bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of camrelizumab plus rivoceranib versus sorafenib as first-line treatment of unresectable hepatocellular carcinoma
Authors: Zou Huimin , Lai Yunfeng , Chen Xianwen , Ung Carolina Oi Lam , Hu Hao 
Published: January 2025

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally. Recent advancements in targeted therapies have improved outcomes for advanced HCC, yet therapeutic options remain limited. The CARES-310 trial demonstrated that camrelizumab plus rivoceranib significantly improves survival compared to sorafenib for advanced HCC. Objectives: This study aimed to evaluate the cost-effectiveness of camrelizumab plus rivoceranib as a first-line treatment for unresectable HCC from the Chinese health system perspective. Design: The cost-effectiveness analysis. Methods: A partitioned survival model was constructed to estimate clinical and economic outcomes for patients with unresectable or metastatic HCC. The model included three health states: progression-free, progression disease, and death. The hypothetical cohort consisted of patients aged ⩾18 with HCC who had not received systemic therapy, reflecting the CARES-310 trial. Clinical data were derived from the CARES-310 trial and extrapolated using standard parameter distributions. Direct medical costs and utilities were sourced from the CARES-310 trial and published literature. Results: The 10-year cost of camrelizumab plus rivoceranib was higher than sorafenib (USD 28,148.01 vs USD 20,997.86). Camrelizumab plus rivoceranib yielded an additional 0.26 quality-adjusted life-years (QALYs) with an incremental cost of USD 7150.15, resulting in an incremental cost-effectiveness ratio of USD 27,633.75/QALY. Sensitivity analyses confirmed the robustness of the base-case results. Conclusion: Camrelizumab plus rivoceranib is likely a cost-effective first-line treatment for unresectable HCC from a Chinese health system perspective. This study highlights the need for additional real-world data to validate these findings and guide clinical decision-making for HCC.
Genomic and epidemiological analysis of SARS-CoV-2 variants isolated in Guinea: a routine sequencing implementation
Authors: Mbaye Aminata , Diallo Haby , Gnimadi Thibaut Armel Cherif , Kadio Kadio Jean Jacques Olivier , Soumah Abdoul Karim , Koivogui Joel Balle , Monemou Jean Louis , Povogui Moriba Kowa , Kaba Djiba , Hounmenou Castro , Serrano Laetitia , Butel Christelle , Nuñez Nicolas Fernandez , Vidal Nicole , Guichet Emilande , Delaporte Eric , Ayouba Ahidjo , Peeters Martine , Toure Abdoulaye , Keita Alpha Kabinet ,   AFROSCREEN Team
Published: January 2025

Abstract
Background
Several variants of SARS-CoV-2 have a demonstrated impact on public health, including high and increased transmissibility, severity of infection, and immune escape. Therefore, this study aimed to determine the SARS-CoV-2 lineages and better characterize the dynamics of the pandemic during the different waves in Guinea.

Methods
Whole genome sequencing of 363 samples with PCR cycle threshold (Ct) values under thirty was undertaken between May 2020 and May 2023. The Illumina iSeq 100 technology was used. The sequences were then analyzed using the GeVarli pipeline to generate consensus sequences and variant calling. All sequences isolated in Guinea and available on GISAID were included in the analysis for phylogenetic tree and phylodynamic determination. Nextstain tools were used for these analyses. Statistical analysis was done using GraphPad Prism version 10.

Results
The circulation of SARS-CoV-2 in Guinea can be distributed in three different periods. The first, lasting from May to June 2020, was characterized by lineages B1 and B.1.1. The second period, from January 2021 to July 2021, was characterized by the lineages B.1.1.7 (Alpha), AY.122, B.1.1.318, R1, B.1.525 and B.1.629. The third period, between December 2021 and May 2023, was characterized by the Omicron variant, with nine subvariant majorities found. In addition, detecting variants in the period out of their circulation was documented. The importation and exportation investigation showed the strong movement viral association between Guinea and Senegal on the one hand and Guinea and Nigeria on the other.

Conclusion
In summary, this study contributes to understanding the epidemic dynamics of the disease by describing the significant variants that circulated in Guinee and the distribution of this variant in the population. It also shows the importation and exportation of the virus during the pandemic. Sub-sampling and degradation of samples for sequences were observed. Organization and collaboration between laboratories are needed for a good sample-collecting and storage system for future direction.
Assessment of older persons with multimorbidity in Norwegian primary care: a qualitative study of healthcare professionals’ experiences and preferences in fostering continuity of care
Authors: Aarønes Turid Rimereit , Taraldsen Kristin , Kvæl Linda Aimée Hartford 
Published: January 2025

Abstract
Background
As the population ages, more people live longer with multimorbidity. Older people with multimorbidity face diverse needs and medical conditions, increasing the risk of adverse health outcomes, and often experience fragmented healthcare. Research has called for better ways to reach, understand and care for this group to enhance care continuity. This study aimed to examine healthcare professionals’ experiences and preferences as they relate to assessments’ role in promoting care continuity for home-dwelling older patients with multimorbidity in community-based healthcare.

Methods
This qualitative study acquired qualitative data from 17 healthcare professionals from reablement teams, interdisciplinary teams, rehabilitation teams and home nursing in three Norwegian municipalities. Representing nursing, physiotherapy, occupational therapy and social work, all participants were experienced in assessing older home-dwelling patients with multimorbidity. Semi-structured focus group and individual interviews were conducted, then the interviews were transcribed and analysed using reflexive thematic analysis.

Results
The analysis elicited three themes: gaining insight beyond diagnoses to promote relational continuity, facilitating interaction to ensure informational continuity, and linking patient journeys to facilitate managerial continuity. The themes underscore the significance of evaluating patients beyond their medical conditions, emphasising assessment’s collaborative nature across disciplines. Healthcare professionals use diverse assessment methods and facilitate interaction to understand patients’ needs. Working together across different healthcare professions is key for care that includes the whole patient, but challenges such as underutilisation of assessments and poor documentation still exist. Furthermore, linking patient journeys remains difficult due to fragmented services and limited resources. Despite these challenges, assessments were viewed as crucial to care continuity.

Conclusions
In this qualitative study, healthcare professionals emphasised that assessment is a complex, continuous process due to the fluctuating health of individuals with multimorbidity. Effective instruments and diverse assessment methods are essential to understanding all aspects of patients’ health and well-being to ensure care continuity across individual, service, and system levels. Our findings highlight the need for systematic and structured use of assessments to improve interdisciplinary collaboration and personalised care for older individuals with multimorbidity. Understanding the patient journey is crucial for achieving these goals, potentially benefiting healthcare professionals, policymakers, and primary care providers.
Estimating relative risks and risk differences in randomised controlled trials: a systematic review of current practice
Authors: Thompson Jacqueline , Watson Samuel I. , Middleton Lee , Hemming Karla 
Published: January 2025

Abstract
Background
Guidelines for randomised controlled trials (RCTs) recommend reporting relative and absolute measures of effect for binary outcomes while adjusting for covariates. There are a number of different ways covariate-adjusted relative risks and risk differences can be estimated.

Objectives
Our goal was to identify methods used to estimate covariate-adjusted relative risk and risk differences in RCTs published in high-impact journals with binary outcomes. Other secondary objectives included the identification of how covariates are chosen for adjustment and whether covariate adjustment results in an increase in statistical precision in practice.

Methods
We included two-arm parallel RCTs published in JAMA, NEJM, Lancet, or the BMJ between January 1, 2018, and March 11, 2023, reporting relative risks or risk differences as a summary measure for a binary primary outcome. The search was conducted in Ovid-MEDLINE.

Results
Of the 308 RCTs identified, around half (49%; 95% CI: 43–54%) reported a covariate-adjusted relative risk or risk difference. Of these, 82 reported an adjusted relative risk. When the reporting was clear (n = 65, 79%), the log-binomial model (used in 65% of studies; 95% CI: 52–76%) and modified Poisson (29%; 95% CI: 19–42%) were most commonly used. Of the 92 studies that reported an adjusted risk difference, when the reporting was clear (n = 56, 61%), the binomial model (used in 48% of studies; 95% CI: 35–62%) and marginal standardisation (21%; 95% CI: 12–35%) were the common approaches used.

Conclusions
Approximately half of the RCTs report either a covariate-adjusted relative risk or risk difference. Many RCTs lack adequate details on the methods used to estimate covariate-adjusted effects. Of those that do report the approaches used, the binomial model, modified Poisson and to a lesser extent marginal standardisation are the approaches used.
Effects of biochar on soil respiration mediated by rainfall events: evidence from one-year field experiment in an urban forest
Authors: Zu Haoran , Deng Zijun , Liu Xin , Luo Junyi , Chen Ying , Yi Meiling , Wang Xiao , Liang Xiaocui , Zhang Xiang , Yan Wende 
Published: January 2025

Abstract
Background
Biochar is widely recognized for its capacity to capture and store carbon in soil attributed to its stable structure. However, in most field studies examining the effects of biochar application on soil respiration, the impact of rainfall events on the experimental outcomes has not been taken into account. To address the existing gap in this research field, we conducted a one-year study on soil respiration in an urban camphor forest and collected the data of soil respiration, soil temperature, soil moisture, and the rainfall events closest to the soil respiration monitoring time. We specifically examined how different stages of rainfall events influenced soil respiration in relation to biochar application.

Results
This study found that the annual average soil respiration rate increased with the doses of biochar application, and the soil respiration rate under the biochar application at the dose of 45 t/ha showed a significant rise. The stages of rainfall events, rainfall amount, and the interaction effect of the two, and biochar doses significantly affected soil respiration. The parameters in the regression model for soil respiration, soil temperature and moisture varied with the different stages of rainfall events and the doses of biochar application. The biochar application eliminated the significant effect of soil moisture on soil respiration during one day after rainfall events. The significant correlation between soil moisture and the temperature sensitivity of soil respiration (Q10) was eliminated by biochar application, both during one day after rainfall events and more than eight days after rainfall events.

Conclusions
Our findings indicated that the rice straw biochar application has a short-term positive effect on soil respiration in urban camphor forests. The rainfall events affect the field soil respiration monitored in the biochar applications, possibly by affecting the soil respiration response to soil temperature and moisture under different doses of biochar application. The impact of rainfall events on soil respiration in biochar application experiments should be considered in future forest monitoring management and practice.
Simulated wind erosion and local dust deposition affect soil micro-food web by changing resource availability
Authors: Zhao Cancan , Li Yujie , Zhou Zeli , Wu Rongrong , Su Mengfei , Song Hongquan 
Published: January 2025

Abstract
Background
Wind erosion and dust deposition are the most common natural geological process in arid and semiarid areas. They significantly affect the redistribution of soil nutrients and ecosystem functioning and services. However, the effects of wind erosion and dust deposition on soil micro-food web are still poorly understood. Therefore, we conducted a field manipulative experiment to investigate the response of soil microbial and nematode communities, energy channels and their cascade effects to wind erosion and dust deposition in a semiarid grassland.

Results
Our results showed that wind erosion had no effect on the abundance of soil microbes and nematodes, but altered the community composition of soil food web. Wind erosion significantly increased fungivore abundance and nematode channel index, leading to a fungal-dominated energy channel, i.e., a slow energy channel. Dust deposition significantly increased soil dissolved organic carbon, microbial phospholipid fatty acids and soil nematode abundance, showing a strong bottom-up trophic cascade effect in soil food web by increasing the quantity of soil resource. Compared with control treatment, both wind erosion and dust deposition declined the complexity and stability of soil micro-food web.

Conclusions
Our findings offer new insight for exploring the effects of aeolian erosion process on soil food web, which can provide parameter estimation for accurate evaluation of the effects of wind erosion on ecosystem function.
Angel investments of small family business entrepreneurs: cross-country evidence
Authors: Fernandez Viviana 
Published: January 2025

AbstractRecent literature has focused on the venture capital investments of large family firms made through their family offices. However, evidence regarding informal venture capital provided to nascent entrepreneurs by small family businesses is scant. I contribute to the literature by modeling the angel investments of about 30,000 family and non-family business entrepreneurs across 49 countries, who contributed about $64 million to businesses started by other entrepreneurs over a 3-year period. Based on this sample, I conclude that in countries with higher rates of small family businesses, angel investors are likely fewer, and the amounts invested in start-ups are also lower. Furthermore, I conclude that the owners/managers of small family businesses invest comparatively less capital in start-ups, irrespective of family relationships. I infer that this is attributable to the financing preferences of family businesses, which favor the use of internal resources for their continuity and the growth of their family capital.
Treatment outcomes of two surgical techniques in secondary reconstruction of unilateral cleft lip and ala nasi utilizing anthropometry assessment: a randomized controlled trial
Authors: Humadi Ebrahim , Karkoutly Mawia , Beit Zafin Kara 
Published: January 2025

Abstract
Background
An orofacial cleft significantly impacts the oral health-related quality of life of children and teenagers. Secondary reconstruction is a more complex procedure due to tissue deficiency and scarring. The study aimed to evaluate the use of Pfeifer's wave-line incision method and the rotational flap method in the secondary reconstruction of unilateral lip clefts in patients with unilateral cleft lip and ala nasi aged 5–25 years utilizing anthropometry assessment.

Methods
It was a double-blinded, randomized, parallel-group, active-controlled trial with two arms. Twenty-four patients were randomly divided into two groups. Group 1: Rotational flap method. Group 2: Control group, Pfeifer's wave-line incision method. The following anthropometric measurements were considered: Lb(X):En-En: The horizontal position of the center of the cupid's bow. Ch-Lt(l:r): The distance between the cheilion and the tip of the cupid’s bow. Lt-Lb(l:r): The length of the cupid’s bow. Lt(Y)(l:r): The size of the upper lip. Lt-Lt'(l:r): The height of the vermilion at the tip of the cupid's bow. Photographs were performed according to the follow-up periods: At the baseline and before surgery (t0). Immediately after surgery (t1). Two weeks after surgery (t2). Six months after surgery (t3).

Results
The rotational flap method did not outperform Pfeifer’s method in the studied anthropometric measurements. In the rotational flap method group, there was a significant improvement in the mean value of Ch-Lt(l:r) from t0 (1.156 ± 0.206) to t3 (0.962 ± 0.098), and in the average value of Lt(Y)(l:r) from t0 (0.944 ± 0.023) to t3 (0.990 ± 0.011) (p < 0.05). In Pfeifer’s method group, the mean value of Ch-Lt(l:r) was (1.141 ± 0.158) at t0, and then improved to become (1.007 ± 0.084) at t3 (p < 0.05), the average value of Ch-Lt(l:r) at t0 was (0.942 ± 0.026), which improved to (0.991 ± 0.012) at t3, and the average value of Lt-Lt'(l:r) increased from t0 (1.308 ± 1.174) to t3 (1.050 ± 0.054) (p < 0.05).

Conclusion
Pfeifer's wave-line incision and rotational flap methods achieve similar aesthetic results in the appearance of the lip or Cupid's bow after a 6-month follow-up.

Trial registration
ISRCTN registry, ISRCTN36320776, registered 06 November 2024.
Adjuvant Dose-Dense Chemotherapy in Hormone Receptor–Positive Breast Cancer
Authors: Metzger Filho Otto , Ballman Karla , Campbell Jordan , Liu Minetta , Ligibel Jennifer , Watson Mark , Chen Eveline , Du Lili , Stover Daniel , Carey Lisa , Partridge Ann , Kirshner Jeffrey , Muss Hyman , Hudis Clifford , Winer Eric P. , Norton Larry , Symmans W. Fraser 
Published: January 2025

PURPOSE
In light of evolving evidence that some patients with node-positive estrogen receptor–positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

METHODS
In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers.

RESULTS

Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction
P
= .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not.

CONCLUSION
At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.
Toward Functional Biomarkers of Response to Neoadjuvant Oncolytic Virus in Stage II Melanoma: Immune-Förster Resonance Energy Transfer and the Dynamic Tumor Immune Microenvironment
Authors: Kirane Amanda R. , Lee David , Lowe Michael , Ahmad M. Usman , Sharma Saurabh , Serasanambati Mamatha , Applebee Christopher J. , Safrygina Elena , Betof Warner Allison , Wang Jennifer , Le Stephanie , Larijani Banafshé , Maverakis Emanual 
Published: January 2025

PURPOSE
Despite the effectiveness of immunotherapy in advanced melanoma, the lack of clinically reliable biomarkers hinders precision medicine approaches. This study investigates the potential of immune time-resolved Förster resonance energy transfer (iFRET) as a novel tool for understanding immunotherapy response in melanoma.

METHODS
Using tissue from a pilot phase II study of neoadjuvant talimogene laherparepvec (TVEC) before standard surgery, we explore iFRET's ability to assess PD-L1:PD-1 interactions in the tumor immune microenvironment (TiME) pre- and post-therapy.

RESULTS
Responsive tumors demonstrated significant increases in iFRET efficiency, diverging from nonresponsive tumors that either decreased in checkpoint engagement or failed to demonstrate immune stimulation with therapy. Changes in PD-L1:PD-1 iFRET efficiency did not correlate with changes in PD-L1 expression. Instead, traditional biomarkers of PD-L1 expression and T-cell phenotyping did not reflect response trends and demonstrated significant heterogeneity inter- and intratumorally. Importantly, tumor-associated macrophage phenotype correlated significantly with TVEC response and the significantly high PD-L1:PD-1 interaction observed in the tumor beds of complete responders.

CONCLUSION
These findings underscore both the role of innate immune profiles in immunotherapy outcomes and the potential of iFRET to serve as a critical companion diagnostic in the classification of immune profiles. This research reveals crucial insights into factors affecting checkpoint function in tumors and emphasizes the need for further investigation into cell-specific interactions within the TiME. By expanding our understanding of distinct patient profiles for tailored therapeutic strategies, we underscore the importance of assessing this type of functional biomarker data in ongoing neoadjuvant trial designs to advance the goal of precision immunotherapy in patients with melanoma.
Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation
Authors: Koch Michael , Ferrarese Luca , Ben-Yehuda Greenwald Maya , Werner Sabine 
Published: January 2025

ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by an impaired epidermal barrier and immunological alterations. The activity of the cytoprotective NRF2 transcription factor is reduced in the epidermis of AD patients. To determine the functional relevance of this deficiency, we used mice lacking fibroblast growth factor receptors 1 and 2 in keratinocytes (K5-R1/R2 mice), which exhibit several AD-like symptoms. Proteomics analysis of their epidermis revealed reduced Nrf2 activity. This was accompanied by an increase in DNA damage and in the number of senescent cells. Genetic deletion of Nrf2 in keratinocytes of these mice further promoted DNA damage and senescence, but time-limited pharmacological activation of Nrf2 in the skin had a mild protective effect. Surprisingly, long-term genetic activation of Nrf2 in keratinocytes of K5-R1/R2 mice caused strong hyperkeratosis, keratinocyte hyperproliferation, epidermal thickening, increased keratinocyte apoptosis and DNA damage, and altered immune cell composition. These results reveal a complex role of Nrf2 in the epidermis and show the necessity to optimize the duration and intensity of NRF2 activation for the treatment of epidermal alterations in patients with AD.