bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE: introducing Adequate Health State
Authors: Hua Nicole , Gomez Alvaro , Lindblom Julius , Emamikia Sharzad , Enman Yvonne , Grannas David , Heintz Emelie , Regardt Malin , Parodis Ioannis 
Published: March 2023

Abstract

Objectives
To investigate the ability of different EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) index scores to discriminate between verum drug and placebo (discriminant validity) as well as between responders and non-responders (known-groups validity) in the SLE patient population of two phase III clinical trials of belimumab.

Methods
Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684), which both showed superiority of belimumab to placebo, were utilized. Responders were defined as SLE Responder Index 4 (SRI-4) achievers at week 52. The Pearson’s χ2 and Mann–Whitney U tests were used for comparisons, and logistic regression analysis was used for adjustments for confounders and assessment of independence.

Results
While full health state (FHS; EQ-5D index score 1) showed the best ability to discriminate between belimumab and placebo [adjusted odds ratio (OR) 1.47; 95% CI 1.11, 1.96; P = 0.008] and between SRI-4 responders and non-responders (adjusted OR 3.47; 95% CI 1.29, 10.98; P = 0.020), the discriminative ability of EQ-5D index scores 0.800 or more reached statistical significance for both discriminant validity (adjusted OR 1.29; 95% CI 1.02, 1.63; P = 0.036) and known-groups validity (adjusted OR 3.08; 95% CI 1.16, 9.69; P = 0.034).

Conclusion
Overall, higher EQ-5D index scores were associated with increasing ability to discriminate between belimumab and placebo, and between responders and non-responders. EQ-5D index scores less stringent than FHS may be clinically relevant health-related quality of life goals of treatment in patients with SLE, introducing the concept of EQ-5D adequate health state when FHS is not achievable.
The chances in the redox priming of nondormant recalcitrant seeds by spermidine
Authors: Fuchs Hanna , Plitta-Michalak Beata P , Małecka Arleta , Ciszewska Liliana , Sikorski Łukasz , Staszak Aleksandra M , Michalak Marcin , Ratajczak Ewelina 
Published: March 2023

Abstract
The problems posed by seed sensitivity to desiccation and aging have motivated the development of various techniques for mitigating their detrimental effects. The redox priming of seeds in antioxidant solution to improve their postharvest performance is one of the approaches. Spermidine (Spd) was tested as an invigorating solution on nondormant recalcitrant (desiccation-sensitive) seeds of the silver maple (Acer saccharinum L.). The treatment resulted in an 8–10% increase in germination capacity in seeds subjected to mild and severe desiccation, while in aged seeds stored for 6 months, no significant change was observed. The cellular redox milieu, genetic stability, mitochondrial structure and function were investigated to provide information about the cellular targets of Spd activity. Spermidine improved the antioxidative capacity, especially the activity of catalase, and cellular membrane stability, protected genome integrity from oxidative damage and increased the efficiency of mitochondria. However, it also elicited a hydrogen peroxide burst. Therefore, it seems that redox priming in nondormant seeds that are highly sensitive to desiccation, although it positively affected desiccated seed performance, may not be a simple solution to reinvigorate stored seeds with a low-efficiency antioxidant system.
The Older, the Less Digitally Fluent? The Role of Age Stereotypes and Supervisor Support
Authors: Hampel Kilian , Kunze Florian 
Published: March 2023

Abstract
Over the last decades, digital technologies have progressively made their way into the workplace. Therefore, it becomes increasingly important for employees to have digital competencies, which can be measured through digital fluency, including its two sub dimensions, namely digital knowledge and digital self-efficacy. This is particularly the case for older workers, who might be affected by a digital divide that proposes younger and older employees have different prerequisites for digital fluency. Drawing from the stereotype embodiment theory, we argue that age is generally negatively related to self-perceptions of digital fluency and particularly impactful when older employees hold negative age stereotypes against older workers and therefore self-stereotype themselves. Furthermore, we argue that developmental support from the direct supervisor has the potential to either amplify or alleviate this negative relation: While a lack of supervisor support may lead to the activation of internalized negative age stereotypes, strong support by the supervisor could strengthen the employees’ self-perceptions in several ways. Performing multiple regression analyses on survey data collected from 1,007 employees, we find support for our three hypotheses. Negative age stereotypes exacerbate the negative relationship between age and digital fluency, whereas the interplay of high individual stereotypes and low supervisor support is the most negative condition for the relation of age on digital fluency. On the other hand, strong supervisor support with low negative stereotypes counteract existing age differences in digital fluency. Therefore, our findings have important theoretical and practical implications.
P4HA2‐mediated HIF‐1α stabilization promotes erdafitinib‐resistance in FGFR3‐alteration bladder cancer
Authors: Li Xuexiang , Li Yunxue , Liu Bing , Chen Liang , Lyu Fang , Zhang Pu , He Qingliu , Cheng Lulin , Liu Chunyu , Song Yarong , Xing Yifei 
Published: March 2023

AbstractErdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor that has shown great therapeutic promise for solid tumor patients with FGFR3 alterations, especially in urothelial carcinoma. However, the mechanisms of resistance to FGFR inhibitors remain poorly understood. In this study, we found Erdafitinib could kill cells by inducing incomplete autophagy and increasing intracellular reactive oxygen species levels. We have established an Erdafitinib‐resistant cell line, RT‐112‐RS. whole transcriptome RNA sequencing (RNA‐Seq) and Cytospace analysis performed on Erdafitinib‐resistant RT‐112‐RS cells and parental RT‐112 cells introduced P4HA2 as a linchpin to Erdafitinib resistance. The gain and loss of function study provided evidence for P4HA2 conferring such resistance in RT‐112 cells. Furthermore, P4HA2 could stabilize the HIF‐1α protein which then activated downstream target genes to reduce reactive oxygen species levels in bladder cancer. In turn, HIF‐1α could directly bind to P4HA2 promoter, indicating a positive loop between P4HA2 and HIF‐1α in bladder cancer. These results suggest a substantial role of P4HA2 in mediating acquired resistance to Erdafitinib and provide a potential target for bladder cancer treatment.
Physical activity‐induced alterations of the gut microbiota are BMI dependent
Authors: Shah Shrushti , Mu Chunlong , Moossavi Shirin , Shen‐Tu Grace , Schlicht Kristina , Rohmann Nathalie , Geisler Corinna , Laudes Matthias , Franke Andre , Züllig Thomas , Köfeler Harald , Shearer Jane 
Published: March 2023

AbstractPhysical inactivity is one of the leading causes of chronic metabolic disease including obesity. Increasing physical activity (PA) has been shown to improve cardiometabolic and musculoskeletal health and to be associated with a distinct gut microbiota composition in trained athletes. However, the impact of PA on the gut microbiota is inconclusive for individuals performing PA in their day‐to‐day life. This study examined the role of PA and hand‐grip strength on gut microbiome composition in middle‐aged adults (40–65 years, n = 350) with normal (18.5–24.9 kg/m2) and overweight (25–29.9 kg/m2) body mass index (BMI). PA was recorded using the International Physical Activity Questionnaire, and hand‐grip strength was measured using a dynamometer. Serum samples were assessed for lipidomics while DNA was extracted from fecal samples for microbiome analysis. Overweight participants showed a higher concentration of triacylglycerols, and lower concentrations of cholesteryl esters, sphingomyelin, and lyso‐phosphotidylcholine lipids (p < .05) compared with those with normal BMI. Additionally, overweight participants had a lower abundance of the Oscillibacter genus (p < .05). The impact of PA duration on the gut microbiome was BMI dependent. In normal but not overweight participants, high PA duration showed greater relative abundance of commensal taxa such as Actinobacteria and Proteobacteria phyla, as well as Collinsella and Prevotella genera (p < .05). Furthermore, in males with normal BMI, a stronger grip strength was associated with a higher relative abundance of Faecalibacterium and F. prausnitzii (p < .05) compared with lower grip strength. Taken together, data suggest that BMI plays a significant role in modeling PA‐induced changes in gut microbiota.
Does Offloading with Felt Foot Plates Heal Diabetic Foot Ulcers?
Authors: Christensen Deborah , Botchway Albert 
Published: March 2023

ABSTRACT

OBJECTIVE
To determine (1) if offloading with a felt foot plate heals a diabetic foot ulcer, (2) the rate of healing with the felt foot plate, and (3) the impact on rate of healing from the confounding factors of patient weight and growth factors on healing times.

METHODS
The researchers conducted a retrospective chart cohort review over 3 years.

RESULTS
Using a multivariable linear and logistic regression model, the data showed a statistically significant reduction in the diabetic foot ulcer area over time. Confounding factors of patient weight and growth factors did not impact healing times.

CONCLUSIONS
Offloading a diabetic foot ulcer with a felt foot plate is adequate for healing.
Cultural Adaptation, Content Validation, and Reliability of the SACS 2.0 Instrument for Colombian Spanish
Authors: Torres Yesly Johana Rincón , Gamboa Sandra Guerrero , Moreno-Ramos Mily Constanza 
Published: March 2023

ABSTRACT

OBJECTIVE
To realize the cultural adaptation and content validation and evaluate the reliability of the SACS 2.0 instrument in Colombian Spanish.

METHODS
The researchers conducted a methodological study with a quantitative approach. The adaptation process was carried out in five stages: translation, synthesis, reverse translation, evaluation by a committee of experts, and testing of the adapted version. In addition, the interobserver reliability was evaluated by four nurses who examined 210 stomas.

RESULTS
All of the proposed stages were carried out successfully, and an adapted version of the instrument in Colombian Spanish was obtained. During the content validation stage, the instrument obtained a content validity index of 1. The adapted version of the test showed substantial agreement for the aspect of clarity, adequacy, and understandability. In the interobserver reliability, there was agreement in 95.7% of the evaluations for the classification of the lesions according to the quadrants (κ = 0.97–0.99).

CONCLUSIONS
Authors achieved a culturally adapted, valid, and reliable instrument for the evaluation and classification of peristomal skin alterations in Colombian Spanish.
Effect of Adding Perineural Methylprednisolone to Peripheral Nerve Blocks Combined With Intravenous Dexamethasone for Prolonged Postdischarge Analgesia After Fast-track Total Knee Arthroplasty
Authors: Akaravinek Piraya , Kampitak Wirinaree , Tanavalee Aree , Ngarmukos Srihatach , Tanavalee Chotetawan , Limsakul Kamonwan 
Published: March 2023

Objectives:
Patients undergoing total knee arthroplasty (TKA) may experience moderate-to-severe subacute pain after hospital discharge that may be undermanaged. We aimed to evaluate the effect of methylprednisolone added to ultrasound-guided peripheral nerve blocks (PNBs) combined with multimodal analgesia including intravenous dexamethasone for prolonged analgesia after early discharge.

Materials and Methods:
We randomized 80 patients who underwent fast-track TKA into 2 groups. All patients received a periarticular injection, PNBs, and multiple doses of intravenous dexamethasone. The methylprednisolone group received 140 mg methylprednisolone in PNBs, while the nonmethylprednisolone group did not. The primary outcome was the incidence of moderate-to-severe pain (Numerical Rating Scale ≥4) during the first 12 postdischarge days. The secondary outcomes included pain scores until 3 postoperative months, incidence of rebound pain, functional performances, patient satisfaction, and adverse events.

Results:
No significant between-group differences were noted in the incidence of moderate-to-severe pain during the first 12 postdischarge days (nonmethylprednisolone vs. methylprednisolone groups: 70% vs. 69.2%, P=0.941). However, this incidence was significantly higher in the methylprednisolone group between 2 weeks and 1 month (P=0.015) and between 1 and 3 months (P=0.004) postoperatively. No between-group differences in the Numerical Rating Scale scores at the postdischarge time points, incidence of rebound pain, and functional performance results were noted.

Discussion:
Adding perineural methylprednisolone to ultrasound-guided PNBs for multimodal analgesia with intravenous dexamethasone did not prolong analgesia and improved the functional ability after fast-track TKA within 12 postdischarge days. However, the incidence moderate-to-severe pain may increase between the 2-week and 3-month follow-up.
Glucocorticoid-induced osteoporosis in premenopausal women: management for the rheumatologist
Authors: Chakrabarti Katherine , McCune W. Joseph 
Published: March 2023

Purpose of review
This review seeks to summarize the literature relevant to the treatment of glucocorticoid-induced osteoporosis in premenopausal women; an issue commonly encountered by rheumatologists and yet lacking good clinical practice guidelines.

Recent findings
Although most of the relevant literature on osteoporosis includes postmenopausal women only, data from both randomized controlled trials and case reports suggest bisphosphonates can be an effective and well tolerated treatment for premenopausal patients. Data for other medications to treat premenopausal osteoporosis is less robust.

Summary
The use of bisphosphonates in young women may be safer than initially thought and should likely be used for the treatment of glucocorticoid-induced osteoporosis in rheumatology clinics. Further research is needed to continue to understand long-term risk.
Is External Beam Radiation Therapy Really Associated With Low Rates of Heterotopic Ossification After Acetabular Surgery?
Authors: Boissonneault Adam , Harkin Elizabeth , Slobogean Gerard , Gupta Jayesh , Benzel Caroline , O'Hara Nathan , O'Toole Robert V 
Published: March 2023

Objectives:
Describe rate of postoperative heterotopic ossification (HO) after acetabular surgery in patients who received external beam radiation (XRT) as HO prophylaxis.

Design:
Retrospective.

Setting:
Level I trauma center.

Patients/Participants:
Consecutive series of patients who presented to a single, level I, academic trauma center over a 10-year period (2008–2018) for surgical fixation of an acetabular fracture. Patients eligible for inclusion were those who underwent surgical fixation of an acetabular fracture through a posterior (Kocher–Langenbeck), combined anterior and posterior, or extensile exposure. Patients were excluded if an isolated anterior approach was performed or if an acute total hip arthroplasty was performed at the time of index surgery.

Intervention:
XRT.

Main Outcome:
Severe HO (Brooker class III or IV).

Results:
The severe HO (Brooker class III or IV) rate for entire cohort was 12% (44 of 361 patients). Of these 44 patients, 30 patients were classified as Brooker III and 14 patients were classified as Brooker IV. The Brooker IV rate for the entire cohort was 4% (14 of 361 patients). Severe HO rates showed a declining trend over the period examined, with a risk reduction of −1.0% per year (95% confidence interval −2.1% to 0.2%; P = 0.10).

Conclusion:
To our knowledge, this is the largest single consecutive series on acetabular fracture patients who received XRT as HO prophylaxis. The overall severe HO rate was 12%, which is similar to other comparably large series data on patients who did not receive XRT after surgical fixation acetabular fractures. Although these data suggest that XRT may not be beneficial when used universally for all patients, comparative studies are required to rule out the benefits of XRT for preventing HO in this population.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Correlation between the Severity of Adhesions and Desmoid Disease in Patients with Familial Adenomatous Polyposis: A Prospective Cohort Study
Authors: Faul Eleanor , Xhaja Xhileta , Church James 
Published: March 2023

BACKGROUND:
Clinical experience teaches that intraperitoneal adhesions are more severe in patients with familial adenomatous polyposis than in patients without it. This impression may come from the common association of familial adenomatous polyposis with desmoid disease.

OBJECTIVES:
To determine whether patients with familial adenomatous polyposis and desmoid disease develop more severe adhesions than those without desmoid disease.

DESIGN:
Prospectively collected data study.

SETTINGS:
Hereditary colorectal cancer center in a tertiary referral hospital.

PATIENTS:
Patients undergoing first reoperative intra-abdominal surgery for familial adenomatous polyposis: controls were those having their initial abdominal surgery.

INTERVENTIONS:
Surgery and adhesiolysis.

MAIN OUTCOME MEASURES:
Presence and type of desmoid disease; presence and severity of non-desmoid intraperitoneal adhesions. Where patients had multiple operations, only the first reoperative surgery was chosen. Desmoid disease was noted as reaction (sheet) or mass. Adhesions were graded as none, mild (<10 minutes for mobilization), average (10 to 30 minutes) and severe (>30 minutes or significant bowel damage). Patients having first abdominal surgery for familial adenomatous polyposis were used as a control group.

RESULTS:
A total of 221 patients had no prior surgery: 5% had desmoids and 1% had adhesions. 137 patients underwent reoperative surgery: 39% had desmoid disease (p < 0.05 vs no prior surgery), the highest rate being in patients after ileal pouch anal anastomosis (57%), and 45% had severe adhesions (p < 0.01 vs no prior surgery), worst after Koch pouch (89%) and total proctocolectomy with ileostomy (82%). 36% of patients without desmoid disease had severe adhesions. Desmoid reaction was associated with severe adhesions in 47% of cases, and desmoid tumors were associated with severe adhesions in 66% of cases.

LIMITATIONS:
Possible limitations include the potential overlap between desmoid adhesions and non-desmoid adhesions as well as the potential for inaccuracy in defining time of adhesiolyses.

CONCLUSION:
Familial adenomatous polyposis is associated with severe postoperative adhesions after reoperative abdominal surgery, especially in patients who develop desmoid disease.
Comparative Safety of Gout Treatment Strategies on Cardiovascular Outcomes Using Observational Data: Clone-censor-weight Target Trial Emulation Approach
Authors: Yoshida Kazuki , Liu Jun , Desai Rishi J. , Glynn Robert J. , Solomon Daniel H. , Kim Seoyoung C. 
Published: March 2023

Background:
We sought to examine the cardiovascular safety of intensive treat-to-target serum urate strategies for gout using Medicare claims data linked to electronic health record laboratory data.

Methods:
We selected patients with gout who initiated urate-lowering therapy. We emulated a hypothetical trial comparing the rate of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) among seven different strategies over 24 months. Three aspects were considered in defining increasingly intensive strategies: (1) continuation of urate-lowering therapy, (2) serum urate monitoring, and (3) modification of urate-lowering therapy when serum urate >6 mg/dl. We applied the “clone-censor-weight” method to account for baseline and time-varying confounding.

Results:
We identified 4402 patients with gout who initiated urate-lowering therapy (mean age 77; male 60%). During a total of 6611 person–years (PY) of follow-up under usual care, the rate of major cardiovascular events (first and recurrent) was 4.5/100 PY (95% CI = 4.0, 5.1). The rate ratios (RRs) suggested reductions (RR point estimates 0.88–0.84) compared with usual care. All 95% CIs were imprecise, but their upper bounds excluded substantial increase in RRs. RRs were closer to 1.0 for the analysis focusing on the first major adverse cardiovascular event during follow-up and on comparison to the strategy requiring continuation of urate-lowering therapy (but not necessarily titration).

Conclusions:
Our treatment strategy trial emulation did not find increased risk of major adverse cardiovascular events with intensive urate-lowering strategies. Results may provide reassurance of the cardiovascular safety of intensive treat-to-target serum urate strategies recommended by rheumatology societies.
Corneal tissue addition keratoplasty: new intrastromal inlay procedure for keratoconus using femtosecond laser–shaped preserved corneal tissue
Authors: Greenstein Steven A. , Yu Austin S. , Gelles John D. , Eshraghi Hamoon , Hersh Peter S. 
Published: March 2023

Purpose:
To report results of Corneal Tissue Addition Keratoplasty (CTAK) for keratoconus (KC) and ectasia after laser in situ keratomileusis.

Setting:
Cornea and refractive surgery practice.

Design:
Single center, prospective, open label clinical trial.

Methods:
21 eyes of 18 patients underwent CTAK. A tissue inlay of preserved corneal tissue was cut to customized specifications with a femtosecond laser and placed in a laser-created channel in the host cornea. Postoperative uncorrected and corrected distance visual acuity (UDVA, CDVA), manifest refraction spherical equivalent (MRSE), topographic mean keratometry (Kmean), maximum keratometry (Kmax), and the point of maximum flattening (Kmaxflat) were measured.

Results:
Average UDVA improved from 1.21 ± 0.35 logMAR lines (LL) (20/327) to 0.61 ± 0.25 LL (20/82) (P < .001). Average CDVA improved from 0.62 ± 0.33 LL (20/82) to 0.34 ± 0.21 LL (20/43) (P = .002), and average MRSE improved from −6.25 ± 5.45 diopters (D) to −1.61 ± 3.33 D (P = .002). Individually, 20 eyes (95.2%) gained more than 2 lines of UDVA, with 10 eyes (47.6%) gaining more than 6 lines, and no eyes worsening. 12 eyes (57.1%) gained at least 2 lines of CDVA, with 1 eye worsening by more than 2 lines. At 6 months, average Kmean flattened by −8.44 D (P = .002), Kmax flattened by −6.91 D (P = .096), and mean Kmaxflat was −16.03 D.

Conclusions:
CTAK is a promising procedure to improve visual acuity and topography in patients with KC and ectasia.