bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the molecular mechanisms that govern anti‐Müllerian hormone synthesis and activity
Authors: Stocker William A. , Howard James A. , Maskey Shreya , Luan Haitong , Harrison Sophie G. , Hart Kaitlin N. , Hok Lucija , Thompson Thomas B. , Walton Kelly L. , Harrison Craig A. 
Published: December 2023

AbstractThe roles of anti‐Müllerian hormone (AMH) continue to expand, from its discovery as a critical factor in sex determination, through its identification as a regulator of ovarian folliculogenesis, its use in fertility clinics as a measure of ovarian reserve, and its emerging role in hypothalamic–pituitary function. In light of these actions, AMH is considered an attractive therapeutic target to address diverse reproductive needs, including fertility preservation. Here, we set out to characterize the molecular mechanisms that govern AMH synthesis and activity. First, we enhanced the processing of the AMH precursor to >90% by introducing more efficient proprotein convertase cleavage sites (RKKR or ISSRKKRSVSS [SCUT]). Importantly, enhanced processing corresponded with a dramatic increase in secreted AMH activity. Next, based on species differences across the AMH type II receptor‐binding interface, we generated a series of human AMH variants and assessed bioactivity. AMHSCUT potency (EC50 4 ng/mL) was increased 5‐ or 10‐fold by incorporating Gln484Met/Leu535Thr (EC50 0.8 ng/mL) or Gln484Met/Gly533Ser (EC50 0.4 ng/mL) mutations, respectively. Furthermore, the Gln484Met/Leu535Thr double mutant displayed enhanced efficacy, relative to AMHSCUT. Finally, we identified residues within the wrist pre‐helix of AMH (Trp494, Gln496, Ser497, and Asp498) that likely mediate type I receptor binding. Mutagenesis of these residues generated gain‐ (Trp494Phe or Gln496Leu) or loss‐ (Ser497Ala) of function AMH variants. Surprisingly, combining activating type I and type II receptor mutations only led to modest additive increases in AMH potency/efficacy. Our study is the first to characterize AMH residues involved in type I receptor binding and suggests a step‐wise receptor‐complex assembly mechanism, in which enhancement in the affinity of the ligand for either receptor can increase AMH activity beyond the natural level.
Orthopaedic Surgery Subspecialty Podcast Effectively Disseminates Peer-reviewed Articles Relative to Traditional Online Publishing
Authors: Paulson Ambika E. , Clement Rutledge Carter , Holt Joshua B. , Sanders Julia S. , Louer Craig R. 
Published: December 2023

Background:
Podcasts have become increasingly utilized in medical education over the past decade, especially in orthopaedic surgery. Compared with more traditional learning tools, podcasts are easily accessible, free, and capable of use while multitasking. Despite these apparent benefits, the effectiveness of podcasts as a dissemination tool for emerging peer-reviewed literature is not well understood. The Peds Ortho Podcast is the official podcast of Pediatric Orthopedic Society of North America that highlights recently published peer-reviewed articles through author interviews and executive summaries of featured articles. The purpose of this study was to compare the distribution of the Peds Ortho Podcast to traditional media by comparing electronic access statistics between the podcast episodes and the journal articles they summarize.

Methods:
Podcast episodes were reviewed to catalog the abstracts and articles discussed therein. Because podcasts and articles utilize different electronic metrics to track distribution, we established a common metric of an “access,” which we defined as an “intent to consume the media.” For articles, we defined an “access” as the largest value of a publisher’s online metrics, be it abstract views, full text views, or article downloads. For podcast episodes, we defined an “access” as any play >0 seconds. Access data were analyzed using independent samples t test and analyses of variance.

Results:
Eighty episodes of the Peds Ortho Podcast have featured 333 published, peer-reviewed articles to date, with 303 included in the final analysis with available article metrics. There were significantly more mean electronic accesses per podcast episode than featured articles (1236 vs. 482, P<0.001). Podcast consumption greatly varies in the first 30 days following episode release; however, recent episodes have a substantial proportion of accesses soon after publication.

Conclusions:
Given that podcast electronic access is greater than traditional media, podcasts appear to be a valuable tool for health care providers and trainees. Podcasts serve a complementary role to traditional media by quickly disseminating main points and raising awareness of emerging research.
Clinical and Histopathologic Spectrum of Toxic Erythema of Chemotherapy: A Series of 56 Cases From a Single Institution
Authors: Cole Daniel W. , Menge Tyler D. , Lowe Lori , Chan May P. , Bresler Scott C. 
Published: December 2023

Introduction:
Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood.

Objective:
To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings.

Methods:
We searched our electronic medical record for “toxic erythema of chemotherapy” or “neutrophilic eccrine hidradenitis.” Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin–stained slides were retrospectively reviewed.

Results:
The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%).

Limitations:
As a retrospective study, it is subject to information bias.

Conclusion:
This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.
Lymphatic-based Lymphosome: A Novel Hypothesis with Clinical Implication for Supermicrosurgical Lymphaticovenous Anastomosis
Authors: Yang Johnson Chia-Shen 
Published: December 2023

Summary:
Understanding the anatomical territories drained by lymphatic vessels (LVs) is essential for a better comprehension of lymphatic anatomy and functionality, and for performing lymphatic procedures such as lymphaticovenous anastomosis (LVA). However, current concepts regarding the lymphatic territory are insufficient to explain some of the clinical observations. As shown in the figures, within one incision for the LVA, one to two lymphatic vessels (LV) remained unenhanced on indocyanine green (ICG) lymphography, whereas the rest of the LVs were enhanced. To answer this question, one must examine the concept of the lymphosome, first described by Suami, defined as a particular region drained by LVs into the same subgroup of regional lymph nodes (LNs) (eg, superficial groin LNs). Suami’s lymphosome concept represents “LN-based lymphosomes.” In addition, Shinaoka identified four distinct lymphatic groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limbs after ICG injection. This represents the concept “group-based lymphosomes.” Nevertheless, neither the LN- nor group-based lymphosome concepts offer an appropriate explanation for the clinical findings described above. In addition to the aforementioned lymphosome concepts, the author proposes a novel hypothesis called “lymphatic-based lymphosome,” which considers each LV as a single lymphosome. Therefore, the normal-type LV remained unenhanced when ICG was not injected into the draining territory. To enhance post-LVA outcomes, an even distribution of anastomoses to different group-based lymphosomes is important, as is avoiding performing all anastomoses onto a single LV or within the same group-based lymphosome.
Evaluation of Retinal Layers in Individuals With Pseudoexfoliation Syndrome and Ocular Hypertension
Authors: Koç Alpaslan , Özcura Fatih , Gültekin Irgat Saadet , Arik Özlem 
Published: December 2023

Précis:
This study investigated the retinal segmental thicknesses in individuals with pseudoexfoliation syndrome and ocular hypertension. Maximum thinning was found at 6 mm inferior to the inner plexiform layer. This layer is very important for the early diagnosis of glaucoma.

Purpose:
To analyze the thickness of the peripapillary retinal nerve fiber layer and 8 macular layers using optical coherence tomography in eyes with ocular hypertension (OHT) and pseudoexfoliation syndrome (PXS) and healthy eyes and to evaluate between-group differences.

Materials and Methods:
In a prospective study, the macular segmentation of retinal layers in 120 eyes of 120 participants was performed automatically using current Heidelberg Spectralis optical coherence tomography software, which provides measurements for 8 retinal layers. Thickness maps divided into nine subfields (ie, 1, 3, and 6 mm) were extracted from the software for each retinal layer and compared between groups.

Results:
The thinnest macular layers appeared in the ocular hypertensive PXS, normotensive PXS, and OHT groups in that order. In the inner retinal layers (macular retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer), statistically significant differences emerged between the PXS and control groups in all quadrants of the 3 and 6 mm areas. No significant difference between the OHT group and control group appeared except in the 6 mm temporal quadrant of the inner plexiform layer (IPL). Receiving operating characteristic analysis revealed quadrants with high area-under-the-curve values at 3 and 6 mm in macular segments in all 3 groups compared with the control group.

Conclusion:
In macular segment analysis, the inner retinal layers showed the most thinning in patients with ocular hypertensive PXS. According to receiving operating characteristic curve analysis, examinations performed 6 mm inferior to the IPL, as the quadrant with the highest area under the curve in all 3 groups, are critical for the early diagnosis of glaucoma.
Long-Term Results of Transscleral Diode Laser Cyclophotocoagulation in Glaucoma: A Real-Life Study
Authors: Sari Cem , Alagoz Nese , Omeroglu Asena , Cakir Ihsan , Pasaoglu Isil , Altan Cigdem , Yasar Tekin 
Published: December 2023

Précis:
Transscleral diode laser cyclophotocoagulation (TDLC) is effective and safe in a large population and different types of glaucoma but is least effective in the neovascular glaucoma (NVG) group.

Objective:
We aimed to investigate the clinical outcomes of TDLC in a large cohort of patients with different types of refractory glaucoma.

Patients and Methods:
Using patient charts, we retrospectively analyzed the success and complications of TDLC performed on eyes categorized into 6 groups: primary glaucoma (116 eyes), trauma (41 eyes), NVG (84 eyes), post-vitreoretinal surgery (post-VRS, 79 eyes), penetrating keratoplasty (47 eyes), and miscellaneous (40 eyes). Failure was defined as intraocular pressure (IOP) >22 mm Hg or <5 mm Hg, the need for further glaucoma surgery, and the loss of light perception during follow-up.

Results:
Overall, the mean follow-up time was 33.4 ± 17.4 months, the mean total energy delivered was 109.2 ± 56.5 J, and the mean IOP reduction rate was 41.8%. Total energy delivered and IOP reduction rates were similar between the groups (all P > 0.05). The probability of success at 36 months was 71.5%, 70.7%, 55.9%, 77.2%, 72.3%, and 72.5% in primary glaucoma, trauma, NVG, post-VRS, penetrating keratoplasty, and miscellaneous groups, respectively. The NVG group showed a significantly lower success rate (P = 0.009) than the other groups. Significant complications consisted of phthisis bulbi in 1 eye (0.2%) in the NVG group and chronic hypotony in 7 eyes (1.7%) in the NVG (3 eyes), trauma (2 eyes), post-VRS (1 eye), and primary glaucoma (1 eye) groups.

Conclusions:
Although TDLC was found to be a safe, effective method in the long term, it was least effective in eyes with NVG.
Comparison of Patterns of Structural Progression in Primary Open Angle Glaucoma and Pseudoexfoliation Glaucoma
Authors: Wy Seoyoung , Lee Yun Jeong , Sun Sukkyu , Bak Eunoo , Kim Young Kook , Park Ki Ho , Kim Hee Chan , Jeoung Jin Wook 
Published: December 2023

Précis:
Primary open angle glaucoma and pseudoexfoliation glaucoma showed different progression patterns of the retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning in OCT-guided progression analysis.

Purpose:
To compare the patterns of progression of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning by guided progression analysis (GPA) of optical coherence tomography (OCT) in primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG).

Materials and Methods:
The progression of RNFL and GCIPL thinning was assessed by the GPA of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). By overlaying the acquired images of the RNFL and GCIPL thickness-change maps, the topographic patterns of progressive RNFL and GCIPL thinning were evaluated. The rates of progression of RNFL and GCIPL thinning were analyzed and compared between patients with POAG and those with PXG.

Results:
Of the 248 eyes of 248 patients with POAG (175 eyes of 175 patients) or PXG (73 eyes of 73 patients) enrolled, 156 POAG eyes and 48 PXG eyes were included. Progressive RNFL thinning was significantly more common in PXG than in POAG (P=0.005). According to the RNFL progression-frequency maps, progression appeared mainly in the superotemporal and inferotemporal areas in POAG, whereas it had invaded more into the temporal area in PXG. According to the GCIPL maps, progression was most common in the inferotemporal area in both POAG and PXG. The average progression rate of GCIPL thinning was faster in PXG than in POAG (P=0.013), and when analyzed in 2 halves (superior/inferior), the progression rate of the inferior half was faster in PXG than in POAG (P=0.011).

Conclusions:
OCT GPA showed progression patterns of RNFL and GCIPL thinning in POAG and PXG. Understanding the specific patterns of progressive RNFL and GCIPL thinning according to glaucoma type may prove helpful to glaucoma-patient treatment and monitoring.
Anterior Segment Optical Coherence Tomography for Cases of High Intraocular Pressure Following XEN Implant for Glaucoma
Authors: Tatti Filippo , Lixi Filippo , Demarinis Giuseppe , Napoli Pietro , Fossarello Maurizio 
Published: December 2023

Précis:
This study showed that the XEN patency should be verified by OCT imaging in cases of encapsulated blebs. Although fibrosis plays the principal role, humor aqueous flow reduction could affect the “spacer” effect that inhibits the fibroblast attachments.

Purpose:
To evaluate the application of the anterior segment optical coherence tomography (AS-OCT) imaging in studying the relationship between a low flow rate through the XEN63 and the development of a cystic bleb.

Methods:
Retrospective case series of 3 eyes presenting a cystic bleb after an XEN63 implantation for uncontrolled intraocular pressure (IOP). Demographic and clinical data were obtained from medical records. The imaging findings, complications, and managements following the surgery were evaluated.

Results:
Three patients, with an average age of 67.3 years, initially showed a patent stent lumen and a functional bleb after surgery. The IOP of all eyes increased on average at 28.3 days from the surgery, with a mean value of 39.66 mm Hg. The slit lamp examination showed a cystic bleb. The AS-OCT imaging confirmed the previous finding and revealed either a partial or total occlusion of the stent internal ostium. A Nd:YAG laser, in proximity to the ostium, was performed to resolve the obstruction. Although the AS-OCT imaging showed the device patency and the IOP immediately decreased, the latter became elevated again. Consequently, in all the cases, a further needling procedure was needed to achieve an adequate IOP reduction. Six months after the two-step procedure, the IOP averaged 13.33 mm Hg, the XEN63 lumens appeared cleared, and the blebs showed a functional morphology. No adverse events were observed.

Conclusion:
The development of a cystic bleb may result from an altered balance between the flow rate through the XEN63 and the fibrosis development in the postoperative healing process. A proper follow-up based on slit lamp biomicroscopy, IOP measurement, and AS-OCT imaging is advisable to estimate and manage a cystic bleb following XEN63 implantation.
Single-Use Lens Compromise During Selective Laser Trabeculoplasty
Authors: Liu Alice S. , Lyons Lance J. , Khanna Cheryl L. , Roddy Gavin W. , Hodge David O. , Sit Arthur J. 
Published: December 2023

Précis:
Damage to disposable selective laser trabeculoplasty (SLT) lenses correlated with the amount of total laser energy. Furthermore, greater lens damage was associated with diminished patient treatment response.

Purpose:
Disposable SLT lenses have been observed to be damaged during use by laser, potentially affecting therapeutic response. This study sought to identify factors associated with the magnitude of lens damage and its effect on treatment outcomes.

Patient and Methods:
We analyzed 113 eyes from 82 patients who underwent SLT between 2020 and 2021 at an American academic medical center. For each procedure, we recorded baseline patient characteristics, procedure settings, physician age (as a possible factor causing laser defocus due to accommodation), and area of lens damage. Treatment response was calculated as the difference between preoperative and postoperative intraocular pressure (IOP).

Results:
Area of lens damage was associated with greater total laser energy (r=0.34, P<0.001) and greater mean energy per application (r=0.37, P<0.001). IOP reduction decreased with increasing lens damage (r=−0.19, P=0.022). Lens damage was not associated with patient characteristics indicative of glaucoma severity or user settings (physician age and slit lamp used). Greater IOP reduction was associated with higher preop IOP (r=0.46, P<0.001) and a smaller cup-to-disc ratio (r=0.22, P=0.036). IOP reduction was not associated with retinal nerve fiber layer thickness, patient age, or the number of glaucoma medications.

Conclusions:
Increased laser damage to disposable SLT lenses was associated with diminished treatment effect. The amount of damage was correlated with total and average laser energy, but not patient or physician factors. Overall, these findings call for reconsideration of using disposable SLT lenses as part of routine practice.
Lessons From The Glaucoma Foundation Think Tank 2023: A Patient-Centric Approach to Glaucoma
Authors: Harris Alon , Verticchio Vercellin Alice , Weinreb Robert N. , Khawaja Anthony , MacGregor Stuart , Pasquale Louis R. 
Published: December 2023

Précis:
The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.

Purpose:
To summarize the main topics discussed during the 28th Annual Glaucoma Foundation Think Tank Meeting “A Patient-Centric Approach to Glaucoma” held in New York on June 9 and 10, 2023.

Methods:
The highlights of the sessions on BIG DATA, genetics, modifiable lifestyle risk factors, female sex hormones, and neuroprotection in the field of primary open angle glaucoma (POAG) were summarized.

Results:
The researchers discussed the importance of BIG DATA repositories available at national and international levels for POAG research, including the United Kingdom Biobank. Combining genotyped large cohorts worldwide, facilitated by artificial intelligence (AI) and machine-learning approaches, led to the milestone discovery of 312 genome-wide significant disease loci for POAG. While these loci could be combined into a polygenic risk score with clinical utility, Think Tank meeting participants also provided analytical epidemiological evidence that behavioral risk factors modify POAG polygenetic risk, citing specific examples related to caffeine and alcohol use. The impact of female sex hormones on POAG pathophysiology was discussed, as was neuroprotection and the potential use of AI to help mitigate specific challenges faced in clinical trials and speed approval of neuroprotective agents.

Conclusions:
The experts agreed on the importance of genetics in defining individual POAG risk and highlighted the additional crucial role of lifestyle, gender, blood pressure, and vascular risk factors. The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.
Patients With Subacute Sclerosing Panencephalitis in Japan: A 2022 Nationwide Survey
Authors: Okabe Hisao , Hashimoto Koichi , Norito Sakurako , Kume Yohei , Chishiki Mina , Hasegawa Shunji , Sakai Yasunari , Nomura Keiko , Shibata Takashi , Suzuki Yasuhiro , Sunagawa Tomimasa , Takao Masaki , Hosoya Mitsuaki 
Published: December 2023

Background:
In Japan, the incidence of subacute sclerosing panencephalitis (SSPE) has reduced; however, the medical conditions and factors associated with disease progression remain unclear.

Methods:
A nationwide survey of SSPE was conducted using a questionnaire in 2022. We conducted a descriptive analysis of the patients with SSPE in 2022 and Cox proportional hazards analyses for disease progression. We compared the patients with SSPE with those in a 2007 survey.

Results:
A total of 37 surviving patients with SSPE were enrolled [median age: 32 years (range: 16–52 years)]. No new cases have been identified since 2017 in the survey. Jabbour stage IV was the most common stage (66.7%). The hazard ratios (95% confidence intervals) of male sex and age at the time of measles infection (years) were 2.56 (1.13–5.76) and 0.57 (0.34–0.93), respectively. Compared with those in 2007, the proportion of patients in hospitals decreased from 13.7% to 2.7%, whereas that of patients in nursing facilities increased from 17.6% to 29.7%. The proportions of patients prescribed inosine pranobex, interferon and ribavirin at the time of the survey decreased from 96.1% to 79.4%, 74.8% to 14.3% and 25.3% to 0%, respectively. The proportions of patients with gastrostomy, tracheostomy and ventilator use increased from 5.9% to 69.7%, 23.3% to 60.0% and 10.8% to 32.4%, respectively.

Conclusions:
Decreased measles cases in Japan reduced new SSPE cases. However, surviving patients in 2022 had advanced disease stages and needed medical care. Male sex and early measles infection were significantly associated with disease progression.
Therapeutic plasma exchange in critical illness
Authors: Koniman Riece , Kaushik Manish 
Published: December 2023

ABSTRACT
Therapeutic plasma exchange (TPE) is widely used for various diseases, particularly in critically ill patients. Most of these indications rely mainly on the removal of pathological molecules in the plasma by TPE. TPE is also used to replace missing plasma components in some diseases. However, there are emerging data on the use of TPE in novel indications because of its potential immunomodulatory effects. This review discusses the techniques of TPE, key considerations when prescribing TPE, indications for TPE in critically ill patients, emerging developments and knowledge gaps in this field.