bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing a mHealth clinical decision support system for Parkinson’s disease: a theoretically grounded user needs approach
Authors: Timotijevic L. , Hodgkins C. E. , Banks A. , Rusconi P. , Egan B. , Peacock M. , Seiss E. , Touray M. M. L. , Gage H. , Pellicano C. , Spalletta G. , Assogna F. , Giglio M. , Marcante A. , Gentile G. , Cikajlo I. , Gatsios D. , Konitsiotis S. , Fotiadis D. 
Published: February 2020

Abstract
Background
Despite the established evidence and theoretical advances explaining human judgments under uncertainty, developments of mobile health (mHealth) Clinical Decision Support Systems (CDSS) have not explicitly applied the psychology of decision making to the study of user needs. We report on a user needs approach to develop a prototype of a mHealth CDSS for Parkinson’s disease (PD), which is theoretically grounded in the psychological literature about expert decision making and judgement under uncertainty.

Methods
A suite of user needs studies was conducted in 4 European countries (Greece, Italy, Slovenia, the UK) prior to the development of PD_Manager, a mHealth-based CDSS designed for Parkinson’s disease, using wireless technology. Study 1 undertook Hierarchical Task Analysis (HTA) including elicitation of user needs, cognitive demands and perceived risks/benefits (ethical considerations) associated with the proposed CDSS, through structured interviews of prescribing clinicians (N = 47). Study 2 carried out computational modelling of prescribing clinicians’ (N = 12) decision strategies based on social judgment theory. Study 3 was a vignette study of prescribing clinicians’ (N = 18) willingness to change treatment based on either self-reported symptoms data, devices-generated symptoms data or combinations of both.

Results
Study 1 indicated that system development should move away from the traditional silos of ‘motor’ and ‘non-motor’ symptom evaluations and suggest that presenting data on symptoms according to goal-based domains would be the most beneficial approach, the most important being patients’ overall Quality of Life (QoL). The computational modelling in Study 2 extrapolated different factor combinations when making judgements about different questions. Study 3 indicated that the clinicians were equally likely to change the care plan based on information about the change in the patient’s condition from the patient’s self-report and the wearable devices.

Conclusions
Based on our approach, we could formulate the following principles of mHealth design: 1) enabling shared decision making between the clinician, patient and the carer; 2) flexibility that accounts for diagnostic and treatment variation among clinicians; 3) monitoring of information integration from multiple sources. Our approach highlighted the central importance of the patient-clinician relationship in clinical decision making and the relevance of theoretical as opposed to algorithm (technology)-based modelling of human judgment.
Physician code creep after the initiation of outpatient volume control program and implications for appropriate ICD-10-CM coding
Authors: Liang Fu-Wen , Wang Liang-Yi , Liu Lin-Yi , Li Chung Yi , Lu Tsung-Hsueh 
Published: February 2020

Abstract
Background
Most studies on the physician code creep (i.e., changes in case mix record-keeping practices to improve reimbursement) have focused on episodes (inpatient hospitalizations or outpatient procedures). Little is known regarding changes in diagnostic coding practices for better reimbursement among a fixed cohort of patients with chronic diseases.

Methods
To examine whether physicians in tertiary medical centers changed their coding practices after the initiation of the Outpatient Volume Control Program (OVCP) in Taiwan, we conducted a retrospective observational study of four patient cohorts (two interventions and two controls) from January 2016 to September 2017 in Taiwan. The main outcomes were the number of outpatient visits with four coding practices: 1) OVCP monitoring code recorded as primary diagnosis; 2) OVCP monitoring code recorded as secondary diagnosis; 3) non-OVCP monitoring code recorded as primary diagnosis; 4) non-OVCP monitoring code recorded as secondary diagnosis.

Results
The percentage change of the number of visits with coding practice 1 between 2016Q1 and 2017Q3 was − 74% for patients with hypertension and − 73% with diabetes in tertiary medical centers and − 23% and − 17% in clinics, respectively. By contrast, the percentage changes of coding practice 3 were + 73% for patients with hypertension and + 46% for patients with diabetes in tertiary medical centers and − 19% and − 2% in clinics, respectively.

Conclusions
Physician code creep occurred after the initiation of the OVCP. Education regarding appropriate outpatient coding for physicians will be relatively effective when proper coding is related to reimbursement.
Extensive genetic diversity of Plasmodium vivax dbp-II in Rio de Janeiro Atlantic Forest and Brazilian Amazon Basin: evidence of positive selection
Authors: Almeida-de-Oliveira Natália Ketrin , Lima-Cury Lidiane , de Abreu-Fernandes Rebecca , de Rosa Lavigne Aline , de Pina-Costa Anielle , de Souza Perce-da-Silva Daiana , Catanho Marcos , Brasil Patrícia , Daniel-Ribeiro Cláudio Tadeu , Ferreira-da-Cruz Maria de Fátima 
Published: February 2020

AbstractBackgroundPlasmodium vivaxis the most widespread human malaria parasite outside Africa and is the predominant parasite in the Americas. Increasing reports ofP. vivaxdisease severity, together with the emergence of drug-resistant strains, underscore the urgency of the development of vaccines againstP. vivax. Polymorphisms on DBP-II-gene could act as an immune evasion mechanism and, consequently, limited the vaccine efficacy. This study aimed to investigate thepvdbp-II genetic diversity in two Brazilian regions with different epidemiological patterns: the unstable transmission area in the Atlantic Forest (AF) of Rio de Janeiro and; the fixed malaria-endemic area in Brazilian Amazon (BA).Methods216 BrazilianP. vivaxinfected blood samples, diagnosed by microscopic examination and PCR, were investigated. The region flankingpvdbp-II was amplified by PCR and sequenced. Genetic polymorphisms ofpvdbp-II were estimated based on the number of segregating sites and nucleotide and haplotype diversities; the degree of differentiation between-regions was evaluated applying Wright’s statistics. Natural selection was calculated using the rate of nonsynonymous per synonymous substitutions with the Z-test, and the evolutionary distance was estimated based on the reconstructed tree.Results79 samples from AF and 137 from BA were successfully sequenced. The analyses showed 28 polymorphic sites distributed in 21 codons, with only 5% of the samples Salvador 1 type. The highest rates of polymorphic sites were found in B- and T cell epitopes. Unexpectedly, the nucleotide diversity inpvdbp-II was higher in AF (0.01) than in BA (0.008). Among the 28 SNPs detected, 18 are shared betweenP. vivaxisolates from AF and BA regions, but 8 SNPs were exclusively detected in AF—I322S, K371N, E385Q, E385T, K386T, K411N, I419Land I419R—and 2 (N375Dand I419M) arose exclusively in BA. These findings could suggest the potential of these geographical clusters as population-specific-signatures that may be useful to track the origin of infections. The sample size should be increased in order to confirm this possibility.ConclusionsThe results highlight that thepvdbp-IIpolymorphisms are positively selected by host’s immune pressure. The characterization ofpvdbp-II polymorphisms might be useful for designing effective DBP-II-based vaccines.
ROCK1 activation-mediated mitochondrial translocation of Drp1 and cofilin are required for arnidiol-induced mitochondrial fission and apoptosis
Authors: Hu Jinjiao , Zhang Hongwei , Li Jie , Jiang Xiuxing , Zhang Yanhao , Wu Qin , Shen liwen , Shi Jingshan , Gao Ning 
Published: February 2020

Abstract
Background
Arnidiol is a pentacyclic triterpene diol that has multiple pharmacological activities. However, the apoptotic activities of arnidiol in human cancer cells have not yet been explored, nor has the mechanism by which arnidiol induces apoptosis been examined in depth.

Methods
MDA-MB-231 cells and xenografted mice were treated with arnidiol. Mitochondrial fission and apoptosis were determined by immunofluorescence, flow cytometry and related molecular biological techniques. The interaction and colocalization of cofilin and Drp1 was determined by immunoprecipitation and immunofluorescence assays.

Results
Arnidiol induces mitochondrial fission and apoptosis through mitochondrial translocation of Drp1 and cofilin. Importantly, the interaction of Drp1 and cofilin in mitochondria is involved in arnidiol-induced mitochondrial fission and apoptosis. Knockdown of either Drp1 or cofilin abrogated arnidiol-induced mitochondrial translocation, interaction of Drp1 and cofilin, mitochondrial fission and apoptosis. Only dephosphorylated Drp1 (Ser637) and cofilin (Ser3) were translocated to the mitochondria. Mutants of Drp1 S637A and cofilin S3A, which mimic the dephosphorylated forms, enhanced mitochondrial fission and apoptosis induced by arnidiol, whereas mutants of Drp1 S637D and cofilin S3E, which mimic the phosphorylated forms, suppressed mitochondrial fission and apoptosis induced by arnidiol. A mechanistic study revealed that ROCK1 activation plays an important role in the arnidiol-mediated Drp1 and cofilin dephosphorylation and mitochondrial translocation, mitochondrial fission, and apoptosis.

Conclusions
Our data reveal a novel role of both Drp1 and cofilin in the regulation of mitochondrial fission and apoptosis and suggest that arnidiol could be developed as a potential agent for the treatment of human cancer.
Autogeny in Culiseta longiareolata (Culicidae: Diptera) mosquitoes in laboratory conditions in Iran
Authors: Khaligh Fereshteh Ghahvechi , Naghian Abdollah , Soltanbeiglou Shadiyeh , Gholizadeh Saber 
Published: February 2020

Abstract
Objectives
Culiseta longiareolata is a cosmopolitan species and has implicated in the transmission of avian malaria, tularemia, and arboviruses. Despite the wide distribution of Cs. longiareolata in Iran, little is known about its biology and physiology. The current research was conducted to study the autogeny behavior in this potential vector. During 2018, larvae and pupae were collected from Nazloo region in Urmia City using standard methods. Mosquitoes were reared in cages and fed by 5% sugar in laboratory conditions and were then dissected in phosphate-buffered saline (PBS) under a stereo microscope.

Results
In total, 230 adult female Cs. longiareolata mosquitoes were dissected. Egg rafts were observed in the ovary of only 10.86% unfed female mosquitoes. Autogeny behavior is a significant factor in the growth of population without a blood feeding. Therefore, it is necessary to study how autogenous reproduction affects mosquito-borne diseases.
Development of a risk calculator of recurrence in inguinal lymph node metastatic (ILNM) patients with surgically resected penile squamous cell carcinoma (PSCC).
Authors: Bandini Marco , Zhu Yao , Ye Dingwei , Ornellas Antonio Augusto , Watkin Nick , Ager Michael , Hakenberg Oliver W. , Heidenreich Axel , Raggi Daniele , Catanzaro Mario , Marandino Laura , Haidl Friederike , Montorsi Francesco , Chipollini Juan , Azizi Mounsif , Albersen Maarten , Salvioni Roberto , Brouwer Oscar , Spiess Philippe E. , Necchi Andrea 
Published: February 2020

1 Background: ILNM PSCC patients (pts) have heterogeneous outcomes. We aimed to identify risk factors of early recurrence in order to optimize the selection of pts for adjuvant (adj) therapies (tx). Methods: In a multicenter database of 924 pts who underwent ILN dissection, we identified 311 ILNM pts. Pts treated with neoadj chemo (CT) and/or radiotherapy (RT) were excluded. Multivariable Cox regression analyses (MVA) tested for predictors of recurrence, after adjusting for adj tx, age, type of surgery of the primary and smoking status. As primary endpoint, a risk calculator predicting early (24-month) risk of recurrence was developed. As secondary endpoint, the overall survival (OS) benefit of adj tx was examined according to the risk calculator-derived tertiles using Kaplan-Meier analysis. Results: Overall, 159 pts (51.1%) had pN1-2 and 203 (65.3%) pT2-4 disease. Overall, 195 (62.7%) and 78 (25.1%) received partial or total penectomy, whereas 6 (1.9%) local excision and 32 (10.3%) other procedures. Median number of removed and positive ILN were 15 (IQR 9-21) and 2 (IQR 1-3). Pelvic LND was performed in 154 (49.5%) pts, and 39% of them had pelvic LNM. In MVA, ILN ratio (HR: 1.01, p= 0.04), pN3 (HR: 2.53, p=0.002) and positive proximal margin of the primary (HR: 2.13, p=0.02) were significantly associated with recurrence. The c-index of our 3-variable risk calculator was 68%, with a net benefit higher that treat-all option from 20% to 90% threshold-probabilities. Within the cohort of adj CT and/or RT (N=127) pts, intermediate-high tertile had similar median OS (NR vs 107m) compared to pts in the low tertile (p=0.1). Conversely, intermediate-high tertile pts who received observation alone had shorter OS (NR vs 40m) compared to the same pts in the lower tertile (p<0.001). Similar results were obtained for CT and RT separately analyzed. Conclusions: We developed and internally validated a risk calculator to predict early recurrence in ILNM surgically-resected PSCC pts. According to our risk-calculator, pts with intermediate/higher risk of early recurrence may benefit from adj tx. Our risk calculator can be used for counseling and enrolment in ongoing studies.
Analysis of the prognostic significance of circulating tumor DNA (ctDNA) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Shaya Justin , Randall James Michael , Millard Frederick E. , Kurzrock Razelle , Parsons J Kellogg , Tamayo Pablo , McKay Rana R. 
Published: February 2020

110 Background: Given the technical limitations of obtaining tissue next-generation sequencing, there has been interest in blood ctDNA to assess genomic alterations in mCRPC. We examined the genomic landscape and prognostic significance of ctDNA in mCRPC. Methods: Single center retrospective analysis of mCRPC patients who underwent ctDNA genomic profiling using Guardant360. Overall survival (OS) and time to progression (TTP) were examined and stratified by the presence of tumor suppressor mutations (p53, PTEN, Rb), androgen receptor (AR) amplification or mutation, number of genomic alterations, and highest allelic fraction of detected mutations. Results: At the time of ctDNA collection, all patients (n=46) had mCRPC with bone metastases present in 100% of patients and visceral metastases present in 17.3%. Median age at ctDNA collection was 71 years, median time from CRPC diagnosis to ctDNA was 13 months (range 0-45), and median follow-up time from CRPC diagnosis was 17.5 months (4-40). The most common alterations present were TP53 mutation (41.3%), AR amplification (30.4%), and CDK6 amplification (21.7%). Actionable mutations were detected in BRCA1 (4.3%), BRCA2 (4.3%), ATM (2.2%), and PMS2 (2.2%). The median number of genomic alterations was 2 (0-8) and the median ctDNA allelic fraction was 4.6% (0-86.9%). Median OS of the cohort was 36 months. The presence of a tumor suppressor mutation, > 2 genomic alterations, and >5% mutation allelic fraction was associated with inferior OS (Table). In terms of time to progression on 1st line abiraterone or enzalutamide, the presence of an AR amplification or mutation was associated with significantly worse median TTP of 6.9 vs 13.5 months ( p- 0.015). Conclusions: ctDNA is frequently detected in mCRPC; and the type, number and frequency of alterations are potentially prognostic of OS in mCRPC. Ongoing studies are needed to assess concordance of ctDNA with tissue NGS and the predictability of ctDNA.[Table: see text]
Phase Ib study of niraparib plus androgen receptor-targeted therapy (ART) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Saad Fred , Chi Kim N. , Shore Neal D. , Graff Julie Nicole , Posadas Edwin M. , Espina Byron M. , Zhu Eugene , Hazra Anasuya , Bradic Branislav , Cheng Shinta , Hayreh Vinny , Rezazadeh Arash 
Published: February 2020

122 Background: Poly ADP-ribose polymerase (PARP) inhibitor and abiraterone acetate + prednisone (AA+P) has activity in pts with mCRPC regardless of DNA repair gene defects (DRD). Methods: This phase 1b study (Bedivere; NCT02924766) began with a 3+3 dose escalation of niraparib (Part 1), followed by expansion (Part 2) of the recommended phase 2 dose (RP2D) of nira + AA+P. Pts with mCRPC received nira 200 or 300 mg/day with AA+P. Dose-limiting toxicities (DLTs) were evaluated the first 28 days. Serial PK for nira were collected on cycle 1 day 1 (C1D1) over 24 h; PK for nira and abiraterone were collected on C2D1 over 10 h. Results: Nira 200 mg + 1000 mg AA+P was selected as the RP2D dose. 4 pts in 200 mg cohort and 8 pts in 300 mg cohort were enrolled in Part 1. During Part 1, 1 patient in the 300 mg cohort had two DLTs: Gr 3 fatigue and Gr 4 increased gamma glutamyltransferase. Therefore, the 200 mg dose was evaluated in 15 pts in Part 2. In 19 total pts treated with 200 mg niraparib, 12 (63%) pts had Gr 3-4 AEs, 5 (26%) pts had an AE with outcome of drug discontinuation and 1 (5%) patient had an AE with outcome of death (general physical health deterioration; unrelated). AEs of special interest were: 6 pts (32%) thrombocytopenia, 6 pts (32%) hypertension, 5 pts (26%) anemia and 3 pts (16%) neutropenia of any grade. 21% pts in 200 mg cohort had treatment emergent serious AE (TESAE) while 50% treated with 300 mg had TESAE. The exposure (AUC24h) on Day 1 of Cycle 2 for 200 mg niraparib with 1000 mg of AA were 17745±9380 ng.h/mL and 712±140 ng.h/mL, respectively. These exposures are consistent with single agent PK. Summaries of all responses will be provided, including a patient with primarily bone disease and carrying an ATM mutation who had a circulating tumor cell conversion and was on study treatment for 22.1 mo. Conclusions: The safety and PK findings support the choice of nira 200 mg in combination with AA+P in pts with mCRPC. The efficacy of nira + AA+P is being evaluated in an ongoing phase 3 MAGNITUDE study (NCT03748641). Clinical trial information: NCT02924766.
Revision of CHAARTED and LATTITUDE criteria among Japanese de novo metastatic prostate cancer patients.
Authors: Sakamoto Shinichi , Yamada Yasutaka , Rii Junryo , Yamamoto Satoshi , Kamada Shuhei , Imamura Yusuke , Nakamura Kazuyoshi , Komiya Akira , Nakatsu Hiroomi , Ichikawa Tomohiko 
Published: February 2020

132 Background: Based on the high response rate to the standard androgen deprivation therapy (ADT), the Japanese cohort in LATTITUDE study failed to show the survival benefit by early Abiraterone. In order to identify the "true high-risk" patients, we studied the prognostic factors among Japanese de novo metastatic prostate cancer patients who fit CHAARTED and LATITUDE criteria. Methods: We retrospectively studied patients who fit CHAARTED (292 patients) and LATITUDE (294 patients) criteria from Japanese multi-institutions. All patients received ADT with bicalutamide as an initial treatment. Factors related to overall survival (OS) and progression-free survival (PFS) were statistically analyzed. Results: The median OS was 56 mo and 57 mo in patients who met the CHAARTED and the LATITUDE criteria, respectively. In patients who met CHAARTED criteria, LDH (HR2.6, p < 0.00001) and CRP (HR1.7, p = 0.042) were independent risk factors for OS. In patients who met LATTITUDE criteria, GS≥9 (HR1.7, p = 0.0378) and LDH (HR2.9, p < 0.0001) were independent risk factors for OS. Modified CHAARTED criteria by adding LDH and CRP showed a significant difference in OS (HR2.8, p < 0.0001) with a comparative median OS (30 mo) to placebo of CHAARTED trial (32 mo). Modified LATTITUDE criteria by adding GS≥9 and LDH, showed a significant difference in OS (HR2.7, p < 0.0001) with a comparative median OS (33 mo) to placebo of LATTITUDE trial (34 mo). Conclusions: Modified criteria may potentially elucidate the true "high-volume" and "high-risk" patients in the Japanese cohort who require early intensive therapy.[Table: see text]
ADRB2 expression in progressive metastatic castration-resistant prostate cancer.
Authors: Kwon Daniel , Zhang Li , Foye Adam , Chen William S. , Feng Felix Y , Bailey Adina , Huang Jiaoti , Quigley David A. , Stuart Josh , Friedl Verena , Weinstein Alana , Beer Tomasz M. , Alumkal Joshi J. , Rettig Matthew , Gleave Martin , Lara Primo , Li Patricia , Lui Austin , Small Eric Jay , Aggarwal Rahul Raj 
Published: February 2020

145 Background: The net oncogenic effect of the G protein-coupled receptor β2 adrenergic receptor ADRB2, which may induce neuroendocrine differentiation via cyclic AMP and protein kinase A and whose expression is epigenetically regulated by EZH2, is controversial. ADRB2 expression and associated clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) are unknown. Methods: This was a retrospective analysis of a cohort of men with mCRPC who were prospectively enrolled in the multi-center SU2C/PCF/AACR West Coast Prostate Cancer Dream Team study, in which biopsies of a metastatic site were obtained at disease progression. Specimens underwent laser capture microdissection and RNA-seq. ADRB2 expression was stratified by histology and transcriptional cluster based on prior unsupervised hierarchical transcriptome clustering, and correlated with EZH2 expression. ADRB2 expression (lowest quartile) was correlated with OS from time of biopsy by log rank test and a multivariable Cox proportional hazard model. Results: One-hundred and twenty-seven men with progressive mCRPC underwent metastatic biopsies and had sufficient tumor for RNA-seq. ADRB2 expression was lowest in the small cell-enriched transcriptional cluster (P<0.001), and correlated inversely with EZH2 expression (r=-0.28, P<0.01). Men with low ADRB2 expression had a shorter median OS than those with high (9.5 vs 18.9 mo, P=0.02). In multivariable analysis adjusting for small cell histology, performance status, LDH, and visceral metastases, high ADRB2 expression was associated with a trend towards longer OS (HR=0.65, 95% CI 0.41-1.02, P=0.06). Conclusions: Low ADRB2 expression is associated with worse OS in men with progressive mCRPC, and may be a means by which EZH2 confers resistance to antiandrogen therapy. Indirect ADRB2 stimulation with EZH2 inhibitors may improve outcomes. Validation in independent cohorts is necessary.