bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment
Authors: Wu Hai-Lin , Wang Xiao-Bin , Li Jing , Zheng Bo-Wen 
Published: July 2024

Abstract
Background
Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness.

Methods
We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness.

Results
Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS.

Conclusion
The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.
Pneumonectomy following penetrating trauma with ECMO as postoperative support: case report – (Lung trauma and ECMO)
Authors: Sánchez-Ortiz Álvaro Ignacio , Peña-González Diego , García Alberto F. , Bautista-Rincón Diego Fernando , García-González Carlos Alejandro , Moreno-Angarita Alejandro , Álvarez-Ortega Astrid Carolina , Torres-España Nicolas Felipe , Cadavid-Alvear Eduardo Alberto , Velásquez-Galvis Mauricio 
Published: July 2024

Abstract
Background
Penetrating thoracic injuries have a significant risk of morbi-mortality. Despite the advancements in damage control methods, a subset of patients with severe pulmonary vascular lesions and bronchial injuries persists. In some of these cases, post-traumatic pneumonectomy is required, and perioperative extracorporeal membrane oxygenation (ECMO) support may be required due to right ventricular failure and respiratory failure.

Case description
A male was brought to the emergency department (ED) with a penetrating thoracic injury, presenting with massive right hemothorax and active bleeding that required ligation of the right pulmonary hilum to control the bleeding. Subsequently, he developed right ventricular dysfunction and ARDS, necessitating a dynamic hybrid ECMO configuration to support his condition and facilitate recovery.

Conclusions
Penetrating thoracic injuries with severe pulmonary vascular lesions may need pneumonectomy to control bleeding. ECMO support reduces the associated mortality by decreasing the complications rate. A multidisciplinary team is essential to achieve good outcomes in severe compromised patients.
Deciphering the benefits and intensity levels of primary metabolites from Allium macrostemon Bunge and Allium chinense G. Don
Authors: Qin Zifei , Li Yuan , Liu Dongmei , Hua Yuzhuo , Lv Yuandong , Zhang Xiaojian , Fan Cailian , Yang Jing 
Published: July 2024

Abstract
Background
Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G. Don (ACGD) and Allium macrostemon Bunge (AMB) are it botanical sources. The aim of this study was to explore the cardioprotective effects, and decipher the visual spatial distribution and absolute content of primary metabolites derived from these two herbs.

Methods
H9c2 cells were used to perform the hypoxia-reoxygenation (H/R)-induced myocardial injury model. Their protective effects were evaluated by apoptosis levels. Furthermore, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry imaging approach (MALDI-TOF MSI) was carried out to present the spatial location of primary metabolites including fatty acids, amino acids, carotenoids, and vitamins in these two Allium herbs. Multiple analytical methods were applied to perform quantitative analysis of these primary metabolites in AMB and ACGD bulbs by liquid chromatography tandem mass spectrometry (LC–MS).

Results
First, AMB and ACGD extracts both could increase the cell viability in H9c2 cells, and attenuate H/R-induced injury. They markedly decreased apoptosis, accompanied by activating the BCL-2/BAX pathway. Further, MALDI-TOF MSI-based relative quantification results showed several amino acids, fatty acids, carotenoids, and vitamins were largely rich in the tunics and outside scales of fresh bulbs, while some primary metabolites were abundant in their developing flower buds. Absolute quantification results displayed total contents of amino acids in ACGD bulbs were higher than those in AMB, while total contents of fatty acids and vitamins provides opposite trends in these two Allium herbs. The total contents of carotenoids and trace elements showed no significant differences between AMB and ACGD samples.

Conclusions
This study would be helpful to understand the myocardial injury protection effects of these two Allium herbs, and the spatial accumulation and quantitative content levels of their main nutrients.

Graphical Abstract
A horizontal and perpendicular interlaminar approach for intrathecal nusinersen injection in patients with spinal muscular atrophy and scoliosis: an observational study
Authors: Huang Chanyan , Zhang Yuanjia , Diedrich Daniel A. , Li Jiawen , Luo Wei , Zhao Xu , Guo Yuting , Luo Yijun , Zhang Tao , Wang Xuan , Huang Wenqi , Xiao Ying 
Published: July 2024

Abstract
Background
Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture.

Methods
Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed.

Results
Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture.

Conclusions
The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.
Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial
Authors: Capion Tenna , Lilja-Cyron Alexander , Juhler Marianne , Møller Kirsten , Sorteberg Angelika , Rønning Pål André , Poulsen Frantz Rom , Wismann Joakim , Schack Anders Emil , Ravlo Celina , Isaksen Jørgen , Lindschou Jane , Gluud Christian , Mathiesen Tiit , Olsen Markus Harboe 
Published: July 2024

Abstract
Background
Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.

Methods
DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.

Conclusion
We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.

Trial registration
ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.
Prenatal affective cognitive training to reduce the risk of postpartum depression (PACT): study protocol for a randomized controlled trial
Authors: Bjertrup Anne J. , Kofoed Jeanne , Egmose Ida , Wendelboe Katrine , Southgate Victoria , Væver Mette S. , Miskowiak Kamilla W. 
Published: July 2024

Abstract
Background
Postpartum depression (PPD) affects 30–50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD.

Methods
The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum.

Discussion
The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children.

Trial registration
ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.
The association between diet quality indices and oxidative stress biomarkers in male footballers and healthy active controls
Authors: Zare Mahsa , Shateri Zainab , Shakeri Mahboobeh , Nouri Mehran , Zare Sahar , Sarbakhsh Parvin , Eftekhari Mohammad Hassan , Gargari Bahram Pourghassem 
Published: July 2024

Abstract
Objective
The aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress.

Results
Based on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (β=-0.29; P = 0.04) and DQI-I (β=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean β=-3.53; P = 0.04) and DQI-I (mean β=-5.53; P = 0.004) with F2a-IP. The quality of the footballers’ diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.
Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus
Authors: Shetty Sanutha , Duesman Samuel J. , Patel Sanil , Huynh Pacific , Toh Pamela , Shroff Sanjana , Das Anika , Chowhan Disha , Keller Benjamin , Alvarez Johana , Fisher-Foye Rachel , Sebra Robert , Beaumont Kristin , McAlpine Cameron S. , Rajbhandari Prashant , Rajbhandari Abha K. 
Published: July 2024

Abstract
Background
Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice.

Methods
To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis.

Results
We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress.

Conclusions
Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.
Ualign: pushing the limit of template-free retrosynthesis prediction with unsupervised SMILES alignment
Authors: Zeng Kaipeng , Yang Bo , Zhao Xin , Zhang Yu , Nie Fan , Yang Xiaokang , Jin Yaohui , Xu Yanyan 
Published: July 2024

Abstract
Motivation
Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency.

Results
This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods.

Scientific contribution
We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5% (top-5) and 5.4% (top-10) increased accuracy over the strongest baseline.
Fish Iridoviridae: infection, vaccination and immune response
Authors: Leiva-Rebollo Rocío , Labella Alejandro M. , Gémez-Mata Juan , Castro Dolores , Borrego Juan J. 
Published: July 2024

AbstractEach year, due to climate change, an increasing number of new pathogens are being discovered and studied, leading to an increase in the number of known diseases affecting various fish species in different regions of the world. Viruses from the family Iridoviridae, which consist of the genera Megalocytivirus, Lymphocystivirus, and Ranavirus, cause epizootic outbreaks in farmed and wild, marine, and freshwater fish species (including ornamental fish). Diseases caused by fish viruses of the family Iridoviridae have a significant economic impact, especially in the aquaculture sector. Consequently, vaccines have been developed in recent decades, and their administration methods have improved. To date, various types of vaccines are available to control and prevent Iridoviridae infections in fish populations. Notably, two vaccines, specifically targeting Red Sea bream iridoviral disease and iridoviruses (formalin-killed vaccine and AQUAVAC® IridoV, respectively), are commercially available. In addition to exploring these themes, this review examines the immune responses in fish following viral infections or vaccination procedures. In general, the evasion mechanisms observed in iridovirus infections are characterised by a systemic absence of inflammatory responses and a reduction in the expression of genes associated with the adaptive immune response. Finally, this review also explores prophylactic procedure trends in fish vaccination strategies, focusing on future advances in the field.
Generation of musculoskeletal cells from human urine epithelium-derived presomitic mesoderm cells
Authors: Gao Huiru , Huang Xingnan , Cai Zepo , Cai Baomei , Wang Kaipeng , Li Junyang , Kuang Junqi , Wang Bo , Zhai Ziwei , Ming Jin , Cao Shangtao , Qin Yue , Pei Duanqing 
Published: July 2024

Abstract
Background
Numerous studies have shown that somite development is a necessary stage of myogenesis chondrogenesis and osteogenesis. Our previous study has established a stable presomitic mesoderm progenitor cell line (UiPSM) in vitro. Naturally, we wanted to explore whether UiPSM cell can develop bone and myogenic differentiation.

Results
Selective culture conditions yielded PAX3 and PAX7 positive skeletal muscle precursors from UiPSM cells. The skeletal muscle precursors undergo in vitro maturation resulting in myotube formation. MYOD effectively promoted the maturity of the skeletal myocytes in a short time. We found that UiPSM and MYOD mediated UiPSM cell-derived skeletal myocytes were viable after transplantation into the tibialis anterior muscle of MITRG mice, as assessed by bioluminescence imaging and scRNA-seq. Lack of teratoma formation and evidence of long-term myocytes engraftment suggests considerable potential for future therapeutic applications. Moreover, UiPSM cells can differentiate into osteoblast and chondroblast cells in vitro.

Conclusions
UiPSM differentiation has potential as a developmental model for musculoskeletal development research and treatment of musculoskeletal disorders.