bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib
Authors: Rebuzzi Sara Elena , Cerbone Luigi , Signori Alessio , Santoni Matteo , Murianni Veronica , De Giorgi Ugo , Procopio Giuseppe , Porta Camillo , Milella Michele , Basso Umberto , Massari Francesco , Maruzzo Marco , Iacovelli Roberto , Battelli Nicola , Carmisciano Luca , Banna Giuseppe Luigi , Buti Sebastiano , Fornarini Giuseppe 
Published: February 2022

Background: The addition of neutrophil-to-lymphocyte ratio (NLR) and bone metastases to the International Metastatic RCC Database Consortium (IMDC) score (by the Meet-URO score) has been shown to better stratify pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. This study aimed to validate the Meet-URO score in patients receiving cabozantinib to assess its predictivity and prognostic role. Methods: A multicenter retrospective analysis evaluated mRCC patients receiving ⩾second-line cabozantinib. NLR, IMDC score and bone metastases were assessed before the start of cabozantinib. The primary endpoint was overall survival (OS). Harrell’s c-index was calculated to compare the accuracy of the prediction of the two scores. Results: Overall, 174 mRCC patients received cabozantinib as second and third line (51.7% and 48.3%, respectively) with a median follow-up of 6.8 months. A shorter median overall survival (mOS) was observed for the IMDC poor-risk group, NLR ⩾3.2 and the presence of bone metastases, while the IMDC intermediate-risk group had a similar mOS to the favourable-risk one. Applying the Meet-URO score, three risk groups were identified: group 1 (55.2% of patients) with a score of 0–3, group 2 (38.5%) with a score of 4–8 and group 3 (6.3%) with a score of 9. Compared to group 1 (mOS: 39.4 months), a statistically significant worse mOS was observed in group 2 (11.2 months) and group 3 (3.2 months) patients, respectively. The Meet-URO c-index score was 0.640, showing a higher discriminative ability than the IMDC score ( c-index: 0.568). Conclusion: This analysis showed that the Meet-URO score provides a more accurate prognostic stratification than the IMDC score in mRCC patients treated with ⩾second-line cabozantinib besides nivolumab. Moreover, it is an easy-to-use tool with no additional costs for clinical practice (web-calculator is available at: https://proviso.shinyapps.io/Meet-URO15_score/ ). Future investigations will include the application of the Meet-URO score to the first-line immunotherapy-based combination therapies.
Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience
Authors: de Castro Tiago , Jochheim Leonie S. , Bathon Melanie , Welland Sabrina , Scheiner Bernhard , Shmanko Kateryna , Roessler Daniel , Ben Khaled Najib , Jeschke Matthias , Ludwig Johannes M. , Marquardt Jens U. , Weinmann Arndt , Pinter Matthias , Lange Christian M. , Vogel Arndt , Saborowski Anna 
Published: February 2022

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results: The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7–19.3] versus 6.0 months (95% CI: 3.2–8.9; p < 0.001) and mPFS: 8.7 months (95% CI: 5.9–11.5) versus 3.7 months (95% CI: 2.7–4.7; p < 0.001)]. Prior systemic treatment did not significantly affect mOS [hazard ratio (HR): 1.32 (95% CI: 0.78–2.23; p = 0.305)]. mOS according to ALBI grades 1/2/3 were 15.0 months (95% CI: not estimable), 8.6 months (95% CI: 5.4–11.7), and 3.2 months (95% CI: 0.3–6.1), respectively. ALBI grade and ECOG score were identified as independent prognostic factors [ALBI grade 2 versus 1; HR: 2.40 (95% CI: 1.34 – 4.30; p = 0.003), ALBI grade 3 versus 1; HR: 7.28 (95% CI: 3.30–16.08; p < 0.001), and ECOG ⩾2 versus 0; HR: 2.09 (95% CI: 1.03 – 4.23; p = 0.042)], respectively. Sixty-seven patients (45.6%) experienced an adverse event classified as CTCAE grade ⩾3. Patients in the IMbrave-OUT group were at increased risk of hepatic decompensation with encephalopathy (13.7% versus 1.4%, p = 0.004) and/or ascites (39.7% versus 9.5%; p < 0.001). Conclusion: In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.
Prevention of Surgical Site Infections in Spine Surgery: An International Survey of Clinical Practices Among Expert Spine Surgeons
Authors: Tkatschenko Dimitri , Hansen Sonja , Koch Julia , Ames Christopher , Fehlings Michael G. , Berven Sigurd , Sekhon Lali , Shaffrey Christopher , Smith Justin S. , Hart Robert , Kim Han Jo , Wang Jeffrey , Ha Yoon , Kwan Kenny , Hai Yong , Valacco Marcelo , Falavigna Asdrubal , Taboada Néstor , Guiroy Alfredo , Emmerich Juan , Meyer Bernhard , Kandziora Frank , Thomé Claudius , Loibl Markus , Peul Wilco , Gasbarrini Alessandro , Obeid Ibrahim , Gehrchen Martin , Trampuz Andrej , Vajkoczy Peter , Onken Julia 
Published: February 2022

Study Design Questionnaire-based survey. Objectives Surgical site infection (SSI) is a common complication in spine surgery but universal guidelines for SSI prevention are lacking. The objectives of this study are to depict a global status quo on implemented prevention strategies in spine surgery, common themes of practice and determine key areas for future research. Methods An 80-item survey was distributed among spine surgeons worldwide via email. The questionnaire was designed and approved by an International Consensus Group on spine SSI. Consensus was defined as more than 60% of participants agreeing to a specific prevention strategy. Results Four hundred seventy-two surgeons participated in the survey. Screening for Staphylococcus aureus (SA) is not common, whereas preoperative decolonization is performed in almost half of all hospitals. Body mass index (BMI) was not important for surgery planning. In contrast, elevated HbA1c level and hypoalbuminemia were often considered as reasons to postpone surgery. Cefazoline is the common drug for antimicrobial prophylaxis. Alcohol-based chlorhexidine is mainly used for skin disinfection. Double-gloving, wound irrigation, and tissue-conserving surgical techniques are routine in the operating room (OR). Local antibiotic administration is not common. Wound closure techniques and postoperative wound dressing routines vary greatly between the participating institutions. Conclusions With this study we provide an international overview on the heterogeneity of SSI prevention strategies in spine surgery. We demonstrated a large heterogeneity for pre-, peri- and postoperative measures to prevent SSI. Our data illustrated the need for developing universal guidelines and for testing areas of controversy in prospective clinical trials.
Identification of drought responsive Elaeis guineensis WRKY transcription factors with sensitivity to other abiotic stresses and hormone treatments
Authors: Lee Fong Chin , Yeap Wan Chin , Appleton David Ross , Ho Chai-Ling , Kulaveerasingam Harikrishna 
Published: February 2022

Abstract
Background
The ability of plants to withstand and thrive in an adverse environment is crucial to ensure their survivability and yield performance. The WRKY transcription factors (TFs) have crucial roles in plant growth, development and stress response, particularly drought stress. In oil palm, drought is recognized as one of the major yield limiting factors. However, the roles of WRKY TFs in the drought response of oil palm is unclear.

Results
Herein, we studied the transcriptome of drought treated oil palm leaf and identified 40 differentially expressed genes (DEGs) of WRKY TFs, of which 32 DEGs were upregulated and 8 DEGs were downregulated in response to drought stress in oil palm. They were categorized into Groups I to IV based on the numbers of WRKY domain and the structural difference in the zinc finger domain. Multiple stress- and hormone-responsive cis-regulatory elements were detected in the drought responsive oil palm EgWRKY (Dro-EgWRKY) genes. Fourteen of the 15 selected oil palm WRKY (EgWRKY) genes demonstrated a tissue-specific expression profile except for EgWRKY28 (Group I), which was expressed in all tissues tested. The expression levels of 15 candidate EgWRKYs were upregulated upon salinity and heat treatments, while several genes were also inducible by abscisic acid, methyl jasmonate, salicylic acid and hydrogen peroxide treatments. Members of the Group III WRKY TFs including EgWRKY07, 26, 40, 52, 59, 73 and 81 displayed multiple roles in drought- and salinity-response under the modulation of phytohormones.

Conclusions
EgWRKY TFs of oil palm are involved in phytohormones and abiotic stress responses including drought, salinity and heat. EgWRKY07, 26, 59 and 81 from Group III maybe important regulators in modulating responses of different abiotic stresses. Further functional analysis is required to understand the underlying mechanism of WRKY TFs in the regulatory network of drought stress.
Dynamic mRNA and miRNA expression of the head during early development in bighead carp (Hypophthalmichthys nobilis)
Authors: Luo Weiwei , Wang Junru , Zhou Ying , Pang Meixia , Yu Xiaomu , Tong Jingou 
Published: March 2022

AbstractBackgroundHead of fish species, an exquisitely complex anatomical system, is important not only for studying fish evolution and development, but also for economic values. Currently, although some studies have been made on fish growth and body shapes, very limited information is available on the molecular mechanism of head development.ResultsIn this study, RNA sequencing (RNA–Seq) and small RNA sequencing (sRNA–Seq) technologies were used to conduct integrated analysis for the head of bighead carp at different development stages, including 1, 3, 5, 15 and 30 Dph (days post hatch). By RNA-Seq data, 26 pathways related to growth and bone formation were identified as the main physiological processes during early development. Coupling this to sRNA–Seq data, we picked out six key pathways that may be responsible for head development, namely ECM receptor interaction, TNF signaling pathway, osteoclast differentiation, PI3K–Akt signaling pathway, Neuroactive ligand–receptor interaction and Jak–STAT signaling pathway. Totally, 114 important candidate genes from the six pathways were obtained. Then we found the top 20 key genes according to the degree value by cytohubba, which regulated cell growth, skeletal formation and blood homeostasis, such aspik3ca,pik3r1,egfr,vegfa,igf1anditga2b. Finally, we also acquired 19 key miRNAs playing multiple roles in the perfection of various tissues in the head (such as brain, eye and mouth) and mineralization of head bone system, such as let–7e, miR–142a–5p, miR–144–3p, miR–23a–3p and miR–223.ConclusionsResults of this study will be informative for genetic mechanisms of head development and also provide potential candidate targets for the interaction regulation during early growth in bighead carp.
Lifestyle counselling – a long-term commitment based on partnership
Authors: Lönnberg Lena , Damberg Mattias , Revenäs Åsa 
Published: March 2022

Abstract
Background
Lifestyle habits are important factors in the development of non-communicable diseases. Different ways of providing counselling in primary care to promote healthier lifestyle habits have been launched and evaluated in recent years. It is important to provide an insight into what makes lifestyle counselling useful for patients and healthcare providers.

Objective
The overall aim of this study was to explore patients´ and community health nurses´(CHNs) experiences of lifestyle counselling in primary care to support healthier lifestyle habits.

Methods
Patients and CHNs were interviewed, face to face. Sixteen patients (eight men, eight women, aged 51–75 years) diagnosed with hypertension or type 2 diabetes mellitus and three CHNs participated. Data material was analysed with qualitative content analysis to explore the participants experiences of lifestyle counselling.

Results
The theme demonstrates that lifestyle counselling is a long-term commitment based on partnership between patients and CHNs. Five categories describe this partnership: respect and mutual interest, understanding of illness, measurements and goal setting, long-term support, and a structure to support counselling within the primary care unit.

Conclusion
The results from this study are consistent with and add to previous understanding of how lifestyle counselling can be performed successfully in the context of primary health care. The results emphasize that lifestyle counselling should encompass a partnership based on mutual respect, recognition of the patient as the expert on his/her current life situation, and the need for both parties to engage in the process of lifestyle change.

Practice implications
A structured lifestyle program with five counselling sessions within primary care was experienced as helpful for enhanced lifestyle habits and considered to be feasible by both patients and CHNs.
Representations of personalised medicine in family medicine: a qualitative analysis
Authors: Boyer Marie S. , Widmer Daniel , Cohidon Christine , Desvergne Béatrice , Cornuz Jacques , Guessous Idris , Cerqui Daniela 
Published: March 2022

Abstract
Background
The promise of personalised medicine (PM) to transform healthcare has sparked great enthusiasm in the last years. Yet, its lack of consensus around the nature and scope of the concept has ended in terminological confusion amongst the users in primary care. We aimed to investigate the perceptions of doctors and their patients in response to this evolving concept. This present article focuses on the general understanding of personalised medicine, underlining the confusion over the concept.

Methods
Semi-structured comprehensive interviews were conducted with 10 general practitioners (GPs) and 10 of their patients. The purposive sampling took into account the doctor’s age, sex, and place of practice (rural/urban); each doctor recruited one patient of the same age and sex. Each interview began with the same open-ended question about the participant’s knowledge of the topic, after which a working definition was provided to continue the discussion. Using the grounded theory method, the analysis consisted of open coding, axial coding and selective coding.

Results
From our present analysis focusing on the general understanding of PM, three main themes representing the concept emerged. The first two representations being “centred on the person as a whole” and “focused on alternative and complementary methods”, in which the therapeutic relationship was stated as key. The third theme “medicine open to innovation” involved the few participants who had a good understanding of the concept and could associate personalised medicine with genomics. For those who value therapeutic relationship, the risks of accepting innovation could result in “fast-food” medicine and interpersonal barriers.

Discussion
PM is predominantly unfamiliar in family medicine. It is misinterpreted as a holistic or integrative type of medicine. This semantic confusion probably lies in the choice of the label “personalised” or from the lack of a uniform definition for the term.
Conceptualization of a cognitively enriched walking program for older adults: a co-design study with experts and end users
Authors: Marent Pieter-Jan , Vangilbergen Arwen , Chastin Sebastien , Cardon Greet , van Uffelen Jannique G. Z. , Beeckman Melanie 
Published: March 2022

AbstractBackgroundResearch in controlled laboratory settings shows that physical activity programs enriched with cognitive challenges enhance the benefits of physical activity on cognition in older adults. This translational study aimed to conceptualise a real-life, cognitively enriched walking program for older adults (65+) by investigating (a) which cognitive tasks are most suited for cognitive enrichment of a walking program, and (b) how to embed these tasks in a walking program to become feasible, enjoyable and effective.MethodsA co-design process was followed with input of 34 academic experts and 535 end users. First, an online, three-rounds Delphi process was used to obtain consensus amongst academic experts on the key characteristics that a real-life cognitively enriched walking program should have. Next, end users provided feedback and suggestions on what the experts concluded, and gave more insight into their preferences and concerns by means of an online/telephone survey.ResultsCombined input from experts and end users resulted in a list of recommendations to guide the further development of the cognitively enriched walking program. First, it is important to provide a range of cognitive tasks to choose from. Each of these tasks should (a) provide variation and differentiation, (b) be implemented with increasing levels of difficulty, and (c) be integrated in the walk. Second, divide the walk into three parts: 5–10 min brisk walking, cognitive tasks for most of the walk, and 5–10 min free walking. Finally, the program should strive for a minimal session frequency of twice a week, include competition occasionally and carefully, ensure safety and keep the walks fun.ConclusionsThe co-design process resulted in recommendations to guide the next steps in the program development process. Additional studies will be performed to improve the enjoyability and feasibility, and to assess the effectiveness of the cognitively enriched walking program to improve cognitive functioning and physical activity in older adults (65+).
Associations of Chinese diagnosis-related group systems with inpatient expenditures for older people with hip fracture
Authors: Meng Zhaolin , Zou Kun , Song Suhang , Wu Huazhang , Han Youli 
Published: March 2022

AbstractBackgroundHip fracture is frequent in older people and represents a major public health issue worldwide. The increasing incidence of hip fracture and the associated hospitalization costs place a significant economic burden on older patients and their families. On January 1, 2018, the Chinese diagnosis-related group (C-DRG) payment system, which aims to reduce financial barriers, was implemented in Sanming City, southern China. This study aimed to evaluate the associations of C-DRG system with inpatient expenditures for older people with hip fracture.MethodsAn uncontrolled before-and-after study employed data of all the patients with hip fracture aged 60 years or older from all the public hospitals enrolled in the Sanming Basic Health Insurance Scheme from January 1, 2016 to December 31, 2018. The ‘pre C-DRG sample’ included patients from January 1, 2016 to December 31, 2017. The ‘post C-DRG sample’ included patients from January 1, 2018 to December 31, 2018. A propensity score matching analysis was used to adjust the difference in baseline characteristic parameters between the pre and post samples. Data were analyzed using generalized linear models adjusted for the demographic, clinical, and institutional factors. Robust tests were performed by accounting for time trend, the fixed effects of the year and hospitals, and clustering effect within hospitals.ResultsAfter propensity score matching, we obtained two homogeneous groups of 1123 patients each, and the characteristic variables of the two matched groups were similar. We found that C-DRG reform was associated with a 19.51% decrease in out-of-pocket (OOP) payments (p < 0.001) and a 99.93% decrease in OOP payments as a share of total inpatient expenditure (p < 0.001); whereas total inpatient expenditure was not significantly associated with the C-DRG reform. All the sensitivity analyses did not change the results significantly.ConclusionThe implementation of C-DRG payment system reduced both the absolute amount of OOP payments and OOP payments as a share of total inpatient expenditure for older patients with hip fracture, without affecting total inpatient expenditure. These results may provide significant insights for policymakers in reducing the financial burden on older patients with hip fracture in other countries.
MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study
Authors: Zeng Hong , Liu Zefu , Zhang Lei , Liu Nenghui 
Published: March 2022

Abstract
Background
Whether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET).

Methods
This is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes.

Results
There is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos (p-value=0.028), decreased number of good-quality embryos (p-value=0.005), and decreased cumulative live birth rate (p-value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols (p-values>0.05).

Conclusions
MTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.