bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment persistence to tolvaptan in patients with autosomal dominant polycystic kidney disease: a secondary use of data analysis of patients in the IMADJIN® dataset
Authors: Thomas Mark , Gois Pedro Henrique Franca , Butcher Belinda E. , Ta Michelle H. T. , Van Wyk Greg W. 
Published: December 2021

Abstract
Background
Tolvaptan is the only available disease-modifying treatment for autosomal dominant polycystic kidney disease (ADPKD). Prior to October 2020 access to tolvaptan in Australia was restricted by a controlled monitoring and distribution program called IMADJIN®. Focusing on hepatic safety, the IMADJIN® program collected real-world data on patients with ADPKD. A retrospective, secondary data analysis of the IMADJIN® dataset was undertaken to determine the time to all-cause discontinuation of tolvaptan in Australia.

Methods
Demographic and treatment data from 17 September 2018 to 30 September 2020 were extracted from the IMADJIN® dataset. Treatment persistence was analyzed using Kaplan-Meier methods, and Cox’s proportional hazard models were used to analyze differences in treatment persistence by age, sex and location.

Results
Four hundred seventy-nine patients with ADPKD were included in the analysis. After a median follow-up of 12.0 months (95% confidence interval [CI] 2.6, 23.4), the Kaplan-Meier estimation of 12-month persistence was 76.7% (95% CI 72.2, 80.5%). 114 (23.8%) patients discontinued treatment; sex, state, and remoteness did not significantly affect treatment persistence. Patients in the youngest tertile were more likely to discontinue compared to older ages (p = 0.049). Reasons for discontinuation included: aquaretic tolerability (4.2%), hepatic adverse events (abnormal liver function tests) (2.1%), disease progression (1.5%), and acute kidney injury (0.2%). Patients with a lack of aquaretic tolerance had shorter time to discontinuation. Hepatic toxicity events were initially observed 3 months after tolvaptan initiation and were less prevalent over time.

Conclusions
Persistence to tolvaptan in the real-world IMADJIN® dataset was 76%. Discontinuation due to hepatic events was low. Prescribers should take extra care when initiating treatment in younger patients as they are more likely to discontinue tolvaptan compared to older individuals. Nevertheless, the precise reason for this observation remains to be elucidated.
Prevalence and characteristics of patients with heart failure needing palliative care
Authors: Arenas Ochoa Luisa Fernanda , González-Jaramillo Valentina , Saldarriaga Clara , Lemos Mariantonia , Krikorian Alicia , Vargas John Jairo , Gómez-Batiste Xavier , Gonzalez-Jaramillo Nathalia , Eychmüller Steffen 
Published: December 2021

Abstract
Background
Few hospitals and heart failure (HF) clinics offer concurrent palliative care (PC) together with life-prolonging therapies. To know the prevalence of patients in HF clinics needing PC and useful tools to recognize them are the first steps to extending PC in those settings. However, it is still unknown whether tools commonly used to identify patients with HF needing PC can correctly distinguish them. Two systematic reviews found that the NECesidades PALiativas (NECPAL) tool was one of the two most commonly used tools to asses PC needs in HF patients. Therefore, we assessed 1) the prevalence of PC needs in HF clinics according to the NECPAL tool, and 2) the characteristics of the patients identified as having PC; mainly, their quality of life (QoL), symptom burden, and psychosocial problems.

Methods
This cross-sectional study was conducted at two HF clinics in Colombia. We assessed the prevalence of PC in the overall sample and in subgroups according to clinical and demographic variables. We assessed QoL, symptom burden, and psychosocial problems using the 12-Item Short-Form Health Survey (SF-12), the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Edmonton Symptom Assessment System (ESAS). We compared the results of these tools between patients identified as having PC needs (+NECPAL) and patients identified as not having PC needs (–NECPAL).

Results
Among the 178 patients, 78 (44%) had PC needs. The prevalence of PC needs was twice as nigh in patients NYHA III/IV as in patients NYHA I/II and almost twice as high in patients older than 70 years as in patients younger than 70 years. Compared to –NECPAL patients, +NECPAL patients had worse QoL, more severe shortness of breath, tiredness, drowsiness, and pain, and more psychosocial problems.

Conclusion
The prevalence of PC needs in outpatient HF clinics is high and is even higher in older patients and in patients at more advanced NYHA stages. Compared to patients identified as not having PC needs, patients identified as having PC needs have worse QoL, more severe symptoms, and greater psychosocial problems. Including a PC provider in the multidisciplinary team of HF clinics may help to assess and cover these needs.
A seven-year analysis of the role and impact of a free community eye clinic
Authors: Rowe Lucas W. , Scheive Melanie , Tso Hanna L. , Wurster Patrick , Kalafatis Nicholas E. , Camp David A. , Thau Avrey , Yung Chi Wah Rudy 
Published: December 2021

AbstractBackgroundThe Indiana University Student Outreach Clinic (IUSOC) Eye Clinic is a monthly student-run eye clinic that provides free visual screening to the Near East Side community of Indianapolis, IN, USA. Screening includes assessments of visual acuity, intraocular pressure, peripheral visual fields, refraction, and non-mydriatic fundus photography.MethodsThis is a retrospective chart review of 875 patients seen at the IUSOC Eye Clinic from October 2013 to February 2020. Data on demographics, insurance coverage, ocular history, physical examination, suspected diagnosis, referral status, and glasses provided were collected and analyzed.Results875 patients were seen at the IUSOC Eye Clinic from October 2013 to February 2020. 39.2% of the patients seen at the clinic reported being uninsured. 61.4% of patients were found to have visual acuity of 20/40 or worse, while 51.3% of patients were found to have a near visual acuity of 20/40 or worse. 20.3% of patients were referred to the local county hospital for further evaluation by an ophthalmologist, 14.4% of patients received free glasses prescriptions, and 27.9% of patients received free reading glasses. Common reasons for referral for further ophthalmology evaluation included glaucoma, decreased visual acuity, and diabetic retinopathy. An estimated value of services provided over the seven years of the clinic was 1271 relative value units.ConclusionThe IUSOC Eye Clinic fills an important role in advancing ocular health and preventing irreversible blindness in an underserved Indianapolis community. Additionally, the clinic demonstrates an educational model for involving medical student volunteers.
Effects of COVID-19 pandemic on ART Service delivery: perspectives of healthcare workers in a Teaching Hospital in Ghana
Authors: Abraham Susanna Aba , Berchie Gifty Osei , Doe Patience Fakornam , Agyare Elizabeth , Addo Stephen Ayisi , Obiri-Yeboah Dorcas 
Published: December 2021

Abstract
Background
Ghana has a generalized HIV epidemic and efforts have been made to curb the spread and reverse its effects on the general population. In the wake of COVID-19 pandemic, the health system was unsettled and antiretroviral therapy (ART) care has been impacted in diverse ways. The study sought to explore the effects of COVID-19 on ART service provision in Ghana from the perspectives of the healthcare workers.

Methods
An exploratory-descriptive qualitative approach was employed in this study. Using maximum variation sampling method, fifteen healthcare workers; nurses, data managers and pharmacists were recruited from an ART clinic in a Teaching Hospital in Ghana. In-depth interviews were conducted and analysed using Braun and Clarke thematic approach.

Results
Three themes emerged from the data; “… And the pandemic struck”, “Impact of the pandemic on ART service delivery”; “Effecting the needed change”. The healthcare workers’ initial reactions to the pandemic and their show of commitment in ensuring continued ART service was evident. COVID-19 impacted service delivery in three main ways; (1) clients’ clinic attendance was erratic at various stages of the pandemic, (2) irregular resource availability as shortage was reported due to affected last mile delivery as a result of the lockdown in Accra, and (3) the health worker-patient interaction became less engaging because of established COVID-19 protocols. The healthcare workers however instituted strategies such as adjusting the patient appointment schedule, health professionals’ work schedule, establishing several work stations, task-shifting, and ensuring the implementation of all the COVID-19 protocols within the ART unit to ensure consistent service delivery as well as patient and staff safety. The study also found a decline in the implementation of several strategies established in the ART clinic during the initial phases of the pandemic such as a decline in the supply of Personal Protective Equipment (PPEs) by hospital management.

Conclusions
Although several strategies were implemented to manage the effects of the pandemic on ART care, there is a need to establish pathways of support for healthcare workers within the ART clinic and to consolidate as well as institutionalise the changes that ensured continuous but safe service delivery.
Impact of global budget combined with pay-for-performance on the quality of care in county hospitals: a difference-in-differences study design with a propensity-score-matched control group using data from Guizhou province, China
Authors: Zhou Wuping , Jian Weiyan , Wang Zhifan , Pan Jay , Hu Min , Yip Winnie 
Published: December 2021

Abstract
Background
Provider payment system has a profound impact on health system performance. In 2016, a number of counties in rural Guizhou, China, implemented global budget (GB) for county hospitals with quality control measures. The aim of this study is to measure the impact of GB combined with pay-for-performance on the quality of care of inpatients in county-level hospitals in China.

Methods
Inpatient cases of four diseases, including pneumonia, chronic asthma, acute myocardial infarction and stroke, from 16 county-level hospitals in Guizhou province that implemented GB in 2016 were selected as the intervention group, and similar inpatient cases from 10 county-level hospitals that still implemented fee-for-services were used as the control group. Propensity matching score (PSM) was used for data matching to control for age factors, and difference-in-differences (DID) models were constructed using the matched samples to perform regression analysis on quality of care for the four diseases.

Results
After the implementation of GB, rate of sputum culture in patients with pneumonia, rate of aspirin at discharge, rate of discharge with β-blocker and rate of smoking cessation advice in patients with acute myocardial infarction increased. Rate of oxygenation index assessment in patient with chronic asthma decreased 20.3%. There are no significant changes in other indicators of process quality.

Conclusions
The inclusion of pay-for-performance in the global budget payment system will help to reduce the quality risks associated with the reform of the payment system and improve the quality of care. Future reform should also consider the inclusion of the pay-for-performance mechanism.
Maternal lithium use and the risk of adverse pregnancy and neonatal outcomes: a Swedish population-based cohort study
Authors: Hastie Roxanne , Tong Stephen , Hiscock Richard , Lindquist Anthea , Lindström Linda , Wikström Anna-Karin , Sundström-Poromaa Inger 
Published: December 2021

Abstract
Background
Lithium is prescribed during pregnancy, but there is limited information about pregnancy and neonatal outcomes following in utero exposure. Thus, this study aimed to investigate the associations between lithium use and adverse pregnancy and neonatal outcomes.

Methods
This population-based cohort study examined associations between maternal lithium use and major adverse pregnancy and neonatal outcomes via inverse probability weighted propensity score regression models.

Results
Of 854,017 women included in this study, 434 (0.05%) used lithium during pregnancy. Among pre-specified primary outcomes, lithium use during pregnancy was associated with an increased risk of spontaneous preterm birth (8.7% vs 3.0%; adjusted relative risk [aRR] 2.64 95% CI 1.82, 3.82) and birth of a large for gestational age infant (9.0% vs 3.5%; aRR 2.64 95% CI 1.91, 3.66), but not preeclampsia nor birth of a small for gestational age infant. Among secondary outcomes, lithium use was associated with an increased risk of cardiac malformations (2.1% vs 0.8%; aRR 3.17 95% CI 1.64, 6.13). In an analysis restricted to pregnant women with a diagnosed psychiatric illness (n=9552), associations remained between lithium and spontaneous preterm birth, birth of a large for gestational age infant, and cardiovascular malformations; and a positive association with neonatal hypoglycaemia was also found. These associations were also apparent in a further analysis comparing women who continued lithium treatment during pregnancy to those who discontinued prior to pregnancy.

Conclusions
Lithium use during pregnancy is associated with an increased risk of spontaneous preterm birth and other adverse neonatal outcomes. These potential risks must be balanced against the important benefit of treatment and should be used to guide shared decision-making.
Dopamine, behavior, and addiction
Authors: Wise Roy A. , Jordan Chloe J. 
Published: December 2021

AbstractAddictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.
Transcriptional regulation and ubiquitination-dependent regulation of HnRNPK oncogenic function in prostate tumorigenesis
Authors: Wu Huan-Lei , Li Sen-Mao , Huang Yao-chen , Xia Qi-Dong , Zhou Peng , Li Xian-Miao , Yu Xiao , Wang Shao-Gang , Ye Zhang-Qun , Hu Jia 
Published: December 2021

Abstract
Background
Heterogeneous nuclear ribonucleoprotein K (HnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, HnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis in various types of human cancers and are therefore pursued as attractive therapeutic targets for select patients. However, both the transcriptional regulation and degradation of HnRNPK in prostate cancer remain poorly understood.

Methods
qRT-PCR was used to detect the expression of HnRNPK mRNA and miRNA; Immunoblots and immunohistochemical assays were used to determine the levels of HnRNPK and other proteins. Flow cytometry was used to investigate cell cycle stage. MTS and clonogenic assays were used to investigate cell proliferation. Immunoprecipitation was used to analyse the interaction between SPOP and HnRNPK. A prostate carcinoma xenograft mouse model was used to detect the in vivo effects of HnRNPK and miRNA.

Results
In the present study, we noted that HnRNPK emerged as an important player in the carcinogenesis process of prostate cancer. miR-206 and miR-613 suppressed HnRNPK expression by targeting its 3’-UTR in PrCa cell lines in which HnRNPK is overexpressed. To explore the potential biological function, proliferation and colony formation of PrCa cells in vitro and tumor growth in vivo were also dramatically suppressed upon reintroduction of miR-206/miR-613. We have further provided evidence that Cullin 3 SPOP is a novel upstream E3 ubiquitin ligase complex that governs HnRNPK protein stability and oncogenic functions by promoting the degradation of HnRNPK in polyubiquitination-dependent proteolysis in the prostate cancer setting. Moreover, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of HnRNPK proteins.

Conclusion
Our findings reveal new posttranscriptional and posttranslational modification mechanisms of HnRNPK regulation via miR-206/miR-613 and SPOP, respectively. More importantly, given the critical oncogenic role of HnRNPK and the high frequency of SPOP mutations in prostate cancer, our results provide a molecular rationale for the clinical investigation of novel strategies to combat prostate cancer based on SPOP genetic status.
Seven-year kinetics of RTS, S/AS01-induced anti-CSP antibodies in young Kenyan children
Authors: Mugo Robert M. , Mwai Kennedy , Mwacharo Jedidah , Shee Faiz M. , Musyoki Jennifer N. , Wambua Juliana , Otieno Edward , Bejon Philip , Ndungu Francis M. 
Published: December 2021

Abstract
Background
RTS,S/AS01, the leading malaria vaccine has been recommended by the WHO for widespread immunization of children at risk. RTS,S/AS01-induced anti-CSP IgG antibodies are associated with the vaccine efficacy. Here, the long-term kinetics of RTS,S/AS01-induced antibodies was investigated.

Methods
150 participants were randomly selected from the 447 children who participated in the RTS,S/AS01 phase IIb clinical trial in 2007 from Kilifi-Kenya. Cumulatively, the retrospective follow-up period was 93 months with annual plasma samples collection. The levels of anti-CSP IgM, total IgG, IgG1, IgG2, IgG3, and IgG4 antibodies were then determined using an enzyme-linked immunosorbent assay.

Results
RTS,S/AS01 induced high levels of anti-CSP IgG antibodies which exhibited a rapid waning over 6.5 months post-vaccination, followed by a slower decay over the subsequent years. RTS,S/AS01-induced anti-CSP IgG antibodies remained elevated above the control group levels throughout the 7 years follow-up period. The anti-CSP IgG antibodies were mostly IgG1, IgG3, IgG2, and to a lesser extent IgG4. IgG2 predominated in later timepoints. RTS,S/AS01 also induced high levels of anti-CSP IgM antibodies which increased above the control group levels by month 3. The controls exhibited increasing levels of the anti-CSP IgM antibodies which caught up with the RTS,S/AS01 vaccinees levels by month 21. In contrast, there were no measurable anti-CSP IgG antibodies among the controls.

Conclusion
RTS,S/AS01-induced anti-CSP IgG antibodies kinetics are consistent with long-lived but waning vaccine efficacy. Natural exposure induces anti-CSP IgM antibodies in children, which increases with age, but does not induce substantial levels of anti-CSP IgG antibodies.
LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
Authors: He Yaomei , Jiang Xiulin , Duan Lincan , Xiong Qiuxia , Yuan Yixiao , Liu Peishen , Jiang Liping , Shen Qiushuo , Zhao Song , Yang Cuiping , Chen Yongbin 
Published: December 2021

Abstract
Background
Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved.

Methods
Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism.

Result
Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis.

Conclusions
Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.
Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases
Authors: Louadi Zakaria , Elkjaer Maria L. , Klug Melissa , Lio Chit Tong , Fenn Amit , Illes Zsolt , Bongiovanni Dario , Baumbach Jan , Kacprowski Tim , List Markus , Tsoy Olga 
Published: December 2021

AbstractAlternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking. To mitigate this, we developed NEASE, a tool integrating pathways with structural annotations of protein-protein interactions to functionally characterize AS events. We show in four application cases how NEASE can identify pathways contributing to tissue identity and cell type development, and how it highlights splicing-related biomarkers. With a unique view on AS, NEASE generates unique and meaningful biological insights complementary to classical pathways analysis.