bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tools for measuring client experiences and satisfaction with healthcare in low- and middle-income countries: a systematic review of measurement properties
Authors: Banda Susan , Nkungula Nthanda , Chiumia Isabel Kazanga , Rylance Jamie , Limbani Felix 
Published: February 2023

Abstract
Background
Perspectives of patients as clients on healthcare offer unique insights into the process and outcomes of care and can facilitate improvements in the quality of services. Differences in the tools used to measure these perspectives often reflect differences in the conceptualization of quality of care and personal experiences. This systematic review assesses the validity and reliability of instruments measuring client experiences and satisfaction with healthcare in low- and middle-income countries (LMICs).

Methods
We performed a systematic search of studies published in PubMed, SCOPUS, and CINAHL. This review was reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies describing the development and psychometric properties of client experience and satisfaction with general health care were included in the review. Critical appraisal of study design was undertaken using the Appraisal tool for Cross-Sectional Studies (AXIS). The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and Terwee’s criteria were used to appraise the psychometric properties of the included studies. A narrative synthesis approach was used in the interpretation of the findings.

Results
Of the 7470 records identified, 12 studies with 14 corresponding instruments met the inclusion criteria and were included in the final review. No study assessed all the psychometric properties highlighted by the COSMIN criteria. In most instruments, we found evidence that initial development work incorporated client participation. The most evaluated measurement properties were content validity, internal consistency, and structural validity. Measurement error and responsiveness were not reported in any study.

Conclusion
Reliability and validity should be considered important elements when choosing or developing an instrument for professionals seeking an effective instrument for use within the population. Our review identified limitations in the psychometric properties of patient experience and satisfaction instruments, and none met all methodological quality standards. Future studies should focus on further developing and testing available measures for their effectiveness in clinical practice. Furthermore, the development of new instruments should incorporate clients' views and be rigorously tested or validated in studies with high methodological quality.

Trial registration
CRD42020150438.
Implementation of a virtual and in-person hybrid hospital-at-home model in two geographically separate regions utilizing a single command center: a descriptive cohort study
Authors: Paulson Margaret R. , Shulman Eliza P. , Dunn Ajani N. , Fazio Jacey R. , Habermann Elizabeth B. , Matcha Gautam V. , McCoy Rozalina G. , Pagan Ricardo J. , Maniaci Michael J. 
Published: February 2023

Abstract
Background
As providers look to scale high-acuity care in the patient home setting, hospital-at-home is becoming more prevalent. The traditional model of hospital-at-home usually relies on care delivery by in-home providers, caring for patients in urban communities through academic medical centers. Our objective is to describe the process and outcomes of Mayo Clinic’s Advanced Care at Home (ACH) program, a hybrid virtual and in-person hospital-at-home model combining a single, virtual provider-staffed command center with a vendor-mediated in-person medical supply chain to simultaneously deliver care to patients living near an urban hospital-at-home command center and patients living in a rural region in a different US state and time zone.

Methods
A descriptive, retrospective medical records review of all patients admitted to ACH between July 6, 2020, and December 31, 2021. Patients were admitted to ACH from an urban academic medical center in Florida and a rural community hospital in Wisconsin. We collected patient volumes, age, sex, race, ethnicity, insurance type, primary hospital diagnosis, 30-day mortality rate, in-program mortality, 30-day readmission rate, rate of return to hospital during acute phase, All Patient Refined-Diagnosis Related Groups (APR-DRG) Severity of Illness (SOI), and length of stay (LOS) in both the inpatient-equivalent acute phase and post-acute equivalent restorative phase.

Results
Six hundred and eighty-six patients were admitted to the ACH program, 408 in Florida and 278 in Wisconsin. The most common diagnosis seen were infectious pneumonia (27.0%), septicemia / bacteremia (11.5%), congestive heart failure exacerbation (11.5%), and skin and soft tissue infections (6.3%). Median LOS in the acute phase was 3 days (IQR 2–5) and median stay in the restorative phase was 22 days (IQR 11–26). In-program mortality rate was 0% and 30-day mortality was 0.6%. The mean APR-DRG SOI was 2.9 (SD 0.79) and the 30-day readmission rate was 9.7%.

Conclusions
The ACH hospital-at-home model was able to provide both high-acuity inpatient-level care and post-acute care to patients in their homes through a single command center to patients in urban and rural settings in two different geographical locations with favorable outcomes of low mortality and hospital readmissions.
Evaluating the implementation fidelity to a successful nurse-led model (INTERCARE) which reduced nursing home unplanned hospitalisations
Authors: Guerbaai Raphaëlle A. , DeGeest Sabina , Popejoy Lori L. , Simon Michael , Wellens Nathalie I. H. , Denhaerynck Kris , Zúñiga Franziska 
Published: February 2023

Abstract
Background
Implementation fidelity assesses the degree to which an intervention is delivered as it should be. Fidelity helps to determine if the outcome(s) of an intervention are attributed to the intervention itself or to a failure of its implementation. Little is known about how fidelity impacts the intended outcome(s) and what elements or moderators can affect the fidelity trajectory over time. We exemplify the meaning of implementation fidelity with INTERCARE, a nurse-led care model that was implemented in eleven Swiss nursing homes (NHs) and showed effectiveness in reducing unplanned hospital transfers. INTERCARE comprises six core elements, including advance care planning and tools to support inter- and interprofessional communication, which were introduced with carefully developed implementation strategies.

Methods
A mixed-methods convergent/triangulation design was used to investigate the influence of implementation fidelity on unplanned transfers. A fidelity questionnaire measuring the degree of fidelity to INTERCARE’s core components was fielded at four time points in the participating NHs. Two-monthly meetings were conducted with NHs (September 2018-January 2020) and structured notes were used to determine moderators affecting fidelity (e.g., participant responsiveness). We used the fidelity scores and generalized linear mixed models to analyze the quantitative data. The Framework method was used for the qualitative analysis. The quantitative and qualitative findings were integrated using triangulation.

Results
A higher overall fidelity score showed a decreasing rate of unplanned hospital transfers post-intervention (OR: 0.65 (CI = 0.43–0.99), p = 0.047). A higher fidelity score to advance care planning was associated with lower unplanned transfers (OR = 0.24 (CI 0.13–0.44), p = < 0.001) and a lower fidelity score for communication tools (e.g., ISBAR) to higher rates in unplanned transfers (OR = 1.69 (CI 1.30–2.19), p = < 0.003). In-house physicians with a collaborative approach and staff’s perceived need for nurses working in extended roles, were important moderators to achieve and sustain high fidelity.

Conclusion
Implementation fidelity is challenging to measure and report, especially in complex interventions, yet is crucial to better understand how such interventions may be tailored for scale-up. This study provides both a detailed description of how fidelity can be measured and which ingredients highly contributed to reducing unplanned NH transfers.

Trial registration
The INTERCARE study was registered at clinicaltrials.gov Protocol Record NCT03590470.
In vitro and in vivo analyses on anti-NSCLC activity of apatinib: rediscovery of a new drug target V600E mutation
Authors: Chen Jiani , Zhai Jingwen , Li Mingming , Liu Shiyi , Gong Xiaobin , Yu Hongyu , Wei Hua , Chen Wansheng 
Published: February 2023

Abstract
Background
Apatinib (YN968D1) is the first small-molecule-targeting drug with anti-tumor activity created in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It showed significant variation in the efficacy for treating cancers, including advanced non-squamous non-small-cell lung cancer (NSCLC). Whether its efficacy could be optimized by subgrouping patients with certain genetic variation remains elusive.

Methods
Here, we firstly used kinase screening to identify any possible target of apatinib against 138 kinases. The effects of apatinib on proliferation rates, cell cycle, cell apoptosis, and cell migration on cancer cell lines were analyzed; the in vitro potential pathways of apatinib on cancer cell lines were screened. The effect of apatinib on mouse cancer models in vivo was also analyzed.

Results
Based on HCC364 cells with BRAF V600E mutation, we have shown that apatinib could inhibit their growth, migration, cell cycle, and induce their apoptosis. Based on mice with transplanted HCC364 cells, we have also shown that apatinib could inhibit the tumor growth. Based on immunohistochemistry, we have demonstrated that apatinib could suppress the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase and extracellular regulated protein kinases. This may account at least part of the apatinib’s inhibitory effect on HCC364 cancer cells.

Conclusions
BRAF V600E protein kinase is a target of apatinib by kinase screening. We have demonstrated that apatinib can effectively inhibit tumor cells with BRAF V600E mutation by in vitro and in vivo experiments. Our results have demonstrated that targeting BRAF V600E mutation, apatinib appears to be effective and safe for treating NSCLC and possibly other cancers with the same mutation.
Calcium-to-phosphorus releasing ratio affects osteoinductivity and osteoconductivity of calcium phosphate bioceramics in bone tissue engineering
Authors: Jin Pan , Liu Lei , Cheng Lin , Chen Xichi , Xi Shanshan , Jiang Tongmeng 
Published: February 2023

AbstractCalcium phosphate (Ca-P) bioceramics, including hydroxyapatite (HA), biphasic calcium phosphate (BCP), and beta-tricalcium phosphate (β-TCP), have been widely used in bone reconstruction. Many studies have focused on the osteoconductivity or osteoinductivity of Ca-P bioceramics, but the association between osteoconductivity and osteoinductivity is not well understood. In our study, the osteoconductivity of HA, BCP, and β-TCP was investigated based on the osteoblastic differentiation in vitro and in situ as well as calvarial defect repair in vivo, and osteoinductivity was evaluated by using pluripotent mesenchymal stem cells (MSCs) in vitro and heterotopic ossification in muscles in vivo. Our results showed that the cell viability, alkaline phosphatase activity, and expression of osteogenesis-related genes, including osteocalcin (Ocn), bone sialoprotein (Bsp), alpha-1 type I collagen (Col1a1), and runt-related transcription factor 2 (Runx2), of osteoblasts each ranked as BCP > β-TCP > HA, but the alkaline phosphatase activity and expression of osteogenic differentiation genes of MSCs each ranked as β-TCP > BCP > HA. Calvarial defect implantation of Ca-P bioceramics ranked as BCP > β-TCP ≥ HA, but intramuscular implantation ranked as β-TCP ≥ BCP > HA in vivo. Further investigation indicated that osteoconductivity and osteoinductivity are affected by the Ca/P ratio surrounding the Ca-P bioceramics. Thus, manipulating the appropriate calcium-to-phosphorus releasing ratio is a critical factor for determining the osteoinductivity of Ca-P bioceramics in bone tissue engineering.
Isolation and proteomic profiling of urinary exosomes from patients with colorectal cancer
Authors: Ma Ling , Yu Haijiao , Zhu Yubing , Xu Kaiyu , Zhao Aimin , Ding Lei , Gao Hong , Zhang Man 
Published: February 2023

AbstractExosomes in the body fluid are effective cell-derived membranous structures transferring various molecules to mediate intercellular communication. The expression of protein in the urinary exosomes from the colorectal cancer (CRC) patients could reflect the characteristics of tumorigenesis. The urinary exosomes with globular membrane structure, the size of 30 ~ 100 nm and positive expression of CD9, CD63 and CD81 were successfully isolated from 9 CRC patients and 3 heathy adults using the density gradient ultracentrifugation. Proteome profiles revealed by label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS) indicated that several proteins were differentially expressed among different stages of CRC. Compared with normal controls, 67 proteins in CRC urinary exosomes were upregulated and 74 proteins were downregulated. The bioinformatics analysis revealed the decreased proteins were related to ESCRT III complex disassembly. The CHMP family was further determined to be the hub of interaction network of proteins enriched in ESCRT signaling. The significant decrease of CHMP4A, CHMP4B, CHMP2A, CHMP2B and CHMP1B were respectively found in the total CRC group and distant metastasis group compared with NC group. Moreover, the CEACAM family also showed significant aberrant changes in the urinary exosomes of CRC patients. The CEACAM7 and CEACAM1 were increased in the CRC patients compared with healthy individuals (P < 0.05). Significant changes of proteomic profile could be found in the urinary exosomes in the CRC patients. The differential expressed urinary exosomes derived proteins showed potential usage in diagnosis and prognosis of CRC.
Abnormal signal pathways and tumor heterogeneity in osteosarcoma
Authors: Sun Yifeng , Zhang Chunming , Fang Qiongxuan , Zhang Wenqiang , Liu Wei 
Published: February 2023

Abstract
Background
Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed.

Methods
We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers.

Results
The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways.

Conclusion
Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies.
The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation
Authors: Reinhold Dirk , Farztdinov Vadim , Yan Yan , Meisel Christian , Sadlowski Henrik , Kühn Joachim , Perschel Frank H. , Endres Matthias , Düzel Emrah , Vielhaber Stefan , Guttek Karina , Goihl Alexander , Venø Morten , Teegen Bianca , Stöcker Winfried , Stubbemann Paula , Kurth Florian , Sander Leif E. , Ralser Markus , Otto Carolin , Streit Simon , Jarius Sven , Ruprecht Klemens , Radbruch Helena , Kjems Jørgen , Mülleder Michael , Heppner Frank , Körtvelyessy Peter 
Published: February 2023

AbstractPatients with COVID-19 can have a variety of neurological symptoms, but the active involvement of central nervous system (CNS) in COVID-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. We studied the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n = 38). Patients with herpes simplex virus encephalitis (HSVE, n = 10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n = 28) served as controls. We used proteomics, enzyme-linked immunoassays, and semiquantitative cytokine arrays to characterize inflammatory proteins. Autoantibody screening was performed with cell-based assays and native tissue staining. RNA sequencing of long-non-coding RNA and circular RNA was done to study the transcriptome. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients with, e.g., downregulation of the apolipoproteins and extracellular matrix proteins. Protein upregulation of the complement system, the serpin proteins pathways, and other proteins including glycoproteins alpha-2 and alpha-1 acid. Importantly, calculation of interleukin-6, interleukin-16, and CXCL10 CSF/serum indices suggest that these inflammatory mediators reach the CSF from the systemic circulation, rather than being produced within the CNS. Antibody screening revealed no pathological levels of known neuronal autoantibodies. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly (p < 0.01) higher in those with bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, and two circRNAs being significantly differentially expressed in COVID-19 than in non-neuroinflammatory controls and neurodegenerative patients. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms deserves further investigation.
Mutagenesis of the di-leucine motif in the cytoplasmic tail of newcastle disease virus fusion protein modulates the viral fusion ability and pathogenesis
Authors: Teng Qingyuan , Tang Lihua , Huang Yahui , Yang Ruihua , He Yizhuo , Zhang Guozhong , Zhao Ye 
Published: February 2023

Abstract
Background
Newcastle disease virus (NDV) is a highly infectious viral disease, which can affect chickens and many other kinds of birds. The main virulence factor of NDV, the fusion (F) protein, is located on the viral envelope and plays a major role in the virus’ ability to penetrate cells and cause host cell fusion during infection. Multiple highly conserved tyrosine and di-leucine (LL) motifs in the cytoplasmic tail (CT) of the virus may contribute to F protein functionality in the viral life cycle.

Methods
To examine the contribution of the LL motif in the biosynthesis, transport, and function of the F protein, we constructed and rescued a NDV mutant strain, rSG10*-F/L537A, with an L537A mutation using a reverse genetic system. Subsequently, we compared the differences in the syncytium formation ability, pathogenicity, and replication levels of wild-type rSG10* and the mutated strain.

Results
Compared with rSG10*, rSG10*-F/L537A had attenuated syncytial formation and pathogenicity, caused by a viral budding defect. Further studies showed that the LL-motif mutation did not affect the replication, transcription, or translation of the virus genome but affected the expression of the F protein at the cell surface.

Conclusions
We concluded that the LL motif in the NDV F CT affected the regulation of F protein expression at the cell surface, thus modulating the viral fusion ability and pathogenic phenotype.
Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration
Authors: Miatmoko Andang , Hariawan Berlian Sarasitha , Cahyani Devy Maulidya , Dewangga Syarifah Sutra , Handoko Kevin Ksatria , Purwati  , Sahu Ram Kumar , Hariyadi Dewi Melani 
Published: February 2023

AbstractChronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients’ quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent.