bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-citrullinated protein antibody profiles predict changes in disease activity in patients with rheumatoid arthritis initiating biologics
Authors: Aripova Nozima , Kremer Joel M , Pappas Dimitrios A , Reed George , England Bryant R , Robinson Bill H , Curtis Jeffrey R , Thiele Geoffrey M , Mikuls Ted R 
Published: May 2023

Abstract

Objectives
To determine whether an expanded antigen-specific ACPA profile predicts changes in disease activity in patients with RA initiating biologics.

Methods
The study included participants from a prospective, non-randomized, observational RA cohort. For this sub-study, treatment groups of interest included biologic-naïve initiating anti-TNF, biologic-exposed initiating non-TNF, and biologic-naïve initiating abatacept. ACPAs to 25 citrullinated peptides were measured using banked enrolment serum. Principal component analysis (PCA) was performed and associations of resulting principal component (PC) scores (in quartiles) and anti-CCP3 antibody (≤15, 16–250 or &gt;250 U/ml) with EULAR (good/moderate/none) treatment response at 6 months were examined using adjusted ordinal regression models.

Results
Participants (n = 1092) had a mean age of 57 (13) years and 79% were women. At 6 months, 68.5% achieved a moderate/good EULAR response. There were three PCs that cumulatively explained 70% of variation in ACPA values. In models including the three components and anti-CCP3 antibody category, only PC1 and PC2 were associated with treatment response. The highest quartile for PC1 (odds ratio [OR] 1.76; 95% CI: 1.22, 2.53) and for PC2 (OR 1.74; 95% CI: 1.23, 2.46) were associated with treatment response after multivariable adjustment. There was no evidence of interaction between PCs and treatment group in EULAR responses (P-value for interaction &gt;0.1).

Conclusion
An expanded ACPA profile appears to be more strongly associated with biologic treatment response in RA than commercially available anti-CCP3 antibody levels. However, further enhancements to PCA will be needed to effectively prioritize between different biologics available for the treatment of RA.
Investigating the effects of 7‐ketocholesterol on retinal pigment epithelium bioenergetics
Authors: Dey Sanchareeka , Catchpole Timothy , Takacs Alison , Csaky Karl G. 
Published: May 2023

AbstractAge‐related macular degeneration (AMD) is associated with formation of drusen, clusters of lipids, and oxidized lipid products under the retinal pigment epithelium (RPE). 7‐Ketocholesterol (7KC) is a form of oxidized cholesterol present in drusen and is hypothesized to play a role in AMD pathogenesis. The association of 7KC with cellular toxicity and inflammation, key elements of AMD pathology, has been demonstrated. However, the effects of 7KC on altering RPE bioenergetics, a potentially important pathologic process in AMD, are unclear. Herein, we describe the effects of non‐lethal doses of 7KC on the bioenergetics and phenotype of RPE cells in culture. Metabolic analysis demonstrated a significant dose‐dependent increase in total ATP production rates that was driven primarily by an increase in glycolysis. The increase in glycolysis was accompanied by an increase in glucose uptake and increased expression of hexokinase 1. Increased levels of Translocase of Outer Mitochondrial Membrane 20 and NADH:Ubiquinone Oxidoreductase Core Subunit S1, Succinate dehydrogenase, Ubiquinol‐Cytochrome C Reductase Core Protein 2, Cytochrome C Oxidase II, and ATP synthase subunit beta, proteins involved in oxidative phosphorylation (OXPHOS), were also seen. However, specific electron transport chain activity remained unchanged. 7KC‐treated cells also demonstrated a change in cellular morphology with decreased expression of epithelial markers. In summary, 7KC has significant effects on the bioenergetics and morphology of RPE cells reflective of findings seen in clinical AMD.
METTL3‐mediated ANXA2 inhibition confers neuroprotection in ischemic stroke: Evidence from in vivo and in vitro studies
Authors: Liu Bin , Xing Zhiqun , Song Feng , Li Dejun , Zhao Bao , Xu Chunyang , Xia Wenjun , Ji Hongsheng 
Published: May 2023

AbstractGiven the important role of m6A, the most common and reversible mRNA modification, in the pathogenesis of ischemic stroke, this study investigates the mechanisms of m6A methyltransferase METTL3 in neuronal damage in ischemic stroke. In silico analysis was used to pinpoint the expression of ANXA2, which was verified in clinical peripheral blood samples. SD rats were used for middle cerebral artery occlusion (MCAO) establishment. The experimental data suggested that T lymphocytes were increased in peripheral blood samples of ischemic stroke patients and MCAO rats. The MCAO rats were treated with anti‐ANXA2 alone or combined with RP101075 (T lymphocyte infiltration inhibitor), followed by brain injury assessment. Oxygen–glucose deprivation/reoxygenation (OGD/R) was induced in primary cortical neurons, where shRNAs targeting ANXA2 or METTL3, or overexpression plasmids of METTL3 were introduced to verify the regulatory function for METTL3. Inhibition of T lymphocyte migration to the ischemic brain reduced brain injury in MCAO rats and neuronal damage in OGD/R‐exposed neurons. Ablation of ANXA2 in T lymphocytes inhibited the migration of T lymphocytes to the ischemic brain and reduced neuronal damage. Mechanistically, METTL3 reduced ANXA2 expression in T lymphocytes through m6A modification and inhibited p38MAPK/MMP‐9 pathway activation, exerting protective effects against neuronal damage in ischemic stroke. Overall, this study reveals the neuroprotective effects of METTL3‐mediated ANXA2/p38MAPK/MMP‐9 inhibition against ischemic stroke.
The plant‐derived alkaloid aloperine prevents ischemia/reperfusion injury‐induced sudden cardiac death
Authors: Hu Zhaoyang , Li Jiaxue , Liu Quanhua , Manville Rían W. , Abbott Geoffrey W. 
Published: May 2023

AbstractSudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti‐inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury‐associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion‐provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage‐gated potassium (Kv) channels were performed using two‐electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK‐MB, α‐HBDH, and cTnI post‐I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT‐3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT‐3 (with Ag490) abolished aloperine‐induced anti‐arrhythmic effects and ERK1/2 and STAT‐3 phosphorylation. Interestingly, while aloperine (100 μM) had no effect on cloned Kv4.3 activity, aloperine (1 μM and up) negative‐shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti‐arrhythmic effects against myocardial ischemia and reperfusion injury‐induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT‐3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.
A New Age of Health Promotion
Authors: Chu Charlene H. , Jibb Lindsay A. , MacInnes Neal , Beekhoo Zoraida D. 
Published: May 2023

Abstract
The COVID-19 pandemic has shifted how nursing education and information are delivered, with many classes being moved to an online platform. This opened opportunities to find creative ways to engage students. As a result, an entirely online infographic assignment for final-year baccalaureate nursing students was created. The focus of this assignment was to engage students to identify important health issues, consider multilevel solutions, and communicate information to relevant stakeholders using visual storytelling for maximum impact.
Routine Diaper Change Alters Kidney Oxygenation in Premature Infants
Authors: Marin Terri , Ghosh Santu , Cockfield Christie , Mundy Cynthia , Mansuri Asifhusen , Stansfield Brian K. 
Published: May 2023

Background:
Reduction in oxygen delivery to developing kidneys of premature infants may be an important source for acute kidney injury in premature infants.

Purpose:
To describe changes in continuous kidney oxygenation (RrSO2) measures before, during, and after routine diaper changes.

Methods:
Non–a priori analysis of a prospective cohort that received continuous measurement of RrSO2 with near-infrared spectroscopy (NIRS) over the first 14 days of life demonstrating acute RrSO2 drops surrounding diaper changes.

Results:
In total, 26 of 38 (68%) infants (≤1800 g) from our cohort exhibited acute drops in RrSO2 that temporally correlated with diaper changes. Mean (SD) RrSO2 baseline prior to each diaper change event was 71.1 (13.2), dropped to 59.3 (11.6) during diaper change, and recovered to 73.3 (13.2). There was a significant difference between means when comparing baseline to diaper change (P < .001; 95% CI, 9.9 to 13.8) and diaper change to recovery (P < .001; 95% CI, −16.9 to −11.2). The mean decrease in RrSO2 during diaper change averaged 12 points (17%) below 15-minute RrSO2 mean prior to diaper change, with quick recovery to prediaper change levels. No decreases in SpO2, blood pressure, or heart rate were documented during the intermittent kidney hypoxic events.

Implications for Practice and Research:
Routine diaper changes in preterm infants may increase the risk for acute reductions in RrSO2 as measured by NIRS; however, the impact on kidney health remains unknown. Larger prospective cohort studies assessing kidney function and outcomes related to this phenomenon are needed.
Comparison of failure risk and outcome scores following meniscus repair among adolescent and adult patients
Authors: Martin Kyle , Magnussen Robert A. , Pappa Nicholas , DiBartola Alex C. , Duerr Robert A. , Kaeding Christopher C. , Flanigan David C. 
Published: May 2023

Background:
There are few studies assessing the impact of age at time of surgery on meniscus repair failure risk and patient-reported outcome scores. We sought to determine whether age at time of meniscus repair surgery affects failure risk and patient-reported outcome scores.

Methods:
Patients who underwent meniscus repair during 2006-2013 were evaluated for meniscus repair failure and patient-reported outcome scores using the Knee Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and Marx Activity score at mean follow-up 6.5±2.0 yr post-operative. A multivariable linear regression analysis was used to assess the influence of patient age on patient-reported outcome scores following meniscus repair.

Results:
A total of 170 patients with mean age 27.8±10.1 yr (59% male) were identified, including 29 patients age 18 and younger and 141 patients over 18. Increasing patient age was associated with significantly lower IKDC (P=0.027), KOOS-ADL (P=0.003), and Marx activity scores (P<0.001). Repair failure occurred in 46 patients (27.1%) overall, including 7 failures (24.1%) in patients 18 and under and 39 failures (27.7%) in patients over 18. The logistic regression analysis demonstrated no association between age and meniscus repair failure risk when controlled for ACL reconstruction and BMI (P=0.69).

Conclusion:
Increased age is associated with poorer IKDC, KOOS-ADL, and Marx Activity scores following meniscus repair. However, there is no difference in failure of healing of meniscus repair between adolescent patients and adults.

Level of Evidence:
III
Machine Learning for Benchmarking Adolescent Idiopathic Scoliosis Surgery Outcomes
Authors: Gupta Aditi , Oh Inez Y. , Kim Seunghwan , Marks Michelle C. , Payne Philip R.O. , Ames Christopher P. , Pellise Ferran , Pahys Joshua M. , Fletcher Nicholas D. , Newton Peter O. , Kelly Michael P. ,   Harms Study Group
Published: May 2023

Study Design.
Retrospective cohort.

Objective.
The aim of this study was to design a risk-stratified benchmarking tool for adolescent idiopathic scoliosis (AIS) surgeries.

Summary of Background Data.
Machine learning (ML) is an emerging method for prediction modeling in orthopedic surgery. Benchmarking is an established method of process improvement and is an area of opportunity for ML methods. Current surgical benchmark tools often use ranks and no “gold standards” for comparisons exist.

Materials and Methods.
Data from 6076 AIS surgeries were collected from a multicenter registry and divided into three datasets: encompassing surgeries performed (1) during the entire registry, (2) the past 10 years, and (3) during the last 5 years of the registry. We trained three ML regression models (baseline linear regression, gradient boosting, and eXtreme gradient boosted) on each data subset to predict each of the five outcome variables, length of stay (LOS), estimated blood loss (EBL), operative time, Scoliosis Research Society (SRS)-Pain and SRS-Self-Image. Performance was categorized as “below expected” if performing worse than one standard deviation of the mean, “as expected” if within 1 SD, and “better than expected” if better than 1 SD of the mean.

Results.
Ensemble ML methods classified performance better than traditional regression techniques for LOS, EBL, and operative time. The best performing models for predicting LOS and EBL were trained on data collected in the last 5 years, while operative time used the entire 10-year dataset. No models were able to predict SRS-Pain or SRS-Self-Image in any useful manner. Point-precise estimates for continuous variables were subject to high average errors.

Conclusions.
Classification of benchmark outcomes is improved with ensemble ML techniques and may provide much needed case-adjustment for a surgeon performance program. Precise estimates of health-related quality of life scores and continuous variables were not possible, suggesting that performance classification is a better method of performance evaluation.
Polyfunctionality of broadly neutralizing HIV-1 antibodies
Authors: Vrignaud Lou-Léna , Schwartz Olivier , Bruel Timothée 
Published: May 2023

Purpose of review
The discovery of broadly neutralizing HIV-1 antibodies (bNAbs) has provided a framework for vaccine design and created new hope toward an HIV-1 cure. These antibodies recognize the HIV-1 Envelope and inhibit viral fusion with unprecedented breadth and potency. Beyond their unique neutralization capacity, bNAbs also activate immune cells and interfere with viral spread through nonneutralizing activities. Here, we review the landscape of bNAbs functions and their contribution to clinical efficacy.

Recent findings
Parallel evaluation of bNAbs nonneutralizing activities using in vivo and in vitro models have revealed how their importance varies across antibodies and strains. Nonneutralizing bNAbs functions target both infected cells and viral particles, leading to their destruction through various mechanisms. Reservoir targeting and prevention in context of suboptimal neutralization highly depends on bNAbs polyfunctionality. We recently showed that bNAbs tether virions at the surface of infected cells, impairing release and forming immune complexes, with consequences that are still to be understood.

Summary
Nonneutralizing activities of bNAbs target infected cells, virions, and immune complexes, promoting viral clearance and possibly improving immune responses. We review how these functions participate to the efficacy of bNAbs and how they can be manipulated to improve bNAbs therapies.
Radiation-Induced Eccrine Squamous Syringometaplasia With Perineural Invasion
Authors: Singh Neha S. , Phillips Mariana A. , Buhle Anna C. , Prickett Kyle , Grider Douglas J. 
Published: May 2023

Abstract:
Eccrine squamous syringometaplasia (ESS) is a benign metaplastic reaction of eccrine ducts that occurs in response to injury and can be a histologic mimic of squamous cell carcinoma (SCC). Reported is an 82-year-old man undergoing Mohs surgery for presumed SCC diagnosed in a field of radiation dermatitis. After 3 Mohs stages, the peculiar squamous proliferation was recognized as ESS and the procedure was aborted. Complicating the interpretation of the Mohs frozen section was the presence of perineural invasion because perineural invasion has not been previously reported to occur with ESS. The histologic features used to distinguish ESS from SCC are discussed.
The Effect of Short-Term Acute Residential Treatment on Psychiatric Rehospitalization
Authors: Lichtenberg Pesach , Friedlander Avraham , Bergman-Levy Tal , Susser Ehud , Yoffe Rinat , Budowski Danny , Kodesh Arad , Tzur Bitan Dana , Weiser Mark 
Published: May 2023

Abstract
Short-Term Acute Residential Treatment (START) homes, located in the community and operating in noninstitutional atmospheres, seek to reduce rehospitalization. This report investigates whether these homes reduced rates and duration of subsequent inpatient stays in psychiatric hospitals. For 107 patients treated in START homes after psychiatric hospitalization, we compared the number and duration of psychiatric hospitalizations before and after their START stay. We found that, compared with the year before the START stay, in the year after the START stay, patients had fewer episodes of rehospitalization (1.60 [SD = 1.23] vs. 0.63 [SD = 1.05], t[106] = 7.097, p < 0.001) and a briefer accumulative duration of inpatient stays (41.60 days [SD = 49.4] vs. 26.60 days [SD = 53.25], t[106] = −2.32, p < 0.03). This suggests that START homes can reduce rehospitalization rates and should be considered a valid alternative to psychiatric hospitalization.
West Michigan Suicide Trends During the COVID-19 Pandemic
Authors: Workman Adrienne , deJong Joyce 
Published: May 2023

Abstract
The COVID-19 pandemic has resulted in increased concern regarding the mental health of individuals navigating this public health crisis. Various risk factors for suicide have increased during the pandemic, including isolation, depression, access to firearms, substance use, and loss of employment. However, the relationship between the COVID-19 pandemic and suicide rates in the United States remains unclear. In this retrospective study, we examined the relationship between suicide rates and COVID-19 cases in 11 West Michigan counties. Suicide rates in the prepandemic (January 2018 to February 2020) and pandemic (March 2020 to February 2022) months were compared after adjusting for seasonal and population size effects. A mixed effects model was used to assess the impacts of local COVID-19 rates and county on the ratio of pandemic to prepandemic monthly suicide rates. The model did not find a significant effect of COVID-19 case rates on suicide rates. Although this study does not find sufficient evidence for a statistical relationship between COVID-19 cases and suicide rates in West Michigan, close surveillance should continue and public health measures should be used because of the increased risk factors for suicide associated with the pandemic.
Comparing Clinical and Aesthetic Outcomes of Digital Artery Flap using Nail Bed Graft for Fingertip Amputation with Replantation
Authors: Kuwahara Yutaro , Hara Tatsuya , Kurahashi Toshikazu , Takeshige Hiroki , Urata Shiro , Oguchi Takeshi 
Published: May 2023

Background:
Digital artery flap (DAF) with nail bed graft is a simple method to preserve finger length for fingertip amputations. This study compared the clinical and aesthetic outcomes between replantation and DAF.

Methods:
Patients who underwent replantation or DAF for a single fingertip amputation (Ishikawa’s subzone II or III) at our hospital from 2013 to 2021 were retrospectively evaluated. The aesthetic and functional outcomes were finger length and nail deformity at the final follow-up, total active motion, grip strength, Semmes-Weinstein monofilament test (S-W), fingertip injuries outcome score (FIOS), and Hand20 scores.

Results:
Overall, for 74 analyzed cases (40, replantation; 34, DAF), the median operation time and the median length of hospital stay in replantation was longer than that in DAF (188 vs. 126 min, p<0.01; 15 vs. 4 days, p<0.01). The success rates of replantation and DAF were 82.5% and 94.1%, respectively. The rate of finger shortening in replantation was significantly lower than that in DAF (42.5% vs. 82.4%; p<0.01). There were fewer nail deformities in replantation than in DAF (45.0% vs. 67.6%, p=0.06). The proportion of patients who achieved excellent or good FIOS and the median Hand20 scores was not significantly different between the groups (89.5% vs. 85.3%, p=0.61; 8.0 vs. 13.5, p=0.42). The median postoperative S-W values were similar between the groups (3.61 vs. 3.61, p=0.23).

Conclusions:
In this retrospective study, DAF for fingertip amputations achieved equivalent postoperative functional outcomes and shorter intraoperative time and hospital stay, but worse aesthetic appearance compared with replantation.
Customized Orthosis for Nonsurgical Correction of Congenital Auricle Deformities in Newborns
Authors: Zhao Hui , Huang Shenghua , Li Suxia , Han Zhenyan , Huang Wenhua 
Published: May 2023

Summary:
A misshaped pinna, caused by extrinsic pressures such as birth canal extrusion or incorrect position, is a common congenital auricular deformity in newborns. Surgery is a routine option to address this deformity, but it is traumatic and may lead to unacceptable aesthetic outcomes. Commercial ear mold orthoses with uniform size have been used for nonsurgical orthotic treatment, but are not applicable in all cases, depending on the auricle morphology. The authors used computer-aided design and three-dimensional (3D) printing technology to develop a novel customized orthosis for congenital auricular deformities. 3D ear models were constructed using computer-aided design software and a novel customized orthosis model was established after a process of correction, adjustment, and construction, with precise matching to allow tight attachment to the outer ear free from uneven skin pressing. After 3D-printing a customized orthosis injection mold, medical silicone injection molding was used to produce customized orthoses. Clinical application was conducted in 3 newborns and achieved satisfactory results. This novel customized auricle orthosis is an effective option for nonsurgical correction of a misshaped pinna.