight was gained on students’ ideal preferences for the CM. Understanding this was important in order to ensure that its co-design remained student-centred prior to its design and launch. This study also highlighted the need to set realistic expectations for students on the role of a CM in preparing them for assessments, and ultimately professional practice.
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

Drug 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

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

Background

In 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.

Methods

Secondary 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.

Results

Among 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.

Conclusions

Although 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

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

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

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

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

Background

Recent 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.

Methods

The 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.

Results

Among 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.

Conclusions

AP000253 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

Newer 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

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.