bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol: development and randomized controlled trial of a preventive blended care parenting intervention for parents with PTSD
Authors: Meijer Laurien , Finkenauer Catrin , Blankers Matthijs , de Gee Anouk , Kramer Jeannet , Shields-Zeeman Laura , Thomaes Kathleen
Published: February 2023

Background

Children of parents with post-traumatic stress disorder (PTSD) are at increased risk of adverse psychological outcomes. An important risk mechanism is impaired parental functioning, including negative parenting behavior, perceived incompetence, and lack of social support. Several parenting interventions for trauma-exposed parents and parents with psychiatric disorders exist, but none have specifically targeted parents with PTSD. Our objective is to evaluate the effectiveness of a blended care preventive parenting intervention for parents with PTSD.

Methods

The intervention was adapted from an existing online intervention, KopOpOuders Self-Help. In co-creation with parents with PTSD and partners, the intervention was adapted into KopOpOuders-PTSD, by adding PTSD-specific content and three in-person-sessions with a mental health prevention professional. Effectiveness will be tested in a randomized controlled trial among N = 142 parents being treated for PTSD at Arkin Mental Health Care (control condition: treatment as usual, n = 71; intervention condition: treatment as usual + intervention, n = 71). Online questionnaires at pretest, posttest, and three-month follow-up and ecological momentary assessment at pretest and posttest will be used. Intervention effects on primary (parenting behavior) and secondary outcomes (perceived parenting competence, parental social support, parenting stress, child overall psychological problems and PTSD symptoms) will be analyzed using generalized linear mixed modeling. We will also analyze possible moderation effects of parental PTSD symptoms at pretest on primary and secondary outcomes.

Discussion

This study protocol describes the randomized controlled trial of KopOpOuders-PTSD, a blended care preventive parenting intervention for parents with PTSD. Findings can contribute to understanding of the effectiveness of parenting support in clinical practice for PTSD.

Trial registration

This protocol (Version 1) was registered on 11-02-2022 at ClinicalTrials.gov under identification number NCT05237999.
Study protocol for a controlled trial of a resilience program on psychological distress in correctional officers in Australia
Authors: Keyan Dharani , Dawson Katie S. , Bryant Richard A.
Published: February 2023

Background

The mental health impacts of workers within correctional settings has been of increasing focus over the past number of years. This paper outlines the study protocol for a trial that tests the efficacy of a brief resilience program, relative to a no intervention control in reducing general psychological distress and absenteeism in a cohort of correctional personnel in NSW, Australia.

Methods

A, parallel, randomized controlled trial will be carried out in a small group format. Following informed consent, corrective personnel within prisons across NSW will volunteer to either attend a clinician delivered resilience program on stress management skills or not (N = 600). The primary outcome will be change in psychological distress including anxiety and depression at 2-months post intervention. Secondary outcomes include help-seeking behaviours and absenteeism.

Discussion

This prevention focused treatment trial will assess whether a brief clinician delivered resilience program will reduce absenteeism and mitigate psychological distress in a cohort of corrective personnel within NSW, Australia. This study will yield insights into the role of a brief psychological program in mitigating the psychological distress reported by personnel in correctional settings.

Trial registration

This trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12622000029796).

Ethics and dissemination

Ethics approval has been obtained from University of New South Wales Human Research Ethics Committee. Results of the trial will be submitted for publication in peer reviewed journals and findings presented at scientific conferences and to key service providers and policy makers.
A factorial experiment grounded in the multiphase optimization strategy to promote viral suppression among people who inject drugs on the Texas-Mexico border: a study protocol
Authors: Sauceda John A. , Lechuga Julia , Ramos Maria Elena , Puentes Jorge , Ludwig-Barron Natasha , Salazar Jorge , Christopoulos Katerina A. , Johnson Mallory O. , Gomez David , Covarrubias Rogelio , Hernandez Joselyn , Montelongo David , Ortiz Alejandro , Rojas Julian , Ramos Luisa , Avila Itzia , Gwadz Marya V. , Neilands Torsten B.
Published: February 2023

Background

People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH.

Methods

The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 24factorial experiment in which participants are randomized to one of 16 intervention conditions, with each condition comprising a different combination of four behavioral intervention components. The components are peer support for methadone uptake and persistence; behavioral activation therapy for depression; Life-Steps medication adherence counseling; and patient navigation for HIV care. Participants will complete a baseline survey, undergo intervention, and then return for 3-,6-,9-, and 12-month follow-up assessments. The primary outcome is sustained viral suppression, defined as viral loads of < 40 copies per mL at 6-,9-, and 12-month follow-up assessments. Results will yield effect sizes for each component and each additive and interactive combination of components. The research team and partners will make decisions about what constitutes the optimized multi-component intervention by judging the observed effect sizes, interactions, and statistical significance against real-world implementation constraints. The secondary aims are to test mediators and moderators of the component-to-outcome relationship at the 6-month follow-up assessment.

Discussion

We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting.

Trial registration

This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022.
Construction and validation of CAPSES scale as a composite indicator of SES for health research: an application to modeling social determinants of cardiovascular diseases
Authors: Asadi-Lari Mohsen , Majdzadeh Reza , Mansournia Mohammad Ali , Nedjat Saharnaz , Mohammad Kazem , Cheraghian Bahman
Published: February 2023

Background

The main objective of this study was to construct and validate a composite socioeconomic status indicator containing material capital, human capital, and social capital (CAPSES scale) and also appropriate it for CVDs in a large population-based study.

Methods

This cross-sectional study, the Urban HEART-2 project, was conducted in Tehran, Iran, in 2011. A total of 34,116 households covering 118,542 individuals were assessed in this study. A 14-parts questionnaire was completed for all selected households. All the gathered data were based on the participants’ self-reports. Literacy, wealth index, expenditure, skill level, and Townsend index were used as SES indexes. CVDs, including Hypertension, Myocardial infarction, and stroke, were considered the main outcomes. A structural equation model (SEM) was used to construct a CAPSES scale and a composition index of SES. Criterion validity and Construct validity were used to assess this scale.

Results

A total of 91,830 subjects consisting of 33,884 (49%) men were included in this analysis. The mean age of the participants was 41.5 ± 11.37 years. Among the assessed participants, 5904(6.4%) reported hypertension, 1507(1.6%) myocardial infarction, and 407(0.4%) strokes. The overall weighted prevalence of self-reported cardiovascular events (hypertension, stroke, and MI) was 8.03% (95%CI: 7.8–8.2). Inverse associations were seen between the CAPSES scale and its domains with CVDs, adjusted for sex, age, BMI, smoking, and diabetes by a multiple logistic regression model.

Conclusion

The CAPSES scale was significantly associated with stroke and hypertension. Our findings showed that the CAPSES index could be useful for public health research.
Validity and reliability of the arabic version of the HLS-EU-Q16 and HLS-EU-Q6 questionnaires
Authors: Bergman Lina , Nilsson Ulrica , Dahlberg Karuna , Jaensson Maria , Wångdahl Josefin
Published: February 2023

Background

Health literacy is an important social determinant of health and affects the ability to make decisions and take action to manage one’s health. The purpose of this study was to psychometrically examine the Arabic versions of HLS-EU-Q16 and HLS-EU-Q6 and their response patterns among Arabic-speaking persons in Sweden.

Methods

By convenience sampling from a variety of settings, a total of 335 participants were invited to participate. The participants completed a self-assessment of comprehensive health literacy by answering the Ar-HLS-EU-Q16 questionnaire, also including the six items for Ar-HLS-EU-Q6. Statistical analysis was guided by The COnsensus-based Standards for the selection of health Measurement Instruments. Floor/ceiling effects, construct, structural and criterion validity, test-retest reliability and internal consistency reliability were analysed.

Results

In total, 320 participants were included in the psychometric evaluation. Mean age was 42.1 (SD 12.5), 63% (n = 199) were females and 53% (n = 169) had at least 10 years of education. No floor or ceiling effect were found for the Ar-HLS-EU-Q16 or Ar-HLS-EU-Q6. For both instruments, construct validity was confirmed in four out of five expected correlations (weak positive correlation to educational level, self-perceived health, and years in Sweden; moderate positive correlation with higher sum score on the Arabic electronic health literacy scale, and strong positive correlation to higher Ar-HLS-EU-Q16/Ar-HLS-EU-Q6). For Ar-HLS-EU-Q16, the principal component analysis resulted in a three-factor model with all items significantly correlating to only one factor. For Ar-HLS-EU-Q6, the principal component analysis supported a one-factor solution. Criterion validity showed poor agreement between the two questionnaires with a Cohen κ 0.58 (p < 0.001). Test-retest reliability showed a substantial agreement, Cohen’s κ for Ar-HLS-EU-Q16 and Ar-HLS-EU-Q6 were both 0.89. The internal consistency of both versions was acceptable, Cronbach alpha for Arabic-HLS-EU-Q16 was 0.91 and for Arabic-HLS-EU-Q6, 0.79. Split-half reliability was 0.95 and 0.78, respectively.

Conclusion

The Arabic version of HLS-EU-Q16 shows good psychometric properties, validated in a Swedish setting. The findings can further inform and guide future validation studies in other settings worldwide. Furthermore, the results of the present study did not support criterion validity of Ar-HLS-EU-Q6.
A multicomponent quasi-experimental ergonomic interventional study: long-term parallel four-groups interventions
Authors: Esmaeili Reza , Shakerian Mahnaz , Esmaeili Sayed Vahid , Jalali Mahdi , Pouya Amin Babaei , Karimi Azim
Published: February 2023

Background

Musculoskeletal disorders (MSDs) are known as one of the main problems affecting the health of industrial workers and can lead to lost working days, functional disability of workers and wasting the financial resources of an organization. Therefore, the present study aimed to evaluating the effect of ergonomic interventions on reducing MSDs and improving working posture in the in a foundry industry workers.

Methods

A field multicomponent cross-interventional study was conducted on workers working in a foundry industry. In this study, 117 male workers were divided into 4 groups, including a control group, a group with specialized ergonomics training, a group with workstation intervention, and a group simultaneously undergoing training and workstation intervention. All 4 groups were evaluated during a period of baseline, 6 and 12-months follow- up. The Cornell Musculoskeletal Discomfort Questionnaire (CMDQ) and direct observations of working postures by using the Quick Exposure Check (QEC) method were used.

Results

The results showed that the implemented interventions in the shoulder/arm, back and stress level were effective and the difference in the final score was significant among different groups (P-value > 0.05). In addition, the interventions led to a significant decrease in the QEC scores and musculoskeletal symptom scores in the neck, shoulder, lower back, knee, and lower leg regions among different groups (P-value > 0.05).

Conclusion

The results showed that workstation modification and training and workstation intervention simultaneously had a greater effect on MSDs and improving working posture compared to training alone.
The relation of energy cost of walking with gait deviation, asymmetry, and lower limb muscle co-activation in children with cerebral palsy: a retrospective cross-sectional study
Authors: Gagnat Yngvild , Brændvik Siri Merete , Ringheim Inge , Roeleveld Karin
Published: February 2023

Background

Compared to typically developing children, children with cerebral palsy (CP) have increased energy expenditure during walking, limiting activity and participation. Insight into whether the also deviating and more asymmetric gait with increased muscle co-activation contributes to this increased energy expenditure is important for clinical decision making. The aim of this study was to investigate the relation between energy cost of walking with gait deviation, asymmetry, and muscle co-activation in children with CP.

Methods

Forty ambulant children with CP, with Gross Motor Function Classification System (GMFCS) level I (N = 35) and II (N = 5), aged between 5-17y, were tested at one or two occasions with 24 weeks in between, resulting in 71 observations. Gross energy cost (J/kg/m) was measured during a 5-min walk test at self-selected speed. From a 3-dimensional gait analyses, kinematic variables and electromyography were extracted to calculate the gait deviation index (GDI) and co-activation index. The relation between energy cost and GDI, GDI asymmetry, and co-activation index of the lower limb muscles was evaluated through mixed model analyses. Height was included to control for growth-related variation.

Results

Gait deviation and height combined explained about 40% of the variance in gross energy cost. No significant contribution was found for gait asymmetry or co-activation index.

Conclusions

This cross-sectional study indicates that increased gait deviation contributes to increased energy cost of walking in children with GMFCS level I and II.
Potential short-term outcome advantage of low vs. high ligation of inferior mesenteric artery for sigmoid and rectal cancer: propensity score matching analysis
Authors: Hsu Chia-Chen , Hsu Yu-Jen , Chern Yih-Jong , Jong Bor-Kang , Liao Chun-Kai , Hsieh Pao-Shiu , Tsai Wen-Sy , You Jeng-Fu
Published: February 2023

Background

Whether to ligate the inferior mesenteric artery at its root during anterior resection for sigmoid colon or rectal cancer is still under debate. This study compared the surgical outcomes, postoperative recovery, and anastomotic leakage between high and low ligation of the inferior mesenteric artery through a subgroup analysis.

Methods

This was a retrospective analysis of prospectively collected data. All patients who underwent colorectal resection for rectosigmoid cancer between December 2016 and December 2019 were enrolled. According to the surgical ligation level of the inferior mesenteric artery, the patients were categorized into either the high or low ligation group. The investigated population was matched using the propensity score method.

Results

Overall, 894 patients with sigmoid or rectal cancer underwent elective anterior resection with high (577 patients) or low (317 patients) ligation of the inferior mesenteric artery. After the propensity score matching, 245 patients in each group were compared. High ligation of the inferior mesenteric artery was associated with higher incidence of anastomotic leakage (14.9% vs. 5.6%, P = 0.041) for mid- to low-rectum tumors and a higher incidence of complications (8.6% vs. 3.3%, P = 0.013) of grades 1–2 according to the Clavien–Dindo classification system.

Conclusion

Compared with high ligation, low ligation of the inferior mesenteric artery resulted in lower likelihood of morbidity and mortality in rectal and sigmoid cancers. Moreover, low ligation was less likely to result in anastomosis leakage in mid- to low-rectal cancers.
Status of information, education, and communication as perceived by clients receiving antenatal care at Chiradzulu District Hospital in Malawi
Authors: Lungu Gaily Graysham , Chodzaza Elizabeth , Kamanga Martha , Chikazinga Wanangwa , Jere Diana
Published: February 2023

Background

Information, education, and communication is a strategy to spread awareness through communication channels to a target audience to achieve a desired positive result. Women are supposed to receive information, education, and communication at each contact with the health worker during antenatal care. In Malawi, information, education, and communication for antenatal care is inadequate despite high antenatal care coverage. Most women do not receive it as stipulated. This could be one of the reasons that maternal and neonatal mortality is high. The provision of information, education, and communication is supposed to help in reducing maternal mortality because it is intended to develop positive attitudes towards health behaviours to support pregnant women accessing health services when required. This study, therefore, assessed the status of information, education, and communication as perceived by clients receiving antenatal care at Chiradzulu District Hospital in Malawi.

Methods

A descriptive study design with a sample of 384 pregnant women attending antenatal care was used. The sample size for the study was calculated using Lemeshow, Hosmer, Klar and Rwanga's formula. Systematic random sampling method was used to select the study participants. Data were analysed using a statistical package for social sciences software version 20.0.

Results

Findings revealed that information, education, and communication provided during antenatal care were inadequate. Most information was offered. However, no topic was rated adequate by 80% of the respondents according to the Likert Scale that was used. The majority of the respondents (71.4%, n = 274) (95% CI 66.5. 75.8) preferred to receive information, education, and communication from midwives who are in the category of skilled attendants. Results further showed that more than half of the respondents participated passively and spent little time receiving information, education, and communication.

Conclusion

The findings signify that information, education, and communication provided to women receiving antenatal care at Chiradzulu District Hospital had some gaps. It was inadequate and some topics were not taught. The target audience participated passively. It is recommended that midwives should provide the information, education, and communication and must have adequate contact time with the women. This is so because they are believed to be trusted sources of information.
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

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

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

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

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

Calcium 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

Exosomes 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

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

Patients 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

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

Chronic 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.
Combined use of CA125, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for the diagnosis of borderline and malignant epithelial ovarian tumors
Authors: Huang Ke , Xu Shengjie , Wang Jiatong , Ge Lili , Xu Juan , Jia Xuemei
Published: February 2023

Background

The mortality rate of ovarian cancer ranks first among three common gynecological malignant tumors due to insidious onset and lack of effective early diagnosis methods. Borderline epithelial ovarian tumor (BEOT) is a type of low malignant potential tumor that is typically associated with better outcomes than ovarian cancer. However, BEOTs are easily confused with benign and malignant epithelial ovarian tumors (EOTs) due to similar clinical symptoms and lack of specific tumor biomarkers and imaging examinations. Notably, a small subset of BEOTs will transform into low-grade serous ovarian carcinoma with a poor prognosis. Therefore, searching for potential biomarkers that can be easily obtained and accurately identify malignant epithelial ovarian tumors (MEOTs) as well as BEOTs is essential for the clinician. Cancer antigen 125 (CA125) is a commonly used biomarker for the diagnosis of EOTs in the preoperative scenario but has low sensitivity and specificity. Nowadays, inflammatory biomarkers including inflammatory cell counts and derived ratios such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been proved to be associated with tumor progression and poor prognosis, and were considered to be the most economically potential surrogate biomarkers for various malignancies. The purpose of this study was to find appropriate combinations of inflammatory and tumor biomarkers to improve the diagnostic efficiency of EOTs, especially the BEOTs.

Results

CA125, NLR and PLR increased steadily among benign, borderline and malignant EOTs and tended to be higher in advanced (stage III-IV) and lymph node metastasis MEOT groups than in early stage (stage I-II) and non-lymph node metastasis MEOT groups. CA125, NLR and PLR could be used separately in the differentiation of EOTs but could not take into account both sensitivity and specificity. The combined use of CA125, NLR and PLR was evaluated to be more efficient, especially in the identification of BEOTs, with both high sensitivity and high specificity.

Conclusions

The levels of CA125, NLR and PLR were closely related to the nature of EOTs and malignant progression of MEOTs. The combination of CA125, NLR and PLR was more accurate in identifying the nature of EOTs than either alone or double combination, especially for BEOTs.
Down Syndrome: how to communicate the diagnosis
Authors: Gori Caterina , Cocchi Guido , Corvaglia Luigi Tommaso , Ramacieri Giuseppe , Pulina Francesca , Sperti Giacomo , Cagnazzo Valeria , Catapano Francesca , Strippoli Pierluigi , Cordelli Duccio Maria , Locatelli Chiara
Published: February 2023

Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own relational skills, but it is also necessary to be confident in some general indications, which are often overlooked in the strict hospital routine. This article is intended as a summary of the main articles published on this subject in the international literature, collecting and summarising the most important indications that have emerged in years of medical practice all over the world as well as in our personal experience. The diffusion of these guidelines is essential to help the doctor in this difficult task, on which there is often little training, and above all to guarantee to the parents the least traumatic communication possible.
Leveraging explainable AI for gut microbiome-based colorectal cancer classification
Authors: Rynazal Ryza , Fujisawa Kota , Shiroma Hirotsugu , Salim Felix , Mizutani Sayaka , Shiba Satoshi , Yachida Shinichi , Yamada Takuji
Published: February 2023

Studies have shown a link between colorectal cancer (CRC) and gut microbiome compositions. In these studies, machine learning is used to infer CRC biomarkers using global explanation methods. While these methods allow the identification of bacteria generally correlated with CRC, they fail to recognize species that are only influential for some individuals. In this study, we investigate the potential of Shapley Additive Explanations (SHAP) for a more personalized CRC biomarker identification. Analyses of five independent datasets show that this method can even separate CRC subjects into subgroups with distinct CRC probabilities and bacterial biomarkers.