bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human recombinant nerve growth factor (Cenegermin) in a patient affected by primary congenital glaucoma with neurotrophic keratopathy
Authors: Riva Ivano , Micheletti Eleonora , Fausto Riccardo , Bruttini Carlo , De Angelis Giovanni , Ceccuzzi Roberto , Quaranta Luciano 
Published: March 2021

Purpose: To report a case of neurotrophic keratopathy (NK) in a patient affected by primary congenital glaucoma (PCG) who undergone glaucoma drainage implant surgery. NK was successfully treated with human recombinant Nerve Growth Factor (Cenegermin) eye drops. Case report description: A 46-years-old patient affected by primary congenital glaucoma underwent Ahmed glaucoma valve implantation in the right eye, after several unsuccessful surgeries to control intraocular pressure (IOP) since the age of three. Surgical intervention was performed without complications, and IOP was well-controlled post-operatively. However, 1 month after surgery, he developed NK with stromal ulceration, initially treated with a topical combination of preservative-free artificial tears and antibiotic ointment. As NK did not resolve, a new treatment with Cenegermin 20 µg/ml eye drops, 6 times daily, was started. Outcome: NK completely resolved after 8 weeks of Cenegermin treatment, with complete restoration of corneal integrity and improvement of corneal sensitivity and transparency. Visual acuity in the operated eye reverted to the pre-operative value. Conclusion: Cenegermin was extremely effective in restoring corneal integrity in this PCG patient with NK.
The characteristics of an effective clinical instructor from the perspective of nursing students: a qualitative descriptive study in Iran
Authors: Soroush Ali , Andaieshgar Bahare , Vahdat Afsoon , Khatony Alireza 
Published: March 2021

Abstract
Background
Clinical instructors have an important role in advancing nursing students to achieve the program objectives. Nursing student perceptions about the characteristics of an effective clinical instructors may help programs improve clinical instruction. As such, the purpose of this study was to understand the characteristics perceived by students to define an effective clinical instructor.

Methods
In this qualitative descriptive study, semi-structured interviews were conducted with undergraduate and postgraduate nursing students. The sample was purposefully selected. MAXQDA software was used for the content analysis. The codes were organized into subcategories and consolidated into categories.

Results
Data saturation was reached with twelve participants, including seven women and five men, between 21 and 36 years of age. General and special characteristics were the two main categories that emerged from the data. These categories were defined by nine subcategories including internal motivation, professional acceptability, clinical competency, teaching skill, clinical experience, values, being a faculty member, appropriate appearance, and communication skills.

Conclusions
Effective clinical instructors have a specific characteristics identified by student. The most important characteristics of effective clinical instructors were related to communication and teaching skills, internal motivation, and professional appearance. More research is necessary to determine the relationship between the characteristics, instructor competency, and student learning outcomes.
Health assessment of wild speckled dwarf tortoises, CHERSOBIUS SIGNATUS
Authors: Galosi Livio , Attili Anna Rita , Perrucci Stefania , Origgi Francesco C. , Tambella Adolfo Maria , Rossi Giacomo , Cuteri Vincenzo , Napoleoni Maira , Mandolini Nicholas Aconiti , Perugini Gianni , Loehr Victor J. T. 
Published: March 2021

Abstract
Background
In free-ranging reptile populations, bacterial, fungal, viral and parasitic pathogens may affect hosts through impairment in movements, thermoregulation, reproduction, survival, and population dynamics. The speckled dwarf tortoise (Chersobius [Homopus] signatus) is a threatened species that is mostly restricted to the Succulent Karoo biome in South Africa, and little information on pathogens of this species is available yet. We derived baseline parameters for five males and five females that were captured to genetically enhance a conservation breeding program in Europe. Upon collection of the tortoises, ticks were removed and identified. Immediately upon arrival in Europe, ocular, nasal, oral and cloacal swabs were taken for viral, bacteriological and mycological examinations. Fecal samples were collected before and 1 month after fenbendazole treatment, and analyzed for parasites. A panel of PCR, aiming to detect herpesviruses, adenoviruses and iridoviruses, was carried out.

Results
Samples were negative for viruses, while bacteriological examination yielded detectable growth in 82.5% of the swabs with a mean load of 16 × 107 ± 61 × 108 colony forming units (CFU) per swab, representing 34 bacterial species. Cloacal and oral swabs yielded higher detectable growth loads than nasal and ocular swabs, but no differences between sexes were observed. Fungi and yeasts (mean load 5 × 103 ± 13 × 103 CFU/swab) were detected in 25% of the swabs. All pre-treatment fecal samples were positive for oxyurid eggs, ranging from 200 to 2400 eggs per gram of feces, whereas after the treatment a significantly reduced egg count (90–100% reduction) was found in seven out of 10 individuals. One remaining individual showed 29% reduction, and two others had increased egg counts. In five tortoises, Nycthocterus spp. and coccidian oocysts were also identified. Soft ticks were identified as Ornithodoros savignyi.

Conclusions
Our baseline data from clinically healthy individuals will help future studies to interpret prevalences of microorganisms in speckled dwarf tortoise populations. The study population did not appear immediately threatened by current parasite presence.
RNA sequencing reveals the expression profiles of circRNA and identifies a four-circRNA signature acts as a prognostic marker in esophageal squamous cell carcinoma
Authors: Wang Weiwei , Zhu Di , Zhao Zhihua , Sun Miaomiao , Wang Feng , Li Wencai , Zhang Jianying , Jiang Guozhong 
Published: March 2021

Abstract
Background
CircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers. However, the expression of circRNAs in esophageal squamous cell carcinoma (ESCC) remain unknown. We aim to identify prognostic circRNAs and construct a circRNA-related signature in ESCC.

Methods
RNA sequencing was used to test the circRNA expression profiles of 73 paired ESCC tumor and normal tissues after RNase R enrichment. Bioinformatics methods, such as principal component analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm, unsupervised clustering and hierarchical clustering were performed to analyze the circRNA expression characteristics. Univariate cox regression analysis, random survival forests-variable hunting (RSFVH), Kaplan–Meier analysis, multivariable Cox regression and ROC (receiver operating characteristic) curve analysis were used to screen the prognostic circRNA signature. Real-time quantitative PCR (qPCR) and fluorescence in situ hybridization(FISH) in 125 ESCC tissues were performed.

Results
Compared with normal tissues, there were 11651 differentially expressed circRNAs in cancer tissues. A total of 1202 circRNAs associated with ESCC prognosis (P < 0.05) were identified. Through bioinformatics analysis, we screened a circRNA signature including four circRNAs (hsa_circ_0000005, hsa_circ_0007541, hsa_circ_0008199, hsa_circ_0077536) which can classify the ESCC patients into two groups with significantly different survival (log rank P < 0.001), and found its predictive performance was better than that of the TNM stage(0.84 vs. 0.66; 0.65 vs. 0.62). Through qPCR and FISH experiment, we validated the existence of the screened circRNAs and the predictive power of the circRNA signature.

Conclusion
The prognostic four-circRNA signature could be a new prognostic biomarker for ESCC, which has high clinical application value.
Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis
Authors: Li Liping , Xing Chao , Zhou Ji , Niu Liangliang , Luo Bin , Song Maomao , Niu Jingping , Ruan Ye , Sun Xinghuai , Lei Yuan 
Published: March 2021

Abstract
Background
Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP).

Methods
To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages.

Results
The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects.

Conclusion
This study ﻿provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.
Monitoring tissue oxygenation index using near‐infrared spectroscopy during pre‐hospital resuscitation among out‐of‐hospital cardiac arrest patients: a pilot study
Authors: Tsukuda Jumpei , Fujitani Shigeki , Rahman Mahbubur , Morisawa Kenichiro , Kawaguchi Takeshi , Taira Yasuhiko 
Published: March 2021

Abstract
Background
Tissue oxygenation index (TOI) using the near infrared spectroscopy (NIRS) has been demonstrated as a useful indicator to predict return of spontaneous circulation (ROSC) among out-of-hospital cardiac arrest (OHCA) patients in hospital setting. However, it has not been widely examined based on pre-hospital setting.

Methods
In this prospective observational study, we measured TOI in pre-hospital setting among OHCA patients receiving cardio-pulmonary resuscitation (CPR) during ambulance transportation between 2017 and 2018. Throughout the pre-hospital CPR procedure, TOI was continuously measured. The study population was divided into two subgroups: ROSC group and non-ROSC group.

Results
Of the 81 patients included in the final analysis, 26 achieved ROSC and 55 did not achieve ROSC. Patients in the ROSC group were significantly younger, had higher ∆TOI (changes in TOI) (5.8 % vs. 1.3 %; p < 0.01), and were more likely to have shockable rhythms and event witnessed than patients in the non-ROSC group. ∆TOI cut-off value of 5 % had highest sensitivity (65.4 %) and specificity (89.3 %) for ROSC. Patients with a cut-off value ≤-2.0 % did not achieve ROSC and while all OHCA patient with a cut-off value ≥ 8.0 % achieved ROSC. In addition, ROSC group had stronger positive correlation between mean chest compression rate and ∆TOI (r = 0.82) than non-ROSC group (r = 0.50).

Conclusions
This study suggests that ∆ TOI could be a useful indicator to predict ROSC in a pre-hospital setting.
Bone marrow biopsy and aspiration: a departmental financial comparison in a rural hospital
Authors: Bethuel Nancy W. , Bravin Eric , Krupa Nicole , Jenkins Paul , Scribani Melissa , Gadomski Anne 
Published: March 2021

Abstract
Objective
The purpose of this study was to compare the charges and payments associated with bone marrow aspiration and biopsies performed by hematology/oncology specialists versus interventional radiology specialists at Bassett Medical Center located in a rural area of New York State. Charges pertained to what the hospital charged for the procedure and payment refers to the reimbursement the hospital received. Our secondary objectives were to compare specimen quality by procedure and to determine whether body mass index was associated with which specialist performed the procedure.

Results
The median charge was significantly higher in the interventional radiology group ($5254 USD) compared to the hematology/oncology group ($413 USD), p < 0.0001. Median payments were also higher in the interventional radiology ($1392 USD) compared to the hematology/oncology group ($1109 USD), p < 0.0001. Adequacy of the samples obtained by either profession was similar. Disease process was not associated with adequacy of the sample. There was no statistically significant difference in the proportion of males and females in the respective groups or in the mean age. However, the patients’ in the interventional radiology group had a significantly higher mean BMI (34.3) compared to those in the hematology/oncology group (28.6), p = 0.0014.
Anti-apoptotic effect of adipose tissue-derived stromal vascular fraction in denervated rat muscle
Authors: El-Habta R. , Andersson G. , Kingham P. J. , Backman L. J. 
Published: March 2021

AbstractBackgroundRecovery of muscle function after peripheral nerve injury is often poor, and this can be attributed to muscle fiber atrophy and cell death. In the current study, we have investigated the effects of stromal vascular fraction (SVF) on muscle cell apoptosis and its potential to preserve muscle tissue following denervation.MethodsRat gastrocnemius muscle was denervated by sciatic nerve transection. At 2 and 4 weeks after injury, muscles were examined histologically and apoptosis was measured using TUNEL assay and PCR array for a range of apoptotic genes. Additionally, an in vitro TNF-α apoptosis model was established using SVF cells co-cultured indirectly with primary rat myoblasts. Annexin V and TUNEL were used together with Western blotting to investigate the signaling pathways.ResultsDenervated muscles showed significantly higher TUNEL reactivity at 2 and 4 weeks following nerve injury, and an increased expression of caspase family genes, mitochondria-related apoptotic genes, and tumor necrosis factor family genes. In cultured rat primary myoblasts, Annexin V labeling was significantly increased at 12 h after TNF-α treatment, and this was followed by a significant increase in TUNEL reactivity at 48 h. Western blotting showed that caspase-7 was activated/cleaved as well as the downstream substrate, poly (ADP-ribose) polymerase (PARP). Co-culture of myoblasts with SVF significantly reduced all these measures of apoptosis. Bax and Bcl-2 levels were not changed suggesting that the TNF-α-induced apoptosis occurred via mitochondria-independent pathways. The protective effect of SVF was also shown in vivo; injections of SVF cells into denervated muscle significantly improved the mean fiber area and diameter, as well as reduced the levels of TUNEL reactivity.ConclusionsThis study provides new insights into how adipose tissue-derived cells might provide therapeutic benefits by preserving muscle tissue.
H3K9ac of TGFβRI in human umbilical cord: a potential biomarker for evaluating cartilage differentiation and susceptibility to osteoarthritis via a two-step strategy
Authors: Qi Yongjian , Li Bin , Wen Yinxian , Yang Xu , Chen Biao , He Zheng , Zhao Zhe , Magdalou Jacques , Wang Hui , Chen Liaobin 
Published: March 2021

AbstractBackgroundEpidemiological investigation and our previous reports indicated that osteoarthritis had a fetal origin and was closely associated with intrauterine growth retardation (IUGR). Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) could be programmable to “remember” early-life stimuli. Here, we aimed to explore an early-warning biomarker of fetal-originated adult osteoarthritis in the WJ-MSCs.MethodsFirstly, two kinds of WJ-MSCs were applied to evaluate their chondrogenic potential in vitro through inducing chondrogenic differentiation as the first step of our strategy, one from newborns with IUGR and the other from normal newborns but treated with excessive cortisol during differentiation to simulate the excessive maternal glucocorticoid in the IUGR newborns. As for the second step of the strategy, the differentiated WJ-MSCs were treated with interleukin 1β (IL-1β) to mimic the susceptibility to osteoarthritis. Then, the expression and histone acetylation levels of transforming growth factor β (TGFβ) signaling pathway and the expression of histone deacetylases (HDACs) were quantified, with or without cortisol receptor inhibitor RU486, or HDAC4 inhibitor LMK235. Secondly, the histone acetylation and expression levels of TGFβRI were further detected in rat cartilage and human umbilical cord from IUGR individuals.ResultsGlycosaminoglycan content and the expression levels of chondrogenic genes were decreased in the WJ-MSCs from IUGR, and the expression levels of chondrogenic genes were further reduced after IL-1β treatment, while the expression levels of catabolic factors were increased. Then, serum cortisol level from IUGR individuals was found increased, and similar changes were observed in normal WJ-MSCs treated with excessive cortisol. Moreover, the decreased histone 3 lysine 9 acetylation (H3K9ac) level of TGFβRI and its expression were observed in IUGR-derived WJ-MSCs and normal WJ-MSCs treated with excessive cortisol, which could be abolished by RU486 and LMK235. At last, the decreased H3K9ac level of TGFβRI and its expression were further confirmed in the cartilage of IUGR rat offspring and human umbilical cords from IUGR newborn.ConclusionsWJ-MSCs from IUGR individuals displayed a poor capacity of chondrogenic differentiation and an increased susceptibility to osteoarthritis-like phenotype, which was attributed to the decreased H3K9ac level of TGFβRI and its expression induced by high cortisol through GR/HDAC4. The H3K9ac ofTGFβRIin human umbilical cord could be a potential early-warning biomarker for predicting neonatal cartilage dysplasia and osteoarthritis susceptibility.
99mTc-labelled PSMA ligand for radio-guided surgery in nodal metastatic prostate cancer: proof of principle
Authors: Mix Michael , Schultze-Seemann Wolfgang , von Büren Moritz , Sigle August , Omrane Mohamed A. , Grabbert Markus T. , Werner Martin , Gratzke Christian , Meyer Philipp T. , Jilg Cordula A. 
Published: March 2021

Abstract
Purpose
Intraoperative identification of prostate cancer (PCa) lymph node (LN) metastases (LNM) detected by preoperative PSMA PET/CT may be facilitated by PSMA radio-guided surgery (RGS) with use of a γ-probe. Earlier we demonstrated excellent performance of the 111In-labelled PSMA ligand DKFZ-617 ([111In]In-PSMA-617) in RGS for ex situ distinction of LN vs LNM at lymphadenectomy (LA) at a single LN level. In comparison with indium-111, technetium-99m has better physical properties for γ-probe measurements, better availability and lower radiation exposure for patients and medical personnel. Against this background, we evaluated the uptake of 99mTc-PSMA-I&S ligand at the level of single LN and its power to discriminate between unaffected LN and LNM.

Methods
Six patients with PCa with the suspicion of LNM on preoperative PSMA-PET/CT underwent [99mTc]Tc-PSMA-I&S RGS (4 salvage LA, 2 primary LA) with intravenous injection of [99mTc]Tc-PSMA-I&S 24 h prior to surgery. Resected samples were isolated manually aiming at the level of single LN. Uptake measurements were done ex situ with a high-purity germanium detector. Receiver operating characteristic (ROC) analysis was performed based on [99mTc]Tc-PSMA-I&S uptake expressed as lean body mass standard uptake value (SUL).

Results
Separation of the tissue samples from 73 subregions resulted in 498 single samples. After final histopathology 356 LN, 160 LNM und 11 non-nodal PCa samples were identified. Median SUL of tumor-free samples (0.26) and samples with cancer (3.5) was significantly different (p < 0.0001). ROC analysis revealed an area under the curve (AUC) of 0.917 (95% CI 0.89–0.95). Using a SUL cutoff of 1.1, sensitivity, specificity, positive predictive value, and negative predictive values were 76.6%, 94.4%, 89.4% and 86.9%.

Conclusion
Ex situ analysis of [99mTc]Tc-PSMA-I&S uptake at single LN level showed good diagnostic performance for the ex situ distinction of tumor-bearing vs tumor-free LN during RGS.
The lipopolysaccharide outer core transferase genes pcgD and hptE contribute differently to the virulence of Pasteurella multocida in ducks
Authors: Zhao Xinxin , Shen Hui , Liang Sheng , Zhu Dekang , Wang Mingshu , Jia Renyong , Chen Shun , Liu Mafeng , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Zhang Ling , Liu Yunya , Yu Yanling , Pan Leichang , Cheng Anchun 
Published: March 2021

AbstractFowl cholera caused byPasteurella multocidaexerts a massive economic burden on the poultry industry. Lipopolysaccharide (LPS) is essential for the growth ofP. multocidagenotype L1 strains in chickens and specific truncations to the full length LPS structure can attenuate bacterial virulence. Here we further dissected the roles of the outer core transferase genespcgDandhptEin bacterial resistance to duck serum, outer membrane permeability and virulence in ducks. TwoP. multocidamutants, ΔpcgDand ΔhptE, were constructed, and silver staining confirmed that they all produced truncated LPS profiles. Inactivation ofpcgDorhptEdid not affect bacterial susceptibility to duck serum and outer membrane permeability but resulted in attenuated virulence in ducks to some extent. After high-dose inoculation, ΔpcgDshowed remarkably reduced colonization levels in the blood and spleen but not in the lung and liver and caused decreased injuries in the spleen and liver compared with the wild-type strain. In contrast, the ΔhptEloads declined only in the blood, and ΔhptEinfection caused decreased splenic lesions but also induced severe hepatic lesions. Furthermore, compared with the wild-type strain, ΔpcgDwas significantly attenuated upon oral or intramuscular challenge, whereas ΔhptEexhibited reduced virulence only upon oral infection. Therefore, thepcgDdeletion caused greater virulence attenuation in ducks, indicating the critical role ofpcgDinP. multocidainfection establishment and survival.