bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment potential of bone marrow-derived stem cells in women with diminished ovarian reserves and premature ovarian failure
Authors: Herraiz Sonia , Pellicer Nuria , Romeu Mónica , Pellicer Antonio 
Published: March 2019

Purpose of review
We review the techniques recently tested in both animal models and humans to provide a state-of-the-art on adult stem cell ovarian transplant to achieve ovarian rejuvenation in patients with diminished ovarian reserves.

Recent findings
As the firsts reports of spontaneous pregnancies achieved after bone marrow transplantation in oncologic women with primary ovarian insufficiency, increasing evidence supports the regenerative effects of stem cell-based therapies in the ovarian niche. Adult stem cells from several origins promote follicular development, increase ovarian local vascularization, increase follicle and stromal cell proliferation and reduce cell apoptosis and follicular atresia, although they do not modify embryo quality. Therefore, residual quiescent follicles of aged or damaged ovaries might produce competent oocytes in an adequate ovarian environment. Nevertheless, further research is needed to properly evaluate underlying mechanisms, identify best cell sources and design less invasive infusion techniques.

Summary
Stem cells may be a relevant therapeutic alternative for ovary regeneration and follicular development in patients with impaired ovaries, such as poor ovarian responders or women diagnosed with primary ovarian insufficiency.
Androgen supplementation in assisted reproduction: where are we in 2019?
Authors: Montoya-Botero Pedro , Rodriguez-Purata Jorge , Polyzos Nikolaos P. 
Published: March 2019

Purpose of review
The purpose of this review is to provide an overview of androgen supplementation in ART with the most updated evidence, from animal studies to its clinical applications in poor ovarian responders (POR) and the future studies to be published.

Recent findings
Animal studies, has shown that testosterone supplementation, can be an option to increase the recruitable follicular pool in POR. However, the potential mechanism of action, dose, and duration of treatment is still under investigation. Early studies in humans reported promising results in favor of androgens [dehydroepiandrosterone (DHEA) or testosterone] in POR. Nevertheless, recent evidence does not appear to follow the initial results, whereas the type, dose, and duration of testosterone administration appear to be crucial for treatment effect.

Summary
Testosterone seems to play an essential role in regulating ovarian function. However, it is worrisome that androgens are used off-label, despite that the available evidence is weak. Although testosterone supplementation may be beneficial in POR, published studies have used inconsistent doses and duration of administration. An ongoing trial (T-TRANSPORT trial) for the first time aims to provide conclusive evidence on whether transdermal testosterone administration can improve the reproductive outcomes in patients undergoing IVF/ICSI.
Computation Speeds and Memory Requirements of Mesh-Type ICRP Reference Computational Phantoms in Geant4, MCNP6, and PHITS
Authors: Yeom Yeon Soo , Han Min Cheol , Choi Chansoo , Han Haegin , Shin Bangho , Furuta Takuya , Kim Chan Hyeong 
Published: March 2019

Abstract
Recently, Task Group 103 of the International Commission on Radiological Protection completed the development of new adult male and female mesh-type reference computational phantoms, which are planned for use in future International Commission on Radiological Protection dose coefficient calculations. In the present study, the performance of major Monte Carlo particle transport codes, i.e., Geant4, MCNP6, and PHITS, were investigated for the mesh-type reference computational phantoms by performing transport simulations of photons, electrons, neutrons, and helium ions for some external and internal exposures, and simultaneously measuring the memory usage, initialization time, and computation speed of the adult male mesh-type reference computational phantom in the codes. The measured results were then compared with the values measured with the current adult male voxel-type reference computational phantom in International Commission on Radiological Protection Publication 110 as well as five voxel phantoms produced from the adult male mesh-type reference computational phantom with different voxel resolutions, i.e., 0.1 × 0.1 × 0.1 mm3, 0.6 × 0.6 × 0.6 mm3, 1 × 1 × 1 mm3, 2 × 2 × 2 mm3, and 4 × 4 × 4 mm3. From the results, it was found that in all of the codes, the memory usage of the mesh-type reference computational phantom is greater than that of the voxel-type reference computational phantom and the lowest resolution voxelized phantom, but it is sufficiently lower than the maximum memory, 64 GB, that can be installed in a personal computer. The required initialization time of the mesh-type reference computational phantom and of the voxel-type reference computational phantom and voxelized phantoms in resolutions lower than 0.6 × 0.6 × 0.6 mm3 was less than a few minutes in all of the codes. As for the computation speed among the codes, MCNP6 showed the worst performance for the mesh-type reference computational phantom, which was slower than that for the voxel-type reference computational phantom by up to ~50 times and slower than that for all of the voxelized phantoms by up to ~40 times. By contrast, PHITS showed the best performance for the mesh-type reference computational phantom, which was faster than that for the voxel-type reference computational phantom by up to ~3 times and faster than that for all of the voxelized phantoms by up to ~20 times. This high performance of PHITS is indeed encouraging considering that it is used nowadays by the International Commission on Radiological Protection for most dose coefficient calculations.
Suicide in European Hodgkin Lymphoma Patients
Authors: Kim Austin I. , Goergen Helen , Engert Andreas , LaCasce Ann S. , Maranda Louise , Barton Bruce , Borchmann Sven 
Published: March 2019

AbstractThe purpose of this study was to determine whether there is an increased risk of suicide in European Hodgkin Lymphoma (HL) patients compared to the general European population.European HL patients enrolled in the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed and standardized mortality ratio (SMR) was calculated using suicide mortality rates for the general European population. Case‐control analysis was performed to identify characteristics associated with risk of death by suicide. Among 12,202 European HL patients observed for 94,972 person‐years, 19 suicides (17 males and 2 females) were identified resulting in a SMR 1.63 (95% CI: 1.01–2.50, p = 0.046). The only characteristic associated with a statistically significant increased risk of suicide was male sex with an odds ratio (OR) 8.42 (95% CI = 1.04–67.85; p = 0.046) on multivariate analysis. These findings were confirmed in an independently analyzed Surveillance, Epidemiology, and End Results Program (SEER) validation dataset. European HL patients have a significantly increased incidence of suicide compared to the general European population. Male HL patients have a greater than 8‐fold increased risk of suicide compared to female HL patients. Further study of social risk factors associated with an increased risk of suicide in HL patients is needed.
DETECTION OF CLINICALLY UNSUSPECTED RETINAL NEOVASCULARIZATION WITH WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: You Qi Sheng , Guo Yukun , Wang Jie , Wei Xiang , Camino Acner , Zang Pengxiao , Flaxel Christina J. , Bailey Steven T. , Huang David , Jia Yali , Hwang Thomas S. 
Published: March 2019

Purpose:
To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR).

Methods:
This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV.

Results:
Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm2 (range 0.17–0.54 mm2). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR.

Conclusion:
Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.
Management of Descemet Membrane's Folds After Deep Anterior Lamellar Keratoplasty: Descemet Membrane—Tucking Technique
Authors: Neri Alberto , Moramarco Antonio , Iovieno Alfonso , Fontana Luigi 
Published: March 2019

Purpose:To describe a surgical maneuver that allows for correction of central Descemet membrane (DM) folds at the end of a deep anterior lamellar keratoplasty (DALK) procedure. We term the present technique “DM tucking.”Methods:A blunt tip spatula is introduced vertically into the trephination cut, 90 degrees away from the main direction of the DM folds, and advanced until it touches the host layer. Gentle pressure is applied, resulting in tucking of the redundant host layer toward the periphery. The tucking maneuver is repeated at different clock hours until a regular graft–host interface is obtained.Results:We applied the present technique to several DALK procedures performed for keratoconus, and found it to be safe and effective.Conclusions:DALK is the procedure of choice for the surgical treatment of corneal stromal diseases with a healthy endothelium, such as keratoconus. DM folds are a possible complication after DALK in patients with advanced corneal ectasia, arising from the compression of the redundant host DM by the donor graft, once it is sutured to the recipient. DM folds after DALK, when they involve the visual axis, cause permanent visual disturbances DM tucking allows the displacement of the central DM folds toward the graft margin, where they do not affect the patient's quality of vision.
The Use of Conjunctival Staining to Measure Ocular Surface Inflammation in Patients With Dry Eye
Authors: Yang Soonwon , Lee Hyun Jung , Kim Da-Yeong , Shin Soojung , Barabino Stefano , Chung So-Hyang 
Published: March 2019

Purpose:
To investigate the expression levels of inflammatory cytokines in the conjunctival epithelium and correlations with clinical parameters in dry eye disease (DED).

Methods:
This study evaluated 28 patients with Sjögren syndrome (SS) DED, 28 patients with non-SS DED, and 10 controls. The messenger ribonucleic acid (mRNA) expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, IL-17, and matrix metalloproteinase 9 (MMP9) from conjunctival epithelium was investigated by real-time polymerase chain reaction. Protein expression was confirmed by immunofluorescence staining. Correlations were evaluated between the mRNA expression of inflammatory cytokines and clinical DED parameters such as ocular surface disease index score, Schirmer I value, tear film breakup time, and corneal and conjunctival staining scores.

Results:
Patients with non-SS DED expressed significantly more IFN-γ, IL-6, and MMP9 genes in the conjunctival epithelium than the controls (P < 0.05), and all cytokine gene expression was significantly higher in patients with SS DED than in the controls (P < 0.01). Tumor necrosis factor-α, IL-1β, IL-6, and IL-17 gene expression was higher in patients with SS DED than in the non-SS DED group (P < 0.05). Immunofluorescence staining of conjunctival epithelium demonstrated that positive cells with IL-6 or MMP9 were significantly higher in non-SS DED than in controls (P < 0.01) and much higher in SS DED than in non-SS DED (P < 0.05). Conjunctival staining scores significantly correlated with the expression of IFN-γ, IL-6, IL-17, and MMP9 in both DED groups (P < 0.05 in non-SS DED and P < 0.01 in SS-DED). Interestingly, correlation coefficients of all cytokines were much higher in SS DED compared to non-SS DED. Corneal staining scores showed positive correlations with IFN-γ, IL-17, and MMP9 (P < 0.05), and correlation coefficients were lower than those of conjunctival staining scores.

Conclusions:
Conjunctival staining scores may be useful to measure ocular surface inflammation in SS and non-SS DED.
Outcomes of gefitinib therapy for disease recurrence in medically inoperable stage I lung adenocarcinoma patients with active EGFR mutations receiving stereotactic body radiotherapy: a single-institute retrospective study
Authors: Kashiwabara Kosuke , Semba Hiroshi , Fujii Shinji , Tsumura Shinsuke 
Published: March 2019

Introduction:
Anticancer therapy for disease recurrence in medically inoperable stage I lung adenocarcinoma patients receiving stereotactic body radiotherapy (SBRT) has not been previously reported. Gefitinib is tolerable and effective in patients with active epidermal growth factor receptor (EGFR) mutations who have an advanced age and/or a low performance status, but whether gefitinib improves the survival of such patients with disease recurrence after SBRT remains unclear.

Patients and methods:
We retrospectively evaluated overall survival after disease recurrence in patients with active EGFR mutations who received gefitinib (GEF group) and patients without active EGFR mutations who did not receive gefitinib (non-GEF group).

Results:
During a follow-up period with a median time of 36.0 months, disease recurrence occurred in 10 of 20 patients with medically inoperable stage I lung adenocarcinoma who received SBRT (2 cases with local tumor recurrence alone and 8 cases with lymph node and/or distant metastasis). The median age or the median Charlson comorbidity index score were 84 years and 2 in the GEF group (n=4) and 81 years and 2 in the non-GEF group (n=6), respectively. Two cases in the GEF group received chemotherapy after first-line gefitinib therapy. Two cases in the non-GEF group received chemotherapy, but the others received best supportive care alone. The median overall survival time from disease recurrence was significantly different between the 2 groups (27.3 vs. 3.6 mo, P=0.038). Two cases with grade 2 radiation pneumonitis did not have a recurrence of pneumonitis during gefitinib therapy.

Conclusions:
Gefitinib might be useful as a salvage therapy in patients who desire to continue anticancer treatment.
Optical Coherence Tomography Segmentation Errors of the Retinal Nerve Fiber Layer Persist Over Time
Authors: Nagarkatti-Gude Nisha , Gardiner Stuart K. , Fortune Brad , Demirel Shaban , Mansberger Steven L. 
Published: March 2019

Précis:
There are errors in automated segmentation of the retinal nerve fiber layer (RNFL) in glaucoma suspects or patients with mild glaucoma that appear to persist over time; however, automated segmentation has greater repeatability than manual segmentation.

Purpose:
To identify whether optical coherence tomography (OCT) segmentation errors in RNFL thickness measurements persist longitudinally.

Methods:
This was a cohort study. We used spectral domain OCT (Spectralis) to measure RNFL thickness in a 6-degree peripapillary circle, and exported the native “automated segmentation only” results. In addition, we exported RNFL thickness results after “manual refinement” to correct errors in the automated segmentation, and used the differences in these measurements as “error” in segmentation. We used Bland-Altman plots and linear regression to determine the magnitude, location, and repeatability of RNFL thickness error in all twelve 30-degree sectors and compared the error at baseline to follow-up time points at 6 months, 2 years, 3 years, and 4 years.

Results:
We included 406 eyes from 213 participants. The 95% confidence interval for errors at baseline was −6.5 to +13.2 μm. The correlation between the baseline error and the errors in the follow-up time periods were high (r>0.5, P<0.001 for all). Automated segmentation had a smaller SD of residuals from the longitudinal trend line when compared to manual refinement (1.56 vs. 1.80 μm, P<0.001), and a higher ability (P=0.009) to monitor progression using an analysis of a longitudinal signal-to-noise ratio.

Conclusions:
Errors in automated segmentation remain relatively stable, and baseline error is highly likely to persist in the same direction and magnitude in subsequent time periods. However, automated segmentation (without manual refinement) is more repeatable and may be more sensitive to glaucomatous progression. Future segmentation algorithms could exploit these findings to improve automated segmentation in the future.
Suture Removal After Trabeculectomy With Fornix-based Conjunctival Flap Leads to Faster Visual Recovery but Not Reduced Astigmatism
Authors: Laspas Panagiotis , Leichsenring Verena , Hoffmann Esther , Preussner Rolf , Wahl Jochen , Pfeiffer Norbert 
Published: March 2019

Précis:
The closing limbal suture after trabeculectomy with a fornix-based conjunctival flap plays no critical role in the development of corneal astigmatism and intraocular pressure (IOP). A standard removal is not recommended.

Purpose:
To investigate the effect of removal of the conjunctival suture after trabeculectomy with fornix-based conjunctival flap on corneal astigmatism, visual acuity, and IOP.

Methods:
Eighty-seven cases of trabeculectomy with mitomycin C with a fornix-based conjunctival flap performed in the eyes of 82 patients (5 patients underwent bilateral trabeculectomy) were enrolled in a prospective randomized study. All surgeries were conducted by the same surgeon (J.W.) in the Ophthalmology Department of the University Medical Center of Mainz, Germany. All eyes received a corneal-conjunctival, continuous, mattress, interlocked suture for closing the conjunctiva at the limbus. After randomization, in 46 cases the suture was removed 6 weeks postoperatively; in 41 patients, the suture was left in place. All patients were examined preoperatively, and at 6 weeks, 3 months, 6 months, and 12 months after surgery. Astigmatism was measured using objective refraction and corneal topography, IOP and visual acuity were also assessed. Results were compared using a Wilcoxon test or Mann-Whitney U test for single time-points.

Results:
During follow-up, no significant differences between the 2 study groups regarding refractive or topographic values were found. Patients in the suture removal group had a significantly higher visual acuity than controls at 3 months, 6 months, and 1 year after surgery. IOP was similar in both groups throughout the study.

Conclusions:
Removal of the conjunctival suture in trabeculectomy with a fornix-based conjunctival flap leads to a faster rehabilitation of visual acuity but does not significantly affect corneal astigmatism or IOP.
The Sutureless Mullerectomy
Authors: Gildener-Leapman Juliana R. , Sheps Iyar , Stein Ran , Benyamini Oren , Milstein Asher , Hartstein Morris E. 
Published: March 2019

Purpose:
Müller’s muscle-conjunctival resection (MMCR) is a well-known approach for ptosis repair. In its standard fashion, it involves resection of Müller’s muscle and conjunctiva, followed by suturing of the conjunctiva and Müller’s muscle to the tarsus with absorbable or nonabsorbable sutures. The authors herein present their experience in performing MMCR without sutures.

Methods:
The study was conducted as a retrospective review of 19 patients (34 eyelids) undergoing sutureless MMCR. Thirty-three eyelids had acquired ptosis and 1 eyelid had congenital ptosis. Surgery consisted of a standard approach and placement of a Putterman clamp. Following excision of the clamped tissues, no internal sutures were placed. Preoperative and postoperative upper margin-to-reflex distances were measured and patients were evaluated for symmetry within 1 mm and the incidence of any complications.

Results:
Nineteen patients underwent 34 sutureless MMCR procedures. Of these, 13 patients had bilateral ptosis repair. Thirty-three of 34 eyelids (97%) showed improvement in margin-to-reflex distances, with an average improvement of 1.4 mm (range, 0–3.5 mm, SD = 0.64) among all patients. Eighteen of the 19 patients (94.7%) showed postoperative symmetry of margin-to-reflex distances within 1 mm (p < 0.001, χ2 test). One patient who underwent unilateral surgery demonstrated a Herring’s response postoperatively, leading to the single case of asymmetry. There was 1 case of corneal abrasion seen postoperatively.

Conclusions:
The sutureless technique is a rapid and effective method for performing MMCR. This technique is especially useful as an adjunct to blepharoplasty where mild ptosis exists for an added rejuvenating effect. It is low-risk and potentially corneoprotective when compared to the standard suture technique. Further studies could determine if a modified algorithm needs to be applied.
Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity
Authors: Sapio Matthew R. , Iadarola Michael J. , LaPaglia Danielle M. , Lehky Tanya , Thurm Audrey E. , Danley Kristen M. , Fuhr Shannon R. , Lee Mark D. , Huey Amanda E. , Sharp Stephen J. , Tsao Jack W. , Yanovski Jack A. , Mannes Andrew J. , Han Joan C. 
Published: March 2019

Abstract
Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.