bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of meningeal immunity in brain function and protection against pathogens
Authors: Rebejac Julie , Eme-Scolan Elisa , Rua Rejane 
Published: January 2024

AbstractThe brain and spinal cord collectively referred to as the Central Nervous System (CNS) are protected by the blood-brain barrier that limits molecular, microbial and immunological trafficking. However, in the last decade, many studies have emphasized the protective role of ‘border regions’ at the surface of the CNS which are highly immunologically active, in contrast with the CNS parenchyma. In the steady-state, lymphoid and myeloid cells residing in the cranial meninges can affect brain function and behavior. Upon infection, they provide a first layer of protection against microbial neuroinvasion. The maturation of border sites over time enables more effective brain protection in adults as compared to neonates. Here, we provide a comprehensive update on the meningeal immune system and its role in physiological brain function and protection against infectious agents.
Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications
Authors: Bianchi Massimiliano G. , Chiu Martina , Taurino Giuseppe , Bergamaschi Enrico , Turroni Francesca , Mancabelli Leonardo , Longhi Giulia , Ventura Marco , Bussolati Ovidio 
Published: January 2024

AbstractAmorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such as toothpastes, food additives, drug excipients, and carriers. Consolidated use and experimental evidence have consistently pointed to the very low acute toxicity and limited absorption of ASNP. However, slow absorption implies prolonged exposure of the intestinal epithelium to ASNP, with documented effects on intestinal permeability and immune gut homeostasis. These effects could explain the hepatic toxicity observed after oral administration of ASNP in animals. More recently, the role of microbiota in these and other ASNP effects has attracted increasing interest in parallel with the recognition of the role of microbiota in a variety of conditions. Although evidence for nanomaterial effects on microbiota is particularly abundant for materials endowed with bactericidal activities, a growing body of recent experimental data indicates that ASNPs also modify microbiota. The implications of these effects are recounted in this contribution, along with a discussion of the more important open issues and recommendations for future research.
Graphical Abstract
A new innovative method to measure the cost of war: future with fewer conflicts via harm reduction approaches
Authors: Jozaghi Ehsan 
Published: January 2024

Abstract
Background
The destruction of World War I (WWI) and World War II (WWII) changed the world forever. In this analysis, the economic costs of WWI and WWII are considered via a harm reduction approach to highlight the cost of war via the mortality of military personnel. The harm reduction philosophy and homeostasis of a biological cell are utilized as a pragmatic approach and analogy to give a greater context to the findings, despite the omission of civilian casualties and military disabilities.

Methods
Tangible (e.g., loss of wages, productivity, and contributions) and intangible (e.g., quality of life) costs are estimated based on the value of each military personnel derived from secondary data and a mathematical model. This is the first study to estimate the cost of war based on soldier’s mortality during the first and second World War.

Results
Based on the tangible value, the WWI and WWII cost for the military personnel was US$43.204 billion ($13 billion ≤ α ≤ $97 billion) and US$540.112 billion ($44 billion ≤ α ≤ $1 trillion). When the intangible cost is considered, it is estimated that the WWI cost was beyond US$124 trillion ($43 trillion ≤ β ≤ $160 trillion), and the WWII cost was above US$328 trillion ($115 trillion ≤ β ≤ $424 trillion). The sensitivity analyses conducted for WWI and WWII demonstrate different ranges based on tangible and intangible values.

Conclusions
In the current climate of increasing hostilities, inequalities, global warming, and an ever-changing world, economic prosperities are directly linked to peace, stability, and security. Therefore, any future decisions for military conflicts need to increasingly consider harm reduction approaches by considering the cost of life and potential disabilities for each nations’ soldiers, sailors, and pilots.
Extracellular succinate derived from ectopic milieu drives adhesion and implantation growth of ectopic endometrial stromal cells via the SUCNR1 signal in endometriosis
Authors: Tian Qi , Ruan Jingyao , Wang Yuning , Xiao Yinping , Cheng Qi , Chen Yun , Li Mingqing , Chang Kaikai , Yi Xiaofang 
Published: January 2024

Abstract
Background
As a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring.

Objective
We mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study.

Methods
In this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms.

Results
By mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis.

Conclusions
Succinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs.
The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage
Authors: Pu Min , Zhang Jing , Hong Fuyan , Wang Yan , Zhang Chengwei , Zeng Yongcheng , Fang Zhenzhen , Qi Weiwei , Yang Xia , Gao Guoquan , Zhou Ti 
Published: January 2024

AbstractBackgroundRenal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis.MethodsMale C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms.ResultsSuccinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3β/β-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells.ConclusionsThe causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3β/β-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.
Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis
Authors: Ottaiano Alessandro , Iacovino Maria Lucia , Santorsola Mariachiara , Facchini Sergio , Iervolino Domenico , Perri Francesco , Nasti Guglielmo , Quagliariello Vincenzo , Maurea Nicola , Ronchi Andrea , Facchini Bianca Arianna , Bignucolo Alessia , Berretta Massimiliano 
Published: January 2024

Abstract
Background
Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis.

Methods
Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot.

Results
Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21–1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13–1.70) for patients with lower VD levels, as indicated by fixed-effects models.

Conclusions
Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.
PITPNC1 Suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155
Authors: Liang Junxian , Liao Limin , Xie Lang , Tang WenWen , Yu Xiang , Lu Yinghao , Chen Hongzhen , Xu Juanli , Sun Lei , Wu Huanmei , Cui Chunhui , Tan Yujing 
Published: January 2024

Abstract
Background
Radioresistance is a primary factor contributing to the failure of rectal cancer treatment. Immune suppression plays a significant role in the development of radioresistance. We have investigated the potential role of phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) in regulating immune suppression associated with radioresistance.

Methods
To elucidate the mechanisms by which PITPNC1 influences radioresistance, we established HT29, SW480, and MC38 radioresistant cell lines. The relationship between radioresistance and changes in the proportion of immune cells was verified through subcutaneous tumor models and flow cytometry. Changes in the expression levels of PITPNC1, FASN, and CD155 were determined using immunohistochemistry and western blotting techniques. The interplay between these proteins was investigated using immunofluorescence co-localization and immunoprecipitation assays. Additionally, siRNA and lentivirus-mediated gene knockdown or overexpression, as well as co-culture of tumor cells with PBMCs or CD8+ T cells and establishment of stable transgenic cell lines in vivo, were employed to validate the impact of the PITPNC1/FASN/CD155 pathway on CD8+ T cell immune function.

Results
Under irradiation, the apoptosis rate and expression of apoptosis-related proteins in radioresistant colorectal cancer cell lines were significantly decreased, while the cell proliferation rate increased. In radioresistant tumor-bearing mice, the proportion of CD8+ T cells and IFN-γ production within immune cells decreased. Immunohistochemical analysis of human and animal tissue specimens resistant to radiotherapy showed a significant increase in the expression levels of PITPNC1, FASN, and CD155. Gene knockdown and rescue experiments demonstrated that PITPNC1 can regulate the expression of CD155 on the surface of tumor cells through FASN. In addition, co-culture experiments and in vivo tumor-bearing experiments have shown that silencing PITPNC1 can inhibit FASN/CD155, enhance CD8+ T cell immune function, promote colorectal cancer cell death, and ultimately reduce radioresistance in tumor-bearing models.

Conclusions
PITPNC1 regulates the expression of CD155 through FASN, inhibits CD8+ T cell immune function, and promotes radioresistance in rectal cancer.
Efficient transformation of the isolated microspores of Chinese cabbage (Brassica rapa L. ssp. pekinensis) by particle bombardment
Authors: Liu Yujia , Zhang Shujiang , Zhang Shifan , Zhang Hui , Li Guoliang , Sun Rifei , Li Fei 
Published: January 2024

Abstract
Background
The low efficiency of genetic transformation in Chinese cabbage (Brassica rapa L. ssp. pekinensis) is the key problem affecting functional verification. Particle bombardment is a widely used method along with the Agrobacterium-mediated method. As a physical means, it has almost no restrictions on the type of host and a wide range of receptor types, which largely avoids the restriction of explants. The bombardment parameters, which include the number of bombardments, the bombardment pressure, and the bombardment distance, may affect the microspores' genetic transformation efficiency.

Results
The transformation efficiency was improved using the particle bombardment method under the combination of bombardment shot times (3, 4, 5) × bombardment pressure (900, 1100, 1350 psi) × bombardment distance (3, 6, 9 cm). The average viability of microspores in the treatment group ranged from 74.76 to 88.55%, while the control group was 88.09%. When the number of shot times was 4, the number of embryos incubated in the treatment group ranged from 16 to 236 per dish, and the control group had 117 embryos per dish. When the bombardment parameters of the biolistic method were 4 shot times—1350 psi—3 cm, 4 times—1100 psi—3 cm, and 4 times—900 psi—3 cm, they had high transient expression efficiency, and the average number of transformed microspores was 21.67, 11.67, and 11.67 per dish (3.5 mL), respectively. When the bombardment parameters were 4 times, 900 psi, and 6 cm, the highest genetically transformed embryos were obtained, and the transformation efficiency reached 10.82%.

Conclusion
A new genetic transformation system with proper parameters for Chinese cabbage microspores was established using particle bombardment. This proper transformation system could provide a useful tool for the improvement of cultivar quality and the investigation of functional genes in Chinese cabbage.
Research on automatic recognition radiomics algorithm for early sacroiliac arthritis based on sacroiliac MRI imaging
Authors: Liu Wen-xi , Wu Hong , Cai Chi , Lai Qing-quan , Wang Yi , Li Yuan-zhe 
Published: January 2024

Abstract
Objective
To create an automated machine learning model using sacroiliac joint MRI imaging for early sacroiliac arthritis detection, aiming to enhance diagnostic accuracy.

Methods
We conducted a retrospective analysis involving 71 patients with early sacroiliac arthritis and 85 patients with normal sacroiliac joint MRI scans. Transverse T1WI and T2WI sequences were collected and subjected to radiomics analysis by two physicians. Patients were randomly divided into training and test groups at a 7:3 ratio. Initially, we extracted the region of interest on the sacroiliac joint surface using ITK-SNAP 3.6.0 software and extracted radiomic features. We retained features with an Intraclass Correlation Coefficient > 0.80, followed by filtering using max-relevance and min-redundancy (mRMR) and LASSO algorithms to establish an automatic identification model for sacroiliac joint surface injury. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. Model performance was assessed by accuracy, sensitivity, and specificity.

Results
We evaluated model performance, achieving an AUC of 0.943 for the SVM-T1WI training group, with accuracy, sensitivity, and specificity values of 0.878, 0.836, and 0.943, respectively. The SVM-T1WI test group exhibited an AUC of 0.875, with corresponding accuracy, sensitivity, and specificity values of 0.909, 0.929, and 0.875, respectively. For the SVM-T2WI training group, the AUC was 0.975, with accuracy, sensitivity, and specificity values of 0.933, 0.889, and 0.750. The SVM-T2WI test group produced an AUC of 0.902, with accuracy, sensitivity, and specificity values of 0.864, 0.889, and 0.800. In the SVM-bimodal training group, we achieved an AUC of 0.974, with accuracy, sensitivity, and specificity values of 0.921, 0.889, and 0.971, respectively. The SVM-bimodal test group exhibited an AUC of 0.964, with accuracy, sensitivity, and specificity values of 0.955, 1.000, and 0.875, respectively.

Conclusion
The radiomics-based detection model demonstrates excellent automatic identification performance for early sacroiliitis.
A shock to the (health) system: experiences of adults with rare disorders during the first COVID-19 wave
Authors: Bogart Kathleen R. , Hartinger Annelise , Klaus Maggie , Jenkinson Elizabeth 
Published: January 2024

Abstract
Background
Before COVID-19, people with rare diseases (RD) experienced numerous disparities in quality of life and healthcare access and quality, yet little is known about the experiences of this underserved group during the pandemic.

Results
During the first wave of the COVID-19 pandemic in the United States, spring and summer of 2020, 759 participants representing 231 unique RDs responded to open-ended questions about the impact of the pandemic on life with a RD, healthcare access, and coping. Qualitative conventional content analysis was used to analyze responses. Identified themes represented positive and negative dimensions of change, including a shock to the (health) system, coping with uncertainty, and the value of social support while isolated.

Conclusions
Limitations in healthcare access and quality were the most frequently described as impacts of COVID-19. Other major negative impacts included exacerbation of symptoms, psychological distress, and a lack of usual social support and reliable information. However, participants also noted silver linings, especially in healthcare. For some, expanded telehealth enhanced their ability to access medical and mental health providers and RD specialists. Finally, many participants hoped that, by highlighting social and health inequities faced by people with RDs and other minorities, the pandemic would prompt greater understanding and policies that could improve the quality of life of the RD community.
Clinical features and outcomes of orthopaedic injuries after the kahramanmaraş earthquake: a retrospective study from a hospital located in the affected region
Authors: Gök Murat , Melik Mehmet Ali 
Published: January 2024

Abstract
Background
The purpose of this retrospective, single-institutional study was to report the clinical features and outcomes of orthopaedic injuries after the Kahramanmaraş earthquake.

Methods
An institutional database review was conducted to evaluate the results of patients who applied to our hospital’s emergency department after the Kahramanmaraş earthquake. Trauma patients referred to orthopaedics and traumatology were identified. Patient records were checked for injury type, fracture site, treatment type (conservative or surgical), surgical technique, and outcome. Diagnosis with crush syndrome and the need for haemodialysis were also noted. Bedside fasciotomy was undertaken based on the urgency of the patient’s condition, number of patients and the availability of the operating theatre. A team consisting of a trauma surgeon, a plastic surgeon, a board-certified physician in infectious disease, a reanimation specialist, a general surgeon and a nephrologist followed up with the patients.

Results
Within the first 7 days following the earthquake, 265 patients were admitted to the emergency department, and 112 (42.2%) of them were referred to orthopaedics and traumatology. There were 32 (28.5%) patients diagnosed with acute compartment syndrome. Fasciotomy was performed on 43 extremities of 32 patients. Of these extremities, 5 (11.6%) were upper and 38 (88.4%) were lower extremities.The surgeries of 16 (50%) of the patients who underwent fasciotomy were performed in the emergency department. There was no significant difference in terms of complications and outcomes between performing the fasciotomy at the bedside or in the operating theatre (p = 0.456).

Conclusions
Fasciotomy appears to be a crucial surgical procedure for the care of earthquake causalities. Fasciotomy can be safely performed as a bedside procedure based on the urgency of the patient’s condition as well as the availability of the operating theatre.
deMULTIplex2: robust sample demultiplexing for scRNA-seq
Authors: Zhu Qin , Conrad Daniel N. , Gartner Zev J. 
Published: January 2024

AbstractSample multiplexing enables pooled analysis during single-cell RNA sequencing workflows, thereby increasing throughput and reducing batch effects. A challenge for all multiplexing techniques is to link sample-specific barcodes with cell-specific barcodes, then demultiplex sample identity post-sequencing. However, existing demultiplexing tools fail under many real-world conditions where barcode cross-contamination is an issue. We therefore developed deMULTIplex2, an algorithm inspired by a mechanistic model of barcode cross-contamination. deMULTIplex2 employs generalized linear models and expectation–maximization to probabilistically determine the sample identity of each cell. Benchmarking reveals superior performance across various experimental conditions, particularly on large or noisy datasets with unbalanced sample compositions.