bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambient nitrogen dioxide is associated with emergency hospital visits for atrial fibrillation: a population-based case-crossover study in Reykjavik, Iceland
Authors: Halldorsdottir Solveig , Finnbjornsdottir Ragnhildur Gudrun , Elvarsson Bjarki Thor , Gudmundsson Gunnar , Rafnsson Vilhjalmur 
Published: January 2022

Abstract
Background
In Iceland air quality is generally good; however, previous studies indicate that there is an association between air pollution in Reykjavik and adverse health effects as measured by dispensing of medications, mortality, and increase in health care utilisation.
The aim was to study the association between traffic-related ambient air pollution in the Reykjavik capital area and emergency hospital visits for heart diseases and particularly atrial fibrillation and flutter (AF).

Methods
A multivariate time-stratified case-crossover design was used to study the association. Cases were those patients aged 18 years or older living in the Reykjavik capital area during the study period, 2006–2017, who made emergency visits to Landspitali University Hospital for heart diseases. In this population-based study, the primary discharge diagnoses were registered according to International Classification of Diseases, 10th edition (ICD-10). The pollutants studied were NO2, PM10, PM2.5, and SO2, with adjustment for H2S, temperature, and relative humidity. The 24-h mean of pollutants was used with lag 0 to lag 4.

Results
During the study period 9536 cases of AF were identified. The 24-h mean NO2 was 20.7 μg/m3. Each 10 μg/m3 increase in NO2 was associated with increased risk of heart diseases (ICD-10: I20-I25, I44-I50), odds ratio (OR) 1.023 (95% CI 1.012–1.034) at lag 0. Each 10 μg/m3 increase in NO2 was associated with an increased risk of AF (ICD-10: I48) on the same day, OR 1.030 (95% CI: 1.011–1.049). Females were at higher risk for AF, OR 1.051 (95% CI 1.019–1.083) at lag 0, and OR 1.050 (95% CI 1.019–1.083) at lag 1. Females aged younger than 71 years had even higher risk for AF, OR 1.077 (95% CI: 1.025–1.131) at lag 0. Significant associations were found for other pollutants and emergency hospital visits, but they were weaker and did not show a discernable pattern.

Conclusions
Short-term increase in NO2 concentrations was associated with heart diseases, more precisely with AF. The associations were stronger among females, and among females at younger age. This is the first study in Iceland that finds an association between air pollution and cardiac arrhythmias, so the results should be interpreted with caution.
Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy
Authors: Li Yan , Yang Chen , Liu Zhicheng , Du Shangce , Can Susan , Zhang Hailin , Zhang Linmeng , Huang Xiaowen , Xiao Zhenyu , Li Xiaobo , Fang Jingyuan , Qin Wenxin , Sun Chong , Wang Cun , Chen Jun , Chen Huimin 
Published: January 2022

Abstract
Background
In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them.

Methods
In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses.

Results
We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined.

Conclusion
Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.
A novel imatinib-upregulated long noncoding RNA plays a critical role in inhibition of tumor growth induced by Abl oncogenes
Authors: Ma Yun , Guo Guijie , Li Tingting , Wen Faxin , Yang Jianling , Chen Biao , Wang Xuefei , Chen Ji-Long 
Published: January 2022

Abstract
Background
Dysregulation of long noncoding RNAs (lncRNAs) has been linked to various human cancers. Bcr-Abl oncogene that results from a reciprocal translocation between human chromosome 9 and 22, is associated with several hematological malignancies. However, the role of lncRNAs in Bcr-Abl-induced leukemia remains largely unexplored.

Methods
LncRNA cDNA microarray was employed to identify key lncRNAs involved in Bcr-Abl-mediated cellular transformation. Abl-transformed cell survival and xenografted tumor growth in mice were evaluated to dissect the role of imatinib-upregulated lncRNA 1 (IUR1) in Abl-induced tumorigenesis. Primary bone marrow transformation and in vivo leukemia transplant using lncRNA-IUR1 knockout (KO) mice were further conducted to address the functional relevance of lncRNA-IUR1 in Abl-mediated leukemia. Transcriptome RNA-seq and Western blotting were performed to determine the mechanisms by which lncRNA-IUR1 regulates Bcr-Abl-induced tumorigenesis.

Results
We identified lncRNA-IUR1 as a critical negative regulator of Bcr-Abl-induced tumorigenesis. LncRNA-IUR1 expressed in a very low level in Bcr-Abl-positive cells from chronic myeloid leukemia patients. Interestingly, it was significantly induced in Abl-positive leukemic cells treated by imatinib. Depletion of lncRNA-IUR1 promoted survival of Abl-transformed human leukemic cells in experiments in vitro and xenografted tumor growth in mice, whereas ectopic expression of lncRNA-IUR1 sensitized the cells to apoptosis and suppressed tumor growth. In concert, silencing murine lncRNA-IUR1 in Abl-transformed cells accelerated cell survival and the development of leukemia in mice. Furthermore, lncRNA-IUR1 deficient mice were generated, and we observed that knockout of murine lncRNA-IUR1 facilitated Bcr-Abl-mediated primary bone marrow transformation. Moreover, animal leukemia model revealed that lncRNA-IUR1 deficiency promoted Abl-transformed cell survival and development of leukemia in mice. Mechanistically, we demonstrated that lncRNA-IUR1 suppressed Bcr-Abl-induced tumorigenesis through negatively regulating STAT5-mediated GATA3 expression.

Conclusions
These findings unveil an inhibitory role of lncRNA-IUR1 in Abl-mediated cellular transformation, and provide new insights into molecular mechanisms underlying Abl-induced leukemogenesis.
A review of disparities in access to infertility care and treatment outcomes among Hispanic women
Authors: Komorowski Allison S. , Jain Tarun 
Published: January 2022

AbstractHispanic women have lower rates of use of infertility services than non-Hispanic White women. There are many barriers that impede access to infertility care including economic, geographic, cultural, and societal factors and there are disparities in treatment outcomes. Hispanic women are less likely to seek infertility care than non-Hispanic White women and even after infertility evaluation, Hispanic women are less likely to receive treatment for their infertility. Lower use of infertility treatments among Hispanic women is unlikely to be driven solely by economic factors. There is disappointingly little data on in-vitro fertilization treatment outcomes including the population of Hispanic women, and existing data has yielded conflicting results. Incomplete and variable reporting of race data across clinics raises the potential for misclassification bias and invalid study conclusions. Addressing disparities in access to reproductive medicine in the Hispanic population will required a multifaceted approach including expanded insurance coverage, improved education for both patients and providers, and additional research on barriers to care.
Diabetes, hypertension, and cardiovascular disease development
Authors: Yen Fu-Shun , Wei James Cheng-Chung , Chiu Lu-Ting , Hsu Chih-Cheng , Hwu Chii-Min 
Published: January 2022

Abstract
Background
We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM.

Methods
From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease.

Results
The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07–2.37), 1.19 (1.16–1.23), and 0.92 (0.82–1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55–1.84), 1.25 (1.21–1.30), and 0.98 (0.93–1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37–3.27), 1.20 (1.13–1.28), and 0.95 (0.88–1.03), respectively.

Conclusions
This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks.
Health service providers’ perspectives on the influence of modern health systems on adolescents’ sexual health practices in Umguza and Mberengwa districts of Zimbabwe
Authors: Nunu Wilfred Njabulo , Makhado Lufuno , Mabunda Jabu Tsakani , Lebese Rachel Tsakani 
Published: January 2022

Abstract
Background
Health service providers play a significant role in crafting and implementing health policies and programs that manage adolescent sexual health-related issues at different health system levels. These influence adolescent sexual behaviours and practices.

Aim
This study explored the roles of health service providers in managing adolescent sexual issues and how this impacts their sexual behaviours and practices. The study further probed the health service providers on how the indigenous health system could be integrated into the modern health system for effective management of adolescent sexual health related issues.

Methods
A qualitative cross-sectional survey was conducted on purposively selected health service providers in health facilities in Mberengwa and Umguza districts. Data was collected using unstructured interviews that were recorded, transcribed verbatim, and thematically analysed. Findings were presented as clearly defined as superordinate and subordinate themes.

Results
A total of five superordinate themes and 19 subordinate themes emerged from the interrogated data. The superordinate themes were: overview of adolescent sexual health issues, role of modern health system in adolescent sexual health issues, challenges encountered, indigenous health system factors that could be factored into modern health systems, and strategies to foster the integration of indigenous health system and modern health system. The subordinate themes explored in-depth the findings of the key stakeholders under the five superordinate themes.

Conclusions
From the findings, it can be concluded that health service providers play an essential role in shaping and providing adolescent sexual health services that adolescents utilise despite challenges that have reduced demand for these services. Therefore, there is a need to point out that there is a window of opportunity to foster collaborations between the indigenous health system and the modern health system as they strive to serve the adolescents to the best of their ability though in different contextual settings.
Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
Authors: Chu Min , Fan Yingchao , Wu Liting , Ma Xiaoyan , Sao Jinfeng , Yao Yonghua , Zhuang Wenfang , Zhang Cui 
Published: January 2022

Abstract
Purpose
This study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM).

Methods
The expression of BDNF-AS, miR-125a-5p, and miR-125b-5p in MM serum and cell lines were detected by quantitative reverse transcriptase PCR (qRT-PCR). The binding relationships between miR-125a/b-5p and BDNF-AS or Bcl-2 were predicted by Starbase and verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining assay. Cell migration was evaluated by wound healing assay. The expression levels of apoptosis-related proteins were evaluated by Western blot analysis. The role of BDNF-AS was also investigated in a xenograft tumor model in vivo.

Results
BDNF-AS was significantly upregulated, while miR-125a-5p and miR-125b-5p were downregulated in MM serum and corresponding cancer cell lines. Knockdown of BDNF-AS effectively inhibited the proliferation and migration of MM.1S and U266 cells, and co-transfection of miR-125a-5p or miR-125b-5p inhibitor and sh-BDNF-AS enhanced cell proliferation and migration compared with that in sh-BDNF-AS group. Knockdown of miR-125a-5p or miR-125b-5p significantly enhanced the proliferation and migration of MM.1S and U266 cells, and co-transfection of sh-Bcl-2 and miR-125a/b-5p inhibitor inhibited cell proliferation compared with that in miR-125a/b-5p inhibitor group. Moreover, knockdown of BDNF-AS increased the expression levels of apoptosis-related proteins (cleaved caspase 3 and cleaved PARP), while knockdown of miR-125a-5p or miR-125b-5p reduced the expression levels of these apoptosis-related proteins compared with knockdown of BDNF-AS. Furthermore, knockdown of BDNF-AS effectively suppressed MM tumor growth in vivo.

Conclusion
Our findings revealed that knockdown of BDNF-AS inhibited the progression of MM by targeting the miR-125a/b-5p-Bcl-2 axis, indicating that BDNF-AS might serve as a novel drug target for MM.
Expression profiles of hsa-miR-148a-3p and hsa-miR-125b-5p in human breast milk and infant formulae
Authors: Chiba Takeshi , Kooka Aya , Kowatari Kiyoko , Yoshizawa Megumi , Chiba Naoko , Takaguri Akira , Fukushi Yoshiyuki , Hongo Fuminori , Sato Hideki , Wada Shinichiro 
Published: January 2022

Abstract
Background
Milk-derived microRNAs (miRNAs), including hsa-miR-148a-3p (miR-148a) and hsa-miR-125b-5p (miR-125b), have been shown to be beneficial to the gastrointestinal function in infants. Here, we investigated their expression during lactation in humans and determined whether the infant formulae available in Japan contain these miRNAs.

Methods
Healthy Japanese women (n = 16) who gave birth vaginally or by cesarean section at the Teine Keijinkai Hospital between 1 September 2020, and 31 April 2021 were included in this study. Breast milk was collected by nurses on days 4 or 5 after delivery (hereinafter, transition milk) and on day 30 of postpartum (hereinafter, mature milk). The levels of miR-148a and miR-125b in breastmilk and six commercially available infant formulae were compared and evaluated using quantitative reverse transcription-polymerase chain reaction.

Results
In all participants, the miR-148a level in mature breastmilk was significantly lower than that in the transition milk. The changes in miR-125b expression during lactation showed similar trends to the changes in miR-148a expression. The miR-148a and miR-125b levels in all analyzed infant formulae were lower than 1/500th and 1/100th of those in mature breastmilk, respectively.

Conclusions
The levels of both miR-148a and miR-125b in human breast milk decreased on day 30 postpartum compared with those in the transition milk. Additionally, the expression of these miRNAs in infant formulae available in Japan was very low. Further studies with larger populations are required to understand precisely the lactational changes in the expression of miR148a and miR-125b in breast milk.
Client satisfaction to methadone maintenance treatment program in Myanmar
Authors: Tun Sun , Vicknasingam Balasingam , Singh Darshan , Wai Nyunt 
Published: January 2022

Abstract
Background
To tackle the long-standing opioid misuse problem, Myanmar introduced the methadone maintenance treatment (MMT) program in 2006, starting with 260 clients. Since then, the program has been expanded across different geographical sites in the country. This study was done in 2017 to explore the treatment satisfaction of the clients towards the MMT program.

Method
A total of 210 clients with a minimum of six-month treatment history enrolled in five MMT program sites across Myanmar were recruited through stratified random sampling. Administering the Verona Service Satisfaction Scale for Methadone-Treatment (VSSS-MT), this study assessed the satisfactory responses under three categories viz., 1) clinic staff professional skills; 2) basic drug intervention; 3) specific intervention (individual rehabilitation and psychotherapy).

Results
The majority (89%, n = 186) of the respondents were satisfied with the current MMT program. Specifically, 89.5% (n = 187) were satisfied with the clinic staff professional skills category, 91.9% (n = 192) with the basic program intervention and 74.6% (n = 156) with specific interventions. Among the respondents, treatment satisfaction with the MMT program was higher (p < 0.05) in those (i) with a higher quality of life score in physical, psychological, social and environmental categories, ii) who were satisfied with their current marital and leisure status, and those iii) who consumed alcohol. Results from stepwise binary logistic regression showed alcohol consumption and physical health status had a significant association with MMT treatment satisfaction.

Conclusion
Treatment satisfaction of the clients, in general is high. However, the lower percentage of satisfied clients (74.6%) for the specific interventions category compared with 89.5 and 91.9% respectively for staff and basic drug management categories highlights the need for improvement in this category for overall enhancement of the MMT program.
Gastric side effects and the stomach dosimetric analysis in left-sided breast cancer radiotherapy in free-breathing and deep inspiration breath-hold technique
Authors: Yang Dong , Piao Ying , Yuan Fengshun , Chen Hongtao , Zhang Ding , Li Xianming 
Published: January 2022

Abstract
Background
Adjuvant radiotherapy following surgery reduces the local recurrence and improves the prognosis. However, a considerable part of patients developed digestive reaction in daily treatment. In order to explore the correlation between breast radiotherapy and gastric toxicity, we investigated the clinic symptoms and stomach dose during DIBH or FB mode while left-sided breast cancer patients (LSBCP) receiving radiotherapy.

Methods
In the study, 124 LSBCP received adjuvant radiotherapy after surgery at our department were analyzed clinical characteristics and enquired about gastrointestinal side effects after treatment. Moreover, dosimetric parameters were assessed.

Results
There was no statistically significant difference between the two groups in age, T staging, N staging, hormone receptors, human epidermal receptor-2 (HER2), surgical methods, fractionated regimen, and chemotherapy conditions. However, larger stomach volumes and higher fractionated dose (Dmax/F) were associated with a statistically significantly greater risk for acute radiotherapy toxicity. In addition, the use of the DIBH gating technique (FB/DIBH) reduced the incidence of digestive reactions.

Conclusion
In order to cut down gastric side effects after breast radiotherapy, large meals should be avoided before treatment. DIBH treatment should be implemented in centers where conditions are satisfied to reduce radiotherapy side effects. Furthermore, dose limitation in stomach should be considered when the radiotherapy plan was formulated, especially for the patients treated with hypofractionated radiotherapy.
Evaluation of plan robustness on the dosimetry of volumetric arc radiotherapy (VMAT) with set-up uncertainty in Nasopharyngeal carcinoma (NPC) radiotherapy
Authors: Ding Zhen , Xiang Xiaoyong , Zeng Qi , Ma Jun , Dai Zhitao , Kang Kailian , Bi Suyan 
Published: January 2022

Abstract
Purpose
To evaluate the sensitivity to set up the uncertainty of VMAT plans in Nasopharyngeal carcinoma (NPC) treatment by proposing a plan robustness evaluation method.

Methods
10 patients were selected for this study. A 2-arc volumetric-modulated arc therapy (VMAT) plan was generated for each patient using Varian Eclipse (13.6 Version) treatment planning system (TPS). 5 uncertainty plans (U-plans) were recalculated based on the first 5 times set-up errors acquired from cone-beam computer tomography (CBCT). The dose differences of the original plan and perturbed plan corresponded to the plan robustness for the structure. Tumor control probability (TCP) and normal tissues complication probability (NTCP) were calculated for biological evaluation.

Results
The mean dose differences of D98% and D95% (ΔD98% and ΔD95%) of PTVp were respectively 3.30 Gy and 2.02 Gy. The ΔD98% and ΔD95% of CTVp were 1.12 Gy and 0.58 Gy. The ΔD98% and ΔD95% of CTVn were 1.39 Gy and 1.03 Gy, distinctively lower than those in PTVn (2.8 Gy and 2.0 Gy). The CTV-to-PTV margin increased the robustness of CTVs. The ΔD98% and ΔD95% of GTVp were 0.56 Gy and 0.33 Gy. GTVn exhibited strong robustness with little variation of D98% (0.64 Gy) and D95% (0.39 Gy). No marked mean dose variations of Dmean were seen. The mean reduction of TCP (ΔTCP) in GTVp and CTVp were respectively 0.4% and 0.3%. The mean ΔTCPs of GTVn and CTVn were 0.92% and 1.3% respectively. The CTV exhibited the largest ΔTCP (2.2%). In OARs, the brain stem exhibited weak robustness due to their locations in the vicinity of PTV. Bilateral parotid glands were sensitive to set-up uncertainty with a mean reduction of NTCP (ΔNTCP) of 6.17% (left) and 7.70% (right). The Dmax of optical nerves and lens varied slightly.

Conclusion
VMAT plans had a strong sensitivity to set-up uncertainty in NPC radiotherapy, with increasing risk of underdose of tumor and overdose of vicinal OARs. We proposed an effective method to evaluate the plan robustness of VMAT plans. Plan robustness and complexity should be taken into account in photon radiotherapy.