bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut microbiota: a possible factor influencing systemic lupus erythematosus
Authors: Neuman Hadar , Koren Omry 
Published: April 2017

Purpose of review
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. In recent years, with the emergence of microbiome research, changes in the gut microbiota composition have been correlated with a variety of autoimmune disorders, and several mechanisms linking these together have been suggested, including the hygiene theory, immune system activation and hormonal effects. It has therefore been suggested that gut microbiota may play a role in SLE. In this review, we summarize recent findings on the SLE-related microbiota compositions in both humans and rodents. Evidence linking microbiome with SLE opens a new avenue in researching the cause of SLE as well as improved future treatments.

Recent findings
Although two studies found a lower Firmicutes/Bacteroidetes ratio in SLE patients vs. controls, there were inconsistencies regarding significant differences in the abundance of specific genera or species. Studies of mouse disease models have shown some correlations between microbial compositions and disease states, also indicating differences between males and females.

Summary
Current data support an association between microbiota composition and SLE. Further research is needed to fully unravel this connection, potentially shedding light on mechanisms in SLE development and on the female bias of the disease, improving diagnosis and treatment.
Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Spondyloarthritis
Authors: Medina Frédéric , Plasencia Chamaida , Goupille Philippe , Paintaud Gilles , Balsa Alejandro , Mulleman Denis 
Published: April 2017

Abstract:
Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration–response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, therapeutic drug monitoring of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.
Penetrating Keratoplasty at a Tertiary Referral Center in Ethiopia: Indications and Outcomes
Authors: Ayalew Menen , Tilahun Yonas , Holsclaw Doug , Indaram Maanasa , Stoller Nicole E. , Keenan Jeremy D. , Rose-Nussbaumer Jennifer 
Published: April 2017

Purpose:
To describe the indications, visual acuity outcomes, and graft survival after penetrating keratoplasty (PKP) in Addis Ababa, Ethiopia.

Methods:
The medical records of patients who underwent PKP at Menelik II Hospital between September 2000 and September 2013 were retrospectively reviewed. The prespecified outcomes were graft survival, visual acuity, and complication rates.

Results:
A total of 321 patients underwent PKP during the study period and were included in the analysis. Indications for surgery were trachoma or leukoma in 141 (44%), keratoconus in 45 (14%), corneal dystrophy in 46 (14%), pseudophakic or aphakic bullous keratopathy in 28 (9%), trauma in 27 (8%), previous graft failure in 18 (6%), active ulcer, burn, or perforation in 9 (3%), and others in 7 (2%). The graft survival rate was 80% overall at 2 years but varied considerably depending on the indication for surgery. Uncorrected visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.09 (SD 0.67) to mean logarithm of the minimum angle of resolution of 1.53 (SD 1.03) at 2 years. A number of factors affected the visual acuity outcomes. Patients were not routinely refracted, and only 18% (N = 60) of patients had access to corrective spectacles or contact lenses postoperatively. Complication rates were high with infectious keratitis being the most common.

Conclusions:
PKP is becoming a viable treatment for corneal opacity in developing countries. However, the high burden of disease and lack of corrective lenses remain significant obstacles to overcome.
Proposal for a Novel Severity Grading System for Pterygia Based on Corneal Topographic Data
Authors: Miyata Kazunori , Minami Keiichiro , Otani Atsushi , Tokunaga Tadatoshi , Tokuda Shouta , Amano Shiro 
Published: April 2017

Purpose:
To propose a grading system of pterygium severity based on corneal higher-order irregularity (HOI) and to evaluate postoperative changes in corneal irregularity of the graded pterygia.

Methods:
In 268 eyes of 226 patients undergoing excision surgery of primary nasal pterygium, Placido corneal topography images were taken before and until 6 months after surgery. The best-corrected visual acuity (BCVA) and pterygium size with respect to the corneal diameter were also measured. HOI components within 1.0-, 3.0-, and 5.0-mm diameters were obtained using Fourier harmonic analysis of corneal topography data. With threshold levels when the HOIs for 3 diameters steeply increased, 4 levels of grading from 0 (mild) to 3 (severe) were determined. Associations of the grades with the preoperative surface regularity index (SRI), irregular components (IRRs) obtained from the 3.0-mm diameter Fourier analysis, and BCVA were examined. Time-course changes in the indexes after surgery were evaluated for each grade.

Results:
There were 62, 65, 41, and 100 eyes in grades 0 to 3, respectively. Preoperatively, the SRI in grade 3 was significantly higher than in the other grades (P < 0.001), and the IRR and BCVA varied with the grade (P < 0.001). Between 1 and 6 months postoperatively, grade 3 pterygia showed significant changes in the SRI and IRR (P = 0.013 and 0.017, respectively), whereas there was no change after 3 months postoperatively in the SRI, IRR, and BCVA for all other grades.

Conclusions:
The proposed grading effectively classified the severity of pterygia and evaluated postoperative restoration of corneal irregularity. Using corneal topographic data allowed for objective evaluation of pterygium severity.
Ocular Surface Parameters Predicting Patient Satisfaction After a Single Vectored Thermal Pulsation Procedure for Management of Symptomatic Meibomian Gland Dysfunction
Authors: Gibbons Allister , Waren Daniel , Yesilirmak Nilufer , Davis Kendra , Valenzuela Felipe , Murillo Juan C. , Perez Victor L. 
Published: April 2017

Purpose:
To evaluate the ocular surface parameters that could predict patient satisfaction after single application of vectored thermal pulsation (VTP).

Methods:
This is a retrospective interventional case series; it included consecutive patients who underwent bilateral VTP for management of symptomatic meibomian gland dysfunction (MGD). Patients received a full ocular surface evaluation. The outcome was patient subjective improvement during the first 3–4 months after 3 follow-up visits. For analysis, patients were divided into responders and nonresponders.

Results:
Forty-nine patients received bilateral treatment, with 32 patients (65.3%) reporting subjective improvement after treatment. Responders had lower tear production (6.9 ± 5.9 mm vs. 13.6 ± 6.8 mm; t test P = 0.002), a higher corneal staining score (4.4 ± 5.0 vs. 0.43 ± 1.1; t test P = 0.003), and a higher conjunctival staining score (3.1 ± 2.4 vs. 1.5 ± 1.8; t test P = 0.023) and presented with a higher tear osmolarity (319.7 ± 23.22 mOsm/L vs. 306.9 ± 9.0 mOsm/L; t test P = 0.029) than the nonresponder group. We found no association between patient age, tear breakup time, Ocular Surface Disease Index score, tear lipid layer thickness, or MGD grading score, as measured before intervention, with patient-perceived success of treatment. No complications to treatment were noted, and no patient reported worsening of preexisting symptoms on follow-up.

Conclusions:
VTP can be effective in treating dry eye symptoms of patients with MGD. Our data show that objective findings of dry eye, as evidenced by lower tear production, higher corneal and conjunctival staining scores, and higher osmolarity, tend to be markers present in the group of patients responding positively to VTP.
Evaluation of Angle Closure as a Risk Factor for Reduced Corneal Endothelial Cell Density
Authors: Varadaraj Varshini , Sengupta Sabyasachi , Palaniswamy Krishnamurthy , Srinivasan Kavitha , Kader Mohideen A. , Raman Ganesh , Reddy Sharmila , Ramulu Pradeep Y. , Venkatesh Rengaraj 
Published: April 2017

Purpose:
Acute angle closure attacks are frequently accompanied by corneal edema. However, little is known about corneal endothelial cell status at different stages of angle closure. Here, we compared endothelial cell density (ECD) in unoperated eyes with that in eyes with open angles (OAs) and various stages of angle closure disease.

Materials and Methods:
The study was conducted at Aravind Eye Hospitals in India. Masked examiners performed gonioscopy to classify each eye as follows: (1) OA, (2) primary angle closure suspect, or (3) primary angle closure (PAC)/primary angle closure glaucoma (PACG). Specular microscopy was performed and differences in ECD were analyzed using hierarchical models.

Results:
A total of 407 patients and 814 eyes were studied, including 127 (15.6%), 466 (57.3%), and 221 (27.1%) with PAC/PACG, primary angle closure suspect, and OA, respectively. Participants were predominantly female (69.8%) and the mean age was 49.2 (SD: 8.6) years. Lower ECD was observed with increasing age [β=−6.3 cells/mm2; 95% confidence interval (CI), −9.3 to −3.3, per year; P<0.001], greater iridotrabecular contact [β=−15.6 cells/mm2; 95% CI, −28.3 to −2.9, per quadrant of contact; P=0.016), and shallow (<2.5 mm) anterior chamber depth (β=−40 cells/mm2; compared to deeper AC's (≥2.5 mm), 95% CI, 78.9-1.1; P=0.044). In age-adjusted analyses, angle closure suspects had lower ECD than OA eyes (β=−54.7 cells/mm2; 95% CI, −47.8 to −85.3; P=0.018), although PAC/PACG eyes were not significantly different from OA eyes (β=−18.6 cells/mm2; 95% CI, −85.9 to 2.5; P=0.058).

Conclusion:
In untreated eyes, only mild, clinically insignificant decrement in ECD was noted with angle closure.
In Vivo Effects of Retrobulbar Bimatoprost Injection on Orbital Fat
Authors: Eftekhari Kian , Vagefi M. Reza , Lee Vivian , Hui James Z. , Zhu Menglong , Dine Kimberly , Anderson Richard L. , Koeberlein Brigitte , Sulaimankutty Reas , Shindler Kenneth S. 
Published: April 2017

Purpose:
Recent publications have reported the adverse effects of prostaglandin analogues on the periocular tissues. These medications may cause periorbital lipodystrophy, enophthalmos, and deepening of the superior sulcus deformity. While these effects may have adverse consequences for some patients, the atrophy of the periorbital fat may have a useful role in diseases that lead to orbital and periorbital fat hypertrophy such as thyroid eye disease. In this pilot study, the authors investigated the effects of retrobulbar bimatoprost injection on the intraocular pressure and orbital fat in a rat animal model.

Methods:
Three rats were sedated and intraocular pressure was measured. A 0.1 ml aliquot of bimatoprost was injected into the right orbit of all rats. In the left orbit, 0.1 ml of phosphate-buffered saline was injected as a control. Three weeks later, all rats were sedated and intraocular pressure was measured before euthanizing. Routine histologic staining was performed and thin sections through the intraconal orbital fat were obtained. Density of intraconal adipocytes was measured and adipocyte heterogeneity was determined using a computer image analysis algorithm.

Results:
The specimens injected with bimatoprost demonstrated atrophy of orbital fat with significantly increased adipocyte density (p = 0.009) and heterogeneity (p = 0.008) when compared with control. Intraocular pressure was not significantly decreased at 3 weeks after injection of retrobulbar bimatoprost.

Conclusions:
In this pilot study, orbital injection of bimatoprost demonstrated atrophy of intraconal adipocytes when compared with control orbits injected with saline. The orbits injected with bimatoprost were noted to have smaller, more heterogeneous adipocytes that were densely packed in the intraconal space. The study limitations include the small sample size, which limited the ability for us to make conclusions about the effect on intraocular pressure. Nevertheless, the findings presented suggest that retrobulbar bimatoprost may present a nonsurgical alternative to induce atrophy of the orbital fat without inducing inflammation or hypotony.
Intravenous Steroids With Antibiotics on Admission for Children With Orbital Cellulitis
Authors: Chen Lena , Silverman Nora , Wu Andrew , Shinder Roman 
Published: April 2017

Purpose:
To compare the outcomes of children with orbital cellulitis treated with intravenous (IV) dexamethasone and antibiotics on admission to patients treated with antibiotics alone.

Methods:
Prospective comparative interventional study. Forty-three children admitted to a tertiary institution with orbital cellulitis were enrolled. On admission, all patients were started on broad spectrum IV antibiotics and parents were offered IV dexamethasone (0.3 mg/kg/d every 6 hours for 3 days). Patients whose parents refused steroid treatment served as the control group.

Results:
Twenty-eight (65%) patients received IV steroids and antibiotics on admission while 15 (35%) received IV antibiotics alone. Children who received IV steroids had significantly shorter hospital stays than those who did not receive steroids (3.8 ± 0.2 days vs. 6.7 ± 0.3 days; p < 0.001). This was true both for children who underwent surgery (5/28 with steroids, 3/15 without; 5.0 ± 0.7 days vs. 7.3 ± 1.2 days; p = 0.011) and for those who did not require surgical intervention (23/28 with steroids, 12/15 without; 3.6 ± 0.6 and 6.5 ± 1.0 days; p < 0.001). Side effects of steroid treatment were mild and did not require termination of therapy. During follow up, all study patients had returned to their baseline health without any cases of decreased vision or disease recurrence.

Conclusions:
The results of the current study give additional evidence to the relative safety and efficacy of systemic steroid use concurrently with IV antibiotics in children with orbital cellulitis. This is the first study to recommend IV steroids on hospital admission and a standardized dosing regimen. Children who received steroids had a shorter hospital stay than those who did not.
Volumization of the Brow at the Time of Blepharoplasty: Treating the Eyebrow Fat Pad as an Independent Unit
Authors: Vrcek Ivan , Chou Eva , Somogyi Marie , Shore John W. 
Published: April 2017

Purpose:
Loss of volume in the sub-brow fat pad with associated descent of the eyebrow is a common anatomical finding resulting in both functional and aesthetic consequences. A variety of techniques have been described to address brow position at the time of blepharoplasty. To our knowledge, none of these techniques treat the sub-brow fat pad as an isolated unit. Doing so enables the surgeon to stabilize and volumize the brow without resultant tension on the blepharoplasty wound. The authors describe a technique for addressing volume loss in the eyebrow with associated brow descent that treats the sub-brow fat pad as an isolated unit.

Methods:
A retrospective review of all patients undergoing brow ptosis repair by a single surgeon (J.W.S.) over an 11-month period was performed.

Results:
Eighteen patients and 33 brows underwent the technique described. Patients were followed for an average of 11 weeks (range: 4 weeks to 20 weeks). All patients preoperatively displayed both visually significant dermatochalasis and brow descent below the orbital rim. Evaluation of pre- and postoperative photos demonstrates successful volumization of the brow with skin redraping without focal dimpling or undue tension on the eyelid wound.

Conclusions:
Performing a dissection that allows the sub-brow fat pad to be elevated in isolation from the overlying orbicularis and underlying periosteum allows for volumization and of the brow without compromising closure. This technique is a safe and effective means of volumizing the brow and treating secondary brow descent.
C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study
Authors: Schistad Elina Iordanova , Stubhaug Audun , Furberg Anne-Sofie , Engdahl Bo Lars , Nielsen Christopher Sivert 
Published: April 2017

Abstract
The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.
Clinical usefulness of controlled attenuation parameter to screen hepatic steatosis for potential donor of living donor liver transplant
Authors: Hong Young Mi , Yoon Ki Tae , Cho Mong , Chu Chong Woo , Rhu Je Ho , Yang Kwang Ho , Lee Jun Woo 
Published: April 2017

Objective
Hepatic steatosis is associated with an increased risk of graft loss. Although the controlled attenuation parameter (CAP), a process based on transient elastography, has been suggested as a noninvasive method of assessing hepatic steatosis, to date, there is no study on the usefulness of CAP as a single screening tool for detecting hepatic steatosis in potential living donor liver. We evaluated the accuracy of CAP for detecting hepatic steatosis in potential liver donors.

Patients and methods
All potential donors of living-donor liver transplantation who underwent a CAP assessment and ultrasonography-guided liver biopsy were enrolled. The steatosis grades were as follows: S0 less than 5%; S1, 5–33%; S2, 34–66%; and S3, more than 66%.

Results
According to the liver biopsies, 19 (34.5%) patients had S0, 30 (54.5%) patients had S1, and 6 (11.0%) patients had S2. The CAP value was correlated positively with BMI (r=0.242, P=0.01), waist circumference (r=0.268, P=0.006), hip circumference (r=0.334, P=0.001), Magnetic resonance fat signal fraction (r=0.465, P=0.001), and histologic steatosis grade (r=0.542, P=0.001). The area under the receiver operator characteristic curve for the diagnosis of steatosis (≥S2) by CAP was 0.88 (sensitivity 83.3% and specificity 81.6% at a cutoff value of 276 dB/m, P<0.0001).

Conclusion
This study suggests that CAP, as a simple and noninvasive preoperative assessment for hepatic steatosis, may be sufficient for identifying and thus excluding significant hepatic steatosis (>33%) in potential liver donors.
Distinct functions of histone H3, lysine 4 methyltransferases in normal and malignant hematopoiesis
Authors: Yang Weiwei , Ernst Patricia 
Published: April 2017

Purpose of review
Histone H3, lysine 4 (H3K4) methylation is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express six main histone methyltransferase (HMT) enzymes that modify H3K4 by monomethylation, dimethylation or trimethylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem data, revealing how these enzymes function.

Recent findings
Murine models have been employed to conditionally or constitutively knockout HMTs (MLL1/KMT2A, MLL2/KMT2B, MLL3/KMT2C, MLL4/KMT2D, SETD1A/KMT2F and SETD1B/KMT2G) as well as specific domains or partners of these enzymes in normal hematopoietic populations and in the context of hematologic malignancies. These studies demonstrate that global or gene-specific changes in H3K4 modification levels can be attributed to particular enzymes in particular tissues.

Summary
Loss-of-function studies indicate largely nonoverlapping roles of the six H3K4 HMTs. These roles are not all necessarily due to differences in enzymatic activity and are not always accompanied by large global changes in histone modification. Both gain-of-function and loss-of-function mutations in hematologic malignancy are restricted to MLL1 and MLL3/MLL4, but emerging data indicate that SETD1A/SETD1B and MLL2 can be critical in leukemia as well.
The new frontier of epigenetic heterogeneity in B-cell neoplasms
Authors: Dominguez Pilar M. , Teater Matt , Shaknovich Rita 
Published: April 2017

Purpose of review
There is mounting evidence that heterogeneity of the epigenome is a feature of many cancers, including B-cell lymphomas, and presents important clinical implications. The purpose of this review is to explain the biological and clinical relevance of this epigenetic phenomenon in B-cell neoplasms.

Recent findings
Here, we summarize new findings demonstrating that B-cell lymphomas display increased DNA methylation heterogeneity compared to their normal counterparts. This plasticity of cytosine methylation manifests both as intertumor and intratumor heterogeneity and is associated with worse prognosis and poor clinical outcome in lymphoma patients. Recent studies of different subtypes of B-cell lymphomas have revealed that epigenetic aberrations and heterogeneous cytosine methylation patterning are common features of all neoplasms derived from B-lymphocytes, irrespective of maturation stage. With regard to mechanisms driving this process, recent reports suggest that cytosine methylation heterogeneity arises through passive and active processes. One factor implicated in active generation of cytosine methylation heterogeneity is activation-induced cytidine deaminase, which mediates DNA methylation changes and introduces epigenetic heterogeneity in normal germinal center B cells, the cells of origin of mature B-cell neoplasms such as diffuse large B-cell lymphoma and follicular lymphoma.

Summary
Understanding the scope and mechanism of epigenetic heterogeneity in cancer is of paramount importance to our understanding of clonal plasticity and treatment responses in B-cell lymphomas.