bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key biomarkers in RF-negative polyarticular and oligoarticular juvenile idiopathic arthritis by bioinformatic analysis
Authors: Liu Yun , Tang Xuemei 
Published: November 2023

Abstract
Objective
Juvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial morbidity such as restricted joint function, which can lead to challenges in employment and independence. This study aims to identify diagnostic biomarkers and investigate the role of immune cells in the pathogenesis of rheumatoid factor-negative polyarticular juvenile idiopathic arthritis (RF-negative pJIA) and oligoarticular juvenile idiopathic arthritis (oJIA).

Methods
We retrieved a JIA dataset from the GEO database and conducted an analysis of differentially expressed genes (DEGs). Subsequently, functional enrichment analysis was performed on the DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Additionally, we constructed a protein‒protein interaction network to identify hub genes that serve as signature genes. Furthermore, we employed CIBERSORT to classify immune cell infiltration.

Results
From the GSE20307 dataset, we identified a total of 1438 DEGs in RF-negative pJIA and 688 DEGs in oJIA. WGCNA clustered the data into 6 modules in pJIA and 4 modules in oJIA. Notably, the ME5 and ME2 modules exhibited significant associations with pJIA and oJIA, respectively. In both pJIA and oJIA, we identified six hub genes, four of which demonstrated high diagnostic sensitivity and specificity in pJIA, while five showed high diagnostic sensitivity and specificity in oJIA. CIBERSORT analysis suggested the potential involvement of these signature genes in immune cell infiltration.

Conclusion
In this study, we identified JUN, CXCL8, SOCS3, and KRAS as biomarkers for RF-negative pJIA and JUN, CXCL8, SOCS3, PTGS2, and NFKBIA as biomarkers for oJIA. Furthermore, our findings suggest that Tfh cells may play a role in the early onset of both RF-negative pJIA and oJIA.
Chronic limping in childhood, what else other than juvenile idiopathic arthritis: a case series
Authors: Tumminelli Cristina , Pastore Serena , Taddio Andrea 
Published: November 2023

Abstract
Background
Limping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician.

Case presentation
We describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease.

Conclusions
although trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture.
Toll-like receptor 4 (TLR4): new insight immune and aging
Authors: Kim Hyo-Jin , Kim Hyemin , Lee Jeong-Hyung , Hwangbo Cheol 
Published: November 2023

AbstractTLR4, a transmembrane receptor, plays a central role in the innate immune response. TLR4 not only engages with exogenous ligands at the cellular membrane’s surface but also interacts with intracellular ligands, initiating intricate intracellular signaling cascades. Through MyD88, an adaptor protein, TLR4 activates transcription factors NF-κB and AP-1, thereby facilitating the upregulation of pro-inflammatory cytokines. Another adapter protein linked to TLR4, known as TRIF, autonomously propagates signaling pathways, resulting in heightened interferon expression. Recently, TLR4 has garnered attention as a significant factor in the regulation of symptoms in aging-related disorders. The persistent inflammatory response triggered by TLR4 contributes to the onset and exacerbation of these disorders. In addition, alterations in TLR4 expression levels play a pivotal role in modifying the manifestations of age-related diseases. In this review, we aim to consolidate the impact of TLR4 on cellular senescence and aging-related ailments, highlighting the potential of TLR4 as a novel therapeutic target that extends beyond immune responses.
Leaving no one behind: successful ageing at the intersection of ageism and ableism
Authors: Langmann Elisabeth , Weßel Merle 
Published: November 2023

Abstract
Background
The concept of ‘successful ageing’ has been a prominent focus within the field of gerontology for several decades. However, despite the widespread attention paid to this concept, its intersectional implications have not been fully explored yet. This paper aims to address this gap by analyzing the potential ageist and ableist biases in the discourse of successful ageing through an intersectional lens.

Method
A critical feminist perspective is taken to examine the sensitivity of the discourse of successful ageing to diversity in societies. The paper analyzes how ageist and ableist biases can manifest in the ways we conceptualize ageing, drawing on examples in the context of mental health.

Results
We argue that the conventional approach to successful ageing is limited in its ability to account for the experiences of people who have faced intersectional discrimination throughout their lives. Drawing on examples in the context of mental health, we explore among others the link between depression and disabilities. Furthermore, we shed light on the negative impact of ageist and ableist attitudes concerning the diagnosis and treatment of dementia.

Discussion
We demonstrate how diversity is often overlooked in discussions of ageing well, and how ageist and ableist biases can manifest in the ways we conceptualize ageing. We argue that focusing solely on the health status as a means of achieving success fails to adequately counter ageism for all people. We further emphasize the role of structural factors, such as ageist attitudes, in shaping the experience of ageing and exacerbating health inequalities.

Conclusion
Overall, our findings emphasize the need for a more nuanced and inclusive understanding of ageing and therefore an intersectional approach to conceptions of ageing well that recognizes and addresses the biases and limitations of current discourses. Thereby, this paper offers valuable insights into the complex intersections between age and disabilities from a bioethical perspective, highlighting the need for a more inclusive and intersectional approach to ageing.
Changes in the small noncoding RNA transcriptome in osteosarcoma cells
Authors: Wang Hui , Cai Guiquan , Yu Fengbin , Li De , Wang Chenglong , Ma Ding , Han Xiuguo , Chen Jiajia , Wang Chuandong , He Jiye 
Published: November 2023

Abstract
Background
Osteosarcoma has the highest incidence among bone malignant tumors and mainly occurs in adolescents and the elderly, but the pathological mechanism is still unclear, which makes early diagnosis and treatment very difficult. Bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the sources of osteosarcoma cells. Therefore, a full understanding of the gene expression differences between BMSCs and osteosarcoma cells is very important to explore the pathogenesis of osteosarcoma and facilitate the early diagnosis and treatment of osteosarcoma. Small noncoding RNAs (sncRNAs) are a class of RNAs that do not encode proteins but directly play biological functions at the RNA level. SncRNAs mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), repeat RNAs and microRNAs (miRNAs).

Methods
In this study, we compared the expression of sncRNAs in BMSCs and osteosarcoma cells by high-throughput sequencing and qPCR and looked for differentially expressed sncRNAs. CCK-8, clone formation and transwell assay were used to detect the effect of sncRNA in MG63 cells.

Results
We found that 66 piRNAs were significantly upregulated and 70 piRNAs were significantly downregulated in MG63 cells. As for snoRNAs, 71 snoRNAs were significantly upregulated and 117 snoRNAs were significantly downregulated in MG63 cells. As for snRNAs, 35 snRNAs were significantly upregulated and 17 snRNAs were significantly downregulated in MG63 cells. As for repeat RNAs, 6 repeat RNAs were significantly upregulated and 7 repeat RNAs were significantly downregulated in MG63 cells. As for miRNAs, 326 miRNAs were significantly upregulated and 281 miRNAs were significantly downregulated in MG63 cells. Overexpression of piRNA DQ596225, snoRNA ENST00000364830.2, snRNA ENST00000410533.1 and miRNA hsa-miR-369-5p inhibited the proliferation and migration of MG63 cells.

Conclusions
Our results provide a theoretical basis for the pathogenesis, early diagnosis and treatment of osteosarcoma.
A new arthroscopic repair technique for triangular fibrocartilage complex using an intracapsular suture: an outside-in transfer all-inside repair
Authors: Zhao Jiasong , Lin Yanming , Li Lang , Huang Yong 
Published: November 2023

Abstract
Background
Arthroscopic repair is a promising, minimally invasive surgical technique for patients with Palmer type 1B peripheral triangular fibrocartilage complex (TFCC) tears. Although several arthroscopic techniques are effective for repairing Palmer type 1B TFCC tears, some shortcomings remain. So, we report an arthroscopic repair technique for the treatment of Palmer type 1B Atzei class 1 TFCC tears using an intracapsular suture: an outside-in transfer all-inside repair.

Methods
A retrospective analysis of 38 Palmer type 1B TFCC injury patients admitted to our hospital were randomly divided into 2 groups. The group A was sutured from the outside to the inside, with a total of 21 cases; the group B was sutured with the new arthroscopic repair technique, with a total of 17 cases. Observe and compare the VAS scores and modified Mayo wrist function scores of all patients before 3, and 6 months after the operation and evaluate the incidence of thread knots in patients with different treatment methods. The methodology was performed an arthroscopic intracapsular suture using an outside-in transfer, all-inside repair technique, which is a modified method of the outside-in and all-inside technique using the needle of a 10-mL sterile syringe, for Palmer type 1B TFCC tears. A No. 2 polydioxanone suture was threaded through the needle and entered the wrist joint. Next, the needle was withdrawn carefully along the suture to the proximal tear ulnar surface of the TFCC and penetrated the TFCC, exiting the articular cavity surface of the ulnar side of the torn TFCC. Finally, arthroscopic knotting was performed.

Results
This new treatment was as effective as the previously arthroscopic techniques and had the advantages of no additional incision and decreased risk of operation-related complications. The incidence of thread knots in the group A (28.57%) was significantly higher than that in the group B (0%), and the difference was statistically significant (P = 0.024). There was no significant difference in VAS score and modified Mayo wrist function scores between the two groups (P > 0.05).

Conclusions
The outside-in transfer, the all-inside repair technique is suitable for Palmer type 1B Atzei class 1 TFCC tears. We recommend this technique as a useful alternative to the conventional methods of repairing Palmer type 1B TFCC tears.
Randomised controlled trial of analgesia for the management of acute severe pain from traumatic injury: study protocol for the paramedic analgesia comparing ketamine and morphine in trauma (PACKMaN)
Authors: Michelet F. , Smyth M. , Lall R. , Noordali H. , Starr K. , Berridge L. , Yeung J. , Fuller G. , Petrou S. , Walker A. , Mark J. , Canaway A. , Khan K. , Perkins G. D. 
Published: November 2023

Abstract
Background
Prehospital analgesia is often required after traumatic injury, currently morphine is the strongest parenteral analgesia routinely available for use by paramedics in the United Kingdom (UK) when treating patients with severe pain. This protocol describes a multi-centre, randomised, double blinded trial comparing the clinical and cost-effectiveness of ketamine and morphine for severe pain following acute traumatic injury.

Methods
A two arm pragmatic, phase III trial working with two large NHS ambulance services, with an internal pilot. Participants will be randomised in equal numbers to either (1) morphine or (2) ketamine by IV/IO injection. We aim to recruit 446 participants over the age of 16 years old, with a self-reported pain score of 7 or above out of 10. Randomised participants will receive a maximum of 20 mg of morphine, or a maximum of 30 mg of ketamine, to manage their pain. The primary outcome will be the sum of pain intensity difference. Secondary outcomes measure the effectiveness of pain relief and overall patient experience from randomisation to arrival at hospital as well as monitoring the adverse events, resource use and cost-effectiveness outcomes.

Discussion
The PACKMAN study is the first UK clinical trial addressing the clinical and cost-effectiveness of ketamine and morphine in treating acute severe pain from traumatic injury treated by NHS paramedics. The findings will inform future clinical practice and provide insights into the effectiveness of ketamine as a prehospital analgesia.
Trial registration: ISRCTN, ISRCTN14124474. Registered 22 October 2020, https://www.isrctn.com/ISRCTN14124474
Effects of exercise prehabilitation before anterior cruciate ligament reconstruction on functional outcomes during pre- and postoperative rehabilitation — protocol for a single-blinded randomised controlled trial
Authors: Abel Rebecca , Niederer Daniel , Offerhaus Christoph , Shafizadeh Sven , Glowa Alexander , Froböse Ingo , Wilke Christiane 
Published: November 2023

Abstract
Background
Although a benefit of preoperative training prior to anterior cruciate ligament (ACL) reconstruction is likely, there is no consensus on the optimal content (criteria-based programme), supervision (one-on-one guidance or self-administered training) and general setting of preoperative training after ACL injuries. The purpose of this trial is to investigate the efficacy of an individually adaptive, guided, structured and criteria-based preoperative rehabilitation programme in comparison to a non-guided and self-administered home training programme.

Methods
The planned single-blinded randomised controlled trial study was approved by the ethics committee of the German Sport University on June 14, 2022 (ethics application no. 093/2022) and prospectively registered (DRKS-ID: DRKS00030312; date of registration: 26.09.2022). N = 114 participants between 16 and 60 years of age with a unilateral ACL rupture and scheduled ACL reconstruction with a hamstring or quadriceps tendon autograft will be randomly (block-randomisation, 1:1 allocation) and blinded assigned to one of two groups: intervention group (structured, criteria-based, guided prehabilitation training) and comparator group (non-guided, self-administered home training). After surgical reconstruction, patients of both groups participate in the same standard, functional measurement-guided, postoperative rehabilitation programme. Stepwise increasing the functional requirements of the assessments, all participants participate in testing at the day of anamnesis (t1), 1–7 days before surgical reconstruction (t2), day of surgical reconstruction (t3) and 30 (t4), 60 (t5), 90 (t6) and 180 (t7) days post-reconstruction.
The primary outcome is the overall self-reported knee condition, assessed by the sum score of all sub-scales of the Knee injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include functional outcomes (range of motion, knee flexors and extensors and plantar flexors strength/torque, functional postural control, jumping ability), workability and return to sport (RTS) (psychological readiness, RTS success).

Discussion
The planned study targets to fill a gap in the evidence regarding effective designs of prehabilitation training before surgical ACL reconstruction. Potential difficulties that could affect the conduct of the study are lack of treatment adherence of the patients and high dropout.

Trial registration
German Register of Clinical Trials DRKS-ID: DRKS00030312. Registered on 26 September 2022.
Disgust-reduction evaluative conditioning (DREC) and brain stimulation in patients with contamination-based obsessive-compulsive disorder: a protocol for a randomized control trial
Authors: Al Mohaddesin Faezeh Raeis , Moghimi Ali , Fadardi Javad Salehi 
Published: November 2023

Abstract
Background
The negative emotional valence of a stimulus can be altered if paired with a pleasant stimulus, a phenomenon referred to as evaluative conditioning. Disgust, as a central emotion in obsessive-compulsive disorder (OCD), particularly in the contamination subtype, may be an appropriate target for such a method. We know that disgust processing and OCD pathophysiology share in some brain areas, including the orbitofrontal cortex, as the neuromodulation techniques targeted in this area have been able to decrease OCD symptoms. We aim to conduct a randomized clinical trial to investigate the evaluative conditioning effect on disgust reduction in patients with contamination-based OCD when administered with or without neuromodulation targeted orbitofrontal cortex.

Method
In a single-blind randomized control trial (RCT), 55 patients with contamination-based OCD will be randomly assigned to four arms. In a factorial design, they will receive 10 sessions of evaluative conditioning training (either sham or real) plus cathodal transcranial direct current stimulation (tDCS) over the orbitofrontal cortex (either sham or real). The intensity of disgust experience and clinical symptoms will be investigated as primary outcomes and quantitative electroencephalogram and cognitive functions as secondary outcomes. The data will be collected at three assessment levels: baseline, after completing intervention sessions, and 2-month follow-up.

Discussion
The present RCT is the first study that applies evaluative conditioning training in the OCD clinical sample. It will clarify the effect of the evaluative conditioning method alone and with tDCS on disgust reduction in patients with contamination-based OCD. It will provide initial evidence for such an emotion modulation method in the OCD population. The effect of this emotion-focused protocol on cognitive functions and electroencephalogram components is also of interest.

Trial registration
ClinicalTrials.gov, NCT05907369. Registered on 16 June 2023. Retrospectively registered.
Homogeneous liquid–liquid microextraction coupled with HPLC/DAD for determination of nirmatrelvir and ritonavir as COVID-19 combination therapy in human plasma
Authors: Abdallah Inas A. , Hammad Sherin F. , Bedair Alaa , Mansour Fotouh R. 
Published: November 2023

AbstractThe study reports the development of a high-performance liquid chromatography/diode array detection method to measure the levels of nirmatrelvir and ritonavir in human plasma. These two antiviral medications are used for the treatment of COVID-19 and are marketed as Paxlovid®. The method employed sugaring-out induced homogeneous liquid–liquid microextraction to improve sensitivity. Optimization of the method was performed using the one variable at a time approach by adjusting several factors such as type of sugar, extractant, amount of sugar, volume of extractant, and pH of the aqueous sample to achieve the highest efficiency. The developed method was validated according to the Food and Drug Administration guidelines and demonstrated good linearity, accuracy, and precision. The range of linearity was from 1000 to 20,000 ng/mL for nirmatrelvir and 200 to 20,000 ng/mL for ritonavir with correlation coefficient values of 0.998 and 0.996, respectively. Selectivity studies revealed that no others peaks appeared in the retention times of the studied drugs. The stability of nirmatrelvir and ritonavir were also investigated through short term and three cycles of freeze–thaw, and both drugs were found stable. This analytical method could be useful for monitoring drug concentrations in patients undergoing treatment with these medications for COVID-19. In this work, for the first time, SULLME was used for the sensitive determination of nirmatrelvir and ritonavir in biological fluids. The developed method was able to determine both drugs in therapeutic levels with no need to sophisticated techniques like LC–MS. In addition to that, SULLME is considered a simple and green sample preparation in comparison with conventional sample preparation methods.
Synthesis of molecularly imprinted polymer by precipitation polymerization for the removal of ametryn
Authors: Roland Rachel Marcella , Bhawani Showkat Ahmad , Ibrahim Mohamad Nasir Mohamad 
Published: November 2023

AbstractAmetryn (AME) is a triazine herbicide which is mainly used to kill unwanted herbs in crops. Despite its importance in agriculture, the usage of AME also poses a risk to humans and the ecosystem due to its toxicity. Hence, it is important to develop a method for the effective removal of AME from various water sources which is in the form of molecular imprinting polymer (MIP). In this study, MIP of AME was synthesized via precipitation polymerization using AME as the template molecule with three different functional monomers including methacrylic acid (MAA), acrylamide (AAm) and 2-vinylpyridine (2VP). The three different synthesized polymers namely MIP (MAA), MIP (AAm) and MIP (2VP) were characterized using Fourier Infra-red spectroscopy (FTIR) and Field Emission Electron Microscopy (FESEM). Then, the batch binding study was carried out using all three MIPs in which MIP (MAA) attained the highest rebinding efficiency (93.73%) among the synthesized polymers. The Energy-Dispersive X-ray spectroscopy (EDX) analysis, Brunauer–Emmett–Teller (BET) analysis and thermogravimetric analysis (TGA) were also conducted on the selected MIP (MAA). Adsorption studies including initial concentration, pH and polymer dosage were also conducted on MIP (MAA). In this study, the highest adsorption efficiency was attained at the optimum condition of 6 ppm of AME solution at pH 7 with 0.1 g of MIP (MAA). MIP (MAA) was successfully applied to remove AME from spiked distilled water, tap water and river water samples with removal efficiencies of 95.01%, 90.24% and 88.37%, respectively.
Graphical Abstract