bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol of an implementation study of a clinician intervention to reduce fear of recurrence in cancer survivors (CIFeR_2 implementation study)
Authors: Liu Jia , Serafimovska Anastasia , He Sharon , Butow Phyllis , Shaw Joanne , McHardy Christopher John , Harris Georgia , Butt Zoe , Beith Jane 
Published: May 2023

Abstract
Background
Fear of cancer recurrence (FCR) affects 50–70% of cancer survivors with 30% reporting an unmet need for help with managing FCR. Patients indicate desire to discuss FCR with clinicians, however clinicians indicate discomfort with managing FCR and no formal educational interventions on how to discuss FCR or worry exists for oncology clinicians. Our team developed a novel clinician-driven brief education intervention to help patients manage FCR (the Clinician Intervention to Reduce Fear of Recurrence (CIFeR) intervention). In earlier work, we demonstrated the feasibility, acceptability, and efficacy of CIFeR in reducing FCR in breast cancer patients. We now aim to explore the barriers and facilitators to implementing this low-cost brief intervention within routine oncology practice in Australia. The primary objective is to assess the adoption of CIFeR in routine clinical practice. Secondary objectives are to identify the uptake and sustainability, perceived acceptability, feasibility, costs, barriers and facilitators of implementation of CIFeR in routine clinical practice, and to assess whether training in CIFeR increases clinicians’ self-efficacy in managing FCR with their patients.

Methods
This multicentre, single-arm Phase I/II implementation study will recruit medical and radiation oncologists and oncology surgeons who treat women with early breast cancer. Participants will complete online CIFeR training. They will then be asked to use CIFeR with suitable patients for the next 6 months. Participants will complete questionnaires prior to, immediately after and 3 and 6 months after training to assess confidence addressing FCR, and 3 and 6 months after training to assess Proctor Implementation outcomes. At 6 months, they will also be asked to participate in a semi-structured telephone interview to elicit their feedback about barriers and facilitators to using CIFeR in routine clinical practice.

Discussion
This study will provide further data to support the routine use of an evidence-based, clinician-lead educational intervention to reduce FCR in breast cancer patients. Additionally, this study will identify any barriers and facilitators to implementing the CIFeR intervention in routine care and evidence for integration of FCR training into oncology communication skills education.

Trial registration
Prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12621001697875.

Trial sponsor
Chris O’Brien Lifehouse.

Protocol version
2.6, Dated 28th February 2023.
Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity testing: a phase 2, single-center, open-label, and non-comparative study
Authors: Jensen Lars Henrik , Rogatto Silvia Regina , Lindebjerg Jan , Havelund Birgitte , Abildgaard Cecilie , do Canto Luisa Matos , Vagn-Hansen Chris , Dam Claus , Rafaelsen Søren , Hansen Torben Frøstrup 
Published: May 2023

Abstract
Background
Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method’s feasibility and clinical outcome as applied to patients with no satisfactory treatment options.

Methods
In this phase 2, single-center, open-label, non-comparative study (ClinicalTrials.gov, register NCT03251612), we enrolled 90 patients with metastatic colorectal cancer following progression on or after standard therapy. Participants were 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–2, adequate organ function, and metastasis available for biopsy. Biopsies from the metastatic site were cultured using organoids model. Sensitivity testing was performed with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the proportion of patients alive without disease progression at two months per local assessment.

Results
Biopsies available from 82 to 90 patients were processed for cell culture, of which 44 successfully generated organoids with at least one treatment suggested. The precision cohort of 34 patients started treatment and the primary endpoint, progression-free survival (PFS) at two months was met in 17 patients (50%, 95% CI 32–68), exceeding the pre-defined level (14 of 45; 31%). The median PFS was 67 days (95% CI 51–108), and the median overall survival was 189 days (95% CI 103–277).

Conclusions
Patient-derived organoids and in-vitro sensitivity testing were feasible in a cohort of metastatic colorectal cancer. The primary endpoint was met, as half of the patients were without progression at two months. Cancer patients may benefit from functional testing using tumor-derived organoids.

Trial registration
ClinicalTrials.gov, register NCT03251612.
Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinoma
Authors: Okuyama Kohei , Naruse Tomofumi , Yanamoto Souichi 
Published: May 2023

AbstractCurrent clinical and observational evidence supports the EXTREME regimen as one of the standards of care for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) followed by the administration of immune checkpoint inhibitors (ICIs). In addition to the inhibition of the epidermal growth factor receptor (EGFR) pathway, cetuximab-mediated EGFR blockade has been shown to modulate tumor microenvironment (TME) characteristics, such as antibody-dependent cellular cytotoxicity (ADCC) activity, cytotoxic T-lymphocyte (CTL) infiltration into the tumor, anti-angiogenesis activity, and cytokine secretion via associated natural killer (NK) cells, etc.. On the other hand, there are reports that nivolumab affects the TME via Programmed cell death 1 (PD-1) inhibition, Interleukin-10 upregulation via T-cells, myeloid-derived suppressor cell-mediated immune escape induction, and tumor vessel perfusion by promoting CD8 + T-cell accumulation and Interferon-γ production in treatment-sensitive tumor cells. Actually, nivolumab administration can give T cells in the TME both immune superiority and inferiority. HNSCC treatment using cetuximab increases the frequency of FoxP3 + intratumoral effector regulatory T cells (Tregs) expressing CTL associated antigen (CTLA)-4, and targeting CTLA-4 + Tregs using ipilimumab restores the cytolytic function of NK cells, which mediate ADCC activity. Treg-mediated immune suppression also contributes to clinical response to cetuximab treatment, suggesting the possibility of the addition of ipilimumab or the use of other Treg ablation strategies to promote antitumor immunity. Moreover, also in hyper progression disease (HPD), intratumoral frequency of FoxP3 + effector Tregs expressing CTLA-4 is increased. Therefore, combination treatment with cetuximab plus anti-CTLA-4 antibody ipilimumab for HNSCC and this combination therapy after nivolumab administration for HPD may be expected to result in a higher tumor-control response. Based on the above evidence, we here suggest the efficacy of using these therapeutic strategies for patients with local-advanced, recurrent, and metastatic HNSCC and patients who do not respond well to nivolumab administration.
Intra-and inter-observer variability of point of care ultrasound measurements to evaluate hemodynamic parameters in healthy volunteers
Authors: Blanca Deborah , Schwarz Esther C. , Olgers Tycho Joan , ter Avest Ewoud , Azizi Nasim , Bouma Hjalmar R. , Ter Maaten Jan Cornelis 
Published: May 2023

Abstract
Background
Point-of-care ultrasound (POCUS) is a valuable tool for assessing the hemodynamic status of acute patients. Even though POCUS often uses a qualitative approach, quantitative measurements have potential advantages in evaluating hemodynamic status. Several quantitative ultrasound parameters can be used to assess the hemodynamic status and cardiac function. However, only limited data on the feasibility and reliability of the quantitative hemodynamic measurements in the point-of-care setting are available. This study investigated the intra- and inter-observer variability of PoCUS measurements of quantitative hemodynamic parameters in healthy volunteers.

Methods
In this prospective observational study, three sonographers performed three repeated measurements of eight different hemodynamic parameters in healthy subjects. An expert panel of two experienced sonographers evaluated the images’ quality. The repeatability (intra-observer variability) was determined by calculating the coefficient of variation (CV) between the separate measurements for each observer. The reproducibility (inter-observer variability) was assessed by determining the intra-class correlation coefficient (ICC).

Results
32 subjects were included in this study, on whom, in total, 1502 images were obtained for analysis. All parameters were in a normal physiological range. Stroke volume (SV), cardiac output (CO), and inferior vena cava diameter (IVC-D) showed high repeatability (CV under 10%) and substantial reproducibility (ICC 0.61–0.80). The other parameters had only moderate repeatability and reproducibility.

Conclusions
We demonstrated good inter-observer reproducibility and good intra-observer repeatability for CO, SV and IVC-D taken in healthy subjects by emergency care physicians.
A systematic literature review of indicators measuring food security
Authors: Manikas Ioannis , Ali Beshir M. , Sundarakani Balan 
Published: May 2023

AbstractMeasurement is critical for assessing and monitoring food security. Yet, it is difficult to comprehend which food security dimensions, components, and levels the numerous available indicators reflect. We thus conducted a systematic literature review to analyse the scientific evidence on these indicators to comprehend the food security dimensions and components covered, intended purpose, level of analysis, data requirements, and recent developments and concepts applied in food security measurement. Data analysis of 78 articles shows that the household-level calorie adequacy indicator is the most frequently used (22%) as a sole measure of food security. The dietary diversity-based (44%) and experience-based (40%) indicators also find frequent use. The food utilisation (13%) and stability (18%) dimensions were seldom captured when measuring food security, and only three of the retrieved publications measured food security by considering all the four food security dimensions. The majority of the studies that applied calorie adequacy and dietary diversity-based indicators employed secondary data whereas most of the studies that applied experience-based indicators employed primary data, suggesting the convenience of collecting data for experience-based indicators than dietary-based indicators. We confirm that the estimation of complementary food security indicators consistently over time can help capture the different food security dimensions and components, and experience-based indicators are more suitable for rapid food security assessments. We suggest practitioners to integrate food consumption and anthropometry data in regular household living standard surveys for more comprehensive food security analysis. The results of this study can be used by food security stakeholders such as governments, practitioners and academics for briefs, teaching, as well as policy-related interventions and evaluations.
What sets cooperative farmers apart from non-cooperative farmers? A transaction cost economics analysis of coffee farmers in Mexico
Authors: Trejo-Pech Carlos Omar , Servín-Juárez Roselia , Reyes-Duarte Álvaro 
Published: May 2023

AbstractThis study investigates what factors relate to the coffee farmer’s cooperative affiliation decision and whether this decision impacts the farmer’s cash holdings. First, we propose a cooperative affiliation model based on transaction cost economics theory. There is a lack of consensus in the literature on what factors explain the farmer’s cooperative affiliation decision in the coffee sector. Overall, we find that the more specialized coffee farmers are, the more likely they will become cooperative affiliates. This is consistent with transaction cost economics predicting that cooperatives are business structures that can reduce transaction costs and safeguard specialized assets from opportunistic behavior. Specifically, logit regression models suggest that shade-grown coffee plantations, off-farm income, coffee farming experience, low-level market competition, farmland size, altitude, and private farmland are statistically related to the farmer’s decision to affiliate with cooperatives. Results on farmland size and shade-grown coffee plantations can be particularly relevant for scholars, policymakers, cooperative leaders, and extension professionals in the region. Second, based on the affiliation model, we employ propensity score matching to evaluate the impact of the farmer’s cooperative affiliation decision on cash holdings, particularly on cash shortness. It is often claimed that farmers do not affiliate with cooperatives because these organizations cannot pay them in full at harvest and coffee collection time. It is believed that cooperatives’ inability to pay farmers early increases the likelihood of farmers’ cash shortness and their need for additional financing to operate or cover household needs. However, this study finds no evidence that the affiliation decision is related to the likelihood of the farmer experiencing cash shortness around harvesting and selling time.
Changes in color and iron ions of commercial iron gall inks after artificial aging
Authors: Xu Zhi , Wang Qiwen , Fan Huiming 
Published: May 2023

Abstract
Iron gall inks consist of vitriols (sulphates of certain metals), gall nut extracts; and gum Arabic: after exposure to oxygen, dark-colored compounds of the inks are formed. As the complexity of the composition of iron gall inks renders documents susceptible to environmental influences, this causes the handwriting thereon to fade. These add technical difficulties to the protection of iron gall inks. Therefore, it is particularly important to understand the changes in the inks during the aging process. For this reason, iron gall ink-stained paper specimens were subject to an intense analytical program to investigate their chemical and physical modifications after aging (temperature/humidity, temperature, and ultraviolet light aging), commercial iron gall ink was used for this experiment, making the study more applicable. The changes of iron gall inks were evaluated using color variation, color density, absorbance, and X-ray photoelectron spectroscopy (XPS). All results indicate that the temperature, humidity, and UV are harmful to the inks in both physical and chemical terms. Physical damage is mainly the aging of the ink color lightening, color density decreases, of which the color of the samples treated with damp heat for 30 days undergoes the greatest change. The chemical change is represented by the ratio of the concentration of iron ions in different valence states, the amount of Fe3+ in the untreated inks is much greater than that of Fe2+, and the amount of Fe2+ exceeds that of Fe3+ after exposure to different methods of aging. Experiments show that UV light causes the most severe damage to handwriting. The main manifestation thereof is color-fade and the paper surface ink part of the iron ion content changes, with the increase of aging time, the Fe2+ content gradually increases. This experimental study of the changes produced by iron gall inks during aging can provide better technical support for the protection of the ink handwriting.
Home-based tDCS for apathy in Alzheimer’s disease: a protocol for a randomized double-blinded controlled pilot study
Authors: Teixeira Antonio L. , Martins Laís Bhering , Cordeiro Thiago Macedo e , Jose Lijin , Suchting Robert , Holmes Holly M. , Acierno Ron , Ahn Hyochol 
Published: May 2023

Abstract
Background
Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer’s disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based tDCS for the treatment of apathy in AD.

Methods/design
This is an experimenter- and participant-blinded, randomized, sham-controlled, parallel-group (1:1 for two groups) pilot clinical trial, involving 40 subjects with AD. After a brief training, caregivers will administer tDCS for participants at home under remote televideo supervision by research staff to ensure the use of proper technique. Participants will be assessed at baseline, during treatment (week 2, week 4, and week 6), and 6 weeks post-treatment. Dependent measures will cover cognitive performance, apathy, and other behavioral symptoms. Data about side effects and acceptability will also be collected.

Discussion
Our study will address apathy, an overlooked clinical problem in AD. Our findings will advance the field of non-pharmacological strategies for neuropsychiatric symptoms, presenting a great potential for clinical translation.

Trial registration
ClinicalTrials.gov, NCT04855643.
Evaluation of short-term outcomes of neoadjuvant chemotherapy followed by radical cystectomy in muscle-invasive bladder cancer: a single Egyptian institution experience
Authors: Abdelrahman Ibrahim , Aboulkassem Hatem , Elazab Abdallah , Abdallah Ahmed Younis , Ismail Yahia , Taher Mohammad 
Published: May 2023

Abstract
Background and aim
Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) became the standard of care for muscle-invasive bladder cancer (MIBC) in the last few years. We aimed to evaluate the radiological, pathological responses to NAC, and the 30-day surgical outcomes after RC in MIBC.

Patients and methods
A retrospective cohort study involving adult patients with localized urothelial MIBC who received NAC followed by RC at the National Cancer Institute of Egypt (NCI-E) for 2 years (2017 and 2018). Out of 235 MIBC cases, we recognized 72 patients (30%) who fitted the eligibility criteria.

Results
A cohort of 72 patients with a median age of 60.5 years (range 34–87). Hydronephrosis, gross extravesical extension (cT3b), and radiologically negative nodes (cN0) were depicted initially in 45.8, 52.8, and 83.3% of patients, respectively. Gemcitabine and cisplatin (GC) was the rampant NAC employed in 95.8%. Radiological evaluation post NAC using RECIST v1.1 revealed a response rate (RR) of 65.3% in bladder tumor and progressive disease in the former and lymph nodes encountered in 19.4 and 13.9%, respectively. The median time from the end of NAC to surgery was 8.1 weeks (range 4–15). Open RC and ileal conduit were the most common types of surgery and urinary diversion, respectively. Pathological down-staging was encountered in 31.9%, and only 11 cases (15.3%) achieved pathological complete response (pCR). The latter was significantly correlated with the absence of hydronephrosis, low-risk tumors, and associated bilharziasis (p = 0.001, 0.029, and 0.039, respectively). By logistic regression, the high-risk category was the only independent factor associated with a poor likelihood of achieving pCR (OR 4.3; 95% CI 1.1–16.7; p = 0.038). Thirty-day mortality occurred in 5(7%) patients, and 16(22%) experienced morbidity, with intestinal leakage being the most frequent complication. cT4 was the only significant factor associated with post-RC morbidity and mortality compared to cT2 and cT3b (p = 0.01).

Conclusions
Our results are further supporting the radiological and pathological benefits of NAC in MIBC, evidenced by tumor downstaging and pCR. The complication rate after RC is still considerable; hence, more larger studies are necessary to postulate a comprehensive risk assessment tool for patients who would get the maximum benefit from NAC, hoping to accomplish higher complete response rates with ultimately increased adoption of the bladder preservation strategies.
Barriers and enablers for the implementation of trauma-informed care in healthcare settings: a systematic review
Authors: Huo Yan , Couzner Leah , Windsor Tim , Laver Kate , Dissanayaka Nadeeka N. , Cations Monica 
Published: May 2023

Abstract
Background
Healthcare services can be re-traumatising for trauma survivors where they trigger memories of past distressing events and exert limits to a survivor’s sense of autonomy, choice, and control. The benefits of receiving trauma-informed healthcare are well established; however, factors that promote or impede the implementation of trauma-informed care are not yet well characterised and understood.
The aim of this review was to systematically identify and synthesise evidence regarding factors that promote or reduce the implementation of TIC in healthcare settings.

Methods
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2.0 guidelines. Scopus, MEDLINE, Proquest, PsycINFO and grey literature were searched for original research or evaluations published between January 2000 and April 2021 reporting barriers and/or facilitating factors for the implementation of trauma-informed care in a healthcare setting. Two reviewers independently assessed the quality of each included study using the Mixed Methods Appraisal Tool (MMAT) Checklist.

Results
Twenty-seven studies were included, 22 of which were published in the USA. Implementation occurred in a range of health settings, predominantly mental health services. The barriers and facilitators of implementing trauma-informed care were categorised as follows: intervention characteristics (perceived relevance of trauma-informed care to the health setting and target population), influences external to the organisation (e.g. interagency collaboration or the actions of other agencies) and influences within the organisation in which implementation occurred (e.g. leadership engagement, financial and staffing resources and policy and procedure changes that promote flexibility in protocols). Other factors related to the implementation processes (e.g. flexible and accessible training, service user feedback and the collection and review of initiative outcomes) and finally the characteristics of individuals within the service or system such as a resistance to change.

Conclusions
This review identifies key factors that should be targeted to promote trauma-informed care implementation. Continued research will be helpful for characterising what trauma-informed care looks like when it is delivered well, and providing validated frameworks to promote organisational uptake for the benefit of trauma survivors.

Registration
The protocol for this review was registered on the PROSPERO database (CRD42021242891).