bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic range size and speciation in honeyeaters
Authors: Hay Eleanor M. , McGee Matthew D. , Chown Steven L. 
Published: June 2022

AbstractBackgroundDarwin and others proposed that a species’ geographic range size positively influences speciation likelihood, with the relationship potentially dependent on the mode of speciation and other contributing factors, including geographic setting and species traits. Several alternative proposals for the influence of range size on speciation rate have also been made (e.g. negative or a unimodal relationship with speciation). To examine Darwin’s proposal, we use a range of phylogenetic comparative methods, focusing on a large Australasian bird clade, the honeyeaters (Aves: Meliphagidae).ResultsWe consider the influence of range size, shape, and position (latitudinal and longitudinal midpoints, island or continental species), and consider two traits known to influence range size: dispersal ability and body size. Applying several analytical approaches, including phylogenetic Bayesian path analysis, spatiophylogenetic models, and state-dependent speciation and extinction models, we find support for both the positive relationship between range size and speciation rate and the influence of mode of speciation.ConclusionsHoneyeater speciation rate differs considerably between islands and the continental setting across the clade’s distribution, with range size contributing positively in the continental setting, while dispersal ability influences speciation regardless of setting. These outcomes support Darwin’s original proposal for a positive relationship between range size and speciation likelihood, while extending the evidence for the contribution of dispersal ability to speciation.
Overexpression of GhABF3 increases cotton(Gossypium hirsutum L.) tolerance to salt and drought
Authors: Zhang Haijun , Mao Lili , Xin Ming , Xing Huixian , Zhang Yanan , Wu Jing , Xu Dongli , Wang Yiming , Shang Yongqi , Wei Liming , Cui Mingshuo , Zhuang Tao , Sun Xuezhen , Song Xianliang 
Published: June 2022

AbstractBackgroundPlants suffer from various abiotic stresses during their lifetime, of which drought and salt stresses are two main factors limiting crop yield and quality. Previous studies have shown that abscisic acid (ABA) responsive element binding protein (AREB)/ ABRE binding factors (ABFs) in bZIP transcription factors are involved in plant stress response in an ABA-dependent manner. However, little is known about the properties and functions of AREB/ABFs, especiallyABF3, in cotton.ResultsHere, we reported the cloning and characterization ofGhABF3. Expression ofGhABF3was induced by drought,salt and ABA treatments. Silencing ofGhABF3sensitized cotton to drought and salt stress, which was manifested in decreased cellular antioxidant capacity and chlorophyll content. Overexpression ofGhABF3significantly improved the drought and salinity tolerance of Arabidopsis and cotton. Exogenous expression ofGhABF3resulted in longer root length and less leaf wilting under stress conditions inArabidopsis thaliana. OverexpressingGhABF3significantly improved salt tolerance of upland cotton by reducing the degree of cellular oxidation, and enhanced drought tolerance by decreasing leaf water loss rate. The increased expression ofGhABF3up-regulated the transcriptional abundance of downstream ABA-inducible genes under salt stress in Arabidopsis.ConclusionIn conclusion, our results demonstrated thatGhABF3plays an important role in plant drought and salt tolerance. Manipulation ofGhABF3by biotechnology might be an important strategy to alter the stress resistance of cotton.
Economic and clinical burden from carbapenem-resistant bacterial infections and factors contributing: a retrospective study using electronic medical records in Japan
Authors: Imai Shinobu , Inoue Norihiko , Nagai Hideaki 
Published: June 2022

Abstract
Background
Antimicrobial resistance is a major threat to global health and the world economy. The economic burden of carbapenem-resistant infections has not previously been evaluated. We aimed to compare the potential economic burden and clinical outcomes between carbapenem-resistant infections and carbapenem-susceptible infections in Japan.

Methods
We conducted a retrospective cohort study using electronic medical records. Patients aged 15 years or older and with the diagnosis of pneumonia, urinary tract infection, biliary infection, and sepsis were included. Multivariable regression models with random effects were used to estimate the impact of carbapenem resistance on cost, length of hospital stay, and in-hospital mortality.

Results
Among the 9,517 patients, 86 (0.9%) had carbapenem-resistant (CR) infections. Compared to carbapenem-susceptible (CS) infections, the patients with the CR infections were significantly more likely to receive mechanical ventilation (37.2 vs. 21.2%, P-value = 0.003), antibiotics (88.4 vs. 63.0%, P-value < 0.001), and especially carbapenem (31.4 vs. 8.3%, P-value < 0.001), before the bacterial culture test positive. Significantly higher median costs were found for the CR infections than the CS infections in the categories of medications (3477 US dollars vs. 1609 US dollars), laboratory tests (2498 US dollars, vs. 1845 US dollars), and hospital stay (14,307 US dollars vs. 10,560 US dollars). In the multivariable regression analysis, the length of stay was 42.1% longer and the cost was 50.4% higher in the CR infections than in the CS infections. The risk of in-hospital mortality did not differ between the two groups (odds ratio 1.24, 95% CI 0.72–2.11), due to the small sample size. The result was robust with a similar trend in the analysis using the inverse probability treatment weighting method.

Conclusions
Compared to carbapenem-susceptible infections, carbapenem-resistant infections were associated with a higher cost and a longer length of stay. Detailed cost analysis showed significant differences in the categories of medication, laboratory tests, and hospital stay. To our knowledge, this study is the first to assess the potential economic burden of carbapenem-resistant infections using a large hospital-based database.
Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer
Authors: Hou Jian , Lu Zhenquan , Cheng Xiaobao , Dong Runan , Jiang Yi , Wu Guoqing , Qu Genyi , Xu Yong 
Published: June 2022

Abstract
Background
Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor-suppressive function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic predictor for bladder cancer (BCa).

Methods
We retrieved BCa-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Least absolute shrinkage and selection operator regression (LASSO) and Cox regression models were used to identify and develop predictive models and validate the model accuracy. Finally, we explored the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes.

Results
Kaplan–Meier analyses screened 11 differentially expressed lncRNAs associated with poor BCa prognosis. The signature (AUC = 0.720) could be utilized to predict BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in the low-risk group. TCGA showed that the p53 signaling pathway, ferroptosis, Kaposi sarcoma − associated herpesvirus infection, IL − 17 signaling pathway, MicroRNAs in cancer, TNF signaling pathway, PI3K − Akt signaling pathway and HIF − 1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were differentially expressed between the two risk groups. m6A methylation-related genes were significantly differentially expressed between the two risk groups.

Conclusion
A new ferroptosis-associated lncRNAs signature developed for predicting the prognosis of BCa patients will improve the treatment and management of BCa patients.
Age heterogeneities in child growth and its associated socio-demographic factors: a cross-sectional study in India
Authors: Yadav Suryakant , Bhandari Pravat 
Published: June 2022

Abstract
Background
The impacts of socio-demographic and environmental risk factors on child growth have been widely documented. However, it remains unclear whether the impacts of such risk factors on child growth have remained static or changed with child’s age. The present study aims to assess the underlying age heterogeneities in child growth and its potential determinants over age in under-five children.

Methods
Cross-sectional data on child height (measured as height-for-age z-score, i.e., HAZ) and weight (measured as weight-for-age z-score, i.e., WAZ) and potential confounding factors from India’s 2015–16 National Family Health Survey (NFHS) were used to construct anthropometric age-profiles by a number of bio-demographic and socioeconomic characteristics. Further, age-interacted multilevel regression analyses were performed to examine differential effects of such/those risk factors on child height and weight by age.

Results
Faltered height and weight growth during first two years of life was noticed in children of all socioeconomic groups studied, albeit with varying magnitude. In case of child’s height, factors such as short birth interval, higher birth order, maternal education, household wealth, district level mortality rate have shown strong interaction with child’s age during the first 23 months, signifying their age-varying role in different developmental stages of child growth. These factors explain the observed upward and downward shifts in height curve during first two years. Some of these variables (e.g., household wealth) have shown even stronger age interactions after the second birthday of children. For child’s weight, interactive effects of most socio-demographic risk factors attenuated parabolically with child’s age.

Conclusions
The impacts of several risk factors, measured at the child, mother, community, and district levels, on child growth indicators varied significantly with the child’s age. Nutritional interventions aimed at preventing poor linear growth in children in India should consider these underlying age heterogeneities for growth determinants into account.
Frequency of leisure activity engagement and health functioning over a 4-year period: a population-based study amongst middle-aged adults
Authors: Elsden Esme , Bu Feifei , Fancourt Daisy , Mak Hei Wan 
Published: June 2022

Abstract
Rationale
Leisure activities have wide-ranging benefits for physical and mental health. However, previous studies have often focused on “leisure” as a homogeneous group of activities. This study was therefore designed to take a prospective and comparative approach exploring different types of leisure activities, as well as investigating whether frequency of engagement is associated with strength of benefits.

Method
Data from the 1970 British Cohort Study Waves 9 (age 42) and 10 (age 46) were analysed (N = 5,639). Eight domains derived from the SF-36 health survey questionnaire were used to measure health functioning (general health, vitality, bodily pain, social functioning, physical functioning, mental health, role limitations due to emotional, and role limitations due to physical problems). Leisure activities included physical activity, culture engagement, arts participation, volunteering or community engagement, and literature activities. Both ordinary least squares and logistic regressions were applied.

Results
Physical activity was associated with greater levels of physical functioning, general health, and vitality at higher frequencies, while cultural engagement was associated with social functioning and physical functioning when engaged in several times a year. Arts participation and literature activities had a general negative association with health functioning. Engagements in volunteering/community groups showed varying associations with health functioning (both positive and negative) depending on the levels of engagements.

Conclusion
This research suggests that the types of leisure activities and levels of engagement can have differential associations with health amongst middle-aged adults. This may be helpful for public health initiatives and programmes such as social prescribing schemes when formulating programmes, especially regarding ‘dosage’ of engagement. Further, the overall benefits of high engagement frequency suggest that increasing leisure engagement could play an important role in supporting improving health and wellbeing at a population level.
Adherence to viral load testing guidelines, barriers, and associated factors among persons living with HIV on ART in Southwestern Uganda: a mixed-methods study
Authors: Lubega Polly , Nalugya Sylivia Juliet , Kimuli Angella Namyalo , Twinokusiima Majoreen , Khasalamwa Mercy , Kyomugisa Richard , Kabami Jane , Owaraganise Asiphas 
Published: June 2022

Abstract
Background
Uganda adapted Viral load (VL) testing for monitoring HIV treatment success and virologic failure. However, there is a paucity of data on how the VL testing guidelines are followed in practice in the HIV clinics. This study determined the adherence to national guidelines on VL testing, barriers, and associated factors in persons living with HIV (PLHIV) on ART in southwestern Uganda.

Methods
We conducted a cross-sectional mixed methods study from April to May 2021 at four HIV clinics in southwestern Uganda. Patient chart review using a checklist that captured age, gender, and level of a healthcare facility, dates of ART initiation, dates VL specimens were drawn, line of ART, patient adherence to ART was done. Continuous data were summarized using mean and median and Chi-square was used for categorical data. We performed regression analysis to determine factors associated with adherence to viral load testing guidelines at a 95% level of significance. Key informant interviews with managers of the health facility, ART clinic and laboratory were carried out, and thematic analysis was conducted to explore barriers to adherence to VL testing guidelines.

Results
The participants’ mean (SD) age was 39.9(± 13.1) years, 39.5% were male, 45.8% received care at a general hospital and median duration on ART was 5 years (IQR;3–7). Of the 395 patient charts reviewed, 317 had their VL testing (80.3%) per the guidelines (defined as up to one month post due date). Receiving care at a hospital (aOR = 2.20; 95%CI 1.30–3.70; p = 0.002) and increasing patient age (aOR = 1.02; 95%CI 1.02–1.06; p = 0.020) were the factors associated with adhering to VL testing guidelines. Long turnaround time of VL results and insufficient VL testing kits were cites by providers as barriers.

Conclusion
We found suboptimal adherence to VL testing guidelines in PLHIV on ART in southwestern Uganda. Increasing patient age and getting care at a higher-level health facility were associated with guideline-based viral VL testing. Long turnaround time of VL test results and inadequate test kits hindered compliance to VL monitoring guidelines. Strategies that target young PLHIV and lower-level health facilities, increase the stock of consumables and shorten VL results turnaround time are needed to improve adherence to VL testing guidelines.
Ceritinib is a novel triple negative breast cancer therapeutic agent
Authors: Dong Shengli , Yousefi Hassan , Savage Isabella Van , Okpechi Samuel C. , Wright Maryl K. , Matossian Margarite D. , Collins-Burow Bridgette M. , Burow Matthew E. , Alahari Suresh K. 
Published: June 2022

Abstract
Background
Triple-negative breast cancers (TNBCs) are clinically aggressive subtypes of breast cancer. TNBC is difficult to treat with targeted agents due to the lack of commonly targeted therapies within this subtype. Androgen receptor (AR) has been detected in 12–55% of TNBCs. AR stimulates breast tumor growth in the absence of estrogen receptor (ER), and it has become an emerging molecular target in TNBC treatment.

Methods
Ceritinib is a small molecule inhibitor of tyrosine kinase and it is used in the therapy of non-small lung cancer patients. Enzalutamide is a small molecule compound targeting the androgen receptor and it is used to treat prostate cancer. Combination therapy of these drugs were investigated using AR positive breast cancer mouse xenograft models. Also, combination treatment of ceritinib and paclitaxel investigated using AR− and AR low mouse xenograft and patient derived xenograft models.

Results
We screened 133 FDA approved drugs that have a therapeutic effect of AR+ TNBC cells. From the screen, we identified two drugs, ceritinib and crizotinib. Since ceritinib has a well- defined role in androgen independent AR signaling pathways, we further investigated the effect of ceritinib. Ceritinib treatment inhibited RTK/ACK/AR pathway and other downstream pathways in AR+ TNBC cells. The combination of ceritinib and enzalutamide showed a robust inhibitory effect on cell growth of AR+ TNBC cells in vitro and in vivo. Interestingly Ceritinib inhibits FAK-YB-1 signaling pathway that leads to paclitaxel resistance in all types of TNBC cells. The combination of paclitaxel and ceritinib showed drastic inhibition of tumor growth compared to a single drug alone.

Conclusions
To improve the response of AR antagonist in AR positive TNBC, we designed a novel combinational strategy comprised of enzalutamide and ceritinib to treat AR+ TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways. Furthermore, we introduced a novel therapeutic combination of ceritinib and paclitaxel for AR negative or AR-low TNBCs and this combination inhibited tumor growth to a great extent. All agents used in our study are FDA-approved, and thus the proposed combination therapy will likely be useful in the clinic.
A prospective study of peer victimization and depressive symptoms among left-behind children in rural China: the mediating effect of stressful life events
Authors: Zhang Xiaoqing , Hong Houlin , Hou Wei , Liu Xia 
Published: June 2022

AbstractBackgroundThe Ministry of Civil Affairs of the People’s Republic of China reported that in 2018, 6.97 million left-behind children (LBC), children who live in rural areas away from their parents, were being cared for by grandparents, relatives, elder siblings, or often living alone. Their parents have migrated to cities for better income opportunities. While a number of studies have detailed elevated depressive symptoms among LBC, relatively little is known about the causes of poorer mental health in LBC.MethodsThis study used longitudinal data to examine associations between peer victimization, stressful life events, and depressive symptom severity in LBC from four randomly-selected middle schools in Guizhou Province, China. A total of 862 children aged 11–18 years, with 472 LBC (54.76%) and 390 non-left-behind children (NLBC) (45.24%), were included in the analysis. T-test was used to compare the depressive symptoms, peer victimization, and stressful life events between LBC and NLBC at baseline and follow-up (6 months later). Multivariable linear regression models were used to examine the mediation effect of follow-up stressful life events on the relationship between baseline peer victimization and follow-up depressive symptoms among LBC.ResultsResults suggested that LBC had higher peer victimization and stressful life events than NLBC (β = 1.28, p = 0.04), and peer victimization and stressful life events at baseline were associated with increased follow-up depressive symptoms among LBC (Peer victimization: β = 0.25, p < 0.0001; Stressful life events: β = 0.15, p < 0.001). Peer victimization affected depressive symptoms partially through stressful life events for female LBC and completely through stressful life events for male LBC, controlling for age, perceived socioeconomic status, and school.ConclusionsThis study highlights the vulnerability of LBC exhibiting negative mental health outcomes as they were found to experience more peer victimization and feel more stressed when stressful life events happened, compared with NLBC. Results of this study suggested that protecting LBC from peer victimization experiences can potentially prevent LBC from experiencing an increased impact of other stressful life events, thus decreasing the likelihood of their depressive symptoms. Intervention design should consider the different mediating effects of stressful life events on the relationship between peer victimization and depressive symptoms among female and male LBC.
Using mHealth to improve adherence and reduce blood pressure in individuals with hypertension and bipolar disorder (iTAB-CV): study protocol for a 2-stage randomized clinical trial
Authors: Levin Jennifer B. , Moore David J. , Depp Colin , Montoya Jessica L. , Briggs Farren , Rahman Mahboob , Stange Kurt C. , Einstadter Douglas , Weise Celeste , Conroy Carla , Yala Joy , Radatz Ethan , Sajatovic Martha 
Published: June 2022

Abstract
Background
Cardiovascular disease in individuals with mental health conditions such as bipolar disorder is highly prevalent and often poorly managed. Individuals with bipolar disorder face significant medication adherence barriers, especially when they are prescribed multiple medications for other health conditions including hypertension. Poor adherence puts them at a disproportionate risk for poor health outcomes. As such, there is a need for effective interventions to improve hypertension medication adherence, particularly in patients that struggle with adherence due to mental health comorbidity.

Methods
This 5-year project uses a 2-stage randomized controlled trial design to evaluate a brief, practical adherence intervention delivered via interactive text messaging (iTAB-CV) along with self-monitoring of medication taking, mood, and home blood pressure (N = 100) compared to self-monitoring alone (N = 100). Prior to randomization, all participants will view an educational video that emphasizes the importance of medication for the treatment of hypertension and bipolar disorder. Those randomized to the texting intervention will receive daily text messages with predetermined content to address 11 salient domains as well as targeted customized messages for 2 months. This group will then be re-randomized to receive either a high (gradual taper from daily to weekly texts) or low booster (weekly texts) phase for an additional 2 months. All participants will be monitored for 52 weeks. The primary outcomes are systolic blood pressure and adherence to antihypertensive medication as determined by a self-reported questionnaire and validated with an automated pill-monitoring device. Secondary outcomes include adherence to bipolar disorder medications, psychiatric symptoms, health status, self-efficacy for medication-taking behavior, illness beliefs, medication attitudes, and habit strength.

Discussion
This study specifically targets blood pressure and mental health symptom control in people with bipolar and includes implementation elements in the study design intended to inform future scale-up. Promising pilot data and a theoretical model, which views sustained medication-taking behavior in the context of habit formation, suggests that this remotely delivered intervention may help advance care for this high-risk population and is amenable to both scale up and easy adaptation for other groups with poor medication adherence.

Trial registration
The study was registered at ClinicalTrials.gov (NCT04675593) on December 19, 2020.