bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway
Authors: Anuradha Rachakatla , Srinivas M. , Satyavani M. , Suresh K. , Muralidhar MN. , Rajender Rao Kalashikam 
Published: June 2024

Abstract
Background
Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.

Methods
High-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent’s reproductive function was assessed by sperm parameters and their DNMT’s mRNA expression levels were also examined. The offspring’s metabolic function was assessed by physiological, biochemical and molecular parameters.

Results
The HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.

Conclusion
The findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.
Associations of lipids and lipid-modifying drug target genes with atrial fibrillation risk based on genomic data
Authors: Tao Yuhang , Wang Yuxing , Yin Yongkun , Zhang Kai , Gong Yingchao , Ying Hangying , Jiang Ruhong 
Published: June 2024

Abstract
Background
The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence.

Methods
Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease.

Results
In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations.

Conclusions
This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.
Mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nanoplatform for promoting bone regeneration
Authors: Qin Danlei , Zhao Yifan , Cheng Rui , Liu Yingyu , Guo Susu , Sun Lingxiang , Guo Yanqin , Hao Fengxiang , Zhao Bin 
Published: June 2024

AbstractSimultaneously modulating the inflammatory microenvironment and promoting local bone regeneration is one of the main challenges in treating bone defects. In recent years, osteoimmunology has revealed that the immune system plays an essential regulatory role in bone regeneration and that macrophages are critical components. In this work, a mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nano platform (Gold/hydroxyapatite nanocomposites functionalized with polydopamine - PDA@Au-HA) is developed to accelerate bone tissues regeneration by regulating the immune microenvironment. PDA coating endows nanomaterials with the ability to scavenge reactive oxygen species (ROS) and anti-inflammatory properties, and it also exhibits an immunomodulatory ability to inhibit M1 macrophage polarization and activate M2 macrophage secretion of osteogenesis-related cytokines. Most importantly, this nano platform promotes the polarization of M2 macrophages and regulates the crosstalk between macrophages and pre-osteoblast cells to achieve bone regeneration. Au-HA can synergistically promote vascularized bone regeneration through sustained release of Ca and P particles and gold nanoparticles (NPs). This nano platform has a synergistic effect of good compatibility, scavenging of ROS, and anti-inflammatory and immunomodulatory capability to accelerate the bone repair process. Thus, our research offers a possible therapeutic approach by exploring PDA@Au-HA nanocomposites as a bifunctional platform for tissue regeneration.
Automatic analysis of nuclear features reveals a non-tumoral predictor of tumor grade in bladder cancer
Authors: Fahoum Ibrahim , Tsuriel Shlomo , Rattner Daniel , Greenberg Ariel , Zubkov Asia , Naamneh Rabab , Greenberg Orli , Zemser-Werner Valentina , Gitstein Gilad , Hagege Rami , Hershkovitz Dov 
Published: June 2024

Abstract
Background & objectives
Tumor grade determines prognosis in urothelial carcinoma. The classification of low and high grade is based on nuclear morphological features that include nuclear size, hyperchromasia and pleomorphism. These features are subjectively assessed by the pathologists and are not numerically measured, which leads to high rates of interobserver variability. The purpose of this study is to assess the value of a computer-based image analysis tool for identifying predictors of tumor grade in bladder cancer.

Methods
Four hundred images of urothelial tumors were graded by five pathologists and two expert genitourinary pathologists using a scale of 1 (lowest grade) to 5 (highest grade). A computer algorithm was used to automatically segment the nuclei and to provide morphometric parameters for each nucleus, which were used to establish the grading algorithm. Grading algorithm was compared to pathologists’ agreement.

Results
Comparison of the grading scores of the five pathologists with the expert genitourinary pathologists score showed agreement rates between 88.5% and 97.5%.The agreement rate between the two expert genitourinary pathologists was 99.5%. The quantified algorithm based conventional parameters that determine the grade (nuclear size, pleomorphism and hyperchromasia) showed > 85% agreement with the expert genitourinary pathologists. Surprisingly, the parameter that was most associated with tumor grade was the 10th percentile of the nuclear area, and high grade was associated with lower 10th percentile nuclei, caused by the presence of more inflammatory cells in the high-grade tumors.

Conclusion
Quantitative nuclear features could be applied to determine urothelial carcinoma grade and explore new biologically explainable parameters with better correlation to grade than those currently used.
125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy
Authors: Di Xuemin , Gao Zhen , Yu Huimin , Liu Xiaoli , Zhao Jinxin , Wang Juan , Zhang Hongtao 
Published: June 2024

Abstract
Objective
To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors.

Methods
Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80–120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values.

Results
The median follow-up was 48.52 months (range, 4–86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy.

Conclusions
The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.
Compliance of volunteers in a fully-enclosed patient rotation system for MR-guided radiation therapy: a prospective study
Authors: Beyer Cedric , Paul Katharina Maria , Dorsch Stefan , Echner Gernot , Dinkel Fabian , Welzel Thomas , Seidensaal Katharina , Hörner-Rieber Juliane , Jäkel Oliver , Debus Jürgen , Klüter Sebastian 
Published: June 2024

Abstract
Background
Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study.

Methods
A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated.

Results
Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants.

Conclusion
Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.
Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing
Authors: Yu Chao , Chen Binbin , Su Hui , Yang Yiqun 
Published: June 2024

Abstract
Background
Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated.

Methods
90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis.

Results
Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation.

Conclusions
LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.
HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer
Authors: Li Xiao , Zheng Zhen , Zhou Wanzhen , Huang Huixian , Zhou Yang , Xu Qinyang , Zhu Xiaolu , Teng Yincheng 
Published: June 2024

AbstractOvarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.
Trastuzumab-functionalized bionic pyrotinib liposomes for targeted therapy of HER2-positive breast cancer
Authors: Du Jiaqun , Liu Xiaobang , Sun Junpeng , Wu Qian , Hu Yu , Shi Huan , Zheng Li , Liu Ying , Wu Chao , Gao Yu 
Published: June 2024

AbstractIn this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.
A review of applications and limitations of using aquatic macroinvertebrate predators for biocontrol of the African malaria mosquito, Anopheles gambiae sensu lato
Authors: Onen Hudson , Kaddumukasa Martha A. , Kayondo Jonathan K. , Akol Anne M. , Tripet Frédéric 
Published: June 2024

AbstractMacroinvertebrate predators such as backswimmers (Heteroptera: Notonectidae), dragonflies (Odonata: Aeshnidae), and predatory diving beetles (Coleoptera: Dytiscidae) naturally inhabit aquatic ecosystems. Some aquatic ecosystems inhabited by these macroinvertebrate predator taxa equally form malaria vector larval habitats. The presence of these predators in malaria vector larval habitats can negatively impact on development, adult body size, fecundity, and longevity of the malaria vectors, which form important determinants of their fitness and future vectorial capacity. These potential negative impacts caused by aquatic macroinvertebrate predators on malaria vectors warrant their consideration as biocontrol agents in an integrated program to combat malaria. However, the use of these macroinvertebrate predators in malaria biocontrol is currently constrained by technical bottlenecks linked to their generalist predatory tendencies and often long life cycles, demanding complex rearing systems. We reviewed the literature on the use of aquatic macroinvertebrate predators for biocontrol of malaria vectors from the An. gambiae s.l. complex. The available information from laboratory and semi-field studies has shown that aquatic macroinvertebrates have the potential to consume large numbers of mosquito larvae and could thus offer an additional approaches in integrated malaria vector management strategies. The growing number of semi-field structures available in East and West Africa provides an opportunity to conduct ecological experimental studies to reconsider the potential of using aquatic macroinvertebrate predators as a biocontrol tool. To achieve a more sustainable approach to controlling malaria vector populations, additional, non-chemical interventions could provide a more sustainable approach, in comparison with the failing chemical control tools, and should be urgently considered for integration with the current mosquito vector control campaigns.
Graphical Abstract
Basing intubation of acutely hypoxemic patients on physiologic principles
Authors: Laghi Franco , Shaikh Hameeda , Caccani Nicola 
Published: June 2024

AbstractThe decision to intubate a patient with acute hypoxemic respiratory failure who is not in apparent respiratory distress is one of the most difficult clinical decisions faced by intensivists. A conservative approach exposes patients to the dangers of hypoxemia, while a liberal approach exposes them to the dangers of inserting an endotracheal tube and invasive mechanical ventilation. To assist intensivists in this decision, investigators have used various thresholds of peripheral or arterial oxygen saturation, partial pressure of oxygen, partial pressure of oxygen-to-fraction of inspired oxygen ratio, and arterial oxygen content. In this review we will discuss how each of these oxygenation indices provides inaccurate information about the volume of oxygen transported in the arterial blood (convective oxygen delivery) or the pressure gradient driving oxygen from the capillaries to the cells (diffusive oxygen delivery). The decision to intubate hypoxemic patients is further complicated by our nescience of the critical point below which global and cerebral oxygen supply become delivery-dependent in the individual patient. Accordingly, intubation requires a nuanced understanding of oxygenation indexes. In this review, we will also discuss our approach to intubation based on clinical observations and physiologic principles. Specifically, we consider intubation when hypoxemic patients, who are neither in apparent respiratory distress nor in shock, become cognitively impaired suggesting emergent cerebral hypoxia. When deciding to intubate, we also consider additional factors including estimates of cardiac function, peripheral perfusion, arterial oxygen content and its determinants. It is not possible, however, to pick an oxygenation breakpoint below which the benefits of mechanical ventilation decidedly outweigh its hazards. It is futile to imagine that decision making about instituting mechanical ventilation in an individual patient can be condensed into an algorithm with absolute numbers at each nodal point. In sum, an algorithm cannot replace the presence of a physician well skilled in the art of clinical evaluation who has a deep understanding of pathophysiologic principles.