bluuebunny/crossref_metadata_2025_split huggingface dataset:
TQB2450 in patients with advanced malignant tumors: results from a phase I dose-escalation and expansion study
Authors: Xue Junli , Xue Liqiong , Tang Wenbo , Ge Xiaoxiao , Zhao Wei , Li Qun , Peng Wei , Dai Congqi , Guo Ye , Li Jin 
Published: January 2024

Background: Immune checkpoint inhibitor therapy has demonstrated impressive clinical benefits in multiple tumor types. TQB2450, a novel monoclonal antibody targeting programmed cell death ligand 1, has shown safety and efficacy in preclinical studies. Objectives: This first-in-human study aimed to evaluate the safety/tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of TQB2450 in patients with advanced malignant tumors. Design and methods: In this phase I study, eligible patients with advanced malignant tumors received intravenous TQB2450 once every 3 weeks. This study consisted of a 3 + 3 dose-escalation phase (1–30 mg/kg) and a specific dose-expansion phase (1200 mg). The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety. The secondary endpoints were PK, immunogenicity, and investigator-assessed response rate. Results: Between April 2018 and February 2020, 40 patients were enrolled (22 in the dose-escalation phase and 18 in the dose-expansion phase). No DLT was reported and the MTD was not reached. Grade ⩾3 or worse treatment-related treatment-emergent adverse events (AEs) occurred in 11 (27.50%) patients, with the most frequent being aspartate aminotransferase increased (5.00%), leukopenia (5.00%), and anemia (5.00%). Treatment-related serious AEs were reported in six patients, the most common of which was decompensated liver function (5.00%). No treatment-related death was reported. The maximum serum concentration of TQB2450 increased in a dose-proportional manner. Treatment-induced anti-drug antibodies were detected in 31.58% (12/38) of patients. The investigator assessed the objective response rate as 5.00% and the disease control rate was 52.50%, including 2 partial responses and 19 stable diseases. The median progression-free survival was 2.69 (95% confidence interval, 2.07–6.14) months. Conclusion: TQB2450 has a manageable safety profile with favorable PK and immunogenicity and has shown early evidence of clinical activity in advanced malignant tumors. ClinicalTrials.gov identifier: NCT03460457.
Combined pre-treatment and middle-treatment Epstein–Barr virus DNA load contributes to prognostication and treatment modification in nasopharyngeal carcinoma patients
Authors: Lan Kaiqi , Mao Jingrong , Sun Xuesong , Li Suchen , Xie Siyi , Sun Rui , Liu Sailan , Mai Haiqiang 
Published: January 2024

Objective: To investigate whether pre-treatment and middle-treatment plasma Epstein–Barr virus (EBV) DNA loads are useful predictors of prognosis and indicators of therapy modification in nasopharyngeal carcinoma (NPC) patients undergoing radical concurrent chemoradiotherapy (CCRT). Methods: Plasma EBV DNA load was measured by quantitative polymerase chain reaction before treatment (pre-DNA) and during the second cycle of DDP (mid-DNA). The primary endpoint was 5-year progression-free survival (PFS). Results: A total of 775 NPC patients treated with CCRT were included. In total, 553 patients with pre-DNA <4000 copies/mL and 222 with ⩾4000 copies/mL. A total of 559 patients had mid-DNA undetectable and 216 had detectable. Multivariate analysis showed that pre- and mid-DNA were independent prognostic predictors of PFS [hazard ratio (HR), 2.035; 95% confidence interval (CI), 1.406–2.944; p < 0.001; HR, 1.597; 95% CI, 1.101–2.316; p = 0.014]. The area under the curve of the combination of pre-DNA and mid-DNA for 5-year PFS was higher than that of pre-DNA, mid-DNA, and tumor node metastasis (TNM) stage (0.679 versus 0.622, 0.608, 0.601). In the low-risk group (pre-DNA <4000 copies/mL and undetectable mid-DNA), patients receiving ⩽200 mg/m2 showed similar efficacy as those receiving >200 mg/m2 cumulative cisplatin dose (CCD) but were associated with fewer all-grade late toxicities. However, in the high-risk group (pre-DNA ⩾4000 copies/mL or detectable mid-DNA), patients receiving >200 mg/m2 CCD showed a higher 5-year PFS (73.1% versus 58.6%, p = 0.027) and locoregional relapse-free survival (88.5% versus 76.1%, p = 0.028) than those receiving ⩽200 mg/m2 CCD. Conclusion: The combination of pre-DNA and mid-DNA could be particularly useful for guiding risk stratification and early treatment modification for NPC treated with CCRT. A total of 200 mg/m2 cisplatin seemed to be the optimal dose for the low-risk patients, while >200 mg/m2 cisplatin may be adequate to achieve satisfactory survival outcomes in the high-risk group.
The Versatility of the Supraclavicular Flap for Head and Neck Reconstruction
Authors: Imanol Zubiate Illarramendi , Leonardo Ferrari , Paolo Cariati , Fernando Monsalve , Ildefonso Martínez Lara 
Published: January 2024

Study Design Descriptive study of 17 patients with primary or secondary reconstruction using a supraclavicular flap. Objective Describe the different options for primary and secondary reconstruction using the supraclavicular flap, as well as the complications that may arise. Methods The present study analyzed the outcomes of 17 patients who underwent reconstruction using the supraclavicular artery island flap at the Maxillofacial Department of Hospital Universitario Virgen de las Nieves (Granada, Spain) from November 2017 to June 2023. Results The SCAIF served as the primary reconstructive option in 9 cases, covering skin defects in the parotid region (4 patients), cervical area (1 patient), partial tongue defects (3 patients), and cheek defects (1 patient). Additionally, the flap was used as a secondary reconstructive option in 8 patients affected by osteoradionecrosis (ORN) with bone and plate exposure. Complications included a single case of shoulder joint septic arthritis and 3 patients who experienced cervical fistula and neck infection. Conclusions The supraclavicular flap represents a highly effective option for oncological reconstruction within the head and neck region. This flap is particularly useful in patients with significant clinical concerns and contraindications, both local and systemic, for microsurgical free flap procedures due to its reliability, versatility, and safety.
Women ownership as a form of leadership: The role of context in understanding its effects on financial performance
Authors: Orozco Collazos Luz Elena , Botero Isabel C 
Published: January 2024

Researchers have acknowledged that women leadership plays an important role in the success of organizations. However, the effects of women leadership on the financial performance of firms are mixed results. This article focuses on women ownership (i.e., critical mass and ownership percentage) as a form of leadership and family ownership as two boundary conditions that help us understand when small and medium enterprises (SMEs) benefit from women leadership. We argue that for women leadership to impact the financial performance of SMEs, women need to have a critical mass to influence outcomes and have power through ownership to influence decisions. We also argue that the effects of these relationships are affected by the context of ownership. These ideas are tested with a sample of 10,696 private SMEs from the country of Colombia. Results indicate that the women leadership enhances SME financial performance through both critical mass and a larger percentage of women ownership. However, family ownership negatively moderates the relationship between percentage of women ownership and SME financial performance. Implications of these results are discussed. JEL CLASSIFICATION: D22; L25
Placement stability and family support after government-mandated rapid return: A two-year follow-up
Authors: Wilke Nicole Gilbertson , Pop Delia , Howard Amanda Hiles 
Published: January 2024

During the COVID-19 pandemic, multiple governments around the world implemented directives that mandated residential care providers to rapidly reunite thousands of children and youth with their families. Organizations were faced with expedited timelines for the reunification process, limited ability to prepare children and families, and restricted capacity to support and monitor families in-person due to lockdown measures. As such, there was significant concern regarding stability of placements, and well-being of the children and families affected by the abrupt and unprepared reunification process. This study examined data from 16 non-government organizations (NGOs) impacted by rapid return mandates in six nations (Kenya, Uganda, India, Ethiopia, Democratic Republic of the Congo, and Mexico). NGOs were serving 15,978 children in residential care at the time of the mandates. NGOs had an average of 21.87 days ( SD = 9.87) to return children to families. Most NGOs felt children and families were inadequately prepared for reunification. After two years, NGOs were in contact with 90% of the children who had been rapidly returned. Of those children, 56% remained in their family placement. Families who received more types of family strengthening services were more likely to remain intact. Concerningly, 2 years following the rapid return mandates, the NGOs in this study were collectively serving a higher number of children in residential care than prior to rapid return mandates. This suggests that rapid return mandates did not seem to decrease the number of children in residential care long-term. Data-informed recommendations for practice are discussed.
Relationship between implementation of systematic advance care planning and the quality of death among nursing home residents: a survey
Authors: Toyoda Yoshie , Tokumasu Aya , Minato Yuki , Sone Takayasu , Oshiro Kyoko , Kojima Hideki , Nishikawa Mitsunori 
Published: January 2024

Background: Advance care planning (ACP) is beneficial for the quality of death (QOD). However, the effects of ACP on the QOD may vary across cultures. Objectives: This study aimed to explore the relationship between the 15-step ACP program and the QOD among Japanese nursing home residents. Design: A cross-sectional survey. Methods: A cross-sectional survey was conducted among the family members of 39 nursing home residents who died between April 2017 and March 2019 by distributing the survey questionnaire by post. The survey included questions about the QOD of residents, and responses were evaluated using the Good Death Inventory (GDI) scale. Results: Responses were obtained from 30 of the 39 bereaved families (76.9%). Data were analyzed using hierarchical clustering to determine five groups and conduct multiple comparisons. The following three domains of interest were identified: ‘Dying in a favorite place’, ‘Good relationship with the medical staff’, and ‘Independence’. GDI scores were significantly higher for residents with higher ACP completion rates than for those with lower rates ( p < 0.01). Residents who had taken ACP interviews had significantly higher GDI scores ( p < 0.01) than those who had not taken interviews. Conclusion: Overall, these findings suggest that systematic ACP might be related to the QOD among Japanese nursing home residents in the above mentioned three domains. Limitations of the present study were small sample size, cross-sectional survey design as opposed to a cohort survey design, and multiple biases, including the emotional instability of bereaved family members, the length of stay of the residents, the degree of dementia of the residents, and their tendency to talk about the place of death and to develop good relationships with the medical staff.
Development of a Vaping Cessation Text Messaging Intervention for Latino Young Adults: A Participatory Research Approach
Authors: Orfin Rafael H , Siddalingaiah Simran , Dontu Vignya , Estrada Bianca , Martinez Chabeli , Guerra Darcy , Carrillo Hanzell , Cervantes-Díaz María José , Rodríguez-Rojas Diana Victoria , Rahman Irfan , McIntosh Scott , Ossip Deborah J. , Cupertino Ana Paula , Cartujano-Barrera Francisco 
Published: January 2024

Objective Describe the participatory research procedures of developing Kick Vaping, a vaping cessation text messaging intervention for Latino young adults, available in English and Spanish. Methods Using community-based recruitment strategies, we convened a Community Advisory Board (CAB) of eight Latino young adults (ages 18–25) with different vaping experiences (never users, ex-users, and current users of e-cigarettes). Members held a series of working meetings to adapt Decídetexto, a smoking cessation text messaging intervention, for vaping cessation. Members provided iterative feedback on the text messages until reaching a consensus on content. Messages were translated from English to Spanish following a committee approach. Readability assessments were used to evaluate the legibility of the text messages Results At baseline, members’ mean age was 22.6 years old (SD 3.1), 75% were female, and 50% used both English and Spanish equally. Three members (37.5%) were ex-users and one member (12.5%) was a current user of e-cigarettes. 18 meetings provided sufficient opportunities for iterative feedback on the text messages for developing the intervention. The Kick Vaping intervention consists of 208 text messages. Readability scores of the text messages in English were equivalent to fourth and fifth grade, and in Spanish were equivalent to easy and somewhat easy. Conclusion It is feasible and practical to build participatory research among Latino young adults focused on vaping cessation. Members of the CAB added innovation and creativity to the development of the vaping cessation text messaging intervention. Future research is needed to evaluate the impact of the intervention on vaping cessation.
Population structure and microscale morphological differentiation in a freshwater snail from the Chilean Altiplano
Authors: Valladares Moisés A. , Fabres Alejandra A. , Sánchez-Rodríguez Fernanda , Collado Gonzalo A. , Méndez Marco A. 
Published: January 2024

Abstract
Background
The diversity and population genetic structure of many species have been shaped by historical and contemporary climatic changes. For the species of the South American Altiplano, the historical climatic changes are mainly related to the wet events of great magnitude and regional influence that occurred during the Pleistocene climatic oscillations (PCOs). In contrast, contemporary climate changes are associated with events of lesser magnitude and local influence related to intensifications of the South American Summer Monsoon (SASM). Although multiple studies have analyzed the effect of PCOs on the genetic patterns of highland aquatic species, little is known about the impact of contemporary climate changes in recent evolutionary history. Therefore, in this study, we investigated the change in population structure and connectivity using nuclear and mitochondrial markers throughout the distribution range of Heleobia ascotanensis, a freshwater Cochliopidae endemic to the Ascotán Saltpan. In addition, using geometric morphometric analyses, we evaluated the concomitance of genetic divergence and morphological differentiation.

Results
The mitochondrial sequence analysis results revealed the presence of highly divergent co-distributed and geographically nested haplotypes. This pattern reflects an extension in the distribution of groups that previously would have differentiated allopatrically. These changes in distribution would have covered the entire saltpan and would be associated with the large-scale wet events of the PCOs. On the other hand, the microsatellite results defined five spatially isolated populations, separated primarily by geographic barriers. Contemporary gene flow analyses suggest that post-PCO, climatic events that would have connected all populations did not occur. The morphometric analyses results indicate that there is significant morphological differentiation in the populations that are more isolated and that present the greatest genetic divergence.

Conclusions
The contemporary population structure and morphological variation of H. ascotanensis mainly reflect the post-PCO climatic influence. Although both markers exhibit high genetic structuring, the microsatellite and morphology results show the preponderant influence of fragmentation in recent evolutionary history. The contemporary genetic pattern shows that in species that have limited dispersal capabilities, genetic discontinuities can appear rapidly, erasing signs of historical connectivity.
Genome-wide identification of the GRF family in sweet orange (Citrus sinensis) and functional analysis of the CsGRF04 in response to multiple abiotic stresses
Authors: Fu Ming-Kang , He Ying-Na , Yang Xiao-Yue , Tang Xi , Wang Min , Dai Wen-Shan 
Published: January 2024

Abstract
Background
Citrus is one of the most valuable fruits worldwide and an economic pillar industry in southern China. Nevertheless, it frequently suffers from undesirable environmental stresses during the growth cycle, which severely restricts the growth, development and yield of citrus. In plants, the growth-regulating factor (GRF) family of transcription factors (TF) is extensively distributed and plays an vital part in plant growth and development, hormone response, as well as stress adaptation. However, the systematic identification and functional analysis of GRF TFs in citrus have not been reported.

Results
Here, a genome-wide identification of GRF TFs was performed in Citrus sinensis, 9 members of CsGRFs were systematically identified and discovered to be scattered throughout 5 chromosomes. Subsequently, physical and chemical properties, phylogenetic relationships, structural characteristics, gene duplication events, collinearity and cis-elements of promoter were elaborately analyzed. In particular, the expression patterns of the CsGRF genes in response to multiple phytohormone and abiotic stress treatments were investigated. Predicated on this result, CsGRF04, which exhibited the most differential expression pattern under multiple phytohormone and abiotic stress treatments was screened out. Virus-induced gene silencing (VIGS) technology was utilized to obtain gene silenced plants for CsGRF04 successfully. After the three stress treatments of high salinity, low temperature and drought, the CsGRF04-VIGS lines showed significantly reduced resistance to high salinity and low temperature stresses, but extremely increased resistance to drought stress.

Conclusions
Taken together, our findings systematically analyzed the genomic characterization of GRF family in Citrus sinensis, and excavated a CsGRF04 with potential functions under multiple abiotic stresses. Our study lay a foundation for further study on the function of CsGRFs in abiotic stress and hormone signaling response.
A case of repeated in-stent restenosis of coronary artery as a primary manifestation of seronegative antiphospholipid antibody syndrome
Authors: Fu Mingqiang , Chang Shufu , Ma Jianying , Ge Junbo 
Published: January 2024

Abstract
Background
Antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disorder which affects many organs or systems; however, coronary artery is relatively less frequently involved.

Case presentation
A 65-year-old female with effort chest pain was hospitalized for unstable angina in Janurary, 2015. Coronary angiography revealed sub-total occlusion of proximal left anterior descending (LAD) coronary artery, where a drug-eluting stent was successfully deployed. The patient experienced multiple in-stent stenosis at LAD coronary artery and coronary artery bypass graft (CABG) surgery was advised. Subsequently, severe stenosis of left circumflex (LCX) coronary artery emerged, and the patient suffered persistent in-stent restenosis. Eventually, the patient was diagnosed with seronegative antiphospholipid antibody syndrome and salvaged by immunosuppressants.

Conclusions
Repeated in-stent restenosis could be a primary manifestation of seronegative antiphospholipid antibody syndrome, and suppression of autoimmune activity and inflammation other than purely coronary revascularization might be a better option.
A large post-stenting intramural hematoma in the left anterior descending artery caused by a small intimal calcium spur; should we respect the calcium shape?
Authors: Samir Ahmad 
Published: January 2024

AbstractCoronary heavy calcification (HC) poses a sturdy challenge to percutaneous coronary intervention (PCI). Scores considering calcification length, thickness, or circumferential extent, are widely accepted to dictate upfront calcium modification to improve PCI outcomes. Although often marginalized, calcification shape (morphology) may require consideration during procedure planning in selected cases. This case demonstrates how a focal but spur-shaped calcification led to a massive proximal left anterior descending (LAD) dissecting intramural hematoma.
Healthcare providers’ perspectives on implementing a brief physical activity and diet intervention within a primary care smoking cessation program: a qualitative study
Authors: Minian Nadia , Mehra Kamna , Lingam Mathangee , Dragonetti Rosa , Veldhuizen Scott , Zawertailo Laurie , deRuiter Wayne K. , Melamed Osnat C. , Moineddin Rahim , Thorpe Kevin E. , Taylor Valerie H. , Hahn Margaret , Selby Peter 
Published: January 2024

AbstractBackgroundPost-smoking-cessation weight gain can be a major barrier to quitting smoking; however, adding behavior change interventions for physical activity (PA) and diet may adversely affect smoking cessation outcomes. The “Picking up the PACE (Promoting and Accelerating Change through Empowerment)” study assessed change in PA, fruit/vegetable consumption, and smoking cessation by providing a clinical decision support system for healthcare providers to utilize at the intake appointment, and found no significant change in PA, fruits/vegetable consumption, or smoking cessation. The objective of this qualitative study was to explore the factors affecting the implementation of the intervention and contextualize the quantitative results.MethodsTwenty-five semi-structured interviews were conducted with healthcare providers, using questions based on the National Implementation Research Network’s Hexagon Tool. The data were analyzed using the framework’s standard analysis approach.ResultsMost healthcare providers reported a need to address PA and fruit/vegetable consumption in patients trying to quit smoking, and several acknowledged that the intervention was a good fit since exercise and diet could improve smoking cessation outcomes. However, many healthcare providers mentioned the need to explain the fit to the patients. Social determinants of health (e.g., low income, food insecurity) were brought up as barriers to the implementation of the intervention by a majority of healthcare providers. Most healthcare providers recognized training as a facilitator to the implementation, but time was mentioned as a barrier by many of healthcare providers. Majority of healthcare providers mentioned allied health professionals (e.g., dieticians, physiotherapists) supported the implementation of the PACE intervention. However, most healthcare providers reported a need for individualized approach and adaptation of the intervention based on the patients’ needs when implementing the intervention. The COVID-19 pandemic was found to impact the implementation of the PACE intervention based on the Hexagon Tool indicators.ConclusionThere appears to be a need to utilize a flexible approach when addressing PA and fruit/vegetable consumption within a smoking cessation program, based on the context of clinic, the patients’ it is serving, and their life circumstances. Healthcare providers need support and external resources to implement this particular intervention.Name of the registryClinicaltrials.gov.Trial registration numberNCT04223336.Date of registration7 January 2020 Retrospectively registered.URL of trial registry recordhttps://classic.clinicaltrials.gov/ct2/show/NCT04223336.