bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of hand preference in cognition and neuropsychiatric symptoms in neurodegenerative diseases
Authors: Saari Toni T , Vuoksimaa Eero 
Published: April 2023

Abstract
Handedness has been shown to be associated with genetic variation involving brain development and neuropsychiatric diseases. Whether handedness plays a role in clinical phenotypes of common neurodegenerative diseases has not been extensively studied. This study used the National Alzheimer’s Coordinating Center database to examine whether self-reported handedness was associated with neuropsychological performance and neuropsychiatric symptoms in cognitively unimpaired individuals (n = 17 670), individuals with Alzheimer’s disease (n = 10 709), behavioural variant frontotemporal dementia (n = 1132) or dementia with Lewy bodies (n = 637). Of the sample, 8% were left-handed, and 2% were ambidextrous. There were small differences in the handedness distributions across the cognitively unimpaired, Alzheimer’s disease, behavioural variant frontotemporal dementia and dementia with Lewy bodies groups (7.2–9.5% left-handed and 0.9–2.2% ambidextrous). After adjusting for age, gender and education, we found faster performance in Trail Making Test A in cognitively unimpaired non-right-handers (ambidextrous and left-handed) compared with right-handers. Excluding ambidextrous individuals, the left-handed cognitively unimpaired individuals had faster Trail Making Test A performance and better Number Span Forward performance than right-handers. Overall, handedness had no effects on most neuropsychological tests and none on neuropsychiatric symptoms. Handedness effect on Trail Making Test A in the cognitively unimpaired is likely to stem from test artefacts rather than a robust difference in cognitive performance. In conclusion, handedness does not appear to affect neuropsychological performance or neuropsychiatric symptoms in common neurodegenerative diseases.
Surgical repair of interrupted right-sided cervical aortic arch with hypoplasia of the descending thoracic aorta in a child with PHACE syndrome
Authors: Al Kindi Hamood , Mohsen Abdullah , Zacharias Sunny , Maddali Madan Mohan 
Published: April 2023

Abstract
Obstruction of a right cervical aortic arch in association with hypoplasia of the descending aorta is a rare congenital cardiac malformation. We report the case of a 6-month-old boy with posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies (PHACE) syndrome and interruption of a right-sided cervical aortic arch. The descending thoracic aorta in the child had a long hypoplastic segment and the patient also had small ventricular septal defect and pulmonary valve stenosis. The surgical technique of reconstruction of the aortic arch and the descending thoracic aorta through a median sternotomy is described.
Sharp, strong and unique minimizers for low complexity robust recovery
Authors: Fadili Jalal , Nghia Tran T A , Tran Trinh T T 
Published: April 2023

Abstract
In this paper, we show the important roles of sharp minima and strong minima for robust recovery. We also obtain several characterizations of sharp minima for convex regularized optimization problems. Our characterizations are quantitative and verifiable especially for the case of decomposable norm regularized problems including sparsity, group-sparsity and low-rank convex problems. For group-sparsity optimization problems, we show that a unique solution is a strong solution and obtains quantitative characterizations for solution uniqueness.
Impact of childhood malnutrition and intestinal microbiota on MDR infections
Authors: Holowka Thomas , van Duin David , Bartelt Luther A 
Published: April 2023

Abstract
The global burden of infection from MDR organisms (MDROs) disproportionately affects children residing in low- and middle-income countries and those with increased healthcare exposure. These populations have high rates of malnutrition making them increasingly vulnerable to infection with intestinal-derived pathogens. Malnourished children experience increased incidence of intestinal carriage and invasive infection with intestinal-derived MDROs including ESBL- and carbapenemase-producing Enterobacterales. However, the relationship between malnutrition and MDRO infection remains to be clearly defined. Impairment in intestinal barrier function and innate and adaptive immunity in malnutrition increases the risk for infection with intestinal-derived pathogens, and there is an increasing appreciation of the role of the intestinal microbiota in this process. Current evidence from human studies and animal models suggests that diet and the intestinal microbiota influence each other to determine nutritional status, with important implications for infectious outcomes. These insights are crucial to developing microbiota-targeted strategies aimed at reversing the growing burden of MDRO infections in malnourished populations worldwide.
Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy
Authors: Norvell Miranda R , Porter Melissa , Ricco Madison H , Koonce Ryan C , Hogan Craig A , Basler Eric , Wong Megan , Jeffres Meghan N 
Published: April 2023

Abstract

Background
Cefazolin is a first-line agent for prevention of surgical site infections (SSIs) after total joint arthroplasty. Patients labeled allergic to beta-lactam antibiotics frequently receive clindamycin or vancomycin perioperatively due to the perceived risk of a hypersensitivity reaction after exposure to cefazolin.

Methods
This single-system retrospective review included patients labeled allergic to penicillin or cephalosporin antibiotics who underwent a primary total hip and/or knee arthroplasty between January 2020 and July 2021. A detailed chart review was performed to compare the frequency of SSI within 90 days of surgery and interoperative hypersensitivity reactions (HSRs) between patients receiving cefazolin and patients receiving clindamycin and/or vancomycin.

Results
A total of 1128 hip and/or knee arthroplasties from 1047 patients were included in the analysis (cefazolin n = 809, clindamycin/vancomycin n = 319). More patients in the clindamycin and/or vancomycin group had a history of cephalosporin allergy and allergic reactions with immediate symptoms. There were fewer SSIs in the cefazolin group compared with the clindamycin and/or vancomycin group (0.9% vs 3.8%; P &lt; .001) including fewer prosthetic joint infections (0.1% vs 1.9%). The frequency of interoperative HSRs was not different between groups (cefazolin = 0.2% vs clindamycin/vancomycin = 1.3%; P = .06).

Conclusions
The use of cefazolin as a perioperative antibiotic for infection prophylaxis in total joint arthroplasty in patients labeled beta-lactam allergic is associated with decreased postoperative SSI without an increase in interoperative HSR.
Sustained release of brimonidine from polydimethylsiloxane-coating silicone rubber implant to reduce intraocular pressure in glaucoma
Authors: Huang Chang , Shen Yuening , Zhao Yujin , Zhang Zhutian , Gao Shunxiang , Hong Jiaxu , Xu Jianjiang , Meng Qingtao , Sun Xinghuai , Sun Jianguo 
Published: April 2023

Abstract
Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit’s conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.
Metformin promotes angiogenesis by enhancing VEGFa secretion by adipose-derived stem cells via the autophagy pathway
Authors: Tao Zihan , Liu Lei , Wu Minliang , Wang Qianqian , Wang Yuchong , Xiong Jiachao , Xue Chunyu 
Published: April 2023

Abstract
Human adipose tissue-derived stem cell (ADSC) derivatives are cell-free, with low immunogenicity and no potential tumourigenicity, making them ideal for aiding wound healing. However, variable quality has impeded their clinical application. Metformin (MET) is a 5′ adenosine monophosphate-activated protein kinase activator associated with autophagic activation. In this study, we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis. We employed various scientific techniques to evaluate the influence of MET on ADSC, assess angiogenesis and autophagy in MET-treated ADSC in vitro, and examine whether MET-treated ADSC increase angiogenesis. We found that low MET concentrations exerted no appreciable effect on ADSC proliferation. However, MET was observed to enhance the angiogenic capacity and autophagy of ADSC. MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release, which contributed to promoting the therapeutic efficacy of ADSC. In vivo experiments confirmed that in contrast to untreated ADSC, MET-treated ADSC promoted angiogenesis. Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.
OA15 IL-13 inhibition used for atopic diseases is associated with risk of psoriatic arthritis
Authors: Zhao Sizheng Steven , Hyrich Kimme L , Yiu Zenas Z N , Barton Anne , Bowes John 
Published: April 2023

Abstract

Background/Aims
Inhibitors of the IL-13 pathway, such as dupilumab and tralokinumab, are licensed to treat atopic diseases such as eczema and asthma. Musculoskeletal adverse events that resemble enthesitis and psoriatic arthritis (PsA) after dupilumab initiation have been reported, but evidence is limited to case reports and spontaneous pharmacovigilance with uncertain causal inference. Naturally occurring genetic variation in drug targets can provide insight into their potential adverse effects. We used population-level data to investigate whether genetically proxied IL-13 inhibition (IL-13i) increases risk of PsA and other spondyloarthritis-related diseases.

Methods
Dupilumab is recognised to reduce eosinophil count in clinical studies; we therefore used it as the biomarker of IL-13i. We instrumented IL-13i using missense (protein coding) variants within the IL13 gene that are associated with circulating eosinophil count at genome-wide significance (p &lt; 5x10-8) in a study of 563,946 individuals. Outcome genetic associations were taken from studies of PsA, psoriasis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and iritis. To examine instrument validity, we used atopic eczema and asthma as positive control outcomes, and rheumatoid arthritis as a negative control. We used the ratio method, with estimates scaled to per standard deviation (SD ∼0.14x109/L) reduction in eosinophil count.

Results
One missense variant, rs20541, was selected to proxy IL-13i. Genetically proxied IL-13i was associated with increased risk of PsA (OR 37.39; 95%CI 11.52, 121.34), psoriasis (OR 20.08; 4.38, 92.01), Crohn’s disease (OR 3.49; 1.38, 8.81), but not ulcerative colitis, ankylosing spondylitis or iritis. IL-13i was associated with reduced risk of positive control outcomes, but not with the negative control (Table 1).

Conclusion
Genetically proxied IL-13 inhibition is associated with increased risk of PsA, psoriasis and Crohn’s disease, which may be a class effect relevant to other IL-13i that are not yet reported to have Th17-type adverse events. These findings are compatible with the hypothesis that Th2 cytokines IL-4/-13 may act as a restraint toward Th17-type disease activation in some organs. Clinicians assessing adverse events after dupilumab initiation should be aware of incident PsA and related features. This study demonstrates the value of MR in evaluating rare adverse events in the study of drug safety.
Disclosure
S. Zhao: None. K.L. Hyrich: None. Z.Z.N. Yiu: None. A. Barton: None. J. Bowes: None.
OA20 Differences in management approaches for lupus nephritis within the UK
Authors: Ibrahim Sara T , Rhodes Benjamin , Griffiths Bridget , Gordon Caroline , Edwards Christopher J , Jayne David , Vital Edward M , Lightstone Liz , Ehrenstein Michael R , Hewins Peter , Mclaren Zoe , Reynolds John A 
Published: April 2023

Abstract

Background/Aims
Outcomes of current therapy for lupus nephritis (LN) are suboptimal. Guidelines offer varied options for treatment of LN at onset, for refractory disease or relapse. Recent randomised trials have demonstrated the efficacy of newer agents and combination therapies, although these are not all permitted within NICE or NHS England funding. Therefore, treatment strategy may vary between clinicians or regions. We aimed to describe variations in usual practice of UK physicians who treat LN.

Methods
We conducted an online survey of simulated LN case scenarios for rheumatologists and nephrologists within the UK to identify treatment preferences for proliferative (class IV) and membranous (class V) LN.

Results
Of 77 respondents who completed the survey 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. 69% of the nephrologists but only 27% of rheumatologists reported having a formal departmental protocol for treating patients with LN (p &lt; 0.001). The first-choice treatment of class IV LN in pre-menopausal female patients differed significantly between nephrologists and rheumatologists (p = 0.026) (see Table 1). For patients who failed to improve on first-line therapy there was no significant difference between nephrologists' and rheumatologists' second-choice therapy (p = 0.50) (see Table 1). However, 55% of nephrologists chose to change to second-choice treatment 3-6 months from the start of first treatment and 34.5% would change after 6-12 months but 81.3% of rheumatologists chose to change after 3-6 months and 10.4% would change in less than 3 months (p = 0.016). For class V LN, MMF was the preferred initial treatment irrespective of whether proteinuria was in nephrotic range or not. For nephrotic range class V LN not responding to first-choice treatment there were significant differences between nephrologists' and rheumatologists' choices for second-line therapy (p = 0.041) (see Table 1).

Conclusion
There is variation in treatment choices for LN between physicians with different choices reported by nephrologists and rheumatologists. These results suggest that: (i) care may not be well coordinated between rheumatologists and nephrologists; (ii) clearer guidelines are required to ensure use of the best therapies; (iii) access to the most effective therapies needs to be improved.
Disclosure
S.T. Ibrahim: None. B. Rhodes: None. B. Griffiths: None. C. Gordon: None. C.J. Edwards: None. D. Jayne: None. E.M. Vital: None. L. Lightstone: None. M.R. Ehrenstein: None. P. Hewins: None. Z. Mclaren: None. J.A. Reynolds: None.
OA26 Characterisation of a basket trial population for arthritis associated with ANA-positive RMDs
Authors: Arnold Jack , Carter Lucy Marie , Hassan Sabih , Dutton Katherine , Wigston Zoe , Dass Shouvik , Md Yusof Yuzaiful Md , Vital Ed 
Published: April 2023

Abstract

Background/Aims
Musculoskeletal inflammation is the most common reason for the inclusion of patients in SLE trials or biologic use. It is also common across other ANA-associated diseases, but these patients do not have access to the same therapies as SLE patients despite a seemingly similar problem. Our aims were to test whether (i) patient-reported impact and (ii) immunological profile of MSK inflammation are equivalent across ANA-associated diseases; (iii) identify features that stratify ANA-associated arthritis; (iv) explore the criterion validity of BILAG-MSK in other ANA-associated arthritis.

Methods
We used cross-sectional analysis of patient-reported outcome measures, antibody, gene expression and flow cytometric data from a study of mixed ANA-associated diseases (DEFINITION). The clinical and immunological implications of legacy diagnosis membership were analysed by comparing QoL measures (SF36, EQ5D-5L, Patient VAS, ICECAP-A, FACIT-F, WPAI and ICECAP-A), gene expression scores (2 IFN Scores, neutrophil, plasmablasts, myeloid and inflammation scores) and flow cytometry using Kruskal Wallis tests. The association between the BILAG MSK domain and physician arthritis VAS was tested for SLE and non-SLE patients.

Results
Of 300 patients, 215 had current or prior joint or tendon inflammation. Only FACIT-F and EQ5DL-5L showed trends to difference between diseases, being worst in the MCTD group. No other clinical or immunological variable differed between groups (Table 1). However, significant associations were found for non-disease-specific variables; worse EQ5D-5l index scores were associated with chromatin antibody positivity (T-Test, p &lt; 0.001) and non-European ancestry (T-Test, p &lt; 0.05). There was a significant association between BILAG-MSK and physician arthritis VAS in both SLE (Kruskal Wallis Chi-Sq=56.8, p &lt; 0.0001), and non-SLE (Kruskal Wallis Chi-Sq=17.468, p &lt; 0.001) patients.

Conclusion
Patients with ANA-associated arthritis appear clinically homogenous across legacy diagnoses so performing trials in a basket population appears appropriate and may be more clinically homogenous than populations currently included in SLE trials who have mixed organ involvement. Furthermore, such a basket trial could benefit from an organ-specific outcome measure, which our preliminary analysis of BILAG-MSK suggests would be valid. Predictors of worse symptoms are not specific to individual diseases, including autoantibody profile and ancestry.
Disclosure
J. Arnold: None. L. Carter: Consultancies; UCB. S. Hassan: None. K. Dutton: None. Z. Wigston: None. S. Dass: Consultancies; Roche, Abbvie, UCB and Chugai. Honoraria; Roche, Abbvie, UCB and Chugai. M. Md Yusof: Consultancies; Aurinia and, UCB. E. Vital: Consultancies; Roche, GSK, AstraZeneca, Aurinia, Lilly, UCB and Novartis. Grants/research support; Roche, AstraZeneca and Sandoz.
OA27 Mortality in patients with moderate-to-severe SLE: results from the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR)
Authors: Dyball Sarah , Rodziewicz Mia , Sutton Emily , Aksoy Aysun , McDonald Stephen , Parker Benjamin ,   BILAG-BR, Bruce Ian N 
Published: April 2023

Abstract

Background/Aims
Individuals with systemic lupus erythematosus (SLE) have an increased rate of mortality compared to the general population. We aimed to assess the cause of death and characteristics of these patients in a large national biologics register.

Methods
Patients receiving biological or standard of care (SoC) treatment recruited to the UK national SLE biologics registry (2010-21) were included. Demographic, clinical and laboratory data were recorded at recruitment. Information relating to date and cause of death were collected from study centres and the UK Office for National Statistics. The relationship between mortality and patient variables was analysed using a Cox proportional hazards model.

Results
There were 54 deaths in 1,477 patients over 6,162 patient years of follow up. The mortality rate was 5.97 (6.92-11.80) per 1000 person years (py). The cause of death was identifiable in 52 (96.2%) patients and included infection (21, 38.9%), active SLE (10, 18.5%), malignancy (6, 11.1%), cardiovascular disease (6, 11%), thrombosis (3, 5.6%), opiate toxicity (1, 1.9%) and cerebral haemorrhage (1, 1.9%). The characteristics of patients who died are described in Table 1. The median time between BILAG-BR registration and death was 679 (251-1,227) days. The mortality rate was 11.34 (8.54-15.04) per 1,000 py in patients on rituximab, 2.52 (0.36-17.90) per 1,000 py in belimumab and 3.32 (1.25-8.86) per 1,000 py in patients on SOC medicines. Factors independently associated with mortality included age at recruitment (HR 1.07 [1.05-1.09]), previous myocardial infarction (HR 5.35 [2.27-12.59]), diabetes mellitus (HR 3.87 [1.81-8.29]), previous cancer (HR 3.30 [1.59-6.86]) and hypertension (HR 1.81 [1.00-3.27]). In multivariate models adjusted for age, gender and presence of co-morbidities at baseline, risk of death was not significantly different between rituximab and belimumab (HR 0.36 [0.05-2.65) or SOC (HR 0.40 [0.12-1.32]) groups.

Conclusion
Risk of mortality was not different between treatment groups after accounting for differences in baseline demographics and co-morbidities. Co-morbidities were independently associated with high risk of death for patients with moderate-to-severe SLE; these should be actively assessed and managed to improve mortality outcomes.
Disclosure
S. Dyball: Grants/research support; MRC. Other; GSK, UCB. M. Rodziewicz: Grants/research support; MRC. Other; UCB. E. Sutton: None. A. Aksoy: None. S. McDonald: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Grants/research support; Genzyme/Sanofi, GSK. Other; Eli Lilly, Roche. I. Bruce: Consultancies; AstraZeneca, Eli Lilly, UCB, ILTOO, Merck Serono, GSK. Grants/research support; UCB, Roche, GSK, Genzyme/Sanofi. Other; AstraZeneca, GSK, UCB.