bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for early recurrence in patients with pancreatic ductal adenocarcinoma who underwent curative resection
Authors: Murakawa Masaaki , Kawahara Shinnosuke , Takahashi Daishi , Kamioka Yuto , Yamamoto Naoto , Kobayashi Satoshi , Ueno Makoto , Morimoto Manabu , Sawazaki Sho , Tamagawa Hiroshi , Ohshima Takashi , Yukawa Norio , Rino Yasushi , Morinaga Soichiro 
Published: August 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and surgical resection is the only potentially curative approach. However, the rate of recurrence remains high, particularly within the first 6 months, and is associated with a poor prognosis. The present study evaluated the clinical characteristics and risk factors for early recurrence in pancreatic ductal adenocarcinoma (PDAC) patients who underwent curative resection, regardless of the use of neoadjuvant chemotherapy, to identify predictive factors associated with early recurrence and poor outcomes as well as to determine the optimal treatment strategy for patients at high risk of early recurrence after surgical resection.

Methods
Patients who underwent pancreatic resection for PDAC at our institution from 2013 to 2021 were included in this study. We investigated the clinicopathological features of patients in groups: those with recurrence within 6 months, recurrence between 6 and 12 months, and recurrence beyond 12 months or no recurrence. A logistic regression analysis identified covariates associated with early recurrence at 6 and 12 months.

Results
The study included 403 patients with a median follow-up of 25.7 months. Recurrence was observed in 279 patients, with 14.6% recurring within 6 months, 23.3% within 6–12 months, and 62% after 12 months or not at all. The preoperative CA19-9 level, modified Glasgow prognostic score (mGPS), and positive peritoneal cytology were significant risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant risk factors for recurrence within 12 months. For patients who received preoperative chemotherapy or chemoradiotherapy, the preoperative CA19-9 level, mGPS, and positive peritoneal cytology were significant independent risk factors for early recurrence within 6 months, while positive peritoneal cytology, lymph node metastasis, and the absence of adjuvant chemotherapy were significant independent risk factors for recurrence within 12 months. The study concluded that the overall survival after surgical resection for potentially resectable PDAC worsened according to the number of risk factors present in the patient.

Conclusions
We clarified that preoperative CA19-9, positive peritoneal cytology, and the lack of adjuvant chemotherapy were consistent predictors for early recurrence within 6 and 12 months. In addition, an increased number of risk factors affecting the patient was associated with a poorer overall survival after potentially curable resection. Calculating the number of risk factors for early recurrence may be an essential predictive factor when considering treatment strategies.
Low-intensity pulsed ultrasound ameliorates glia-mediated inflammation and neuronal damage in experimental intracerebral hemorrhage conditions
Authors: Su Wei-Shen , Wu Chun-Hu , Song Wen-Shin , Chen Szu-Fu , Yang Feng-Yi 
Published: August 2023

Abstract
Background
Intracerebral hemorrhage (ICH) is a condition associated with high morbidity and mortality, and glia-mediated inflammation is a major contributor to neurological deficits. However, there is currently no proven effective treatment for clinical ICH. Recently, low-intensity pulsed ultrasound (LIPUS), a non-invasive method, has shown potential for neuroprotection in neurodegenerative diseases. This study aimed to investigate the neuroprotective effects and potential mechanisms of LIPUS on glia-mediated inflammation in ICH.

Methods
This study used 289 mice to investigate the effects of LIPUS on ICH. ICH was induced by injecting bacterial collagenase (type VII-S; 0.0375 U) into the striatum of the mice. LIPUS was applied noninvasively for 3 days, including a 2-h-delayed intervention to mimic clinical usage. The study evaluated neurological function, histology, brain water content, hemoglobin content, MRI, and protein expression of neurotrophic factors, inflammatory molecules, and apoptosis. In vitro studies investigated glia-mediated inflammation by adding thrombin (10 U/mL) or conditioned media to primary and cell line cultures. The PI3K inhibitor LY294002 was used to confirm the effects of PI3K/Akt signaling after LIPUS treatment.

Results
LIPUS treatment improved neurological deficits and reduced tissue loss, edema, and neurodegeneration after ICH. The protective effects of LIPUS resulted from decreased glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling, which reduced cytokine expression and attenuated microglial activation-induced neuronal damage in vitro.

Conclusions
LIPUS treatment improved neurological outcomes and reduced glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling after ICH. LIPUS may provide a non-invasive potential management strategy for ICH.
An arrhythmogenic metabolite in atrial fibrillation
Authors: Krause Julia , Nickel Alexander , Madsen Alexandra , Aitken-Buck Hamish M. , Stoter A. M. Stella , Schrapers Jessica , Ojeda Francisco , Geiger Kira , Kern Melanie , Kohlhaas Michael , Bertero Edoardo , Hofmockel Patrick , Hübner Florian , Assum Ines , Heinig Matthias , Müller Christian , Hansen Arne , Krause Tobias , Park Deung-Dae , Just Steffen , Aïssi Dylan , Börnigen Daniela , Lindner Diana , Friedrich Nele , Alhussini Khaled , Bening Constanze , Schnabel Renate B. , Karakas Mahir , Iacoviello Licia , Salomaa Veikko , Linneberg Allan , Tunstall-Pedoe Hugh , Kuulasmaa Kari , Kirchhof Paulus , Blankenberg Stefan , Christ Torsten , Eschenhagen Thomas , Lamberts Regis R. , Maack Christoph , Stenzig Justus , Zeller Tanja 
Published: August 2023

Abstract
Background
Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting.

Methods and results
Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF.

Conclusion
Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.
Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation
Authors: Zheng Yueyuan , Ziman Benjamin , Ho Allen S. , Sinha Uttam K. , Xu Li-Yan , Li En-Min , Koeffler H Phillip , Berman Benjamin P. , Lin De-Chen 
Published: August 2023

Abstract
Background
As one of the most common malignancies, esophageal cancer has two subtypes, squamous cell carcinoma and adenocarcinoma, arising from distinct cells-of-origin. Distinguishing cell-type-specific molecular features from cancer-specific characteristics is challenging.

Results
We analyze whole-genome bisulfite sequencing data on 45 esophageal tumor and nonmalignant samples from both subtypes. We develop a novel sequence-aware method to identify large partially methylated domains (PMDs), revealing profound heterogeneity at both methylation level and genomic distribution of PMDs across tumor samples. We identify subtype-specific PMDs that are associated with repressive transcription, chromatin B compartments and high somatic mutation rate. While genomic locations of these PMDs are pre-established in normal cells, the degree of loss is significantly higher in tumors. We find that cell-type-specific deposition of H3K36me2 may underlie genomic distribution of PMDs. At a smaller genomic scale, both cell-type- and cancer-specific differentially methylated regions (DMRs) are identified for each subtype. Using binding motif analysis within these DMRs, we show that a cell-type-specific transcription factor HNF4A maintains the binding sites that it generates in normal cells, while establishing new binding sites cooperatively with novel partners such as FOSL1 in esophageal adenocarcinoma. Finally, leveraging pan-tissue single-cell and pan-cancer epigenomic datasets, we demonstrate that a substantial fraction of cell-type-specific PMDs and DMRs identified here in esophageal cancer are actually markers that co-occur in other cancers originating from related cell types.

Conclusions
These findings advance our understanding of DNA methylation dynamics at various genomic scales in normal and malignant states, providing novel mechanistic insights into cell-type- and cancer-specific epigenetic regulations.
Development and validation of an effective and sensitive technique for nitrate determination in fruits and vegetables using HPLC/PDA
Authors: Uddin Rayhan , Islam G. M. Rabiul , Uddin Mohammad Zia , Thakur Mostak Uddin 
Published: August 2023

AbstractThis study aims to develop an effective and sensitive HPLC (High Performance Liquid Chromatography) method to determine the nitrate concentration in fruits and vegetables (F & V) using a C18 column (ZORBAX Eclipse XDB-C18, 80Å, 250 × 4.6 mm, 5 μm (Agilent Technologies)) maintained at 40 0 C, a mobile phase made up of methanol and buffer (pentane sulfonic acid sodium salt solution), and a Photo Diode Array Detector (PDA) at 225 nm. The developed method is validated in terms of selectivity, linearity, accuracy, precision, suitability, the limit of detection (LOD), and the limit of quantification (LOQ) according to the European Union Decision 2002/657/EC. The result revealed that a ratio of 30: 70 of the organic modifier methanol and buffer with pH 2.8 shows the highest efficiency. The calibration curve shows linearity with a correlation coefficient (r) of 0.9985. The LOD and LOQ were found to be 2.26 mg/kg and 7.46 mg/kg. The recovery was in the range of 98.96–100.21%. Moreover, the greenness assessment scores of different approaches (eco-scale score of 76, AGREE score of 0.71, and few red shades in GAPI portray) were at a very excellent level. Thus, our developed method is fully validated and can determine the nitrate content in F & V.
CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer
Authors: Tejedor Juan Ramón , Peñarroya Alfonso , Gancedo-Verdejo Javier , Santamarina-Ojeda Pablo , Pérez Raúl F. , López-Tamargo Sara , Díez-Borge Ana , Alba-Linares Juan J. , González-del-Rey Nerea , Urdinguio Rocío G. , Mangas Cristina , Roberti Annalisa , López Virginia , Morales-Ruiz Teresa , Ariza Rafael R. , Roldán-Arjona Teresa , Meijón Mónica , Valledor Luis , Cañal María Jesús , Fernández-Martínez Daniel , Fernández-Hevia María , Jiménez-Fonseca Paula , García-Flórez Luis J. , Fernández Agustín F. , Fraga Mario F. 
Published: August 2023

Abstract
Background
Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated.

Results
In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines. As a proof of concept, we combined recent CRISPR-Cas9 epigenome editing tools (dCas9-TET1, dCas9-TET-IM) with a customized arrayed gRNA library to modulate the DNA methylation status of 56 promoters previously linked with strong epigenetic repression in CRC, and we monitored the potential functional consequences of this DNA methylation loss by means of a high-content cell proliferation screen. Overall, the epigenetic modulation of most of these DNA methylated regions had a mild impact on the reactivation of gene expression and on the viability of cancer cells. Interestingly, we found that epigenetic reactivation of RSPO2 in the tumour context was associated with a significant impairment in cell proliferation in p53−/− cancer cell lines, and further validation with human samples demonstrated that the epigenetic silencing of RSPO2 is a mid-late event in the adenoma to carcinoma sequence.

Conclusions
These results highlight the potential role of DNA methylation as a driver mechanism of CRC and paves the way for the identification of novel therapeutic windows based on the epigenetic reactivation of certain tumour suppressor genes.
The relationship between stigma and psychological distress among people with diabetes: a meta-analysis
Authors: Guo Xiajun , Wu Sijia , Tang Haishan , Li Yuanyuan , Dong Wanglin , Lu Guangli , Liang Shuang , Chen Chaoran 
Published: August 2023

Abstract
Background & aims
Diabetes may perceive or experience varying degrees of stigma and psychological distress. The association between diabetes-related stigma and psychological distress has been examined in many studies, but no research has used a quantitative synthesis method to investigate the severity of this association and the moderators of the relationship. Thus, we conducted a meta-analysis to quantitatively integrate previous findings to identify the magnitude of the association between stigma and psychological distress among people with diabetes.

Review methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched four English academic databases (PubMed, Embase, Web of Science, and PsycINFO) and three Chinese databases (China National Knowledge Infrastructure [CNKI], WANFANG Data, China Science and Technology Journal Database [VIP]). The databases were searched from the inception of each database to the end of March 2023. The pooled correlation coefficient of the association between stigma and psychological distress among people with diabetes was calculated by a random effects model using Stata software (version 17.0), and several moderators that impacted this relationship were identified.

Results
Eligible studies (N = 19) with a total of 12,777 participants were analysed. The pooled correlation was high between diabetes-related stigma and psychological distress (r = 0.50, 95% CI: [0.43–0.57]). Moreover, the association was moderated by the diabetes stigma measurement tools and diabetes distress measurement tools used. However, the relationship was not moderated by type of diabetes, age, gender, geographical location, or type of stigma.

Conclusions
The results of the meta-analysis showed that stigma is strongly related to psychological distress among people with diabetes. Longitudinal or experimental research should be expanded in the future to further identify the causal pathways in the relationship between diabetes stigma and diabetes distress.
Recent progress of low-temperature plasma technology in biorefining process
Authors: Qin Lusha , Li Oi Lun 
Published: August 2023

AbstractIn recent years, low-temperature plasma-assisted processes, featuring high reaction efficiency and wide application scope, have emerged as a promising alternative to conventional methods for biomass valorization. It is well established that charged species, chemically energetic molecules and radicals, and highly active photons playing key roles during processing. This review presents the major applications of low-temperature plasma for biomass conversion in terms of (i) pretreatment of biomass, (ii) chemo fractionation of biomass into value-added chemicals, and (iii) synthesis of heterogeneous catalyst for further chemo-catalytic conversion. The pretreatment of biomass is the first and foremost step for biomass upgrading to facilitate raw biomass transformation, which reduces the crystallinity, purification, and delignification. The chemo-catalytic conversion of biomass involves primary reactions to various kinds of target products, such as hydrolysis, hydrogenation, retro-aldol condensation and so on. Finally, recent researches on plasma-assisted chemo-catalysis as well as heterogeneous catalysts fabricated via low-temperature plasma at relatively mild condition were introduced. These catalysts were reported with comparable performance for biomass conversion to other state-of-the-art catalysts prepared using conventional methods.
Graphical Abstract
Using experience-based co-design to develop mobile/tablet applications to support a person-centred and empowering stroke rehabilitation
Authors: Marwaa Mille Nabsen , Guidetti Susanne , Ytterberg Charlotte , Kristensen Hanne Kaae 
Published: August 2023

Abstract
Aim
To investigate and describe the process of using experience-based co-design (EBCD) to develop mobile/tablet applications to support a person-centred and empowering stroke rehabilitation.

Setting
Two cross-sectoral stroke rehabilitation settings in Denmark comprising six rehabilitation units.

Participants
Stroke survivors (n = 23), significant others (n = 18), occupational therapists (n = 12), physiotherapists (n = 9), representative of a patient organization (n = 1), application developers (n = 3) and researchers (n = 2).

Method
A structured, facilitated EBCD approach comprising six stages was used to co-design a service that aimed to address the priorities and needs of all relevant end-users. Data were collected by interviews, participant observations, notes on “flip sheets” and written feedback on the content in the apps and on the instruction pages. Data were analyzed descriptively and with a constructivist grounded theory analysis.

Results
The content in the application solutions “Mit Sygehus” and “Genoptræn.dk” were co-designed to support the needs identified by all end-users. Relevant evidence-based knowledge, person-centred exercises and guidelines using video recordings were the most important among the developed content in the applications to support person-centred and empowering stroke rehabilitation. Furthermore, easy, and seamless communication were considered important.

Conclusions
EBCD facilitated the development of content in the applications to support a person-centred and empowering stroke rehabilitation. Participants experienced that their contribution was considered important and valued.
Parental leave policies, work (re)entry, and second birth: Do differences between migrants and non-migrants in Germany increase?
Authors: Milewski Nadja , Brehm Uta 
Published: August 2023

AbstractThe paper investigates migrant–nonmigrant differentials over time among women in Germany after their first childbirth; we look at the transitions to paid work or to a second child. Our observation period covers almost 30 years, in which family policies changed substantially. Most notably, the year 2007 marked a shift in (West) Germany’s parental leave policy from a conservative family model to a policy directed toward fostering work and family reconciliation. Across these policy periods, we investigate whether population subgroups, i.e., first-generation migrants and migrant descendants, show different patterns in their transitions after the first childbirth compared to the non-migrant majority population. We use data of the German Socio-economic Panel Study (GSOEP). Our sample consists of 3555 mothers of one child, about 13% of whom are first-generation migrants and 16% are migrant descendants. We estimate event-history models: using competing risks analyses, we study transitions following the first birth, specifically, (re)entering work and having a second child. We find that the transition (back) to work increased significantly from one policy period to the next among non-migrants. Increases among migrants varied between the migrant generations, were smaller and occurred later. Hence, we find an increasing gap between first-generation migrants and non-migrants across policy periods, with migrant descendants in between. To some extent, the migrant–nonmigrant gap traces back to different compositional and institutional effects and varies across origin groups. By contrast, the transition rates to a second child decreased among non-migrants, but hardly varied across periods among migrants. Thus, our results demonstrate increasing differentials between societal groups in their work-family reconciliation behavior, to which the modern parental leave policies may have contributed. We discuss the implications of these results for researchers, society and policymakers.
Mental health around retirement: evidence of Ashenfelter’s dip
Authors: Vo Thang T. , Phu-Duyen Tran T. 
Published: August 2023

Abstract
Background
Mental health issues among retirees have become increasingly concerning because the aging population presents a significant challenge globally, particularly in Western countries. Previous studies on this issue are plagued with bias owing to lacking panel data and estimation strategies. This study investigated the depression levels of European adults around the time of retirement.

Methods
We used data obtained from Waves 1–7 of the Survey of Health, Ageing, and Retirement in Europe (SHARE) to create panel data covering the 2004–2017 period. Wave 3 (SHARELIFE) was excluded from the sample because it provided mismatched information. Fixed-effects (FE) and fixed-effects instrumental variables (FE-IV) models with multiple imputations were employed to examine the impacts of retirement on mental health before and after retirement, where being over pension age (normal and early) was used as the instrument variable.

Results
Our results indicated that retirement based on aspirational motivations (β =  − 0.115, p < 0.001) and positive circumstances (β =  − 0.038, p < 0.001) significantly reduced depression, whereas retiring under negative circumstances could deteriorate one’s mental health (β = 0.087, p < 0.001). FE and FE-IV models indicated that overall, retiring reduced retirees’ depression (β =  − 0.096, p < 0.001 and β =  − 0.261, p < 0.001, respectively). The results of FE-IV models showed that adults planning to retire in the next two years experienced less depression compared with others in the workforce (λ =  − 0.313, p < 0.01). These adults must have adjusted their lifestyles in response to their impending retirement, thereby evincing Ashenfelter’s dip. Two years after retirement, when the “honeymoon” phase was over, retirees may have completely adapted to their new lives and the effect of retirement was no longer important.

Conclusions
Retirement improves mental health before it happens, but not after. Increasing the pension eligibility age may postpone the beneficial effects of retirement on health. However, policy implications should be tailored according to the unique situations of each country, job sector, and population. Providing flexible schemes regarding retirement timing decisions would be better than a generalized retirement policy.