bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Bimatoprost Implant on Glaucoma Patients: An Observational Study
Authors: Choi Eun Young , Johnson Nicholas A. , Stinnett Sandra , Rosdahl Jullia , Moya Frank , Herndon Leon W. 
Published: March 2024

Précis:
In this retrospective study of glaucoma patients receiving the bimatoprost implant at Duke Eye Center, the number of topical intraocular pressure–lowering medications was significantly reduced through 12 months after the implant.

Purpose:
To study the effects of the bimatoprost implant on intraocular pressure (IOP) and the need for topical IOP-lowering medications in glaucoma patients in the clinical practice setting.

Patients and Methods:
Patients who received the bimatoprost implant at Duke Eye Center from November 2020 to October 2021 were identified. Exclusion criteria included addition of other IOP-lowering medications concurrent with the implant and <1 month of follow-up. The change in IOP and number of topical IOP-lowering medications from baseline to months 1, 3, 6, 9, and 12 after the implant was calculated. Subgroup analysis was performed for different glaucoma severities.

Results:
A total of 63 patients and 92 eyes were included (mean age 77.8 ± 10.1 years). Glaucoma severity ranged from mild (11%), moderate (30%), to severe (54%). There was a nonsignificant decrease in IOP at all timepoints. The mean number of topical IOP-lowering medications significantly decreased by 0.81, 0.75, 0.63, 0.70, and 0.67 at month 1, 3, 6, 9, and 12, respectively (all P < 0.001). There was no significant change in the total number of medications, including the bimatoprost implant. When divided by glaucoma severity, the reduction in the number of topical medications was significant at 1, 3, and 6 months for mild/moderate disease and at 1 month for severe disease. During the follow-up period, 19 eyes underwent additional laser or surgical procedures, 68% of which had a history of prior incisional glaucoma surgery.

Conclusions:
The bimatoprost implant may reduce the need for topical IOP-lowering agents over a 1-year period, especially in mild to moderate–stage glaucoma. The efficacy of the implant may be more limited in severe glaucoma, and further work is needed to characterize its long-term effects.
Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial
Authors: Muñoz-Negrete Francisco J. , Topouzis Fotis , Oddone Francesco , Nisslé Sylvie , Rokicki Dariusz , Januleviciene Ingrida , Harasymowycz Paul , Stalmans Ingeborg 
Published: March 2024

Précis:
Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed.

Purpose:
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%).

Design:
Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration.

Methods:
Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia.

Results:
The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were −9.72±2.97 and −9.47±3.06 mm Hg, respectively, at 8 am, −9.41±3.03 and −9.19±3.12 mm Hg at 10 am, and −8.99±3.36 and −8.54±3.44 mm Hg at 4 pm. Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively).

Conclusions:
PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.
Bardet–Biedl syndrome with unique manifestations of congenital giant nevi and refractory anemia: a case report from Palestine
Authors: Milhem Mohammad , Shehadeh Daleen , Abu Nawa Yasmeen , Arman Roa , Masri Lara , Salman Zeena , Najajreh Mohammad 
Published: March 2024

Introduction and importance:
Bardet–Biedl syndrome (BBS) is a rare autosomal recessive disorder impacting multiple organs. Characterized by renal dysfunction, retinal dystrophy, obesity, polydactyly, intellectual disability, and hypogonadism, it lacks targeted treatment. Diagnosis relies on clinical criteria, and management emphasizes early detection, complication screening, and genetic counselling.

Case presentation:
A 4-year-old boy, born to first-cousin parents, presented with refractory iron-deficiency anaemia (IDA) and recurrent respiratory infections. Prenatal ultrasound revealed renal and limb anomalies. Physical examination showed dysmorphic features, polydactyly, and a giant-congenital naevus. Genetic testing revealed a homozygous MKKS variant. Despite oral iron, severe IDA persisted. Intravenous iron therapy yielded significant improvement.

Clinical discussion:
BBS, an autosomal recessive ciliopathy, involves various genes. In this case, the MKKS gene variant contributed to the syndrome. The incidence of BBS in the Arab population is discussed, emphasizing its rarity and varied clinical presentations. Incidence in the Arab population, including Palestine, is 1 in 13 500. Diagnostic criteria, encompassing major and minor features, highlight BBS complexity. Renal anomalies, visual disturbances, and cutaneous manifestations are common. Multidisciplinary care addresses systemic involvement with emerging treatments like setmelanotide.

Conclusion:
This case underscores BBS's rarity and complexity, featuring unique aspects like giant nevi and refractory IDA. Comprehensive management addresses renal, visual, cardiac, and neurologic aspects. Genetic counselling, prenatal testing, and preimplantation genetic diagnosis prevent transmission. Limitations include lacking local epidemiological data and prior studies in Palestine. This case contributes insights, stressing multidisciplinary management and prompting further research in underexplored populations.
A rare case of retained metallic foreign body in liver: case report and review of literature
Authors: Dev Santosh , Yadav Manish , Shah Newton Ashish , Dev Barsha , Devkota Shishir , Khadka Laxman , Das Dhiraj Kumar , Yadav Samridhi , Sah Jayant Kumar , Ghimire Bikal 
Published: March 2024

Introduction and importance:
Foreign bodies in the liver are uncommon but can lead to severe conditions like liver abscess and sepsis. They typically enter through direct penetration, migration from the gastrointestinal tract, or through the blood. Common foreign objects include metal pins, or sewing needles swallowed accidentally.

Case presentation:
A 25-year-old male presented to our OPD with pain over the right abdomen with a prior history of projectile injury causing laceration over the right anterior abdomen with primary suturing. On radiological investigation, a retained foreign body was revealed. The metallic foreign body was embedded in the liver for 5 months. Removal of the foreign body was performed without any complications.

Clinical discussion:
Intrahepatic foreign bodies (FBs) in the liver can result from penetrating injuries, iatrogenic causes, or ingestion, particularly in children. Clinical presentations vary, and complications such as abscess formation may occur. Diagnosis involves imaging modalities like X-rays, ultrasonography, and computed tomography (CT) scans. The presented case highlights the importance of meticulous follow-up, as chronic pain manifested despite conservative management. The management of intrahepatic FBs depends on factors like size, location, and symptoms, with conservative approaches for stable patients. Surgical removal remains the mainstay of the treatment. Long-term monitoring is crucial to detect potential complications, and imaging studies play a key role in regular follow-up.

Conclusion:
Hepatic foreign bodies are rare, and symptoms vary based on size, type, and location, ranging from asymptomatic to complications such as abscess formation. Surgical removal is the main treatment, but in cases of noncomplicated hepatic foreign bodies, close follow-up is necessary.
Trends in Blood Mosaicism and Clinical Phenotype Score in Patients with Beckwith–Wiedemann Syndrome Evaluated for Tongue Reduction Surgery
Authors: Romeo Dominic J. , Wagner Connor S. , Massenburg Benjamin B. , Reddy Neil , Wu Meagan , Ng Jinggang J. , DeMarchis Madison , Liao Eric C. , Kalish Jennifer M. , Taylor Jesse A. 
Published: March 2024

Background:
Most patients with Beckwith–Wiedemann syndrome (BWS) have macroglossia, with some requiring tongue reduction surgery (TRS). This study reports correlations between levels of affected cells (mosaicism) and BWS clinical score in patients evaluated for TRS. The authors also show correlations of clinical score and mosaicism with obstructive sleep apnea (OSA) severity.

Methods:
Blood mosaicism levels and BWS clinical score were recorded in patients with macroglossia referred to plastic surgery for evaluation. Associations among blood mosaicism, BWS clinical score, TRS, and OSA were assessed with appropriate statistics.

Results:
Of the 225 patients included, BWS blood testing was available in 128 (56.9%). Mosaicism levels were higher in those who underwent TRS compared with those who did not (85.9% [56.5 to 95.9] versus 29.7% [2.8 to 73.1]; P < 0.001). BWS clinical score was also higher in those requiring TRS (9.0 [8.0 to 11.0] versus 7.0 [6.0 to 9.0]; P < 0.001). There was a positive correlation between clinical score and obstructive apnea-hypopnea index (r = 0.320, P = 0.011). Receiver operating characteristic curve analysis showed that a clinical score of 11 or greater had 100% specificity and 36.4% sensitivity for detecting patients requiring TRS. Blood mosaicism of 80% or greater had 63.6% sensitivity and 83.6% specificity for predicting surgery. A combined criteria of BWS clinical score of 11 or greater or mosaicism of 80% or greater had 72.7% sensitivity and 83.6% specificity for predicting TRS.

Conclusions:
Blood mosaicism levels and higher BWS clinical scores seem to be associated with a greater frequency of having surgery in patients with macroglossia referred for surgical evaluation. Elevations in BWS clinical scoring are associated with increased OSA severity; increased blood mosaicism is not.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
On the Kermack–McKendrick with Weibull residence times
Authors: Cruz–López M. , Murillo-Salas A. , Velasco-Hernández J.X. 
Published: March 2024

AbstractIn this paper we develop a generalization of the Kermack-McKendrick SIR model where the time of infectiousness follows the Weibull distribution. We compute the equivalent classical results available for the classical SIR model, particularly a general expression for the basic reproduction number. We comment about the implications of this generalization in epidemic and metapopulation dynamics and illustrate our findings with some numerical simulations.
Optimisation strategies for directed evolution without sequencing
Authors: James Jess , Towers Sebastian , Foerster Jakob , Steel Harrison 
Published: March 2024

AbstractDirected evolution can enable engineering of biological systems with minimal knowledge of their underlying sequence-to-function relationships. A typical directed evolution process consists of iterative rounds of mutagenesis and selection that are designed to steer changes in a biological system (e.g. a protein) towards some functional goal. Much work has been done, particularly leveraging advancements in machine learning, to optimise the process of directed evolution. Many of these methods, however, require DNA sequencing and synthesis, making them resource-intensive and incompatible with developments in targetedin vivomutagenesis. Operating within the experimental constraints of established sorting-based directed evolution techniques (e.g. Fluorescence-Activated Cell Sorting, FACS), we explore approaches for optimisation of directed evolution that do not require sequencing information. We then expand our methods to the context of emerging experimental techniques in directed evolution, which allow for single-cell selection based on fitness objectives defined from any combination measurable traits. Finally, we validate the developed selection strategies on the GB1 empirical landscape, demonstrating that they can lead to up to a 7.5 fold increase in the probability of attaining the global fitness peak.Author summaryThe standard approach to sorting-based selection in directed evolution is to take forward only the top-performing variants from each generation of a single population. In this work, we begin to explore alternative selection strategies within a simulated directed evolution framework. We propose “selection functions”, which allow us to tune the balance of exploration and exploitation of a fitness landscape, and we demonstrate that splitting a population into sub-populations can improve both the likelihood and magnitude of a successful outcome. We also propose strategies to leverage emerging selection methods that can implement single-cell selection based on any combination of measurable traits. We validate our optimised directed evolution approaches on the empirical fitness landscape of the GB1 immunoglobulin protein.
Sexual dimorphism and allometry in human scapular morphology
Authors: Lee Erin C.S. , Lawrence Rebekah L. , Rainbow Michael J. 
Published: March 2024

AbstractScapular morphology is highly variable across the human population and appears to be sexually dimorphic – differing significantly between males and females. However, previous investigations of sexual dimorphism in scapula shape have not considered the effects of allometry (the relationship between size and shape). Disentangling allometry from sexual dimorphism is necessary because apparent sex-based differences in morphology could be due to inherent differences in body size. This study aimed to investigate sexual dimorphism in scapula shape and examine the role of allometry in sex-based variation. We used three-dimensional geometric morphometrics with Procrustes ANOVA to quantify scapula shape variation associated with sex and size in 125 scapulae. Scapular morphology significantly differed between males and females, and males tended to have larger scapulae than females for the same body height. We found that males and females exhibited distinct allometric relationships, and sexually dimorphic shape changes did not align with male- or female-specific allometry. A secondary test revealed that sexual dimorphism in scapula shape persisted between males and females of similar body heights. Overall, our findings indicate that sex-based differences in scapular shape are independent of size-shape relationships. Our results shed light on the potential role of sexual selection in human shoulder evolution, present new hypotheses for biomechanical differences in shoulder function between sexes, and identify relevant traits for improving sex classification accuracy in forensic analyses.
PIPETS: A statistically informed, gene-annotation agnostic analysis method to study bacterial termination using 3’-end sequencing
Authors: Furumo Quinlan , Meyer Michelle 
Published: March 2024

AbstractBackgroundOver the last decade the drop in short-read sequencing costs has allowed experimental techniques utilizing sequencing to address specific biological questions to proliferate, oftentimes outpacing standardized or effiective analysis approaches for the data generated. There are growing amounts of bacterial 3’-end sequencing data, yet there is currently no commonly accepted analysis methodology for this datatype. Most data analysis approaches are somewhatad hocand, despite the presence of substantial signal within annotated genes, focus on genomic regions outside the annotated genes (e.g. 3’ or 5’ UTRs). Furthermore, the lack of consistent systematic analysis approaches, as well as the absence of genome-wide ground truth data, make it impossible to compare conclusions generated by diffierent labs, using diffierent organisms.ResultsWe present PIPETS, (PoissonIdentification ofPEaks fromTerm-Seq data), an R package available on Bioconductor that provides a novel analysis method for 3’-end sequencing data. PIPETS is a statistically informed, gene-annotation agnostic methodology. Across two diffierent datasets from two diffierent organisms, PIPETS identified significant 3’-end termination signal across a wider range of annotated genomic contexts than existing analysis approaches, suggesting that existing approaches may miss biologically relevant signal. Furthermore, assessment of the previously called 3’-end positions not captured by PIPETS showed that they were uniformly very low coverage.ConclusionsPIPETS provides a broadly applicable platform to explore and analyze 3’-end sequencing data sets from across diffierent organisms. It requires only the 3’-end sequencing data, and is broadly accessible to non-expert users.
Identification of a Conserved B-Cell Epitope on the Capsid Protein of Porcine Circovirus Type 4
Authors: Fang Zheng , Sun Mingxia , Cai Xuehui , An Tongqing , Tu Yabin , Wang Haiwei 
Published: March 2024

ABSTRACTPorcine circovirus type 4 (PCV4), a recently identified circovirus, is prevalent in numerous provinces in China, as well as in South Korea, Thailand, and Europe. PCV4 virus rescued from an infectious clone showed pathogenicity, suggesting the economic impact of PCV4. However, there remains a lack of understanding regarding the immunogenicity and epitopes of PCV4. This study generated a monoclonal antibody (MAb) 1D8 by immunizing mice with PCV4 virus-like particles (VLPs). Subsequently, the epitope recognized by the MAb 1D8 was identified by truncated protein expression and alanine scanning mutagenesis analysis. Results showed that the225PKQG228located at the C-terminus of the PCV4 Cap protein is the minimal motif binding to the MAb. Homology modeling analysis and immunoelectron microscopy revealed that the epitope extends beyond the outer surface of the PCV4 VLP. Moreover, the epitope is highly conserved among PCV4 strains and does not react with other PCVs. Together, the MAb 1D8 recognized epitope shows potential for detecting PCV4. These findings significantly contribute to the design of antigens for PCV4 detection and control strategies.IMPORTANCEPorcine circovirus type 4 (PCV4) is a novel circovirus. Although PCV4 has been identified in several countries, including China, Korea, Thailand, and Spain, no vaccine is available. Given the potential pathogenic effects of PCV4 on pigs, PCV4 could threaten the global pig farming industry, highlighting the urgency for further investigation. Thus, epitopes of PCV4 remain to be determined. Our finding of a conserved epitope significantly advances vaccine development and pathogen detection.
Anion exchange regulates intestinal mucus expansion while Cftr regulatesde novomucus secretion
Authors: Ljungholm Penny L , Ermund Anna , Garsveden Molly M Söderlund , Pettersson Victor L , Gustafsson Jenny K 
Published: March 2024

SummaryThe intestinal epithelium is covered by mucus that protects the tissue from the luminal content. Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in regulation of mucus formation during steady state, and in response to carbamylcholine (CCh) and prostaglandin E2(PGE2). CftrΔF508 (CF) mice were used to assess the role of Cftr, and 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS) was used to inhibit anion exchange. In the distal colon, steady state mucus expansion was reduced by apical DIDS, and normal in CF mice. PGE2stimulated mucus expansion withoutde novomucus secretion in wild type (WT) and CF distal colon via DIDS sensitive mechanisms, while CCh inducedde novomucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE2, stimulatedde novomucus secretion in CF colon via DIDS sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE2with DIDS sensitivede novomucus secretion. In conclusion, this study suggests that apical anion exchange regulates intestinal mucus expansion, while Cftr regulatesde novomucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, activation of anion exchange can help release mucus from intestinal goblet cells.
Presence of Ecuador in the Web of Science from open access in post-pandemic period 2019-2021: A multivariate analysis
Authors: Álvarez Muñoz Patricio , Pacheco Olea Fernando Erasmo , Peralta Gamboa Dennis Alfredo , Angelo Marcos Aviles Valenzuela 
Published: March 2024

AbstractThe study analyzed the presence of Ecuador in the post-pandemic Web of Science (WoS) from a multivariate dynamic, highlighting a significant transformation in scientific communication towards open access (OA). The methodology integrated multivariate statistical techniques, using R and specialized tools, to process 9,085 relevant articles. Between 2019 and 2021, 52% of Ecuadorian publications in WoS were open access. This movement reflects a commitment to quality research and accessibility, evidencing an increase in publications and citations under OA. The research highlights the importance of establishing robust national OA policies in Ecuador to promote scientific collaboration and an equitable distribution of knowledge. The dynamic biplot showed how universities in the post-pandemic period had stable and erratic behaviors towards open access. Of all the universities, the State University of Cuenca stands out in terms of quantity of production and migration to open access.
Molecular Phylogeny and Cryptic Morphology: A Combined Approach to Taxonomic Novelties inPolycarpaea(Caryophyllaceae) from Vietnam
Authors: Truong Thanh Hoang , Le Le Ba , Thi Kim Ngan Le , Thi Ai Minh Nguyen , Thi Lan Anh Truong , Thi Nhung Tran , Thai Vinh Tran , Van Son Le , Thi Kim Duong , Viet Bach Khoa Hoang , Ngoc Tieu Le , Van Binh Nguyen , Van Tien Tran 
Published: March 2024

AbstractThree new species ofPolycarpaeafrom Vietnam,P. vanana,P. chungana,P. duonganaare described and illustrated based on evidence of molecular sequence data from two markers (ITS1-5.8S-ITS2 andrps16) and combined morphological characteristics.Polycarpaea vananais closely related toPolycarpaea gaudichaudi,P. arenaria,P. duonganabut differs by its stem glabrous, leaf ovate to elliptic, glabrous, ovary oblong ovoid, base obtuse, apex attenuate, capsule oblong void, 3.8 mm long.P. duonganadiffers from the three species mentioned above by its stem being densely villous, leaf spathulate, ciliate, ovary ovoid, base acute, apex obtuse, capsule ovoid, 1.2 mm long.Polycarpaea chunganais most similar toP. lignosabut differs in having leaf oblong or linear, sparse ciliate, sepal and petal apex deeply concaved or slightly bifid, ovary ovoid, ovoid, 0.8–1.0 mm long. Furthermore, the achievements of analysis using molecular data on the systematic positions of 7 other species are results that have not been in previous molecular analyses.