bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in inpatient care coordinators’ clinical workflow and opportunities in designing a health IT solution: A mixed methods study
Authors: Wu Danny TY , Murdock Paul , Vennemeyer Scott , Mynatt Janie M , Chih Ming-Yuan 
Published: July 2022

Introduction Inpatient care coordinators (ICCs) in the United States play a critical role in case management and care transition. ICCs spend a large amount of time in chart review and documentation through electronic health record (EHR) systems. However, significant knowledge gaps exist regarding their workflow barriers and their use of health information technology (Health IT). Using only quantitative or quantitative methods does not provide a comprehensive picture about ICC’s workflow due to its complex and dynamic nature. This work aimed to address this gap by conducting a mixed-methods study to understand the workflow of ICCs and identifying challenges in care deliver and documentation activities. Methods The study adopted a concurrent triangulation design including qualitative interviews with 12 ICC staff members in the United States followed by extraction of their EHR event logs for one month. The qualitative interview data were analyzed thematically, and the log data were analyzed statistically. The results were triangulated and interpreted. Results Three major workflow barriers faced by ICCs were identified: long travel time, heavy documentation load, and suboptimal communication. The event logs provided empirical evidence to support the workflow barriers identified in the interviews, especially in travel time and documentation load. Discussion ICC workflow has several inefficiencies. The study generated four design considerations to develop a Health IT solution: Mobility, EHR integration, Team-based Communication, and User Adoption to improve workflow efficiency and care coordination. Using a mixed-methods approach is effective and efficient in collecting and analyzing clinical workflow.
Challenges and solutions to the implementation of studies within a trial: The experiences of the PROMETHEUS programme
Authors: Arundel Catherine E , Clark Laura , Coleman Elizabeth , Doherty Laura , Parker Adwoa , Torgerson David J 
Published: July 2022

Background Effective and efficient conduct of randomised controlled trials (RCTs) ensures accurate, timely results and prevents research waste. There is however limited evidence available to inform the design, conduct and reporting of RCTs. A self-contained, randomised Study Within A Trial (SWAT), embedded within a host RCT or cohort study, offers an opportunity to fill this evidence gap. While SWATs are generally easy to implement, a range of challenges to undertaking SWATs have also been identified, however there is limited detail regarding practical solutions to tackle these. Methods Information and observations collected from PROMETHEUS members and participating trials, focusing on SWATs across a wide range of questions and settings, was reviewed to identify the challenges and solutions of delivery of a programme of SWATs. Results A range of challenges to undertaking SWATs (e.g., obtaining governance approvals) were identified along with potential solutions to these, which were implemented accordingly during programme delivery. Central to the solutions to resolve SWAT challenges is education to develop knowledge and understanding in the wider research community on the importance, purpose, and key methodological principles in relation to SWATs. In addition, the sharing of experience, best practice or resources to prevent or help negotiate the barriers to undertaking SWAT evaluation is also recommended. Conclusions Potential solutions to the barriers experienced in the design, conduct and implementation of a programme of SWATs have been identified. As more SWATs are completed, this will further develop evidence to support the mitigation or removal of barriers and in doing so this should increase the efficiency of randomised controlled trials.
Effects of the media conditioned by various macrophage subtypes derived from THP-1 cells on tunneling nanotube formation in pancreatic cancer cells
Authors: Lee Chia-Wei , Kuo Chia-Chen , Liang Chi-Jung , Pan Huei-Jyuan , Shen Chia-Ning , Lee Chau-Hwang 
Published: July 2022

AbstractBackgroundTunneling nanotubes (TNTs) are special membrane structures for intercellular communications. Vital cargoes (such as mitochondria) could be delivered from healthy cells to rescue damaged ones through TNTs. The TNTs could be utilized for the purpose of systematic delivery of therapeutic agents between cells. However, there are insufficient studies on the controlled enhancement of TNT formations. The purpose of this study is to understand how macrophages influence the TNT formation in cancer cells.ResultsHere we compared the capabilities of inducing TNTs in human pancreatic cancer cells (PANC-1) of the media conditioned by M0, M1 and M2 macrophages derived from THP-1 cells. The M0 and M1 macrophage conditioned media promoted TNT formation. Using a focused ion beam to cut through a TNT, we observed tunnel-like structures inside dense cytoskeletons with scanning electron microscopy. The TNT formation correlated with raised motility, invasion, and epithelial–mesenchymal transition in the PANC-1 cells. Mitochondria and lysosomes were also found to be transported in the TNTs.ConclusionsThese results suggest that TNT formation could be one of the responses to the immune stress in pancreatic cancer cells caused by M0 and M1 macrophages. This finding is valuable for the development of macrophage-targeting cancer therapy.
Evaluation of nine statistics to identify QTLs in bulk segregant analysis using next generation sequencing approaches
Authors: de la Fuente Cantó Carla , Vigouroux Yves 
Published: July 2022

AbstractBackgroundBulk segregant analysis (BSA) combined with next generation sequencing is a powerful tool to identify quantitative trait loci (QTL). The impact of the size of the study population and the percentage of extreme genotypes analysed have already been assessed. But a good comparison of statistical approaches designed to identify QTL regions using next generation sequencing (NGS) technologies for BSA is still lacking.ResultsWe developed an R code to simulate QTLs in bulks of F2 contrasted lines. We simulated a range of recombination rates based on estimations using different crop species. The simulations were used to benchmark the ability of statistical methods identify the exact location of true QTLs. A single QTL led to a shift in allele frequency across a large fraction of the chromosome for plant species with low recombination rate. The smoothed version of all statistics performed best notably the smoothed Euclidean distance-based statistics was always found to be more accurate in identifying the location of QTLs. We propose a simulation approach to build confidence interval statistics for the detection of QTLs.ConclusionWe highlight the statistical methods best suited for BSA studies using NGS technologies in crops even when recombination rate is low. We also provide simulation codes to build confidence intervals and to assess the impact of recombination for application to other studies. This computational study will help select NGS-based BSA statistics that are useful to the broad scientific community.
Long-term prognosis and clinical course of choking-induced cardiac arrest in patients without the return of spontaneous circulation at hospital arrival: a population-based community study from the Shizuoka Kokuho Database
Authors: Miyoshi Takahiro , Endo Hideki , Yamamoto Hiroyuki , Shimada Koki , Kumamaru Hiraku , Ichihara Nao , Miyachi Yoshiki , Miyata Hiroaki 
Published: July 2022

Abstract
Background
The risk of choking increases with aging, and the number of cases of choking-induced cardiac arrest is increasing. However, few studies have examined the prognosis of choking-induced cardiac arrest. The aim of this study was to reveal the rates of survival and dependence on devices in the long term after choking-induced cardiac arrest.

Methods
We analyzed data from the Shizuoka Kokuho Database, which consists of claims data of approximately 2.2 million people, from April 2012 to September 2018. We selected patients with choking-induced cardiac arrest who received cardiopulmonary resuscitation in the hospital. Patients were excluded if they were less than 20 years old, had an upper airway tumor, received ventilation assistance, or received enteral nutrition in the month prior to cardiac arrest. The primary outcome was death, and the secondary outcomes were the rates of survival at 3-months and independence on devices. Descriptive statistics are presented and compared among age groups (20–64 years, 65–74 years, 75–84 years, 85 years and older), and survival time analysis (Kaplan-Meier method) was performed.

Results
In total, 268 patients were analyzed, including 26 patients in the 20–64 age group, 33 patients in the 65–74 age group, 70 patients in the 75–84 age group, and 139 patients in the ≥85 age group. The overall 3-month survival rate was 5.6% (15/268). The 3-month survival rates were 3.8% (1/26) in the 20–64 age group, 15.2% (5/33) in the 65–74 age group, 8.6% (6/70) in the 75–84 age group, and 2.2% (3/139) in the ≥85 age group. The overall 12-month survival rate was 2.6% (7/268). Of the 7 patients who survived for 12 months, 3 received ventilation management and 5 received tube or intravenous feedings at 3 months. These survivors were still receiving ventilation assistance and tube feedings in the hospital and had not been discharged at 12 months.

Conclusions
The prognosis of choking-induced cardiac arrest was extremely poor when patients were not resuscitated before hospital arrival. Those who survived were mostly dependent on assistive devices. Additionally, none of the survivors dependent on assistive devices had discontinued the use of the devices at the long-term follow-up.
Early use of probiotics might prevent antibiotic-associated diarrhea in elderly (>65 years): a systematic review and meta-analysis
Authors: Zhang Liying , Zeng Xiaofeng , Guo Daxin , Zou Yupei , Gan Huatian , Huang Xiaoli 
Published: July 2022

AbstractBackgroundAntibiotic-associated diarrhea (AAD) is diarrhea associated with consuming antibiotics that cannot be explained by other causes. AAD prolongs admission time and increases mortality and financial costs. Elderly individuals are more prone to receive antibiotic treatment and develop AAD. The finding that living probiotic microorganisms decrease AAD incidence in adults (<65 years) has been clarified. However, it is controversial among elderly individuals.MethodsWe aimed to explore whether probiotics could prevent AAD in elderly individuals. We searched three electronic databases (PubMed, EMBASE, and The Cochrane Library), and two reviewers independently screened and assessed the studies. RevMan5.4 software was used to perform a meta-analysis according to the PRISMA guidelines.ResultsEight RCTs of 4691 participants were included. We excluded two large studies because probiotics were used 48 hours after the first dose of antibiotics, and there was no effect. Subgroup analysis of 6 RCTs showed that probiotics given within two days of antibiotic treatment produced a lower AAD prevalence rate in elderly individuals.ConclusionWe recommend that elderly individuals could be routinely distributed probiotics to prevent AAD development when receiving antibiotic treatment.Trial registrationThe review was not registered.
PROMPT to improve speech motor abilities in children with cerebral palsy: a wait-list control group trial protocol
Authors: Fiori S. , Ragoni C. , Podda I. , Chilosi A. , Amador C. , Cipriani P. , Guzzetta A. , Sgandurra G. 
Published: July 2022

Abstract
Background
Children with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses.

Methods
A randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2.

Discussion
This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications.

Trial registration
Trial registration date 06/12/2019; ClinicalTrials.gov Identifier: NCT04189159.
Targeting autophagy increases the efficacy of proteasome inhibitor treatment in multiple myeloma by induction of apoptosis and activation of JNK
Authors: Salimi Azam , Schroeder Kema Marlen , Schemionek-Reinders Mirle , Vieri Margherita , Maletzke Saskia , Gezer Deniz , Masouleh Behzad Kharabi , Appelmann Iris 
Published: July 2022

Abstract
Background
The therapeutic armamentarium in multiple myeloma has been significantly broadened by proteasome inhibitors, highly efficient means in controlling of multiple myeloma. Despite the developments of therapeutic regimen in treatment of multiple myeloma, still the complete remission requires a novel therapeutic strategy with significant difference in outcomes. Proteasome inhibitors induce autophagy and ER stress, both pivotal pathways for protein homeostasis. Recent studies showed that the IRE1α-XBP1 axis of the unfolded protein response (UPR) is up-regulated in multiple myeloma patients. In addition, XBP1 is crucial for the maintenance of viability of acute lymphoblastic leukemia (ALL).

Results
We analyzed the efficacy of targeting IRE1α-XBP1 axis and autophagy in combination with proteasome inhibitor, ixazomib in treatment of multiple myeloma. In this present study, we first show that targeting the IRE1α-XBP1 axis with small molecule inhibitors (STF-083010, A106) together with the ixazomib induces cell cycle arrest with an additive cytotoxic effect in multiple myeloma. Further, we examined the efficacy of autophagy inhibitors (bafilomycin A, BAF and chloroquine, CQ) together with ixazomib in multiple myeloma and observed that this combination treatment synergistically reduced cell viability in multiple myeloma cell lines (viable cells Ixa: 51.8 ± 3.3, Ixa + BAF: 18.3 ± 7.2, Ixa + CQ: 38.4 ± 3.7) and patient-derived multiple myeloma cells (Ixa: 59.6 ± 4.4, Ixa + CQ: 7.0 ± 2.1). We observed, however, that this combined strategy leads to activation of stress-induced c-Jun N-terminal kinase (JNK). Cytotoxicity mediated by combined proteasome and autophagy inhibition was reversed by addition of the specific JNK inhibitor JNK-In-8 (viable cells: Ixa + BAF: 11.6 ± 7.0, Ixa + BAF + JNK-In-8: 30.9 ± 6.1).

Conclusion
In this study we showed that combined inhibition of autophagy and the proteasome synergistically induces cell death in multiple myeloma. Hence, we consider the implication of pharmaceutical inhibition of autophagy together with proteasome inhibition and UPR-directed therapy as promising novel in vitro treatment strategy against multiple myeloma.
Molecular pathology testing for non-small cell lung cancer: an observational study of elements currently present in request forms and result reports and the opinion of different stakeholders
Authors: Dufraing Kelly , Van Casteren Kaat , Breyne Joke , D’Haene Nicky , Van Campenhout Claude , Vander Borght Sara , Zwaenepoel Karen , Rouleau Etienne , Schuuring Ed , von der Thüsen Jan , Dequeker Elisabeth 
Published: July 2022

AbstractBackgroundFor patients with non-small cell lung cancer (NSCLC), targeted therapies are becoming part of the standard treatment. It is of question which information the clinicians provide on test requests and how the laboratories adapt test conclusions to this knowledge and regulations.MethodsThis study consisted of two components; 1) checking the presence of pre-defined elements (administrative and key for therapy-choice) on completed requests and corresponding reports in Belgian laboratories, both for tissue- and liquid biopsy (LB)-testing and b) opinion analysis from Belgian pathologists/molecular biologists and clinicians during national pathology/oncology meetings.ResultsData from 4 out of 6 Belgian laboratories with ISO-accreditation for LB-testing were analyzed, of which 75% were university hospitals. On the scored requests (N = 4), 12 out of 19 ISO-required elements were present for tissue and 11 for LB-testing. Especially relevant patient history, such as line of therapy (for LB), tumor histology and the reason for testing were lacking. Similarly, 11 and 9 out of 18 elements were present in the reports (N = 4) for tissue and LB, respectively.Elements that pathologists/molecular biologists (N = 18) were missing on the request were the initial activating mutation, previous therapies, a clinical question and testing-related information. For reporting, an item considered important by both groups is the clinical interpretation of the test result. In addition, clinicians (N = 28) indicated that they also wish to read the percentage of neoplastic cells.ConclusionsCommunication flows between the laboratory and the clinician, together with possible pitfalls were identified. Based on the study results, templates for complete requesting and reporting were proposed.
Use of computed tomography-derived body composition to determine the prognosis of patients with primary liver cancer treated with immune checkpoint inhibitors: a retrospective cohort study
Authors: Xiao Lu-shan , Li Rui-ning , Cui Hao , Hong Chang , Huang Chao-yi , Li Qi-mei , Hu Cheng-yi , Dong Zhong-yi , Zhu Hong-bo , Liu Li 
Published: July 2022

Abstract
Background
Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC.

Methods
In this retrospective cohort study of 172 patients with PLC, we measured the skeletal muscle index (SMI), skeletal muscle density, visceral adipose tissue index, subcutaneous adipose tissue index, total adipose tissue index (TATI), and visceral-to-subcutaneous adipose tissue area ratio using CT. In addition, we analyzed the impact of body composition on the prognosis of the patients. Multivariate Cox regression analysis was used to screen for influencing factors.

Results
Among the seven body composition components, low SMI (sarcopenia) and low TATI were significantly associated with poor clinical outcomes. Multivariate analysis revealed that sarcopenia (hazard ratio [HR], 5.39; 95% confidence interval [CI], 1.74–16.74; p = 0.004) was a significant predictor of overall survival (OS). Kaplan–Meier curves showed that sarcopenia and TATI were significant predictors of OS. Body mass index was not associated with survival outcomes.

Conclusions
Sarcopenia and fat tissue content appear to be independently associated with reduced survival rates in patients with PLC treated with ICIs.
Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents
Authors: Wenger Michael J. , Murray Kolb Laura E. , Scott Samuel P. , Boy Erick , Haas Jere D. 
Published: July 2022

AbstractBackgroundIron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels—blood, brain, and behavior—are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents.MethodsMale and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG).ResultsOverall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator.ConclusionsA dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition.Trial registrationRegistered at ClinicalTrials.gov,NCT02152150, 02 June 2014.