bluuebunny/crossref_metadata_2025_split huggingface dataset:
2-Bromo-1,4-Naphthalenedione promotes CD8+ T cell expansion and limits Th1/Th17 to mitigate experimental autoimmune encephalomyelitis
Authors: Yang Cuixia , Ma Yuanchen , Lu Qiying , Qu Yuliang , Li Yuantao , Cheng Shimei , Xiao Chongjun , Chen Jinshuo , Wang Chuangjia , Wang Feng , Xiang Andy Peng , Huang Weijun , Tang Xiaorong , Zheng Haiqing 
Published: July 2024

AbstractTreating Multiple sclerosis (MS), a well-known immune-mediated disease characterized by axonal demyelination, is challenging due to its complex causes. Naphthalenedione, present in numerous plants, is being explored as a potential medicine for MS due to its immunomodulatory properties. However, its effects on lymphocytes can vary depending on factors such as the specific compound, concentration, and experimental conditions. In this study, we aim to explore the therapeutic potential of 2-bromo-1,4-naphthalenedione (BrQ), a derivative of naphthalenedione, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and to elucidate its underlying mechanisms. We observed that mice treated with BrQ exhibited reduced severity of EAE symptoms, including lower clinical scores, decreased leukocyte infiltration, and less extensive demyelination in central nervous system. Furthermore, it was noted that BrQ does not directly affect the remyelination process. Through cell-chat analysis based on bulk RNA-seq data, coupled with validation of flow analysis, we discovered that BrQ significantly promotes the expansion of CD8+ T cells and their interactions with other immune cells in peripheral immune system in EAE mice. Subsequent CD8+ T cell depletion experiments confirmed that BrQ alleviates EAE in a CD8+ T cell-dependent manner. Mechanistically, expanded CD8+ cells were found to selectively reduce antigen-specific CD4+ cells and subsequently inhibit Th1 and Th17 cell development in vivo, ultimately leading to relief from EAE. In summary, our findings highlight the crucial role of BrQ in modulating the pathogenesis of MS, suggesting its potential as a novel drug candidate for treating MS and other autoimmune diseases.
Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy
Authors: Wahl Devin , Risen Sydney J. , Osburn Shelby C. , Emge Tobias , Sharma Sadhana , Gilberto Vincenzo S. , Chatterjee Anushree , Nagpal Prashant , Moreno Julie A. , LaRocca Thomas J. 
Published: July 2024

AbstractNeuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. In this study, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old (aged 19 months) wildtype mice, and in rTg4510 tau pathology mice (aged 2 months). We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and rTg4510 mice. These effects of NF-κB/NLRP3-targeting Nanoligomers were also associated with reduced glial cell activation and pathology, favorable changes in transcriptome signatures of glia-associated inflammation (reduced) and neuronal health (increased), and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting both NF-κB and NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegeneration.
Influence of virtual reality and task complexity on digital health metrics assessing upper limb function
Authors: Kanzler Christoph M. , Armand Tom , Simovic Leonardo , Sylvester Ramona , Domnik Nadine , Eilfort Antonia M. , Rohner Carola , Gassert Roger , Gonzenbach Roman , Lambercy Olivier 
Published: July 2024

Abstract
Background
Technology-based assessments using 2D virtual reality (VR) environments and goal-directed instrumented tasks can deliver digital health metrics describing upper limb sensorimotor function that are expected to provide sensitive endpoints for clinical studies. Open questions remain about the influence of the VR environment and task complexity on such metrics and their clinimetric properties.

Methods
We aim to investigate the influence of VR and task complexity on the clinimetric properties of digital health metrics describing upper limb function. We relied on the Virtual Peg Insertion Test (VPIT), a haptic VR-based assessment with a virtual manipulation task. To evaluate the influence of VR and task complexity, we designed two novel tasks derived from the VPIT, the VPIT-2H (VR environment with reduced task complexity) and the PPIT (physical task with reduced task complexity). These were administered in an observational longitudinal study with 27 able-bodied participants and 31 participants with multiple sclerosis (pwMS, VPIT and PPIT only) and the value of kinematic and kinetic metrics, their clinimetric properties, and the usability of the assessment tasks were compared.

Results
Intra-participant variability strongly increased with increasing task complexity (coefficient of variation + 56%) and was higher in the VR compared to the physical environment (+ 27%). Surprisingly, this did not translate into significant differences in the metrics’ measurement error and test–retest reliability across task conditions (p > 0.05). Responsiveness to longitudinal changes in pwMS was even significantly higher (effect size + 0.35, p < 0.05) for the VR task with high task complexity compared to the physical instrumented task with low task complexity. Increased inter-participant variability might have compensated for the increased intra-participant variability to maintain good clinimetric properties. No significant influence of task condition on concurrent validity was present in pwMS. Lastly, pwMS rated the PPIT with higher usability than the VPIT (System Usability Scale + 7.5, p < 0.05).

Conclusion
The metrics of both the VR haptic- and physical task-based instrumented assessments showed adequate clinimetric properties. The VR haptic-based assessment may be superior when longitudinally assessing pwMS due to its increased responsiveness. The physical instrumented task may be advantageous for regular clinical use due to its higher usability. These findings highlight that both assessments should be further validated for their ideal use-cases.
Which government policies to create sustainable food systems have the potential to simultaneously address undernutrition, obesity and environmental sustainability?
Authors: Burgaz Celia , Van-Dam Iris , Garton Kelly , Swinburn Boyd A. , Sacks Gary , Asiki Gershim , Claro Rafael , Diouf Adama , Bartoletto Martins Ana Paula , Vandevijvere Stefanie 
Published: July 2024

Abstract
Introduction
A transformation of food systems is urgently needed, given their contribution to three ongoing and interlinked global health pandemics: (1) undernutrition and food insecurity, (2) obesity and non-communicable diseases (NCDs), and (3) climate change and biodiversity loss. As policymakers make decisions that shape food systems, this study aimed to identify and prioritise policies with double- or triple-duty potential to achieve healthier and more environmentally sustainable food systems.

Methods
This study undertook a 4-step methodological approach, including (i) a compilation of international policy recommendations, (ii) an online survey, (iii) four regional workshops with international experts and (iv) a ranking for prioritisation. Policies were identified and prioritised based on their double- or triple-duty potential, synergies and trade-offs. Using participatory and transdisciplinary approaches, policies were identified to have double- or triple-duty potential if they were deemed effective in tackling two or three of the primary outcomes of interest: (1) undernutrition, (2) obesity/NCDs and (3) environmental degradation.

Results
The desk review identified 291 recommendations for governments, which were merged and classified into 46 initially proposed policies. Based on the results from the online survey, 61% of those policies were perceived to have double- or triple-duty potential. During the workshops, 4 potential synergies and 31 trade-offs of these policies were identified. The final list of 44 proposed policies for healthier and more environmentally sustainable food systems created was divided into two main policy domains: ‘food supply chains’ and ‘food environments’. The outcome with the most trade-offs identified was ‘undernutrition’, followed by ‘environmental sustainability’, and ‘obesity/NCDs’. Of the top five expert-ranked food supply chain policies, two were perceived to have triple-duty potential: (a) incentives for crop diversification; (b) support for start-ups, and small- and medium-sized enterprises. For food environments, three of the top five ranked policies had perceived triple-duty potential: (a) affordability of healthier and more sustainable diets; (b) subsidies for healthier and more sustainable foods; (c) restrictions on children's exposure to marketing through all media.

Conclusion
This study identified and prioritised a comprehensive list of double- and triple-duty government policies for creating healthier and more environmentally sustainable food systems. As some proposed policies may have trade-offs across outcomes, they should be carefully contextualised, designed, implemented and monitored.
Association of increasing gross tumor volume dose with tumor volume reduction and local control in fractionated stereotactic radiosurgery for unresected brain metastases
Authors: Kanayama Naoyuki , Ikawa Toshiki , Takano Koji , Arita Hideyuki , Morimoto Masahiro , Hirata Takero , Ogawa Kazuhiko , Teshima Teruki , Konishi Koji 
Published: July 2024

Abstract
Background
Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis.

Methods
This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30–35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7–66 months).

Results
GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01).

Conclusions
GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required.
Injectable bone cement cannulated pedicle screw for lumbar degenerative disease in osteoporosis - clinical follow-up of over 5 years
Authors: Li Cong-can , Yang Xiu-lun , Wu Wen-wen , Zhou Rui , Jiang Yi-fan , Xiao Jun , Zhang Yu-Xuan , Song Lei , Dai Fei 
Published: July 2024

Abstract
Objective
The aim of this study is to evaluate the clinical efficacy of injectable cemented hollow pedicle screw (CICPS) in the treatment of osteoporotic lumbar degenerative diseases through a large sample long-term follow-up study. Additionally, we aim to explore the risk factors affecting interbody fusion.

Methods
A total of 98 patients who underwent CICPS for transforaminal lumbar interbody fusion (TLIF) for osteoporotic lumbar degenerative disease from March 2011 to September 2017 were analyzed. X-ray and electronic computed tomography (CT) imaging data were collected during preoperative, postoperative, and follow-up periods. The data included changes in intervertebral space height (ΔH), screw failure, cement leakage (CL), and intervertebral fusion. The patients were divided into two groups based on their fusion status one year after surgery: satisfied group A and dissatisfied group B. Surgical data such as operation time, intraoperative bleeding volume and surgical complications were recorded, and visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the improvement of lumbar and leg pain.

Results
The mean follow-up time was 101.29 months (ranging from 70 to 128 months). A total of 320 CICPS were used, with 26 screws (8.13%) leaking, 3 screws (0.94%) experiencing cement augmentation failure, and 1 screw (0.31%) becoming loose and breaking. The remaining screws were not loose or pulled out. Female gender, decreased bone density, and CL were identified as risk factors affecting interbody fusion (P < 0.05). Early realization of interbody fusion can effectively prevent the loss of intervertebral space height (P < 0.05) and maintain the surgical treatment effect. Both VAS and ODI scores showed significant improvement during the follow-up period (P < 0.05). Binary logistic regression analysis revealed that decreased bone density and cement leakage were risk factors for prolonged interbody fusion.

Conclusions
The results of long-term follow-up indicate that PMMA enhanced CICPS has unique advantages in achieving good clinical efficacy in the treatment of osteoporosis lumbar degenerative diseases. Attention should be paid to identify female gender, severe osteoporosis, and CL as risk factors affecting interbody fusion.
Biomechanical analysis of patient specific cone vs conventional stem in revision total knee arthroplasty
Authors: Piovan Gianluca , Bori Edoardo , Padalino Marika , Pianigiani Silvia , Innocenti Bernardo 
Published: July 2024

Abstract
Background
In revision total knee arthroplasty, addressing significant bone loss often involves the use of cemented or press-fit stems to ensure implant stability and long-term fixation. A possible alternative to stem was recently introduced utilizing custom-made porous metaphyseal cones, designed to reconstruct the missing tibial and femoral geometries. Early clinical and radiological assessments have shown promising results. The objective of this research was to biomechanically evaluate the performances of these custom-made cones.

Methods
The biomechanical study was conducted using a validated finite element model. The bone geometries of a patient (selected for their history of four knee revisions due to infection and periprosthetic fractures, followed by a successful treatment with custom-made 3D-printed metaphyseal cones) were employed for the study. On these bone models, different revision scenarios were simulated and examined biomechanically: (A) custom-made cementless metaphyseal cones; (B) cemented stems; (C) press-fit stems; (D) distal femoral reconstruction with press-fit stem. All the models were analyzed at 0 °and 90 °of flexion, under physiological load conditions simulating daily activities; stress distribution, average Von-Mises stresses and risk of fracture were then analyzed and compared among configurations.

Results
The use of custom-made 3D-printed cones exhibited the most favorable stress distribution in both femoral and tibial bones. Tibial bone stress was evenly distributed in custom-made cone configurations, while stress concentration was observed in distal regions for the other scenarios. Additionally, custom-made cones displayed overall homogeneity and lower stress levels, potentially contributing to limit pain. Symmetrical stress distribution was observed between the lateral and medial proximal tibia in custom-made cone models, whereas other scenarios exhibited uneven stress, particularly in the anterior tibial bone.

Conclusions
The biomechanical analysis of porous custom-made metaphyseal cones in re-revision arthroplasties is in agreement with the positive clinical and radiological outcomes. These findings provide valuable insights into the potential benefits of using custom-made cones, which offer more uniform stress distribution and may contribute to improve patient outcomes in revision TKA procedures. Further studies in this direction are warranted to validate these biomechanical findings.
Current indications and surgical strategies for myocardial revascularization in patients with left ventricular dysfunction: a scoping review
Authors: Moreno-Angarita Alejandro , Peña Diego , de León Juan David Lopez-Ponce , Estacio Mayra , Vila Lidy Paola , Muñoz Maria Isabel , Cadavid-Alvear Eduardo 
Published: July 2024

Abstract
Background
Ischemic cardiomyopathy (ICM) accounts for more than 60% of congestive heart failure cases and is associated with high morbidity and mortality rates. Myocardial revascularization in patients with left ventricular dysfunction (LVD) and a left ventricular ejection fraction (LVEF) ≤35% aims to improve survival and quality of life and reduce complications associated with heart failure and coronary artery disease. The majority of randomized clinical trials have consistently excluded those patients, resulting in evidence primarily derived from observational studies.

Main body
We performed a scoping review using the Arksey and O'Malley methodology in five stages: 1) formulating the research question; 2) locating relevant studies; 3) choosing studies; 4) organizing and extracting data; and 5) compiling, summarizing, and presenting the findings. This literature review covers primary studies and systematic reviews focusing on surgical revascularization strategies in adult patients with ischemic left ventricular dysfunction (LVD) and a left ventricular ejection fraction (LVEF) of 35% or lower. Through an extensive search of Medline and the Cochrane Library, a systematic review was conducted to address three questions regarding myocardial revascularization in these patients. These questions outline the current knowledge on this topic, current surgical strategies (off-pump vs. on-pump), and graft options (including hybrid techniques) utilized for revascularization.
Three independent reviewers (MAE, DP, and AM) applied the inclusion criteria to all the included studies, obtaining the full texts of the most relevant studies. The reviewers subsequently assessed these articles to make the final decision on their inclusion in the review. Out of the initial 385 references, 156 were chosen for a detailed review. After examining the full articles were examined, 134 were found suitable for scoping review.

Conclusion
The literature notes the scarcity of surgical revascularization in LVD patients in randomized studies, with observational data supporting coronary revascularization's benefits. ONCABG is recommended for multivessel disease in LVD with LVEF < 35%, while OPCAB is proposed for older, high-risk patients. Strategies like internal thoracic artery skeletonization harvesting and postoperative glycemic control mitigate risks with BITA in uncontrolled diabetes. Total arterial revascularization maximizes long-term survival, and hybrid revascularization offers advantages like shorter hospital stays and reduced costs for significant LAD lesions.
Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer
Authors: Cheng Weishi , Kang Kai , Zhao Ailin , Wu Yijun 
Published: July 2024

AbstractCancer immunotherapies, represented by immune checkpoint inhibitors (ICIs), have reshaped the treatment paradigm for both advanced non-small cell lung cancer and small cell lung cancer. Programmed death receptor-1/programmed death receptor ligand-1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are some of the most common and promising targets in ICIs. Compared to ICI monotherapy, which occasionally demonstrates treatment resistance and limited efficacy, the dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 operates at different stages of T cell activation with synergistically enhancing immune responses against cancer cells. This emerging dual therapy heralds a new direction for cancer immunotherapy, which, however, may increase the risk of drug-related adverse reactions while improving efficacy. Previous clinical trials have explored combination therapy strategy of anti-PD-1/PD-L1 and anti-CTLA-4 agents in lung cancer, yet its efficacy remains to be unclear with the inevitable incidence of immune-related adverse events. The recent advent of bispecific antibodies has made this sort of dual targeting more feasible, aiming to alleviate toxicity without compromising efficacy. Thus, this review highlights the role of dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in treating lung cancer, and further elucidates its pre-clinical mechanisms and current advancements in clinical trials. Besides, we also provide novel insights into the potential combinations of dual blockade therapies with other strategies to optimize the future treatment mode for lung cancer.
SLC14A1 and TGF-β signaling: a feedback loop driving EMT and colorectal cancer metachronous liver metastasis
Authors: Zhang Yixun , Yang Yumeng , Qi Xuan , Cui Peng , Kang Yi , Liu Haiyi , Wei Zhigang , Wang Haibo 
Published: July 2024

Abstract
Background
Colorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis.

Methods
We conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects.

Results
SLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-β/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TβRII and stabilized TβRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-β/Smad signaling. Furthermore, TGF-β1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1’s transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers.

Conclusions
Our findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-β/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.