bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term effects on healthcare utilisation among spouses of persons with stroke
Authors: Labori Frida , Bonander Carl , Svensson Mikael , Persson Josefine
Published: November 2023

Background

Stroke is a common and costly disease affecting the person with stroke and their relatives. If the negative effect on the health of informal caregivers to a person with stroke translates into an increased healthcare consumption has not yet been studied. Further, the importance of including costs and health consequences of informal caregiving in health economic evaluation supporting decision-making is an ongoing discussion. Therefore, this study aims to estimate the long-term effect on healthcare utilisation among spouses of persons with a first-ever stroke.

Method

The study population consists of spouses of persons with first-ever stroke events in 2010–2011 and a reference population matched on age, sex and municipality of residence. We have access to information on healthcare utilisation five years before and five years after the stroke event for the whole study population. Using a difference-in-difference approach, the main analysis estimates the effects on primary and specialist outpatient care visits and days with inpatient care per year. Further, we analyse the healthcare utilisation among spouses depending on the modified Rankin Scale (mRS) of the person with stroke.

Results

Our main analysis indicates that spouses have slightly more days with inpatient care five years after the stroke event than the reference population (p = 0.03). In contrast, spouses have fewer primary and specialist outpatient care visits than the reference population following the stroke event. In the analysis where spouses’ healthcare utilisation is analysed according to the mRS status of the person with stroke, we identify the most notable change in the number of visits to specialist outpatient and days with inpatient care among spouses of persons with mRS 3 (dependency in daily activities).

Conclusion

Our study suggests that being the spouse of a person with stroke has minor effects on healthcare utilisation. Further, healthcare utilisation is most affected among the spouses of persons with stroke and dependency in daily activities (mRS 3). According to our results, it does not seem vital to include spouses of persons with stroke healthcare utilisation in health economic evaluations.
Addressing complexity when developing an education program for the implementation of a stroke Electronic Medical Record (EMR) enhancement
Authors: Robertson Samantha T. , Rosbergen Ingrid C. M. , Brauer Sandra G. , Grimley Rohan S. , Burton-Jones Andrew
Published: November 2023

Background

Digital interventions in health services often fail due to an underappreciation of the complexity of the implementation. This study develops an approach to address complexity through an evidenced-based, theory-driven education and implementation program for an Electronic Medical Record (EMR) digital enhancement for acute stroke care.

Methods

An action research approach was used to design, develop, and execute the education and implementation program over several phases, with iterative changes over time. The study involved collaboration with multiple statewide and local key stakeholders and was conducted across two tertiary teaching hospitals and a regional hospital in Australia.

Results

Insights were gained over five phases. Phase 1 involved a review of evidence that supported blended learning strategies for the education and training of staff end-users. In Phase 2, contextual assessment was conducted via observation of study sites, providing awareness of local context variability and insight into key implementation considerations. The Non-adoption, Abandonment, Scale-Up, Spread and Sustainability (NASSS) framework assisted in Phase 3 to identify and manage the key domains of complexity. Phase 4 involved the design of the program which included group-based training and an e-learning package, endorsed and evaluated by key leaders. Throughout implementation in Phase 5, further barriers were identified, and iterative changes were tailored to each context.

Conclusions

The NASSS framework, combined with a multi-phased approach employing blended learning techniques, context evaluations, and iterative modifications, can serve as a model for generating theory-driven and evidence-based education strategies that adresss the complexity of the implementation process and context.
Evidence for widespread existence of functional novel and non-canonical human transcripts
Authors: Xu Dongyang , Tang Lu , Zhou Junjun , Wang Fang , Cao Huifen , Huang Yu , Kapranov Philipp
Published: November 2023

Background

Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches.

Results

In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs.

Conclusions

Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions.
Exploring the hypolipidemic effects of bergenin from Saxifraga melanocentra Franch: mechanistic insights and potential for hyperlipidemia treatment
Authors: Zhang Li , Tong Yingying , Fang Yan , Pei Jinjin , Wang Qilan , Li Gang
Published: November 2023

Objective

The goal of this study was to explore the hypolipidemic effects of bergenin extracted from Saxifraga melanocentra Franch (S. melanocentra), which is a frequently utilized Tibetan medicinal plant known for its diverse bioactivities. Establishing a quality control system for black stem saxifrage is crucial to ensure the rational utilization of its medicinal resources.

Methods

A one-step polyamide medium-pressure liquid chromatography technique was applied to isolate and prepare bergenin from a methanol extract of S. melanocentra. A zebrafish model of hyperlipidemia was used to investigate the potential hypolipidemic effects of bergenin.

Results

The results revealed that bergenin exhibited substantial hypo efficacy in vivo. Specifically, bergenin significantly reduced the levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) while simultaneously increasing high-density lipoprotein cholesterol (HDL-c) levels. At the molecular level, bergenin exerted its effects by inhibiting the expression of FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-1β, and TNF while promoting the expression of IL-4 at the transcriptional level. Molecular docking analysis further demonstrated the strong binding affinity of bergenin to proteins such as FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-4, IL-1β, and TNF.

Conclusions

Findings indicate that bergenin modulates lipid metabolism by regulating lipid and cholesterol synthesis as well as inflammatory responses through signaling pathways associated with FASN, SREBF1, and RORα. These results position bergenin as a potential candidate for the treatment of hyperlipidemia.
Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair
Authors: Chen Xiaohang , Xing Xiaojie , Lin Shuoqi , Huang Liyu , He Lianghang , Zou Yuchun , Zhang Xuyang , Su Bohua , Lu Youguang , Zheng Dali
Published: November 2023

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Graphical Abstract
Device-measured movement behaviours in over 20,000 China Kadoorie Biobank participants
Authors: Chen Yuanyuan , Chan Shing , Bennett Derrick , Chen Xiaofang , Wu Xianping , Ke Yalei , Lv Jun , Sun Dianjianyi , Pan Lang , Pei Pei , Yang Ling , Chen Yiping , Chen Junshi , Chen Zhengming , Li Liming , Du Huaidong , Yu Canqing , Doherty Aiden ,   on behalf of the China Kadoorie Biobank Collaborative Group
Published: November 2023

Background

Movement behaviours, including physical activity, sedentary behaviour, and sleep have been shown to be associated with several chronic diseases. However, they have not been objectively measured in large-scale prospective cohort studies in low-and middle-income countries. We aim to describe the patterns of device-measured movement behaviours collected in the China Kadoorie Biobank (CKB) study.

Methods

During 2020 and 2021, a random subset of 25,087 surviving CKB individuals participated in the 3rd resurvey of the CKB. Among them, 22,511 (89.7%) agreed to wear an Axivity AX3 wrist-worn triaxial accelerometer for seven consecutive days to assess their habitual movement behaviours. We developed a machine-learning model to infer time spent in four movement behaviours [i.e. sleep, sedentary behaviour, light intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA)]. Descriptive analyses were performed for wear-time compliance and patterns of movement behaviours by different participant characteristics.

Results

Data from 21,897 participants (aged 65.4 ± 9.1 years; 35.4% men) were received for demographic and wear-time analysis, with a median wear-time of 6.9 days (IQR: 6.1–7.0). Among them, 20,370 eligible participants were included in movement behavior analyses. On average, they had 31.1 mg/day (total acceleration) overall activity level, accumulated 7.7 h/day (32.3%) of sleep time, 8.8 h/day (36.6%) sedentary, 5.7 h/day (23.9%) in light physical activity, and 104.4 min/day (7.2%) in moderate-to-vigorous physical activity. There was an inverse relationship between age and overall acceleration with an observed decline of 5.4 mg/day (17.4%) per additional decade. Women showed a higher activity level than men (32.3 vs 28.8 mg/day) and there was a marked geographical disparity in the overall activity level and time allocation.

Conclusions

This is the first large-scale accelerometer data collected among Chinese adults, which provides rich and comprehensive information about device-measured movement behaviour patterns. This resource will enhance our knowledge about the potential relevance of different movement behaviours for chronic disease in Chinese adults.
TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study
Authors: Rajasundaram Skanda , Zebardast Nazlee , Mehta Puja , Khawaja Anthony P. , Warwick Alasdair , Duchinski Katherine , Burgess Stephen , Gill Dipender , Segrè Ayellet V. , Wiggs Janey
Published: November 2023

Background

In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm’s canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking.

Methods

GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment.

Results

Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (− 0.21 mmHg per SD increase in sTIE1, 95% CI = − 0.09 to − 0.33 mmHg, P = 6.57 × 10–4, and − 0.14 mmHg per SD decrease in sTEK, 95% CI = − 0.03 to − 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium.

Conclusions

This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target.
Identification of key biomarkers in RF-negative polyarticular and oligoarticular juvenile idiopathic arthritis by bioinformatic analysis
Authors: Liu Yun , Tang Xuemei
Published: November 2023

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

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

TLR4, 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

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

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

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

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

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

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

The 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

Ametryn (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
Assessment of axial spondyloarthritis activity using a magnetic resonance imaging-based multi-region-of-interest fusion model
Authors: Xin Peijin , Wang Qizheng , Yan Ruixin , Chen Yongye , Zhu Yupeng , Zhang Enlong , Ren Cui , Lang Ning
Published: November 2023

Background

Identifying axial spondyloarthritis (axSpA) activity early and accurately is essential for treating physicians to adjust treatment plans and guide clinical decisions promptly. The current literature is mostly focused on axSpA diagnosis, and there has been thus far, no study that reported the use of a radiomics approach for differentiating axSpA disease activity. In this study, the aim was to develop a radiomics model for differentiating active from non-active axSpA based on fat-suppressed (FS) T2-weighted (T2w) magnetic resonance imaging (MRI) of sacroiliac joints.

Methods

This retrospective study included 109 patients diagnosed with non-active axSpA (n = 68) and active axSpA (n = 41); patients were divided into training and testing cohorts at a ratio of 8:2. Radiomics features were extracted from 3.0 T sacroiliac MRI using two different heterogeneous regions of interest (ROIs, Circle and Facet). Various methods were used to select relevant and robust features, and different classifiers were used to build Circle-based, Facet-based, and a fusion prediction model. Their performance was compared using various statistical parameters. p < 0.05 is considered statistically significant.

Results

For both Circle- and Facet-based models, 2284 radiomics features were extracted. The combined fusion ROI model accurately differentiated between active and non-active axSpA, with high accuracy (0.90 vs.0.81), sensitivity (0.90 vs. 0.75), and specificity (0.90 vs. 0.85) in both training and testing cohorts.

Conclusion

The multi-ROI fusion radiomics model developed in this study differentiated between active and non-active axSpA using sacroiliac FS T2w-MRI. The results suggest MRI-based radiomics of the SIJ can distinguish axSpA activity, which can improve the therapeutic result and patient prognosis. To our knowledge, this is the only study in the literature that used a radiomics approach to determine axSpA activity.
Impact of IL6R genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis
Authors: Sainz Luis , Riera Pau , Moya Patricia , Bernal Sara , Casademont Jordi , Díaz-Torné Cesar , Millán Ana Milena , Park Hye Sang , Lasa Adriana , Corominas Hector
Published: November 2023

Background

Sarilumab, an IL-6 receptor antagonist, is a first-line biologic disease-modifying anti-rheumatic drug for rheumatoid arthritis. The identification of genetic biomarkers as predictors of response to sarilumab could allow for a personalized treatment strategy to improve clinical outcomes.

Methods

We conducted a retrospective cohort study of 62 patients treated with sarilumab to determine whether single-nucleotide polymorphisms (SNP) in the IL6R gene could predict efficacy and toxicity responses. Six SNPs previously described in the IL6R gene (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625) were genotyped in DNA samples obtained from these patients. Using parametric tests, we evaluated the association between these polymorphisms and clinicopathological features. Treatment response was assessed six months after treatment initiation. Satisfactory response was based on EULAR criteria. Low disease activity was determined according to DAS28 and CDAI and quantitative improvements in DAS28 and CDAI scores.

Results

Three SNPs (rs4845625, rs4329505 and rs11265618) were significantly associated with response outcomes. All of the SNPs, except for rs12083537, had at least one significant association with dyslipidemia or hepatotoxicity.

Conclusions

These findings support the potential clinical value of SNPs, particularly rs4845625, as potentially useful biomarkers to predict response to sarilumab in patients with RA.
Last dental visit and severity of tooth loss: a machine learning approach
Authors: Bomfim Rafael Aiello
Published: November 2023

The aims of the present study were to investigate last dental visit as a mediator in the relationship between socioeconomic status and lack of functional dentition/severe tooth loss and use a machine learning approach to predict those adults and elderly at higher risk of tooth loss. We analyzed data from a representative sample of 88,531 Brazilian individuals aged 18 and over. Tooth loss was the outcome by; (1) functional dentition and (2) severe tooth loss. Structural Equation models were used to find the time of last dental visit associated with the outcomes. Moreover, machine learning was used to train and test predictions to target individuals at higher risk for tooth loss. For 65,803 adults, more than two years of last dental visit was associated with lack of functional dentition. Age was the main contributor in the machine learning approach, with an AUC of 90%, accuracy of 90%, specificity of 97% and sensitivity of 38%. For elders, the last dental visit was associated with higher severe loss. Conclusions. More than two years of last dental visit appears to be associated with a severe loss and lack of functional dentition. The machine learning approach had a good performance to predict those individuals.
Results of a diagnostic imaging audit in a randomised clinical trial in rectal cancer highlight the importance of careful planning and quality control
Authors: Prata Ilaria , Eriksson Martina , Krdzalic Jasenko , Kranenbarg Elma Meershoek-Klein , Roodvoets Annet G. H. , Beets-Tan Regina , van de Velde Cornelis J. H. , van Etten Boudewijn , Hospers Geke A. P. , Glimelius Bengt , Nilsson Per J. , Marijnen Corrie A. M. , Peeters Koen C. M. J. , Blomqvist Lennart K.
Published: November 2023

Background

Magnetic resonance (MR) imaging is the modality used for baseline assessment of locally advanced rectal cancer (LARC) and restaging after neoadjuvant treatment. The overall audited quality of MR imaging in large multicentre trials on rectal cancer is so far not routinely reported.

Materials and methods

We collected MR images obtained within the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) trial and performed an audit of the technical features of image acquisition. The required MR sequences and slice thickness stated in the RAPIDO protocol were used as a reference.

Results

Out of 920 participants of the RAPIDO study, MR investigations of 668 and 623 patients in the baseline and restaging setting, respectively, were collected. Of these, 304/668 (45.5%) and 328/623 (52.6%) MR images, respectively, fulfilled the technical quality criteria. The main reason for non-compliance was exceeding slice thickness 238/668, 35.6% in the baseline setting and 162/623, 26.0% in the restaging setting. In 166/668, 24.9% and 168/623, 27.0% MR images in the baseline and restaging setting, respectively, one or more of the required pulse sequences were missing.

Conclusion

Altogether, 49.0% of the MR images obtained within the RAPIDO trial fulfilled the image acquisition criteria required in the study protocol. High-quality MR imaging should be expected for the appropriate initial treatment and response evaluation of patients with LARC, and efforts should be made to maximise the quality of imaging in clinical trials and in clinical practice.

Critical relevance statement

This audit highlights the importance of adherence to MR image acquisition criteria for rectal cancer, both in multicentre trials and in daily clinical practice. High-resolution images allow correct staging, treatment stratification and evaluation of response to neoadjuvant treatment.

Key points

- Complying to MR acquisition guidelines in multicentre trials is challenging.

- Neglection on MR acquisition criteria leads to poor staging and treatment.

- MR acquisition guidelines should be followed in trials and clinical practice.

- Researchers should consider mandatory audits prior to study initiation.

Graphical Abstract
Congenital duodenal web causing partial obstruction with recurrent vomiting and abdominal distention in a toddler boy: a case report
Authors: Ekram Khesrow , Razawi Farida , Jalal Sayed Najmuddin , Sultani Mohammad Nader , Wali Abdul Wali , Sediqi Mohammad Sharif , Hamdard Abdul Ghafar , Hemat Massoud , Sahibzada Mohammad Mustafa
Published: November 2023

Background

The duodenal web is a thin, elongated, web-like structure that is one of the factors contributing to duodenal obstruction. Only 100 cases have been reported in the literature. We present a 2.5-year-old cachectic Afghan child who did not have any overt signs and symptoms of intestinal obstruction, like recurrent vomiting, abdominal distention, and weight loss. The web was discovered near the intersection of the third and fourth portions, which is an uncommon location for the duodenal web. The late presentation of congenital duodenal web with partial obstruction is rare but well-known and has been reported in this case.

Case presentation

A 2.5-year-old cachectic Afghan child who had recurrent vomiting and experienced abdominal distention was brought to Maiwand Teaching Hospital from the Jabelsuraj region of Parwan province. The patient was suffering from unusual signs and symptoms like recurrent vomiting, abdominal distention, weight loss, and constipation. The diagnosis of these anomalies was established by a detailed history, clinical features, and abdominal CT scan. In the computerized tomography scanning (CT-Scan) image reported, there was a web with stenosis and partial obstruction in the distal aspect of the third-to-fourth portion of the duodenum. After preoperative stabilization, the child was taken for surgery. The abdomen was opened by a right upper abdominal transverse incision. After web resection and duodenoplasty, the patient was shifted to the recovery room in satisfactory condition. The child was allowed to feed after 8 days, which he tolerated well.

Conclusion

Congenital duodenal web with partial obstruction is typically observed in the second and third years of life. It is suspected in patients with recurrent vomiting, abdominal distention, weight loss, and constipation. Partial obstruction may not have an overt presentation, making it a challenging diagnosis for general practitioners. Abdomen X-ray and CT scan usually confirm the diagnosis, and successful surgical intervention is recommended.