bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of neurotrophic tyrosine receptor kinase can promote pan-cancer immunity and the efficacy of immunotherapy
Authors: Wang Congren , Li Yingying , Huang Jinyuan , Yan Huimeng , Zhao Bin 
Published: April 2024

AbstractThe Neurotrophic tyrosine receptor kinase (NTRK) family plays important roles in tumor progression and is involved in tumor immunogenicity. Here, we conducted a comprehensive bioinformatic and clinical analysis to investigate the characteristics of NTRK mutations and their association with the outcomes in pan-cancer immunotherapy. In 3888 patients across 12 cancer types, patients with NTRK-mutant tumors showed more benefit from immunotherapy in terms of objective response rate (ORR; 41.7% vs. 27.5%; P < 0.001), progress-free survival (PFS; HR = 0.80; 95% CI, 0.68–0.96; P = 0.01), and overall survival (OS; HR = 0.71; 95% CI, 0.61–0.82; P < 0.001). We further constructed and validated a nomogram to estimate survival probabilities after the initiation of immunotherapy. Multi-omics analysis on intrinsic and extrinsic immune landscapes indicated that NTRK mutation was associated with enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, NTRK mutation may promote cancer immunity and indicate favorable outcomes in immunotherapy. Our results have implications for treatment decision-making and developing immunotherapy for personalized care.
Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?
Authors: Lingwood Clifford 
Published: April 2024

AbstractDisturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central in many transmembrane signaling pathways (including mTOR) and changes in raft cholesterol content affect their order function. Cholesterol levels are controlled by several mechanisms, including endoplasmic reticulum associated degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase cholesterol via temporary ERAD blockade using a benign bacterial toxin-derived competitor for the ERAD translocon is suggested.A new lock and key model for cholesterol/lipid raft dependent signaling is proposed in which the rafts provide both the afferent and efferent ‘tumblers’ across the membrane to allow ‘lock and key’ receptor transmembrane signals.
Polar lipids modify Alzheimer’s Disease pathology by reducing astrocyte pro-inflammatory signaling through platelet-activating factor receptor (PTAFR) modulation
Authors: Hans Sakshi , Stanton Janelle E. , Sauer Ann Katrin , Shiels Katie , Saha Sushanta Kumar , Lordan Ronan , Tsoupras Alexandros , Zabetakis Ioannis , Grabrucker Andreas M. 
Published: April 2024

Abstract
Background
Pro-inflammatory processes triggered by the accumulation of extracellular amyloid beta (Aβ) peptides are a well-described pathology in Alzheimer's disease (AD). Activated astrocytes surrounding Aβ plaques contribute to inflammation by secreting proinflammatory factors. While astrocytes may phagocytize Aβ and contribute to Aβ clearance, reactive astrocytes may also increase Aβ production. Therefore, identifying factors that can attenuate astrocyte activation and neuroinflammation and how these factors influence pro-inflammatory pathways is important for developing therapeutic and preventive strategies in AD. Here, we identify the platelet-activating factor receptor (PTAFR) pathway as a key mediator of astrocyte activation. Intriguingly, several polar lipids (PLs) have exhibited anti-inflammatory protective properties outside the central nervous system through their inhibitory effect on the PTAFR pathway. Thus, we additionally investigated whether different PLs also exert inhibitory effects on the PAF pathway in astrocytes and whether their presence influences astrocytic pro-inflammatory signaling and known AD pathologies in vitro.

Methods
PLs from salmon and yogurt were extracted using novel food-grade techniques and their fatty acid profile was determined using LC/MS. The effect of PLs on parameters such as astrocyte activation and generation of oxygen species (ROS) was assessed. Additionally, effects of the secretome of astrocytes treated with these polar lipids on aged neurons was measured.

Results
We show that PLs obtained from salmon and yogurt lower astrocyte activation, the generation of reactive oxygen species (ROS), and extracellular Aβ accumulation. Cell health of neurons exposed to the secretome of astrocytes treated with salmon-derived PLs and Aβ was less affected than those treated with astrocytes exposed to Aβ only.

Conclusion
Our results highlight a novel underlying mechanism, why consuming PL-rich foods such as fish and dairy may reduce the risk of developing dementia and associated disorders.
Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics
Authors: Sharifi Majid , Kamalabadi-Farahani Mohammad , Salehi Majid , Ebrahimi-Barough Somayeh , Alizadeh Morteza 
Published: April 2024

AbstractSeveral studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches.
Graphical Abstract
An unusual case of primary splenic soft part alveolar sarcoma: case report and review of the literature with emphasis on the spectrum of TFE3-associated neoplasms
Authors: Guérin René , Menard Anne-Lise , Angot Emilie , Piton Nicolas , Vera Pierre , Schwarz Lilian , Sabourin Jean-Christophe , Laé Marick , Thiébaut Pierre-Alain 
Published: April 2024

Abstract
Background
Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis.

Case presentation
In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis.

Conclusion
We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.
Outcomes of surgical treatment of patellar instability in children with Down syndrome
Authors: Zein Assem , Hassan Alaa Zenhom Mahmoud , Soliman Amr Mohamed , Mohamed Mohamed Mohamed Azmy 
Published: April 2024

Abstract
Background
patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed).

Materials and methods
This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score.

Results
The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39–56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31–74), and at final follow-up, it was 92.2 ± 4.4 (range: (88–98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39–62), and at final follow-up it was 92.4 ± 5.3 (range: 82–96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury.

Conclusions
Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved.

Level of evidence
IV; retrospective case series.
Del nido cardioplegia in adults: a retrospective observational study in comparison to modified St. Thomas cardioplegia in cardiac surgery
Authors: Garg Sanjeeve Kumar , Rawat Rajinder Singh , Saad Dina Afifi , Omar Ihab 
Published: April 2024

Abstract
Background
St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido’s cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido’s in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido’s to modified St. Thomas cardioplegia in adults.

Methods
This study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study.

Results
There was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido’s group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido’s group.

Conclusion
This study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido’s in adults.
Giant unruptured sinus of Valsalva aneurysms causing angina pectoris
Authors: Hu Peng , Wan Zhedong , Sun Qianhui , Teng Peng , Ma Liang 
Published: April 2024

Abstract
Background
Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia.

Case presentation
We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved.

Conclusions
Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.
Enhanced recovery after surgery program focusing on chest tube management improves surgical recovery after video-assisted thoracoscopic surgery
Authors: Yang Dan , Zheng Xi 
Published: April 2024

Abstract
Objective
Chest drainage is a standard procedure in thoracoscopic surgery for lung cancer. However, chest tube placement may deteriorate the ventilation capacity and increase difficulty of postoperative management of patients. The study investigated on the effects of enhanced recovery after surgery (ERAS) program focusing on chest tube management on surgical recovery of lung cancer patients.

Methods
The study population consisted of 60 patients undergoing video-assisted thoracoscopic surgery (VATS) after implementation of ERAS program and another group of 60 patients undergoing VATS before implementation of ERAS program.

Results
The mean time of first food intake was 12.9 h required for the ERAS group, which was significantly shorter than 18.4 h required for the control group (p < 0.0001). The mean time of out-of-bed activity was 14.2 h taken for the ERAS group, which was notably shorter than 22.8 h taken for the control group (p < 0.0001). The duration of chest tube placement was 68.6 h in the ERAS group, which was remarkably shorter than 92.8 h in the control group (p < 0.0001). The rate overall postoperative complications were notably lower in the ERAS group than in the control group (p = 0.018). The visual analogue score (VAS) scores on the second postoperative day exhibited significant differences between the ERAS group and the control group (p = 0.017). The patients in the ERAS group had a shorter hospitalization stay than those in the control group (p < 0.0001).

Conclusion
The study suggests the ERAS program focusing on chest tube management could improve surgical recovery, remove patient chest tube earlier, and relieve patient pain after VATS.
A case of pulmonary visceral subpleural hematoma treated by hematoma evacuation during care of post-cardiopulmonary resuscitation
Authors: Funaki Yutaka , Hirai Kyoji 
Published: April 2024

Abstract
Background
The occurrence of pulmonary visceral subpleural hematoma during care of post-cardiopulmonary resuscitation including chest compressions and anticoagulant and antiplatelet therapies is extremely rare. Also, there are few reports of treatment of visceral subpleural hematoma, most of which are treated by lung resection. Here we describe a rare case that pulmonary visceral subpleural hematoma arose during post-cardiopulmonary resuscitation care and was treated by hematoma evacuation.

Case presentation
A 58-year-old male with no smoking history and, past medical histories of rheumatoid arthritis, chronic atrial fibrillation, hypertension, diabetes, and dyslipidemia developed ventricular fibrillation due to myocardial infarction and fainted. He received bystander cardiopulmonary resuscitation and defibrillation by the ambulance crew and had return of spontaneous circulation. After transfer to our hospital, the patient underwent percutaneous catheter intervention and stenting with a diagnosis of myocardial infarction, followed by anticoagulant and antiplatelet therapies. On the 8th hospital day, chest radiography suggested right lower lobe pneumonia, and subsequent chest computed tomography revealed pulmonary hematoma in the visceral subpleural area from S6 to S10. Since no improvement was observed in hypoxemia, treatment was considered necessary. First, an attempt at computed tomography-guided drainage of hematoma was made, but insertion of the Pig-tail catheter was difficult due to hardness of the hematoma. Next, evacuation of hematoma was performed on the 13th hospital day. The hematoma was located in the visceral subpleural area and was removed by incising the pleura. TachoSil Tissue Sealing sheet and Polyglycoal acid sheet were applied to the sites of air leakage and oozing after hematoma evacuation. No re-bleeding or air leakage was observed after the treatment, and the patient was discharged on the 26th hospital day after an uneventful course.

Conclusions
Pulmonary visceral subpleural hematoma may occur during post-cardiopulmonary resuscitation care, including chest compressions and anticoagulant and antiplatelet therapies. In our case, CT-guided puncture and drainage was difficult and surgical treatment by incision of the visceral pleura and hematoma evacuation alone was done successfully.
Feasibility and applicability of self-sampling based online cervical cancer screening: findings from the China online cervical cancer screening trial
Authors: Zhang Yi , Du Hui , Wang Chun , Huang Xia , Qu Xinfeng , Wu Ruifang 
Published: April 2024

Abstract
Objective
This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method.

Methods
A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach.

Results
A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30–59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30–34 and 45–49 age groups (p < 0.05), while no significant differences were found among other age groups. 99.7% of the samples were tested qualified, and there was no significant difference in sampling failure rate among age groups. Analysis of demographic and social elements showed no significant impact on the rates of sample provision among groups in most of the social elements but the medical insurance and the monthly family-incomes.

Conclusion
The findings demonstrate that online cervical cancer screening is reliable for self-registration, self-sampling, and self-ordering for specimen transportation. It is suitable for women of all ages needing to be screened, irrespective of social elements, and effectively facilitates screening for women with limited access to medical resources. Therefore, online screening holds promise as an effective approach to increase screening coverage.
Kidney and urogenital abnormalities in Down syndrome: a meta-analysis
Authors: Rossetti Caterina Maria , Simonetti Giacomo D. , Bianchetti Mario G. , Lava Sebastiano A. G. , Treglia Giorgio , Agostoni Carlo , Milani Gregorio P. , de Winter J. Peter 
Published: April 2024

Abstract
Background
Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.

Methods
A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used.

Results
Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78–16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15–7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome.

Conclusions
This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.
Echinococcus granulosus ubiquitin-conjugating enzymes (E2D2 and E2N) promote the formation of liver fibrosis in TGFβ1-induced LX-2 cells
Authors: Du Xiaodi , Hua Ruiqi , He Xue , Hou Wei , Li Shengqiong , Yang Aiguo , Yang Guangyou 
Published: April 2024

Abstract
Background
Cystic echinococcosis (CE) is a widespread zoonosis caused by the infection with Echinococcus granulosus sensu lato (E. granulosus s.l.). CE cysts mainly develop in the liver of intermediate hosts, characterized by the fibrotic tissue that separates host organ from parasite. However, precise mechanism underlying the formation of fibrotic tissue in CE remains unclear.

Methods
To investigate the potential impact of ubiquitin-conjugating enzymes on liver fibrosis formation in CE, two members of ubiquitin-conjugating (UBC) enzyme of Echinococcus granulosus (EgE2D2 and EgE2N) were recombinantly expressed in Escherichia coli and analyzed for bioinformatics, immunogenicity, localization, and enzyme activity. In addition, the secretory pathway and their effects on the formation of liver fibrosis were also explored.

Results
Both rEgE2D2 and rEgE2N possess intact UBC domains and active sites, exhibiting classical ubiquitin binding activity and strong immunoreactivity. Additionally, EgE2D2 and EgE2N were widely distributed in protoscoleces and germinal layer, with differences observed in their distribution in 25-day strobilated worms. Further, these two enzymes were secreted to the hydatid fluid and CE-infected sheep liver tissues via a non-classical secretory pathway. Notably, TGFβ1-induced LX-2 cells exposed to rEgE2D2 and rEgE2N resulted in increasing expression of fibrosis-related genes, enhancing cell proliferation, and facilitating cell migration.

Conclusions
Our findings suggest that EgE2D2 and EgE2N could secrete into the liver and may interact with hepatic stellate cells, thereby promoting the formation of liver fibrosis.

Graphical Abstract