bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring patients’ perspectives: a mixed methods study on Outpatient Parenteral Antimicrobial Therapy (OPAT) experiences
Authors: Peter Sophie , Oberröhrmann Charlotte , Pfaff Holger , Lehmann Clara , Schmidt-Hellerau Kirsten , Brandes Vanessa , Leisse Charlotte , Lindemann Christoph Heinrich , Ihle Peter , Küpper-Nybelen Jutta , Hagemeier Anna , Scholten Nadine 
Published: April 2024

Abstract
Background
Outpatient Parenteral Antimicrobial Therapy (OPAT), an alternative to inpatient intravenous antibiotic therapy, has shown benefits in international studies such as increased patient satisfaction. Because OPAT has been used only sporadically in Germany so far, no structured results on patients’ experiences and concerns regarding OPAT have yet been available. This study therefore aims to explore the experiences of OPAT patients in a pilot region in Germany.

Methods
This is an observational study in a German pilot region, including a survey of 58 patients on their experiences with OPAT, and in-depth interviews with 12 patients (explanatory-sequential mixed-methods design).

Results
Patients reported that they were satisfied with OPAT. That a hospital discharge was possible and anti-infective therapy could be continued in the home environment was rated as being particularly positive. In the beginning, many patients in the interviews were unsure about being able to administer the antibiotic therapy at home on their own. However, healthcare providers (doctors and pharmacy service provider staff) were able to allay these concerns. Patients appreciated regular contact with care providers. There were suggestions for improvement, particularly concerning the organization of the weekly check-up appointments and the provision of information about OPAT.

Conclusions
Patients were generally satisfied with OPAT. However, the treatment structures in Germany still need to be expanded to ensure comprehensive and high-quality OPAT care.

Trial registration
NCT04002453, https://www.clinicaltrials.gov/, (registration date: 2019–06-21).
Temporal dynamics of apoptosis-induced proliferation in pupal wing development: implications for regenerative ability
Authors: Ahmed-de-Prado Sara , Estella Carlos , Baonza Antonio 
Published: April 2024

Abstract
Background
The ability of animals to regenerate damaged tissue is a complex process that involves various cellular mechanisms. As animals age, they lose their regenerative abilities, making it essential to understand the underlying mechanisms that limit regenerative ability during aging. Drosophila melanogaster wing imaginal discs are epithelial structures that can regenerate after tissue injury. While significant research has focused on investigating regenerative responses during larval stages our comprehension of the regenerative potential of pupal wings and the underlying mechanisms contributing to the decline of regenerative responses remains limited.

Results
Here, we explore the temporal dynamics during pupal development of the proliferative response triggered by the induction of cell death, a typical regenerative response. Our results indicate that the apoptosis-induced proliferative response can continue until 34 h after puparium formation (APF), beyond this point cell death alone is not sufficient to induce a regenerative response. Under normal circumstances, cell proliferation ceases around 24 h APF. Interestingly, the failure of reinitiating the cell cycle beyond this time point is not attributed to an incapacity to activate the JNK pathway. Instead, our results suggest that the function of the ecdysone-responsive transcription factor E93 is involved in limiting the apoptosis-induced proliferative response during pupal development.

Conclusions
Our study shows that apoptosis can prolong the proliferative period of cells in the wing during pupal development as late as 34 h APF, at least 10 h longer than during normal development. After this time point, the regenerative response is diminished, a process mediated in part by the ecdysone-responsive transcription factor E93.
Membrane lipid remodeling eradicates Helicobacter pylori by manipulating the cholesteryl 6'-acylglucoside biosynthesis
Authors: Ong Lih-Lih , Jan Hau-Ming , Le Hong-Hanh Thi , Yang Tsai-Chen , Kuo Chou-Yu , Feng Ai-Feng , Mong Kwok-Kong Tony , Lin Chun-Hung 
Published: April 2024

Abstract
Background
Helicobacter pylori, the main cause of various gastric diseases, infects approximately half of the human population. This pathogen is auxotrophic for cholesterol which it converts to various cholesteryl α-glucoside derivatives, including cholesteryl 6’-acyl α-glucoside (CAG). Since the related biosynthetic enzymes can be translocated to the host cells, the acyl chain of CAG likely comes from its precursor phosphatidylethanolamine (PE) in the host membranes. This work aims at examining how the acyl chain of CAG and PE inhibits the membrane functions, especially bacterial adhesion.

Methods
Eleven CAGs that differ in acyl chains were used to study the membrane properties of human gastric adenocarcinoma cells (AGS cells), including lipid rafts clustering (monitored by immunofluorescence with confocal microscopy) and lateral membrane fluidity (by the fluorescence recovery after photobleaching). Cell-based and mouse models were employed to study the degree of bacterial adhesion, the analyses of which were conducted by using flow cytometry and immunofluorescence staining, respectively. The lipidomes of H. pylori, AGS cells and H. pylori–AGS co-cultures were analyzed by Ultraperformance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) to examine the effect of PE(10:0)2, PE(18:0)2, PE(18:3)2, or PE(22:6)2 treatments.

Results
CAG10:0, CAG18:3 and CAG22:6 were found to cause the most adverse effect on the bacterial adhesion. Further LC–MS analysis indicated that the treatment of PE(10:0)2 resulted in dual effects to inhibit the bacterial adhesion, including the generation of CAG10:0 and significant changes in the membrane compositions. The initial (1 h) lipidome changes involved in the incorporation of 10:0 acyl chains into dihydro- and phytosphingosine derivatives and ceramides. In contrast, after 16 h, glycerophospholipids displayed obvious increase in their very long chain fatty acids, monounsaturated and polyunsaturated fatty acids that are considered to enhance membrane fluidity.

Conclusions
The PE(10:0)2 treatment significantly reduced bacterial adhesion in both AGS cells and mouse models. Our approach of membrane remodeling has thus shown great promise as a new anti-H. pylori therapy.

Graphical Abstract
Liraglutide and not lifestyle intervention reduces soluble CD163 after comparable weight loss in obese participants with prediabetes or type 2 diabetes mellitus
Authors: Grannes Helene , Ueland Thor , Simeone Paola , Liani Rossella , Guagnano Maria Teresa , Aukrust Pål , Michelsen Annika E. , Birkeland Kåre , di Castelnuovo Augusto , Cipollone Francesco , Consoli Agostino , Halvorsen Bente , Gregersen Ida , Santilli Francesca 
Published: April 2024

Abstract
Background
The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus.

Method
Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase‐associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13).

Results
At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group.

Conclusion
Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide.
The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes
Authors: Rokicka Dominika , Hudzik Bartosz , Wróbel Marta , Stołtny Tomasz , Stołtny Dorota , Nowowiejska-Wiewióra Alicja , Rokicka Sonia , Gąsior Mariusz , Strojek Krzysztof 
Published: April 2024

Abstract
Background
Cardiovascular disease is the major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Novel markers of insulin resistance and progression of atherosclerosis include the triglycerides and glucose index (TyG index), the triglycerides and body mass index (Tyg-BMI) and the metabolic score for insulin resistance (METS-IR). Establishing independent risk factors for in-hospital death and major adverse cardiac and cerebrovascular events (MACCE) in patients with myocardial infarction (MI) remains critical. The aim of the study was to assess the risk of in-hospital death and MACCE within 12 months after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with and without T2DM based on TyG index, Tyg-BMI and METS-IR.

Methods
Retrospective analysis included 1706 patients with STEMI and NSTEMI hospitalized between 2013 and 2021. We analyzed prognostic value of TyG index, Tyg-BMI and METS-IR for in-hospital death and MACCE as its components (death from any cause, MI, stroke, revascularization) within 12 months after STEMI or NSTEMI in patients with and without T2DM.

Results
Of 1706 patients, 58 in-hospital deaths were reported (29 patients [4.3%] in the group with T2DM and 29 patients [2.8%] in the group without T2DM; p = 0.1). MACCE occurred in 18.9% of the total study population (25.8% in the group with T2DM and 14.4% in the group without T2DM; p < 0.001). TyG index, Tyg-BMI and METS-IR were significantly higher in the group of patients with T2DM compared to those without T2DM (p < 0.001). Long-term MACCE were more prevalent in patients with T2DM (p < 0.001). The area under the ROC curve (AUC-ROC) for the prediction of in-hospital death and the TyG index was 0.69 (p < 0.001). The ROC curve for predicting in-hospital death based on METS-IR was 0.682 (p < 0.001). The AUC-ROC values for MACCE prediction based on the TyG index and METS-IR were 0.582 (p < 0.001) and 0.57 (p < 0.001), respectively.

Conclusions
TyG index was an independent risk factor for in-hospital death in patients with STEMI or NSTEMI. TyG index, TyG-BMI and METS-IR were not independent risk factors for MACCE at 12 month follow-up. TyG index and METS-IR have low predictive value in predicting MACCE within 12 months after STEMI and NSTEMI.
CD8+ T cell-based cancer immunotherapy
Authors: Chen Yanxia , Yu Dingning , Qian Hui , Shi Yinghong , Tao Zhimin 
Published: April 2024

AbstractThe immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8+ T cells play a crucial role in opposing pathological threats. Various immunotherapies based on CD8+ T cells have emerged in recent decades, showing their promising results in treating intractable diseases. However, in the fight against the constantly changing and evolving cancers, the formation and function of CD8+ T cells can be challenged by tumors that might train a group of accomplices to resist the T cell killing. As cancer therapy stepped into the era of immunotherapy, understanding the physiological role of CD8+ T cells, studying the machinery of tumor immune escape, and thereby formulating different therapeutic strategies become the imperative missions for clinical and translational researchers to fulfill. After brief basics of CD8+ T cell-based biology is covered, this review delineates the mechanisms of tumor immune escape and discusses different cancer immunotherapy regimens with their own advantages and setbacks, embracing challenges and perspectives in near future.
Artificial intelligence assists identification and pathologic classification of glomerular lesions in patients with diabetic nephropathy
Authors: Lei Qunjuan , Hou Xiaoshuai , Liu Xumeng , Liang Dongmei , Fan Yun , Xu Feng , Liang Shaoshan , Liang Dandan , Yang Jing , Xie Guotong , Liu Zhihong , Zeng Caihong 
Published: April 2024

Abstract
Background
Glomerular lesions are the main injuries of diabetic nephropathy (DN) and are used as a crucial index for pathologic classification. Manual quantification of these morphologic features currently used is semi-quantitative and time-consuming. Automatically quantifying glomerular morphologic features is urgently needed.

Methods
A series of convolutional neural networks (CNN) were designed to identify and classify glomerular morphologic features in DN patients. Associations of these digital features with pathologic classification and prognosis were further analyzed.

Results
Our CNN-based model achieved a 0.928 F1-score for global glomerulosclerosis and 0.953 F1-score for Kimmelstiel-Wilson lesion, further obtained a dice of 0.870 for the mesangial area and F1-score beyond 0.839 for three glomerular intrinsic cells. As the pathologic classes increased, mesangial cell numbers and mesangial area increased, and podocyte numbers decreased (p for all < 0.001), while endothelial cell numbers remained stable (p = 0.431). Glomeruli with Kimmelstiel-Wilson lesion showed more severe podocyte deletion compared to those without (p < 0.001). Furthermore, CNN-based classifications showed moderate agreement with pathologists-based classification, the kappa value between the CNN model 3 and pathologists reached 0.624 (ranging from 0.529 to 0.688, p < 0.001). Notably, CNN-based classifications obtained equivalent performance to pathologists-based classifications on predicting baseline and long-term renal function.

Conclusion
Our CNN-based model is promising in assisting the identification and pathologic classification of glomerular lesions in DN patients.
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives
Authors: Shen Ke-Yu , Zhu Ying , Xie Sun-Zhe , Qin Lun-Xiu 
Published: April 2024

AbstractHepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs have been the major trend in this area. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective treatment for advanced HCC. However, the majority of HCC patients obtain limited benefits. Understanding the immunological rationale and exploring novel ways to improve the efficacy of immunotherapy has drawn much attention. In this review, we summarize the latest progress in this area, the ongoing clinical trials of immune-based combination therapies, as well as novel immunotherapy strategies such as chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, and bispecific antibodies.
Long-term benefits of exclusive human milk diet in small for gestational age neonates: a systematic review of the literature
Authors: Pagano Federica , Gaeta Emanuele , Morlino Francesca , Riccio Maria Teresa , Giordano Maurizio , De Bernardo Giuseppe 
Published: April 2024

AbstractEvidence about feeding practices’ consequences in small for gestational age newborns is not well established because they are less likely to initiate and continue breastfeeding than other newborns. Our aim was to study current knowledge about the benefits of exclusive human milk diet after 2 years of age in small for gestational age newborns. A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria. Pubmed and Scopus were searched for studies published from databases inception until June 2, 2023. Included articles were analysed and synthesised. Risk of bias and level of evidence assessments were performed. They were enrolled small for gestational age newborns fed by breastfeeding, breast milk or donor milk. The systematic review included 9 articles which were related to 4 health domains: neurodevelopment, cardiovascular, somatic growth and bone mineralization and atopy. Extracted data support a beneficial effect of breastfeeding on these outcomes. Better quality of evidence and longer follow-up are needed.
Italian neonatal birthweight charts derived from INeS not separated by birth order
Authors: Spada Elena , Peila Chiara , Coscia Alessandra 
Published: April 2024

Abstract
Background
Identifying high-risk neonates with abnormal fetal growth is crucial for health risk prediction and early intervention. Small for gestational age (SGA) and large for gestational age (LGA) classifications highlight neonates having a higher risk for postnatal diseases. Accurate diagnosis depends on precise anthropometric measurements and appropriate reference data. In 2010, specific neonatal charts for Italian singletons (INeS charts) were published, tracing separately for first- and later-born neonates due to a 3% birth weight difference. We present INeS charts for birth weight non-separated by first- and later-born babies useful when information on parity is unavailable or unreliable, or for better comparisons with other neonatal charts that are not separated by birth-order.

Methods
INeS charts were traced using a parametric function. Starting with the parameters estimates published in a different paper, INeS charts not separated by birth order were traced for the gestational age range of 23 to 42 weeks. In a second step the charts were parametrized as Cole and Green Lambda Mu and Sigma (LMS) model, allowing computation of standard deviation scores.

Results
The centiles of non-separated INeS charts follow between first- and later-born charts. Distances varied due to changing first-born proportions with gestational age, Max differences of about 100g with later born and 70g with first-born were observed at term. S and L functions have a similar shape for boys and girls. S function shows a pick at about 29 weeks, L function has positive values in all the range of gestational age with a pick at 39 weeks.

Conclusions
The study presents non-separated Birth Weight INeS charts, bridging the gap when parity information is unavailable. Differences with separated charts were generally small, making them reliable for neonatal health assessment. Insights from L and S parameters contribute to standardized birth weight and adjust it by sex and Gestational Age, useful for defining SGA or LGA neonates. The paper enhances neonatal care tools, showcasing INeS chart flexibility in different clinical scenarios and supporting neonatology research.
NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury
Authors: Huang Yingying , Li Xiao , Wei Lin , Ma Shinan , Ma Liming , Zan Yuxin , He Xiju , Tang Yijun , Ding Yan 
Published: April 2024

Abstract
Background
Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism.

Methods
In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe.

Results
NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5′UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2.

Conclusion
NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.
Giant intraperitoneal non-pancreatic pseudocyst: a case report
Authors: Molla Yohannis Derbew , Abraha Aklilu Yiheyis , Belay Yilkal Ademe , Alemu Bewketu Abebe , Alemu Hirut Tesfahun , Abera Samuel Addisu 
Published: April 2024

Abstract
Introduction
Non-pancreatic pseudocysts are rare lesions that typically form from the omentum and mesentery. These cysts have a thick fibrotic wall made up of fibrous tissue and may show signs of calcifications and inflammatory changes. The fluid inside them can vary, ranging from hemorrhage and pus to serous or sometimes chylous content. In most cases, these cysts appear as a result of trauma, surgery, or infection.

Case presentation
A 35-year-old male patient from Ethiopia presented with swelling in his lower abdomen that had been present for 2 years. Initially, the swelling was small but gradually increased in size. The patient experienced frequent urination but no pain or difficulty during urination, urgency, intermittent urination, or blood in the urine. The swelling was initially painless but became painful 2 months prior to his presentation. Abdominal computed tomography scans revealed a well-defined, lobulated peritoneal lesion measuring 16 × 12 × 10 cm, consisting primarily of fluid-filled cysts with a thick, enhancing wall and septa. Additionally, there was a large, heterogeneous enhancing soft tissue component measuring 8 × 6 cm. As a result, the cystic mass was surgically removed in its entirety with partial removal of the bladder wall, and the patient was discharged in an improved condition.

Conclusion
Primary non-pancreatic pseudocysts are extremely rare lesions that must be differentiated from other possible causes of cystic lesions within the peritoneal or retroperitoneal regions. Surgeons should be aware of the potential occurrence of these lesions, which may have an unknown origin.