bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles
Authors: Saygin Didem , Kim Hanna , Douglas Christian , Erman Brian , Wilkerson Jesse , McGrath John A , Oddis Chester V , Lundberg Ingrid E , Amato Anthony A , García-De La Torre Ignacio , Chinoy Hector , Fiorentino David , Chung Lorinda , Song Yeong-Wook , Miller Frederick W , Ruperto Nicolino , Vencovsky Jiri , Aggarwal Rohit , Rider Lisa G ,   for the International Myositis Assessment and Clinical Studies Group (IMACS), Kim Susan , Pinal-Fernandez Iago , Ascherman Dana , Schiffenbauer Adam 
Published: March 2023

Abstract

Objective
The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening.

Methods
Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC.

Results
Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories.

Conclusion
The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.
Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications
Authors: Yeo Jina , Yoon Soon Ho , Kim Ju Yeon , Lee Jeong Seok , Lee Eun Young , Goo Jin Mo , Pourzand Lila , Goldin Jonathan G , Kim Grace-Hyun J , Ha You-Jung 
Published: March 2023

Abstract

Objectives
To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD).

Methods
The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes.

Results
The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1–43.8). The QILD was significantly correlated with forced vital capacity (r = −0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = −0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD &gt;2%, P = 0.015). Patients with higher baseline QILD scores (&gt;28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed.

Conclusion
QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.
A NEW DOSE DETERMINATION METHOD FOR HP(3) AND DP LENS FOR BETA REFERENCE RADIATION QUALITIES
Authors: Teng Zhongbin , Song Mingzhe , Liu Senlin , Ni Nin , Wei Kexin , Liu Yuntao , Hang Zhongbin , Geng Xuan , Hu Kaixuan , Li Qiao , Jia Minghan , Li Dehong 
Published: March 2023

Abstract
For the purpose of obtaining the smaller uncertainties for Hp(3) and Dp lens in 90Sr/90Y beta reference fields, a new dose determination method based on the Monte-Carlo simulation was proposed. The conversion coefficients from the absorbed dose in air, at the reference point of the extrapolation ionisation chamber, Dair, det to Hp(3; α) and the conversion factors from Dair, det to Dp lens(α) were calculated with EGSnrc, respectively, for the irradiation angles from 0° to 60°. Compared with the dose determination method in International Organization for Standardization (ISO) 6980 standard, the uncertainty reductions of 7.7–52.8% for Hp(3; α) and 7.9–55.0% for Dp lens(α) were achieved, respectively. In addition, for the conversion coefficients from the reference absorbed dose DR to Hp(3; α), the calculations were performed for more irradiation conditions, which are not included in the current ISO 6980 standard. For the calculations of the conversion factors from DR to Dp lens(α), the eye and head phantoms with Chinese characteristics were utilised, which makes the conversion factors more suitable for use in China.
Long-term exposure to di(2-ethylhexyl) phthalate, diisononyl phthalate, and a mixture of phthalates alters estrous cyclicity and/or impairs gestational index and birth rate in mice
Authors: Laws Mary J , Meling Daryl D , Deviney Ashley R K , Santacruz-Márquez Ramsés , Flaws Jodi A 
Published: March 2023

Abstract
Phthalates are found in plastic food containers, medical plastics, and personal care products. However, the effects of long-term phthalate exposure on female reproduction are unknown. Thus, this study investigated the effects of long-term, dietary phthalate exposure on estrous cyclicity and fertility in female mice. Adult female CD-1 mice were fed chow containing vehicle control (corn oil) or 0.15–1500 ppm of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), or a mixture of phthalates (Mix) containing DEHP, DiNP, benzyl butyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, and diethyl phthalate. Measurements of urinary phthalate metabolites confirmed effective delivery of phthalates. Phthalate consumption for 11 months did not affect body weight compared to control. DEHP exposure at 0.15 ppm for 3 and 5 months increased the time that the mice spent in estrus and decreased the time the mice spent in metestrus/diestrus compared to control. DiNP exposure (0.15–1500 ppm) did not significantly affect time in estrus or metestrus/diestrus compared to control. Mix exposure at 0.15 and 1500 ppm for 3 months decreased the time the mice spent in metestrus/diestrus and increased the time the mice spent in estrus compared to control. DEHP (0.15–1500 ppm) or Mix (0.15–1500 ppm) exposure did not affect fertility-related indices compared to control. However, long-term DiNP exposure at 1500 ppm significantly reduced gestational index and birth rate compared to control. These data indicate that chronic dietary exposure to phthalates alters estrous cyclicity, and long-term exposure to DiNP reduces gestational index and birth rate in mice.
Kcnma1 is involved in mitochondrial homeostasis in diabetes‐related skeletal muscle atrophy
Authors: Gao Shan‐Yan , Liu Yong‐Ping , Wen Ri , Huang Xin‐Mei , Li Ping , Yang Yu‐Hang , Yang Ni , Zhang Tie‐Ning 
Published: March 2023

AbstractUncontrolled diabetes causes a catabolic state with multi‐organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore‐forming α‐subunit of Ca2+‐ and voltage‐gated K+ channels of large conductance (BK channels), and loss‐of‐function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time‐course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor‐deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle‐specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno‐associated virus‐9 (AAV9)‐encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9‐shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9‐shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis‐related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate‐treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
Long non‐coding RNA SNHG11 regulates the Wnt/β‐catenin signaling pathway through rho/ROCK in trabecular meshwork cells
Authors: Liu Lu , Yang Xuejiao , Zhang Jingjing , Jiang Wenlan , Hou Tianyu , Zong Yao , Bai Haiqing , Yang Kun , Yang Xian 
Published: March 2023

AbstractTrabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non‐coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM3) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real‐time PCR analysis (qRT‐PCR), western blotting, and CCK‐8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/β‐catenin pathway activity was inferred from qRT‐PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT‐PCR and western blotting. SNHG11 was downregulated in GTM3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/β‐catenin signaling pathway, and activated Rho/ROCK. Wnt/β‐catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/β‐catenin signaling through Rho/ROCK by increasing GSK‐3β expression and β‐catenin phosphorylation at Ser33/37/Thr41 while decreasing β‐catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/β‐catenin signaling through Rho/ROCK via β‐catenin phosphorylation at Ser675 or GSK‐3β‐mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, apoptosis, and autophagy. Through its effects on Wnt/β‐catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.
Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission
Authors: Casciaro Christopher , Hamada Hirotaka , Kostaki Alisa , Matthews Stephen G. 
Published: March 2023

AbstractApproximately 1%–3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring. Here, we hypothesized that sGC exposure will alter the miRNA profile of sperm in the epididymis in a region‐specific manner. Adult male guinea pigs were exposed to regular drinking water (Ctrl) or water with the sGC dexamethasone (Dex; 3mg/kg) (n = 6/group) every other day for 48 days. Sperms were collected from epididymal seminal fluid in the caput and cauda regions of the epididymis and total RNA was extracted. miRNAs were assessed by miRNA 4.0 microarray; data were processed by TAC 4.0.1 and R. miRNA analysis revealed one miRNA in the caput that was significantly decreased by Dex in sperm. In the cauda, 31 miRNAs were reduced in sperm following Dex‐exposure. The findings of this study demonstrate that Dex‐exposure influences miRNA profile of sperm in the cauda but not the caput of the epididymis. This suggests that glucocorticoids target the epididymis to modify sperm miRNA and do not modify the miRNA content during spermiation in the testes.
Measuring hepatitis B pgRNA stability using an updated automated HBV pgRNA assay with increased sensitivity
Authors: Anderson Mark , Stec Michael , Thi Emily P. , Picchio Gaston , Mbanya Dora , Cloherty Gavin 
Published: March 2023

Background:
HBV pregenomic RNA (pgRNA) is a circulating biomarker for covalently closed circular DNA activity in HBV-infected individuals and has been studied for treatment efficacy, disease staging, and off-therapy outcomes; however, data on the stability are scarce. Increasing HBV pgRNA assay sensitivity may improve its predictive value and provide additional insights at low viral levels.

Methods:
Modifications to a fully automated first (v1) generation HBV pgRNA assay improved sensitivity up to 15-fold over the previous assay. Flexible sample input volumes yielded lower limits of quantitation of 10 and 22 copies/mL for 0.6 and 0.2 mL assays, respectively. Results are standardized to secondary standards that are traceable to the WHO HBV DNA standard, and internal and external controls are included.

Results:
Comparison between v1 and modified v2 assays showed increased sensitivity from 152 copies/mL with v1 to 10 (0.6 mL) and 22 (0.2 mL) copies/mL with v2, respectively. Quantitated v2 results were indistinguishable from v1, indicating that comparisons can be made to previous studies. Single timepoint treatment-naive blood donors or longitudinal draws from patients with chronic hepatitis B on AB-729, an investigational siRNA therapy, showed improved detection and quantifiable pgRNA with v2 compared with v1. Stability testing demonstrated excellent HBV pgRNA plasma stability after 3 freeze-thaw cycles, for at least 7 days at 25–37 °C and at least 30 days at 4°C, with ≤0.25 Log U/mL decrease.

Conclusion:
HBV pgRNA v2 assays with increased sensitivity and flexible input volumes demonstrated increased detection and quantitation of low viral titer samples. Highly sensitive HBV pgRNA assays may be useful in refining predictive treatment outcomes based on this marker. HBV pgRNA was stable under multiple conditions, which increases the reliability of this marker.
TEMPORAL EFFICACY AND STERILITY TESTING OF POVIDONE-IODINE FROM AN OPEN BOTTLE
Authors: Yousuf Salman J. , Alfaqih Murad , Hicken Rachel , Ramadan Ali 
Published: March 2023

Purpose:
To investigate the temporal efficacy and sterility of povidone-iodine (PI) against bacteria associated with postinjection endophthalmitis in an in vitro study.

Methods:
A single PI bottle was opened and tested for sterility and antibacterial efficacy. Povidone-iodine from the open bottle was inoculated onto a blood agar plate and evaluated for growth 24 hours later to test sterility; this was repeated for five consecutive days. To test for antibacterial efficacy, PI was instilled onto the surface of plates of Staphylococcus, Streptococcus, Enterococcus, Pseudomonas, and Haemophilus species. The plates were then evaluated 24 hours later for a clear zone of inhibition (i.e., no growth) where the PI was placed. This process was repeated for five consecutive days.

Results:
Sterility testing showed no growth of organisms on the blood agar plates for each of the five days of testing. For antibacterial efficacy testing, zones of inhibition of growth were seen on each plate of bacterial colonies only where PI was placed, for each of the five days of testing.

Conclusion:
In this study, PI from an open bottle maintained its sterility and antibacterial efficacy for five days. These data could help support repeated use of the same bottle, reducing waste and costs for retina practices.
Retinal Nerve Fiber Layer Thickness/Minimum Rim Width Ratio Differentiates Glaucoma From Other Optic Neuropathies
Authors: Boussion François , Guindolet Damien , Deschamps Romain , Lamirel Cédric , Vignal-Clermont Catherine 
Published: March 2023

Précis:
Global peripapillary retinal nerve fiber layer thickness (pRNFL)/Bruch membrane opening–minimum rim width (BMO–MRW) ratio is an objective and effective parameter to separate glaucomatous optic neuropathies (GONs) from nonGONs (NGONs).

Purpose:
This study was undertaken to evaluate the diagnostic capability of the pRNFL/ BMO–MRW ratio to differentiate GONs from NGONs.

Patients and Methods:
This retrospective study included patients with an optic neuropathy (ON), visual loss for>6 months and a confirmed single etiology. pRNFL thickness and BMO–MRW were measured with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The diagnostic accuracies of pRNFL, BMO–MRW and the global pRNFL/BMO–MRW ratio were evaluated with the areas under receiver operating characteristics curves.

Results:
One eye each from 171 patients was investigated: 50 primary open angle glaucomas, 15 normal pressure glaucomas, 50 optic neuritises, 15 nonarteritic anterior ischemic ONs, 24 compressive ONs, 10 dominant optic atrophies, and 7 nutritional ONs. The global pRNFL/BMO–MRW ratio had the highest area under receiver operating characteristics curve [0.97 vs. 0.92; P=0.01]. It was able to distinguish between GONs and NGONs with a cutoff value of 0.34. Increased mean deviation of the visual field-defect severity was associated with a higher ratio for GONs and a lower ratio for NGONs.

Conclusion:
Compared with NGONs and for the same degree of pRNFL thinning, lower BMO– MRW was found to be a specific marker of glaucoma, reflecting the neuroglial architecture changes within the optic nerve head typical of glaucoma and supporting fundamental pathophysiological differences.
Five-Year Clinical Outcomes of Inferior Quadrant Trabectome Surgery for Open Angle Glaucoma
Authors: Weber Constance , Ludwig Elisabeth , Hundertmark Sarah , Brinkmann Christian Karl , Petrak Michael , Holz Frank G. , Mercieca Karl 
Published: March 2023

Précis:
This retrospective study of 264 eyes having inferior quadrant trabectome surgery confirms its safety and relative effectiveness. Most patients however still require IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery.

Purpose:
To report outcomes from a large single-center cohort of inferiorly-applied trabectome surgery.

Patients and Methods:
Retrospective review of patients undergoing trabectome surgery for chronic open angle glaucoma (COAG) at the University Eye Clinic Bonn, Germany, from 2012 to 2020.

Results:
Two hundred sixty-four eyes of 206 patients with COAG were included. The mean review period was 45.43 (range 12–101) months. One hundred five eyes (39.8%) underwent standalone surgery, of which 74 were pseudophakic and 31 phakic. The mean preoperative IOP was 17.58 mm Hg (range 12–50 mm Hg). One hundred five eyes (39.8%) developed a ‘failure event’ according to pre-defined criteria at a mean interval of 14.8 months postoperative. In absolute terms, 211 patients (79.9%) had a long-term IOP >14 mm Hg at 7.6 months, 174 patients (65.9%) >16 mm Hg at 10.6 months, 127 patients (48.1%) >18 mm Hg at 10.9 months, and 77 patients (29.2%) >21 mm Hg at 11.1 months. Over a five-year period, overall mean IOP remained stable at 13 mm Hg. The majority of patients were still on glaucoma drops (the mean number reduced from 2.9 to 2.7 agents). Subgroup analyses showed that a higher preoperative IOP was a positive predictor for failure, whereas combined surgery (with phaco) had better IOP outcomes (16.5 mm Hg vs. 19.3 mm Hg, respectively). Forty-one patients (15.5%) developed minor complications: 22 had high postoperative IOP within 3 months, 11 developed a self-resorbing hyphema, and 6 had fibrinous uveitis.

Conclusions:
Trabectome surgery is a safe and relatively effective procedure for lowering IOP, but most patients still need IOP-lowering agents, and a considerable proportion may need additional glaucoma surgery within a relatively short time. Inferior quadrant treatment may result in inferior IOP outcomes when compared with nasal quadrant surgery.
Effect of Online Instruction on the Level of Knowledge About Clostridium difficile Infection Among Undergraduate Nursing Students in a Developing Country
Authors: Najjar Yahya W. , Hassan Zeinab M. , Al-saraireh Mahmoud M. 
Published: March 2023

Abstract

Background

Clostridium difficile infection is a life-threatening hospital-acquired infection worldwide. Nursing students need to be able to identify patients who have a high chance of contracting C. difficile infection. The study objective is to determine the level of knowledge on C. difficile infection before and after online instruction in undergraduate nursing students.

Methods
A group pretest-posttest design was implemented to measure the effectiveness of an online instructional program, in which 170 nursing students participated in this study. The level of knowledge was assessed by the percentage of correct answers in the following subsections: (a) basic knowledge; (b) risk factors; (c) modes of transmission; and (d) infection control measures, by using a questionnaire that contained 20 true/false statements.

Results
Overall, the nurses in this study had a low level of knowledge about C. difficile pre–online instruction and a significant increase in knowledge regarding C. difficile infection in all sections after online instruction.

Conclusions
Online instruction should be integrated into the undergraduate nursing curriculum in developing countries. Self-directed instruction is an effective approach for nursing students to teach them infectious diseases in developing countries.
A Unique Case of Purulent Malignant Otitis Externa Causing Community-Acquired Klebsiella Pneumonia Meningitis in a Marshallese Male
Authors: Belote Alex , Conde Daniel , Young Daniel 
Published: March 2023

Abstract
Bacterial meningitis secondary to malignant otitis externa is a rare but dreaded complication. Malignant otitis externa typically results from infection with Pseudomonas aeruginosa. Community-acquired bacterial meningitis most commonly stems from Streptococcus pneumoniae or Neisseria meningitidis. We report a unique case of community-acquired Klebsiella pneumoniae meningitis, a rare culprit in the United States. Klebsiella pneumoniae disproportionally affects people of Southeast Asian descent. Dramatically increased rates of K. pneumoniae infection have been reported in Asian countries and in expatriates living abroad. Our case afflicted a 48-year-old man originally from the Marshall Islands residing in the United States. This case displays a unique constellation of anomalies and afflictions, including extension from MOE, bacteremia, facial nerve paralysis, dural sinus thrombosis, and rapid recovery.