bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Ki-67 Positive Index is a Prognostic Factor for Better Survival Outcomes of Patients Treated with Intracavitary Cisplatin-Fibrin
Authors: Meerang M , Mengers J , Haberecker M , Kirschner M B , Bosbach N , Lauk O , Opitz I 
Published: June 2023

Abstract

Background
Novel therapeutic approaches are needed for patients with pleural mesothelioma (PM), an aggressive cancer driven by asbestos exposure. Our phase II clinical trial for localized chemotherapy with cisplatin-fibrin after surgery (INFLuenCe – Meso) investigated safety and efficacy of this novel approach.

Aims
To identify biomarkers associated with outcomes for future application in patient selection.

Methods
We collected tumor tissues at surgery, before start of localized treatment, from all patients enrolled (n=23). FFPE tissues were immunohistochemically stained for p21 (cisplatin resistance) and Ki-67 (proliferation). Using Qupath software, we classified tumor cells from stroma. Number of positive cells (%) were automatically counted from 1,050 - 208,751 tumor cells/slide. For P21, we also differentiated weak (1), moderate (2) and strong (3) staining. Thus, we also acquired H-score (sum of intensity x % positive cells). The association between marker expression and clinical parameters and disease outcomes including progression free survival (PFS) and overall survival (OS) was analysed by SPSS software.

Results
Ki-67 staining index (%) ranged from 1.2 - 44 (median 12.4). P21 staining index and H–score (range (median)) are 0 - 96 (21) and 0 - 225 (32), respectively. High Ki-67 labelling index was significantly associated with shorter PFS (p=0.001, median (95% CI): 26.6 (11.7 - 41.6) vs 8.6 (6.8 -10.4) months) and OS (p&lt;0.001, 39 (27.2–50.9) vs 16 (12.3–19.6) months). There was no association between clinical parameters and Ki-67 or p21 staining. P21 staining index and H-score showed no association with disease outcomes.

Conclusions
Although a small patient cohort, Ki-67 showed significant association with disease outcomes for patients receiving localized cisplatin-fibrin. We are currently assessing Ki-67 in tissues collected at diagnosis to confirm the association with survival prior to therapy. Ki-67 may be useful for the selection of patients for this treatment regimen.
Neoadjuvant Treatment versus Upfront Surgery for Primary Resectable Pancreatic Cancer: An Update Meta-Analysis of Comparative Studies
Authors: Roesel R , Cristaudi A , Deantonio L , de Dosso S , Berneardi L 
Published: June 2023

Abstract

Background
The role of neoadjuvant chemotherapy with or without radiotherapy in resectable pancreatic cancer has yet to be defined.

Aims
This meta-analysis aims to explore the benefit of a neoadjuvant treatment in resectable pancreatic cancer compared with upfront surgery in terms of overall survival.

Methods
MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with primary resectable pancreatic cancer treated with or without neoadjuvant treatment from January 2000 to December 2022. The quality assessment of the included studies was based on the Newcastle–Ottawa quality scale. Secondary outcomes included disease free survival, pathological lymph-node rate, overall and R0 resection rate.

Results
A total of eleven studies (seven randomized controlled trials and four cohort studies) with 9774 patients were included. Neoadjuvant treatment was found to be significantly associated to increased overall survival (p&lt;0.001; OR: 0.82; 95% CI: 0.73–0.92) and disease-free survival (p&lt;0.001; OR: 0.73; 95% CI: 0.59–0.89). The association of radiotherapy showed no additional benefit to chemotherapy alone in terms of overall survival in the subgroup analysis. Patients undergoing neo-adjuvant treatment were also found to be significantly associated with a higher R0 resection rate (p&lt;0.001; OR: 1.67; 95% CI: 1.31–2.15) and negative lymph-node status (p&lt;0.001; OR: 0.41; 95% CI: 0.26–0.64).

Conclusions
Neoadjuvant treatment seems to offer an advantage in terms of overall and disease-free survival in comparison to patients undergoing up-front surgery for primary resectable pancreatic cancer. Further RCTs should confirm these findings to generalize the indication of neoadjuvant treatment in this setting.
Fertility in patients with Hirschsprung's disease: population-based cohort study
Authors: Byström Cornelia , Örtqvist Lisa , Gunnarsdóttir Anna , Wester Tomas , Löf Granström Anna 
Published: June 2023

Abstract

Background
The aim of this study was to assess fertility in patients treated for Hirschsprung’s disease.

Methods
This was a nationwide, population-based cohort study, including all patients with Hirschsprung’s disease registered in the Swedish National Patient Register between 1964 and 2004. Five age- and sex-matched controls per patient were randomly selected by Statistics Sweden. Outcome data were retrieved from the Multi-Generation Register, and the Swedish National Patient Register. Study exposure was Hirschsprung’s disease and the primary outcome was fertility, defined as having one or more children. Individuals with chromosomal anomalies were excluded.

Results
The study cohort comprised 597 patients with Hirschsprung’s disease (143 female) and 2969 controls (714 female). The mean(s.d.) age at follow-up was 29.6(10.0) years for patients and 29.8(10.1) years for the controls. A total of 191 (32.0 per cent) patients compared with 1072 (36.1 per cent) controls had one or more children (P = 0.061). The analysis showed that fewer female patients with Hirschsprung’s disease had a child (29.4 versus 38.7 per cent, P = 0.037), they were older when they gave birth to their first child (28.1 versus 26.4 years, P = 0.033), and they had fewer children. Of the female patients with Hirschsprung’s disease, 19 (45.2 per cent) had only one child, compared with 79 (28.6 per cent) of the female control group (P = 0.047). No difference was noted in the male group in this regard.

Conclusion
Female patients with Hirschsprung’s disease were less likely to have a child, had fewer children, and were older when they gave birth to their first child compared with the controls, indicating impaired fertility. There was no significant difference between male patients with Hirschsprung's disease and controls.
Back to Basics on Economic Value: Review Article of Dave Elder-Vass’s Inventing Value: The Social Construction of Monetary Worth, Cambridge University Press, 2022
Authors: Sayer Andrew 
Published: June 2023

Abstract
The paper discusses concepts of economic value via a review of Dave Elder-Vass’s book Inventing Value. Setting the review in the context of the need to re-evaluate theories of economic value in light of the environmental crisis, it outlines and assesses the book’s critical realist approach to the subject, its critiques of existing value theories, the alternative offered by the author—‘the social construction of monetary worth’—and its application to the valuation of financial assets. It goes on to discuss whether economic value can be said to be ‘invented’, the relation between positive and normative theories of value, and what can be salvaged from existing theories of value. It ends by briefly summarising where value theory in the context of the wider economy might go from here.
Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway
Authors: Wei Xiangxiang , Jin Jiayu , Wu Jian , He Yunquan , Guo Jieyu , Yang Zhaohua , Chen Liang , Hu Kui , Li Liliang , Jia Mengping , Li Qinhan , Lv Xiaoyu , Ge Fei , Ma Siyu , Wu Huijie , Zhi Xiuling , Wang Xinhong , Jiang Lindi , Osto Elena , Zhang Jianyi , Meng Dan 
Published: June 2023

Abstract

Aims
BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy.

Methods and results
Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan.

Conclusion
This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.
Preheating Prosocial Behaviour
Authors: Wichman Casey J , Chan Nathan W 
Published: June 2023

Abstract
We provide new evidence on motivations for voluntary contributions to public goods in a natural setting. Using natural language processing on users’ Twitter posts, we measure revealed sentiment changes before and after making a donation to Wikipedia. We find strong evidence that sentiment improves in the hour and minutes directly before contributing, which we call ‘preheating’. Results are robust to alternative fixed effects and approaches to inference and supported by a complementary online experiment with randomised mood inducement among Twitter users. Preheating suggests that affective states influence giving in addition to reward-seeking, utility-maximising behaviour that has been documented in other contexts.
Core outcomes for orofacial clefts: reconciling traditional and ICHOM minimum datasets
Authors: Mossey Peter A , Lai Jason , Meazzini Maria Costanza , Breugem Corstiaan , Mark Hans , Mink van der Molen Aebele B , Persson Martin , Davies Gareth , Ozawa Terumi Okada 
Published: June 2023

Summary

Objective/Design/Setting
This retrospective study sought voluntary participation from leading cleft centres from Europe and Brazil regarding core outcome measures. The results of this study would inform the debate on core outcome consensus pertaining to the European Reference Network for rare diseases (ERN CRANIO) and achieve a core outcome set for cleft care providers worldwide.

Intervention/Method
Five orofacial cleft (OFC) disciplines were identified, within which all of the International Consortium of Health Outcomes Measurement (ICHOM) outcomes fall. One questionnaire was designed for each discipline and comprised 1. the relevant ICHOM’s outcomes within that discipline, and 2. a series of questions targeted to clinicians. What core outcomes are currently measured and when, did these align with the ICHOM minimum, if not how did they differ, and would they recommend modified or additional outcomes?.

Results
For some disciplines participants agreed with the ICHOM minimums but urged for earlier and more frequent intervention. Some clinicians felt that some of the ICHOM standards were compatible but that different ages were preferred and for others the ICHOM standards were acceptable but developmental stages should be preferred to absolute time points.

Conclusion/Implications
Core outcomes for OFC were supported in principle but there are differences between the ICHOM recommendations and the 2002 WHO global consensus. The latter are established in many centres with historical archives of OFC outcome data, and it was concluded that with some modifications ICHOM could be moulded into useful core outcomes data for inter-centre comparisons worldwide.
Usability of a digital health platform to support home hospitalization in heart failure patients: a multicentre feasibility study among healthcare professionals
Authors: Leenen Jobbe P L , Scherrenberg Martijn , Bruins Wendy , Boyne Josiane , Vranken Julie , Brunner la Rocca Hans-Peter , Dendale Paul , van der Velde Astrid E 
Published: June 2023

Abstract

Aims
Heart failure (HF) is a common cause of mortality and (re)hospitalizations. The NWE-Chance project explored the feasibility of providing hospitalizations at home (HH) supported by a newly developed digital health platform. The aim of this study was to explore the perceived usability by healthcare professionals (HCPs) of a digital platform in addition to HH for HF patients.

Methods and results
A prospective, international, multicentre, single-arm interventional study was conducted. Sixty-three patients and 22 HCPs participated. The HH consisted of daily home visits by the nurse and use of the platform, consisting of a portable blood pressure device, weight scale, pulse oximeter, a wearable chest patch to measure vital signs (heart rate, respiratory rate, activity level, and posture), and an eCoach for the patient. Primary outcome was usability of the platform measured by the System Usability Scale halfway and at the end of the study. Overall usability was rated as sufficient (mean score 72.1 ± 8.9) and did not differ between the measurements moments (P = 0.690). The HCPs reported positive experiences (n = 7), negative experiences (n = 13), and recommendations (n = 6) for the future. Actual use of the platform was 79% of the HH days.

Conclusion
A digital health platform to support HH was considered usable by HCPs, although actual use of the platform was limited. Therefore, several improvements in the integration of the digital platform into clinical workflows and in defining the precise role of the digital platform and its use are needed to add value before full implementation.

Registration
clinicaltrials.gov NCT04084964.
Ancient hybridization leads to the repeated evolution of red flowers across a monkeyflower radiation
Authors: Short Aidan W , Streisfeld Matthew A 
Published: June 2023

Abstract
The reuse of old genetic variation can promote rapid diversification in evolutionary radiations, but in most cases, the historical events underlying this divergence are not known. For example, ancient hybridization can generate new combinations of alleles that sort into descendant lineages, potentially providing the raw material to initiate divergence. In the Mimulus aurantiacus species complex, there is evidence for widespread gene flow among members of this radiation. In addition, allelic variation in the MaMyb2 gene is responsible for differences in flower color between the closely related ecotypes of subspecies puniceus, contributing to reproductive isolation by pollinators. Previous work suggested that MaMyb2 was introgressed into the red-flowered ecotype of puniceus. However, additional taxa within the radiation have independently evolved red flowers from their yellow-flowered ancestors, raising the possibility that this introgression had a more ancient origin. In this study, we used repeated tests of admixture from whole-genome sequence data across this diverse radiation to demonstrate that there has been both ancient and recurrent hybridization in this group. However, most of the signal of this ancient introgression has been removed due to selection, suggesting that widespread barriers to gene flow are in place between taxa. Yet, a roughly 30 kb region that contains the MaMyb2 gene is currently shared only among the red-flowered taxa. Patterns of admixture, sequence divergence, and extended haplotype homozygosity across this region confirm a history of ancient hybridization, where functional variants have been preserved due to positive selection in red-flowered taxa but lost in their yellow-flowered counterparts. The results of this study reveal that selection against gene flow can reduce genomic signatures of ancient hybridization, but that historical introgression can provide essential genetic variation that facilitates the repeated evolution of phenotypic traits between lineages.
Development of a monitoring system for Huangjiu storage based on electrical conductivity
Authors: Hu Jian , Liu Shuangping , Nan Mujia , Liu Caixia , Han Xiao , Mao Jian 
Published: June 2023

Abstract
In order to quickly detect the rancidification of Huangjiu in pottery jars, this study developed a fast detection method based on the principle of electrical conductivity changes caused by microbial contamination. The change in total acid in Huangjiu was positively correlated with the increase of electrical conductivity. This method was applied to an online monitoring system for Huangjiu storage in stainless steel tanks. When the electrical conductivity exceeds the normal fluctuation range (mean+3 standard deviations) of previous data, the monitoring system recognizes microbial contamination. By optimizing the conductivity-temperature compensation coefficient and conductivity statistical method, the standard deviation of the method was reduced and the sensitivity of microbial pollution monitoring was improved. The ranges of conductivity and compensation coefficient of common types of Huangjiu were estimated. Interference in conductivity measurements due to environmental factors was minimised through the synchronous comparison of conductivity data for multiple tanks of Huangjiu. The standard deviation, which indicates the fluctuation range of the system, decreased from 143 to 2 μS/cm. The monitoring system was then applied in Huangjiu storage tanks with capacities of 60 t and 300 t. Through the comparison of conductivity data change, the abnormal signals caused by microbial contamination during the storage of Huangjiu were found over time. Meanwhile, through offline detection of total acid in Huangjiu, the effectiveness of microbial contamination online detection was verified.
Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice
Authors: Wang Peng , Li Ruikai , Li Yuqi , Tan Siwei , Jiang Jie , Liu Huiling , Wei Xiuqing 
Published: June 2023

Abstract

Background
Berberine effectively alleviates non-alcoholic fatty liver disease (NAFLD). Nevertheless, the mechanism is incompletely comprehended. It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of SIRT1 in hepatocytes. We hypothesized that SIRT1 mediated the effect of berberine on NAFLD.

Methods
The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet (HFD) and in mouse primary hepatocytes and cell lines exposed to palmitate. The change of fatty acid oxidation (FAO) and the activity of CPT1A were observed in HepG2 cells. Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of SIRT1 and lipid metabolism-related molecules. The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells.

Results
Berberine treatment attenuated hepatic steatosis, reduced triglyceride (190.1 ± 11.2 μmol/g liver vs 113.6 ± 7.6 μmol/g liver, P &lt; 0.001) and cholesterol (11.3 ± 2.5 μmol/g liver vs 6.3 ± 0.4 μmol/g liver, P &lt; 0.001) concentration in the liver, and improved lipid and glucose metabolism disorders compared with the HFD group. The expression of SIRT1 was reduced in the liver of NAFLD patients and mouse models. Berberine increased the expression of SIRT1 and promoted the protein level of CPT1A and its activity in HepG2 cells. SIRT1 overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells, whereas SIRT1 knock-down attenuated the effect of berberine. Mechanistically, berberine increased the expression of SIRT1. SIRT1 deacetylated CPT1A at the Lys675 site, which suppressed its ubiquitin-dependent degradation, thereby promoting FAO and alleviating non-alcoholic liver steatosis.

Conclusions
Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site, which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.
Co-Design of a Financial and Legal Planning Tool for Care Partners of People Living With Alzheimer’s Disease and Related Dementias
Authors: Jolliff Anna , Dudek Alex , Zuraw Matthew , Parks Reid , Linden Anna , Elliott Christian , Werner Nicole E 
Published: June 2023

Abstract

Background and Objectives
Care partners of people living with Alzheimer’s disease and related dementias (ADRD) are faced with substantial legal and financial planning related to their care partner role. However, many care partners lack the legal and financial support needed to manage this role. The purpose of this study was to engage ADRD care partners in a remote participatory design process to create a technology-based financial and legal planning tool that meets care partner needs.

Research Design and Methods
We formed 2 researcher-facilitated co-design teams comprised of n = 5 ADRD care partners each. We conducted a series of 5 parallel co-design sessions aimed to engage co-designers in interactive discussions and design activities to create the financial and legal planning tool. We used inductive thematic analysis of design session recordings to identify design requirements.

Results
Co-designers were 70% female with a mean age of 67.3 years (standard deviation 9.07) and cared for a spouse (80%) or a parent (20%). Between Sessions 3 and 5, the average system usability scale score of the prototype increased from 89.5 to 93.6, indicating high usability. Analyses yielded 7 overarching design requirements for a legal and financial planning tool: support for action now (eg, prioritized to-do lists); support for action later (eg, reminders for keeping legal documents up-to-date); knowledge when I need it (eg, tailored learning modules); connection to resources I need (eg, state-specific financial support opportunities); everything where I can see it (eg, comprehensive care budgeting tool); sense of privacy and security (eg, password protection); and accessibility for all (eg, tailoring for low-income care partners).

Discussion and Implications
The design requirements identified by co-designers provide a foundation from which we can build technology-based solutions to support ADRD care partners in financial and legal planning.