bluuebunny/crossref_metadata_2025_split huggingface dataset:
LYP's implications cause both increased or decreased susceptibility towards autoimmune and acquired diseases (LB96)
Authors: Babinski Alexander , Fernandez Michelle , Georgieva Darina , Gui Michael , Huettl Maggie , Prebble Lara , Roselle Anna , Schultz Eric , Shukla Neehal , Fassler Amy , Schrodi Steve 
Published: June 2021

When functioning properly, the immune system protects the body from foreign invaders with the help of T‐cells. An error in the formation of T‐cells in the thymus can lead to autoimmune diseases in which the T‐cells attack normal body tissues. When a T‐cell binds to an antigen, a signal transduction pathway is activated, forming a multimeric signaling complex known as the TCR signalosome. LCK, part of the signalosome, is a lymphocyte‐specific protein tyrosine kinase that phosphorylates a variety of proteins in order to activate the T‐cell receptor pathway. TCR stimulation also leads to the activation of LYP, a lymphoid tyrosine phosphatase that down regulates TCR signaling by removing phosphates from the signaling intermediates of the TCR signalosome. LYP also dephosphorylates Y394 of LCK, thus inactivating the kinase and inhibiting TCR signaling. The LYP R620W mutation prevents LYP from binding to the signalosome, resulting in a gain‐of‐function, leading to increased inhibition of TCR signaling. The LYP R620W mutation has been linked to a wide spectrum of human diseases, including a decreased risk in Crohn’s disease and increased risk to rheumatoid arthritis, and possible links to non‐autoimmune disorders such as cardiovascular disease. The Marshfield SMART (Students Modeling A Research Topic) Team modeled the mutated protein LYP R620W using 3D technology.Grant Funding Source: Supported by grants from NIH‐CTSA and NIH‐SEPA.
Calcium channel blockers improve prognosis of patients with coronavirus disease 2019 and hypertension
Authors: Peng Chi , Wang Hao , Guo Yu-Feng , Qi Ge-Yao , Zhang Chen-Xu , Chen Ting , He Jia , Jin Zhi-Chao 
Published: June 2021

Abstract

Background:
Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.

Methods:
We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.

Results:
Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13–0.76, χ
2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13–1.43, χ
2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53–2.69, χ
2 = 0.17, P = 0.6777).

Conclusions:
In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.
A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy
Authors: Xia Hai-Zhui , Bi Hai , Yan Ye , Yang Bin , Ma Ruo-Zhuo , He Wei , Zhu Xue-Hua , Zhang Zhi-Ying , Zhang Yu-Ting , Ma Lu-Lin , Hou Xiao-Fei , Wirth Gregory J. , Lu Jian 
Published: June 2021

Abstract

Background:
Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).

Methods:
A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.

Results:
A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.

Conclusions:
PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.
Ginkgo Biloba Extract EGB761 Alleviates Warfarin-induced Aortic Valve Calcification Through the BMP2/Smad1/5/Runx2 Signaling Pathway
Authors: Liu Jing , Liu Cuiying , Qian Chunqi , Abela George , Sun Wei , Kong Xiangqing 
Published: June 2021

Abstract:
Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.
Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study
Authors: Dixon Dave L. , Billingsley Hayley E. , Canada Justin M. , Trankle Cory R. , Kadariya Dinesh , Cooke Richard , Hart Linda , Van Tassell Benjamin , Abbate Antonio , Carbone Salvatore 
Published: June 2021

Abstract:
The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (−12.5 to 19.5) mg/dL versus −8 (−19 to −1) mg/dL (P = 0.82) and triglyceride levels was −4 (−26 to 9) mg/dL and −10.5 (−50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.
Fournier's Gangrene with Edwardsiella tarda: A Gas Production Case by Bacterial Synergism with Streptococcus anginosus
Authors: Tsuge Itaru , Matsui Miho , Kanno Toru , Kaisho Junichi , Takahashi Toshifumi , Yamanaka Hiroki , Katsube Motoki , Sakamoto Michiharu , Morimoto Naoki 
Published: June 2021

Summary:

Edwardsiella tarda is an anaerobe associated with freshwater and marine life. Necrotizing soft tissue infection caused by E. tarda is rare, but its mortality rate is extremely high (61.1%). We experienced a survival case of Fournier’s gangrene with E. tarda. A key clinical feature for the diagnosis was gas production; however, there have been no previous reports of such a phenomenon in relation to E. tarda. A 64-year-old man was admitted with a 3-day history of a high fever. His medical history, which included paraplegia from the Th6 level down, made the focus of inflammation at the perineum difficult to notice. Whole-body CT revealed subcutaneous gas from the posterior scrotum around the entire circumference of the anus. During emergency surgery, an incision at the posterior scrotum revealed extensive fascia necrosis, and E. tarda and Streptococcus anginosus were identified. We speculated the gas production in this case to be the product of a mixed infection of aerobes and anaerobes, which acted synergistically to induce bacterial growth. Timely surgical debridement and antibiotic therapy led to the patient’s survival.
Applying Unsterile Microporous Tape onto Surgical Wounds: Tape Contamination and Clinical Rationale
Authors: Ausen Kjersti , Kroknes Marthe L. , Gunnarson Gudjon , Radtke Andreas 
Published: June 2021

Background:
Fomites are surfaces that carry contaminants and may cause infection. We wanted to assess the bacterial load on rolls of nonsterile microporous tape in a hospital setting and explore the scientific rationale behind the existing practice of applying unsterile adhesives onto a surgical wound.

Methods:
We analyzed the aerobic bacterial contamination in rolls of microporous tape collected from surgical theaters, outpatient clinics, and storage rooms at St. Olav’s University Hospital, Trondheim, Norway between 2018 and 2020. We also reviewed the literature for relevant publications.

Results:
A total of 58 rolls were collected; 55 were included for final analysis. Exposed tape surfaces were significantly more contaminated than unexposed surfaces. Tape rolls from outpatient clinics were significantly more contaminated and contained a significantly greater variety of microbes than rolls from operation theaters and storage rooms. Unexposed surfaces from both operation theaters and storage rooms demonstrated very little contamination.

Conclusions:
Rolls of tape may act as fomites, but widespread use of adhesives is inevitable in hospital settings. Removing the outer layer of a tape roll before use may significantly reduce bacterial contamination. Given sufficient vigilance to avoid cross-contamination, inner layers of tape may represent a close-to-sterile alternative as surgical dressing. However, the economic savings constitute a negligible fraction of the total costs of the surgery, and the risk of contamination seems apparent. Scientific support of dressing a fresh surgical wound with unsterile microporous tape is lacking, and we therefore do not recommend the practice except in situations with very limited resources.
Results From the German Fungal Keratitis Registry: Significant Differences Between Cases With and Without a History of Contact Lens Use
Authors: Roth Mathias , Holtmann Christoph , Daas Loay , Kakkassery Vinodh , Kurzai Oliver , Geerling Gerd ,   and German Fungal Keratitis Registry Study Group
Published: June 2021

Purpose:
Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome.

Methods:
Data from 173 cases reported in the German FK registry until August 2019 were evaluated regarding CL behavior, other ophthalmological and general risk factors, age, sex, identified pathogens, conservative and surgical therapy, visual acuity, and findings at admission and follow-up.

Results:
One hundred seventy-four eyes from 173 patients between 2000 and 2019 were included [64.4% women, median age 54 (39; 72) years]; 49.7% wore CL, of which 81.3% were soft CL, and 50.3% had no history of contact lens use (NCL). CL users were significantly more often women and otherwise healthy (CL: 80.2% vs. NCL: 48.9%; P < 0.0001). The spectrum of pathogens among CL users showed a significantly higher proportion of infections with filamentous pathogens, in particular Fusarium sp. (total filament: CL 69.8% vs. NCL 27.3%; P = 0.0001; Fusarium sp.: CL 50.0% vs. NCL 14.8%; P < 0.0001). Overall, 54.6% required keratoplasty and 8.6% enucleation.

Conclusions:
CLS are the most important risk factor for FK in Germany. With CLs, typically, the infection is caused by molds, and patients are comparably younger and otherwise healthy. Often, extensive surgery is needed. To evaluate changes in the pathogen and resistance spectrum and to further monitor possible CL-related risk factors, a consistent collection of data remains paramount.
The Role of Corneal Donor Rim Fungal Cultures: Pro Side
Authors: Ritterband David 
Published: June 2021

Abstract:
Fungal infection after corneal transplantation is a rare but potentially devastating complication. It is of paramount concern for transplant surgeons and the eye banking community. The value of universal corneal rim cultures for keratoplasty remains controversial. In 2016, The Eye Bank Association for America reported an increasing trend in the incidence of post keratoplasty fungal infections and a higher incidence of post keratoplasty [penetrating keratoplasty and endothelial keratoplasty (EK)] fungal endophthalmitis cases. This increasing trend in rate over time from previous Eye Bank Association for America reports was disproportionately associated with EK and Candida species. Additionally, several studies confirmed a high correlation between positive corneoscleral donor rim fungal cultures and postoperative infections, and a higher risk to the mate eye of a cornea that had the positive fungal corneal rim culture and developed an infection. Positive fungal donor rim cultures-especially in the setting of interface keratitis after EK surgery-can raise the index of suspicion for a fungal cause and may help direct therapy, especially in the early stages, where the symptoms and signs of spread may not be obvious and obtaining direct cultures is inherently difficult without surgical intervention.
Scheimpflug Corneal Densitometry Values and Severity of Guttae in Relation to Visual Acuity in Fuchs Endothelial Corneal Dystrophy
Authors: Shah Khushali , Eghrari Allen O. , Vanner Elizabeth A. , O'Brien Terrence P. , Koo Ellen H. 
Published: June 2021

Purpose:
The purpose of this study was to investigate the association between corneal densitometry (CD) values from Scheimpflug tomography imaging, severity of guttae, and visual acuity in eyes with Fuchs endothelial corneal dystrophy (FECD).

Methods:
This was a retrospective, cross-sectional study. Patients with FECD were examined at the Bascom Palmer Eye Institute from January 2015 to September 2019. We extracted CD values at central annuli of 0-2, 2-6, 6-10 and 10-12 mm from Scheimpflug tomography images. We investigated the association of corrected distance visual acuity (CDVA) with CD values, severity of guttae, central corneal thickness (CCT), cataract grade, refractive error, corneal edema grade, age, and gender using multivariate generalized estimating equation regression models.

Results:
One hundred ninety-two eyes from 110 patients were included in this study. Increase in central CD values at the 0 to 2 mm zone (P < 0.001), severity of guttae (P = 0.046), age (P < 0.001), cataract grade (P < 0.001), corneal edema grade (P < 0.001), and type of refractive error (P = 0.008) were significantly associated with decreased CDVA. Central corneal thickness, sex, and the peripheral CD values (2–6, 6–10, and 10–12 mm) were not significantly associated with CDVA (P > 0.05) in the final multivariate regression model.

Conclusions:
Our study demonstrates that central CD values at 0 to 2 mm and severity of guttae are each associated with decreased CDVA in FECD. These findings carry implications for patients with FECD considering surgical intervention for phacoemulsification alone, Descemet stripping only, or endothelial cell transplantation and provide a multifactorial perspective on vision loss in FECD.
Multicountry clinical outcomes of a new nondiffractive presbyopia-correcting IOL
Authors: Bala Chandra , Poyales Francisco , Guarro Mercè , Mesa Ramón Ruiz , Mearza Ali , Varma Devesh Kumar , Jasti Srichand , Lemp-Hull Jessie 
Published: June 2021

Purpose:
To evaluate the effectiveness and safety of a new presbyopia-correcting intraocular lens (IOL) with a nondiffractive design, DFT015, compared with an aspheric monofocal IOL, SN60WF.

Setting:
19 investigational sites in 4 countries: Australia, Canada, Spain, and the United Kingdom.

Design:
Prospective, randomized, parallel-group, controlled, assessor- and patient-masked clinical study.

Methods:
Participants aged ≥22 years with bilateral cataracts were randomized to DFT015 or SN60WF in a 5:4 ratio and masked until final postoperative follow-up at month 6. The primary effectiveness objective was superiority of DFT015 over SN60WF in mean monocular photopic distance-corrected intermediate visual acuity (DCIVA) at month 3. Secondary effectiveness objectives included noninferiority of DFT015 to SN60WF in mean monocular photopic corrected distance visual acuity (CDVA) and superiority in the mean monocular photopic distance-corrected near visual acuity (DCNVA) at month 3. Visual disturbances were assessed at month 6.

Results:
282 patients were randomized to DFT015 (n = 159) or SN60WF (n = 123). All effectiveness objectives were achieved at month 3 in first eyes. For monocular photopic results in first eyes, DFT015 demonstrated superior mean DCIVA (least squares means of −0.139 logMAR in favor of DFT015, P < .001), noninferior mean CDVA (97.5% upper confidence limit [UCL] of the difference was <0.1 logMAR) and superior mean DCNVA (95% UCL of the difference was <0.0 logMAR) compared with SN60WF at month 6. DFT015 exhibited a similar visual disturbance profile to that of SN60WF.

Conclusions:
DFT015 provided superior intermediate and near vision and a similar visual disturbance profile compared with an aspheric monofocal IOL.
The Implementation of the Sexual Assault Forensic Examination Telehealth Center: A Program Evaluation
Authors: Miyamoto Sheridan , Thiede Elizabeth , Wright Elizabeth N. , Berish Diane , Perkins Daniel F. , Bittner Cynthia , Dorn Lorah , Scanlon Dennis 
Published: June 2021

ABSTRACT

Introduction
Substantial disparities in the quality of post-sexual-assault (SA) care exist in the United States, particularly in rural areas. This study evaluates the implementation of the Sexual Assault Forensic Examination Telehealth Center, a program to improve SA care by increasing access to experienced sexual assault nurse examiners via telehealth, in three rural hospitals.

Materials and Methods
The Dynamic Sustainability Framework (DSF) guided the implementation of the intervention. Survey and implementation data were evaluated 1 year after implementation using a nonexperimental pre–post design. Outcomes include patient and nurse perceptions of telehealth, local site nurse (LSN) confidence, and hospital protocol/policy changes.

Results
Forty-one telehealth consultations were completed in the program's first year. An average of 34 system-level protocol changes were made per site. LSNs demonstrated statistically significant increases in confidence to provide SA care at 1 year. LSNs and telehealth sexual assault nurse examiners (expert consultants) reported that quality of SA care improved (87% and 83%, respectively). Patients highly rated the care they received (83%), reported telehealth improved care (78%), and reported feeling better after the examination (74%).

Discussion
Using the DSF for implementation supported a tailored approach and successful adoption and also allowed for program iteration based on lessons learned.

Conclusions
The Sexual Assault Forensic Examination Telehealth model resulted in improved local nurse confidence in provision of SA care, nurse perception of improvement in care quality, and high patient care experience ratings. These findings and the use of the DSF have implications for SA specialty care implementation in rural communities.