bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of chitin grafting: thermal, antioxidant and antitumor properties
Authors: Çankaya Nevin , Temüz Mehmet Mürşit , Can Burak 
Published: January 2025

Abstract
In this study, firstly chitin was reacted with chloracetyl chloride to synthesize the macroinitiator chitinchloroacetate (Ch.ClAc). Then, graft copolymers of methacrylamide (MAM), diacetone acrylamide (DAAM), N-(4-nitrophenyl)acrylamide (NPA), and 2-hydroxyethyl methacrylate (HEMA) monomers were synthesized by atom transfer radical polymerization (ATRP). All of the polymers were characterized by FTIR spectra and elemental analysis. According to the elemental analysis results, the mole percent (y) of the macro initiator was found to be 17.39%. The thermal stability of all the polymers (chitin, Ch.ClAc and its graft copolymers) was determined by thermogravimetric analysis (TGA) method and the highest thermal stability was observed in the ungrafted raw chitin. DPPH• scavenging activity and antitumor activity of all polymers were then investigated. Ch.ClAc was found to be the polymer that inhibited the proliferation of tumor cells more than chitin and graft copolymers. It was observed that the antitumor (L1210 cell lines) effect increased with increasing time and concentration in all polymers.
Behavioral, biochemical, immune, and histological responses of Nile tilapia (Oreochromis niloticus Linnaeus, 1758) to lead, mercury, and pendimethalin exposure: individual and combined effects
Authors: Reda Rasha M. , Zaki Eman M. , A. A. Aioub Ahmed , Metwally Mohamed M. M. , Yassin Aya M. , Mahsoub Fatma 
Published: January 2025

Abstract
The aquaculture sector is facing environmental issues because of rising chemical pollution of aquatic systems, which may be caused by man-made or natural causes. The combined action of these mixtures can produce an effect that is either severalfold higher or severalfold lower than the overall toxicity of the individual components. The objective of this study is to evaluate the impact of three individual toxicants: lead (Pb 0.088 mg L−1), mercury (Hg 0.084 mg L−1), and pendimethalin (PM 0.355 mg L−1) and their combinations on the behavior, oxidative stress, immunology, biochemistry, and histopathological changes in Nile tilapia. The results show that mortality was evident across all treatment groups and was highest in the mixture (MIX) group, at 33.4%. Some of these behavioral changes included increased mucus secretion, fin rot, and dark skin coloration of the fish, all of which were evidently exacerbated in the MIX group. The erythrocyte and hemoglobin indices presented marked reductions in the MIX and PM groups in comparison to the control group. The MIX group had higher levels of serum creatinine and urea, as well as the liver enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. They also had higher levels of malondialdehyde and lower levels of total antioxidant capacity, which showed oxidative stress. The stress biomarkers, cortisol and glucose, showed greater impact on the MIX and PM groups. The neurobehavioral assessment demonstrated noticeable decreased acetylcholinesterase levels in PM and MIX-exposed groups. In the serum immunological parameters, levels of nitric oxide and lysozyme were lower, especially in the MIX and PM groups. In all experimental groups, especially the MIX group, the levels of spleen pro-inflammatory cytokine genes were higher. The histopathological examination revealed marked lesions in the gills, liver, and brains in the form of inflammation, necrosis, and circulatory alterations. Among the exposed groups, the MIX group exhibited the highest histopathological changes. Collectively, our findings demonstrated significant toxic effects of heavy metals and herbicides on Nile tilapia, revealing a synergistic impact on both physiological and histopathological responses resulting from combined exposures. The data evidently indicate the ecological hazards associated with heavy metals and herbicides in aquatic ecosystems.
Continuous high-soy protein soymilk intake affects ordinary walking speed in the Japanese pre-frail and frail elderly: a randomized controlled trial
Authors: Sato Nene , Terashima Yuji , Sugawara Makoto , Unno Ryoichi , Asao Hiroaki , Iwasaki Mitsuhiro , Watanabe Tomoyuki , Uno Tomoko , Maruyama Mitsuo 
Published: January 2025

Abstract

Background
To investigate whether continuous intervention using soymilk containing high soy protein improves physical frailty, a randomized controlled trial was conducted among the Japanese pre-frail and frail elderly.

Methods
Japanese pre-frail and frail elderly participants (n = 73) were randomly assigned to the high-soy protein and control groups, who then ingested soymilk containing 14.5 g/200 ml and 3.2 g/200 ml of soy protein, respectively. Before and after the 12-week intervention, walking speed, skeletal muscle mass, grip strength, and the revised Japanese CHS questionnaire regarding fatigue and physical activity were examined to evaluate the impact of each soymilk on physical frailty and compare the variation between the two groups. Physical activity (monitored using a pedometer), dietary intake (determined by questionnaire), and estimated protein intake (determined by casual urine testing) were also recorded before and after the intervention.

Results
For the final analysis of the entire cohort (n = 70), there were no significant differences in the endpoints between the two groups. In the subgroup analysis, among participants with a walking speed of at least 1 m/s (n = 35, P = 0.012) and at least 5,000 steps/day before intervention (n = 27, P = 0.0083), the variation in walking speed after the 12-week intervention was significantly higher in the high-soy protein group than in the control group. Estimated protein intake was also significantly higher in the high-soy protein group than in the control group after the intervention. Regarding physical activity and dietary intake, no significant differences were observed between the groups before or after the intervention.

Conclusion
The continuous 12-week intervention of high soy protein increased the walking speed among the Japanese pre-frail and frail elderly participants who had an ordinarily high walking speed and high step counts.

Trial registration
UMIN Clinical Trials Registry, UMIN000044999. Registered July 29, 2021; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051409.
Latent class analysis of the capacity of countries to manage diabetes and its relationship with diabetes-related deaths and healthcare costs
Authors: Akyirem Samuel , Ekpor Emmanuel , Kwanin Charles Boakye 
Published: January 2025

Abstract

Background
The prevalence of diabetes is escalating globally, underscoring the need for comprehensive evidence to inform health systems in effectively addressing this epidemic. The purpose of this study was to examine the patterns of countries’ capacity to manage diabetes using latent class analysis (LCA) and to determine whether the patterns are associated with diabetes-related deaths and healthcare costs.

Methods
Eight indicators of country-level capacity were drawn from the World Health Organization Global Health Observatory dataset: the widespread availability of hemoglobin A1C (HbA1c) testing, existence of diabetes registry, national diabetes management guidelines, national strategy for diabetes care, blood glucose testing, diabetic retinopathy screening, sulfonylureas, and metformin in the public health sector. We performed LCA of these indicators, testing 1–5 class solutions, and selecting the best model based on Bayesian Information Criteria (BIC), entropy, corrected Akaike Information Criteria (cAIC), as well as theoretical interpretability. Multivariable linear regression was used to assess the association between capacity to manage diabetes (based on the latent class a country belongs) and diabetes-related deaths and healthcare costs.

Results
We included 194 countries in this secondary analysis. Countries were classified into “high capacity” (88.7%) and “limited capacity” (11.3%) countries based on the two-class solution of the LCA (entropy = 0.91, cAIC = 1895.93, BIC = 1862.93). Limited capacity countries were mostly in Africa. Limited capacity countries had significantly higher percentage of their deaths attributable to diabetes (adjusted beta = 1.34; 95% CI: 0.15, 2.53; p = 0.027) compared to high capacity countries even after adjusting for income status and diabetes prevalence.

Conclusions
Our findings support the report by the Lancet commission on diabetes, which suggests that differences in diabetes outcomes among countries may be explained by variations in the capacity of and investments made in their health systems. Future studies should evaluate initiatives such as the WHO Global Diabetes Compact that are currently underway to improve the capacity of resource-limited countries.
Exploring the barriers to cervical screening and perspectives on new self-sampling methods amongst under-served groups
Authors: Gillibrand Stephanie , Gibson Helen , Howells Kelly , Urwin Sean , Davies Jennifer C. , Crosbie Emma J. , Sanders Caroline 
Published: January 2025

Abstract

Background
Cervical screening rates have fallen in recent years in the UK, representing a health inequity for some under-served groups. Self-sampling alternatives to cervical screening may be useful where certain barriers prohibit access to routine cervical screening. However, there is limited evidence on whether self-sampling methods address known barriers to cervical screening and subsequently increase uptake amongst under-screened groups. Addressing this research gap, the study aims to understand experiences during and barriers to attending cervical screening for under-screened groups and; explore the views of individuals eligible for screening towards self-sampling (vaginal swabbing and urine sampling) as alternative screening methods and how this may address existing barriers to screening.

Methods
We draw on three integrated theoretical frameworks (access to primary care services, intersectional and feminist perspectives) to examine participants’ barriers to screening and views toward self-sampling methods. We undertook primary qualitative data collection (interviews and focus groups) with 46 participants, facilitated by collaborations with the VCSE sector which successfully enhanced reach to under-served communities.

Results
Known barriers to cervical screening persist for under-screened participant groups, but we also find numerous examples of good practice where some participants’ needs were met throughout the screening process. Both positive and negative experiences tend to centre around experiences with healthcare professionals, with negative experiences also centring around the use of the speculum. Self-sampling methods (vaginal swab and urine collection) were positively received by participants, and may address some existing barriers through the proponents of enhanced choice – between method and location (which also dovetailed with convenience) leading to greater empowerment. The removal of the speculum and lack of invasive examination by a healthcare professional was also positively received.

Conclusions
Whilst barriers to cervical screening remain for under-served groups, examples of good practice are prevalent. Such examples should be implemented more widely to ensure consistency in patient experience and to ensure needs are better met for under-served groups. The introduction of self-sampling alongside traditional methods may reduce barriers to screening, and may boost screening rates for under-screened groups but only if they are implemented with appropriate information and sufficient communication. Failure to implement self-sampling without these considerations may threaten to undermine the identified and important benefits of self-sampling methods.
Scale-up of CHO cell cultures: from 96-well-microtiter plates to stirred tank reactors across three orders of magnitude
Authors: Neuss Anne , Steimann Thomas , Tomas Borges Jacinta Sofia , Dinger Robert , Magnus Jørgen Barsett 
Published: January 2025

Abstract

Background
For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks. A scale-up from those small shaken devices to a stirred tank reactor is barely stated in literature for mammalian cells. Thus, this study aims to address data-driven scale-up for CHO DP12 cells. The oxygen transfer rate is used as a database.

Results
The cultivation conditions in microtiter plates and shake flasks are comparable when choosing the maximum oxygen transfer capacity as a scale-up parameter. The minimum cultivation volume was reduced to 400 µL in round and square 96-deep-well microtiter plates. Using a scale-up based on the maximum oxygen transfer capacity to a stirred tank reactor led to conditions with excessive hydromechanical stress. However, cultivation conditions could be reproduced in a stirred tank reactor by utilizing the volumetric power input as a scale-up parameter. Key metabolites behaved the same in all three scales and the final antibody titer was equal.

Conclusion
This study presents a successful replication of cultivation results for mammalian cells in microtiter plates, shake flasks and stirred tank reactors. The working volumes ranged from 0.4 to 50 and 600 mL. It offers the opportunity to adapt the method to other, more sensitive mammalian cells and to perform cost- and time-effective experiments in high-throughput.
Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma
Authors: Oyon Daniel , Lopez-Pascual Amaya , Castello-Uribe Borja , Uriarte Iker , Orsi Giulia , Llorente Sofia , Elurbide Jasmin , Adan-Villaescusa Elena , Valbuena-Goiricelaya Emiliana , Irigaray-Miramon Ainara , Latasa Maria Ujue , Martinez-Perez Luz A. , Bonetti Luca Reggiani , Prosper Felipe , Ponz-Sarvise Mariano , Vicent Silvestre , Pineda-Lucena Antonio , Ruiz-Clavijo David , Sangro Bruno , Larracoechea Urko Aguirre , Tian Tian V. , Casadei-Gardini Andrea , Amat Irene , Arechederra Maria , Berasain Carmen , Urman Jesus M. , Avila Matias A. , Fernandez-Barrena Maite G. 
Published: January 2025

Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy. This study aimed to investigate the expression and prognostic significance of a key epigenetic complex encompassing DNA methyltransferase-1 (DNMT1), the histone methyltransferase G9a, and the scaffold protein UHRF1 in PDAC. We also evaluated the therapeutic potential of an innovative inhibitor targeting these epigenetic effectors.

Methods
Immunohistochemical analysis of DNMT1, G9a, and UHRF1 expression was conducted in human PDAC tissue samples. Staining was semi-quantitatively scored, and overexpression was defined as moderate to strong positivity. The prognostic impact was assessed by correlating protein expression with patient survival. The antitumoral effects of the dual DNMT1-G9a inhibitor CM272 were tested in PDAC cell lines, followed by transcriptomic analyses to identify underlying mechanisms. The in vivo antitumoral efficacy of CM272 was evaluated in PDAC xenograft and syngeneic mouse models, both alone and in combination with anti-PD1 immunotherapy.

Results
DNMT1, G9a, and UHRF1 were significantly overexpressed in PDAC cells and stroma compared to normal pancreatic tissues. Simultaneous overexpression of the three proteins was associated with significantly reduced survival in resected PDAC patients. CM272 exhibited potent antiproliferative activity in PDAC cell lines, inducing apoptosis and altering key metabolic and cell cycle-related genes. CM272 also enhanced chemotherapy sensitivity and significantly inhibited tumor growth in vivo without detectable toxicity. Combination of CM272 with anti-PD1 therapy further improved antitumor responses and immune cell infiltration, particularly CD4 + and CD8 + T cells.

Conclusions
The combined overexpression of DNMT1, G9a, and UHRF1 in PDAC is a strong predictor of poor prognosis. CM272, by targeting this epigenetic complex, shows promising therapeutic potential by inducing apoptosis, reprogramming metabolic pathways, and enhancing immune responses. The combination of CM272 with immunotherapy offers a novel, effective treatment strategy for PDAC.
Peripheral oxygen saturation levels as a guide to avoid hyperoxia: an observational study
Authors: Stolmeijer Renate , ter Maaten Jan C. , Ligtenberg Jack , ter Avest Ewoud 
Published: January 2025

Abstract

Background
As iatrogenic hyperoxia has been related to adverse outcomes in critically ill patients, guidelines advise to titrate oxygen to physiological levels. In the prehospital setting where partial arterial oxygen (PaO2) values are often not readily available, titration of oxygen is based on peripheral oxygen saturations (SpO2). In this study we aimed to investigate the efficacy of SpO2 guided oxygen titration in the prevention of hyperoxia.

Methods
In a retrospective observational cohort study of patients included in the Acutelines data- and biobank of the University Medical Center Groningen between September 2020 and March 2023, we collected blood gas samples and triage data of sequentially included patients who received oxygen at the moment they were presented in the emergency department (ED). PaO2 values were compared to (concurrently measured) SpO2 values, and to patient- and treatment characteristics and P/F ratios were calculated in order to investigate the efficacy of SpO2 based oxygen titration for various subgroups.

Results
Blood gas samples were obtained for 1042 patients, of which 178 (17.1%) had hyperoxia (PaO2 levels > 13.5 kPa). SpO2 readings were available for 170 of these, 68 of which (40%) had SpO2 values above the recommended target range (94–98%; 88–92% for patients with COPD) whereas 102 patients (60%) had SpO2 values within- or even below the recommended target range. Many of these patients (44.1%) received oxygen through a low-flow device (nasal canula), and these patients almost invariably (84.4%) were not compromised in their ventilation (P/F ratio’s > 300).

Conclusion
When oxygen is titrated based on SpO2 levels, this results in hyperoxemia in a significant proportion of the patients. Health care providers should especially be reluctant to administer (low flow) oxygen as a standard of care to patients who do not have clear respiratory compromise, as these patients are at a high risk of developing (occult) hyperoxia.
Diagnostic performance of CT for extrarenal fat invasion in renal cell carcinoma: a meta-analysis and systematic review
Authors: Ma Junchao , Yuan Enyu , Feng Shijian , Yao Jin , He Chunlei , Chen Yuntian , Song Bin 
Published: January 2025

Abstract

Objectives
Renal cell carcinoma (RCC) with extrarenal fat (perinephric or renal sinus fat) invasion is the main evidence for the T3a stage. Currently, computed tomography (CT) is still the primary modality for staging RCC. This study aims to determine the diagnostic performance of CT in RCC patients with extrarenal fat invasion.

Methods
The PubMed, Web of Science, Cochrane Library, and EMBASE databases were systematically searched up to October 11, 2023. Study quality was assessed by the QUADAS-2 tool. Standard methods recommended for meta-analyses of diagnostic evaluation were used. Heterogeneity was analyzed through meta-regression analysis.

Results
Fifteen studies were included in this meta-analysis. Among them, six studies focused on perinephric fat invasion (PFI) only, four on renal sinus fat invasion (RSFI) only, and five on both. Pooled weighted estimates of sensitivity, specificity, area of SROC curve, PLR, and negative likelihood ratio (NLR) of CT for PFI were 0.69 (95% CI: 0.55–0.79), 0.82 (95% CI: 0.69–0.90), 0.81 (95% CI: 0.77–0.84), 3.85 (95% CI: 2.22–6.67), and 0.38 (95% CI: 0.27–0.55). Pooled weighted estimates of sensitivity, specificity, area of SROC curve, PLR, and NLR of CT for RSFI were 0.81 (95% CI: 0.76–0.85), 0.79 (95% CI: 0.66–0.88), 0.82 (95% CI: 0.78–0.85), 3.91 (95% CI: 2.26–6.77), and 0.24 (95% CI: 0.18–0.31).

Conclusion
CT has the ability to detect the PFI and RSFI in patients with RCC. However, the diagnostic performance of CT has suffered from the limitation of slightly lower accuracy, resulting from the low positive sample in the current studies. Additionally, the current PLR is low.

Critical relevance statement
This study provides radiologists and urologists with a systematic and comprehensive summary of CT and CT-related morphological features in assessing extrarenal fat invasion in patients with RCC.

Key Points

CT can detect extrarenal fat invasion in patients with RCC, but the diagnostic performance is inconsistent.

The diagnostic performance of CT is acceptable, but primarily affected by the low positive rate of included patients.

Further large-scale trials are necessary to determine the true diagnostic capabilities of CT for extrarenal fat invasion.

Graphical Abstract
Poikiloderma with neutropenia: a case report
Authors: Chekr Jebran , Andraws Jan , Elias Jubran , Alasmar Diana 
Published: January 2025

Abstract

Background
Poikiloderma with neutropenia is a rare genetic disorder primarily characterized by the presence of poikiloderma and congenital chronic neutropenia. Mutations in the C16orf57 gene, which encodes the USB1 protein, are implicated as the underlying cause of poikiloderma with neutropenia.

Case presentation
Our patient, an 11-year-old Syrian male child who presented with poikiloderma, palmoplantar keratoderma, pachyonychia, recurrent infections, and neutropenia, is considered to be the first documented case in Syria. Clinical examinations, laboratory tests, radiographic imaging, and genetic analyses have been conducted, with the latter being essential and definitive for diagnosis.

Conclusion
This study aimed to evaluate whether poikiloderma with neutropenia should be considered for differential diagnosis because of its diagnostic complexity, emphasizing the importance of follow-up for the early identification of potential complications.