bluuebunny/crossref_metadata_2025_split huggingface dataset:
Krill oil for knee osteoarthritis: A meta-analysis of randomized controlled trials
Authors: Meng Jiahao , Wang Xuanyu , Li Yinghui , Xiang Yuqing , Wu Yumei , Xiong Yilin , Liu Pan , Gao Shuguang 
Published: February 2025

Background:
Knee osteoarthritis, a prevalent musculoskeletal disorder, significantly impacts global health and quality of life. Unfortunately, there is no disease modifying osteoarthritis drugs until now. Krill oil is being explored as a potential alternative, however its efficacy in managing knee symptoms remains unclear. Therefore, the meta-analysis of krill oil in knee osteoarthritis would be interesting and useful.

Methods:
We conducted a systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases from their inception through November 28, 2024, employing predefined search terms, including “krill oil” and “knee osteoarthritis.” We included all relevant randomized controlled trials to ensure a comprehensive analysis. Visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of pain, stiffness and function were served as primary outcomes. Moreover, blood markers and adverse events were also included.

Results:
Five randomized controlled trials involving 730 participants were included. Relative to the usual care group, the krill oil group demonstrated no significant improvement in knee osteoarthritis as measured by visual analog scale; however, it exhibited significant benefits in terms of pain (standardized mean difference [SMD] −0.60; 95% confidence interval [CI] −0.99 to −0.21), stiffness (SMD −0.59; 95%CI −1.04 to −0.14), and functional outcomes (SMD −0.68; 95% CI −1.09 to −0.27) based on WOMAC assessments. Analysis of blood markers also revealed no significant effects of krill oil group compared to the usual care group. Moreover, adverse events in the krill oil group and usual care group also showed no statistical difference. The safety profiles were similar between the 2 groups.

Conclusion:
Krill oil presents as a promising safe therapeutic option for knee osteoarthritis; however, its efficacy in pain relief requires further investigation.
Clinical study to evaluate the efficacy and safety of home-used LED and IRED mask for crow’s feet: A multi-center, randomized, double-blind, sham-controlled study
Authors: Park Sang Hyun , Park Seong Oh , Jung Jae-A 
Published: February 2025

Background:
As the elderly population continues to grow, the demand for antiaging products is increasing concurrently. On our face, wrinkles begin to form first around the eyes, where the skin is the thinnest. Previous studies have suggested that irradiating the skin with light-emitting diode (LED)/infrared emitting diode (IRED) light at 600 to 660 nm/800 to 860 nm, stimulates the cells of the dermis and epidermal tissue and is effective in wrinkle improvement and antiaging. Therefore, we aimed to evaluate the efficacy and safety of low-level light therapy masks.

Materials and methods:
A randomized, sham device-controlled, double-blind clinical trial was conducted at 2 institutions. Sixty Asian descent individuals between the ages of 30 and 65 years who showed type II to V skin type on the Fitzpatrick scale were included. Among participants with a score of 2 to 4 on the crow’s feet grading scale (CFGS) at rest (without expression), those who sought temporary improvement in both crow’s feet were selected. The participants were categorized into 2 groups: the experimental group, which used a device with a combination of 630 nm LED (max 10 mW/cm3) and 850 nm IRED (max 10 mW/cm3), and the control group, which used the sham device. Efficacy evaluation included various evaluations, including the CFGS as rated by independent raters, CFGS scores assigned by investigators, and the Global Aesthetic Improvement Scale evaluation by both investigators and the participants.

Results:
After using the LED mask for 16 weeks, the CFGS score of the independent raters and investigators showed significant differences at 8, 12, and 16 weeks. In addition, considering the success criteria of this study, a comparison of independent raters showed an improvement rate of ≥69.2% (full analysis set [FAS]: 86.2%, per-protocol set [PPS]: 89.3%) and a difference of ≥49.2% from the control group (FAS: 69.5%, PPS: 72.6%). The change in scores from the baseline showed significant differences between the test group and the control groups at 8, 12, and 16 weeks for both independent raters and investigators.

Conclusion:
LED and IRED phototherapies at 630 nm and 850 nm, respectively, are effective, safe, well-tolerated, and painless treatment for skin rejuvenation.
Ovarian Stem Cells: Will the Dream of Neo-Folliculogenesis After Birth Become Real?
Authors: Canosa Stefano , Silvestris Erica , Carosso Andrea Roberto , Ruffa Alessandro , Evangelisti Bernadette , Gennarelli Gianluca , Cormio Gennaro , Loizzi Vera , Rolfo Alessandro , Benedetto Chiara , Revelli Alberto 
Published: February 2025

Importance
Ovarian stem cells (OSCs) represent a promising tool in reproductive medicine, particularly for the treatment of premature ovarian failure and fertility preservation.

Objective
Herein, we summarize the main characteristics of adult stem cells, their status, needs, and new challenges in the application in reproductive medicine.

Evidence Acquisition
Clinical studies have shown that OSCs transplantation can restore ovarian function and stimulate neo-folliculogenesis in patients with premature ovarian failure, enabling them to conceive naturally or through in vitro fertilization techniques. Moreover, OSCs gained increasing interest as a chance to preserve fertility in cancer patients undergoing gonadotoxic treatments affecting their fertility, as chemotherapy or radiotherapy.

Results
The recruitment of OSCs from fresh or thawed ovarian fragments coupled with their capability to differentiate in vitro to mature oocytes could provide a novel opportunity to verify their suitability to be expanded in vitro as oocyte like cells.

Conclusions and Relevance
Research into OSCs and their applications in reproductive medicine is still in its infancy, but the results so far are promising and offer new possibilities for patients suffering from premature ovarian failure or cancer.

Target Audience
Obstetricians and gynecologists, family physicians

Learning Objectives
After completing this activity, the learner will be better able to (1) describe the main characteristics of stem cells and the sources from which they can be isolated; (2) discuss the presence of OSCs in the ovary of adult women and how they can support the process of neo-folliculogenesis; and (3) explain how OSCs may be used as a possible therapeutic strategy for cancer patients or patients at risk of premature ovarian insufficiency.
The Clinical Utility of Measures of Ovarian Reserve
Authors: Baker Katherine M. , FernandezCriado Rodolfo , Eaton Jennifer L. , Mensah Virginia A. 
Published: February 2025

Importance
Measures of ovarian reserve, particularly anti-Müllerian hormone, have been increasingly and inaccurately utilized as “fertility tests.” It is important to understand the available measures of ovarian reserve and how to appropriately interpret and integrate their use into clinical practice.

Objective
The objectives of this article are to review the process of reproductive aging, define ovarian reserve, describe the available measures of ovarian reserve, and discuss the clinical utility of these measures.

Evidence Acquisition
A literature search was performed using the electronic database PubMed. Relevant guidelines, systematic reviews, and original research articles investigating ovarian reserve parameters and their clinical utility were reviewed.

Results
The fecundity of women gradually declines with increasing reproductive age as oocyte quantity and quality decline. Ovarian reserve is defined as the quantity of oocytes remaining in the ovary. Ovarian reserve can be measured indirectly with the use of serum blood tests or ultrasound imaging. Measures of ovarian reserve are clinically useful in several circumstances, particularly for use during fertility treatment and cycles of assisted reproductive technology. However, measures of ovarian reserve are poor predictors of reproductive potential and should not be used as “fertility tests.”

Conclusions and Relevance
Measures of ovarian reserve are poor predictors of reproductive potential and should not be used as “fertility tests.” Age remains a stronger predictor of reproductive success than measures of ovarian reserve.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After completing this activity, the learner will be better able to define ovarian reserve, describe the available measures of ovarian reserve, and discuss the clinical utility of measures of ovarian reserve.
Fertility Outcomes Several Years After Urgent Fertility Preservation for Patients With Breast Cancer
Authors: Peigné Maëliss , Mur Pauline , Laup Laëtitia , Hamy Anne-Sophie , Sifer Christophe , Mayeru Anne , Eustache Florence , Sarandi Solmaz , Vinolas Claire , Rakrouki Sophia , Benoit Alexandra , Grynberg Michaël , Sonigo Charlotte 
Published: February 2025

(Abstracted from Fertil Steril 2024;122:504–513)
The most common cancer among women in their childbearing years is breast cancer (BC), and many patients who are diagnosed in this period of their lives are not yet finished building their families. In cases such as these, fertility preservation can be undertaken, and patients can potentially be good candidates for pregnancy after completing cancer treatment.
Simulation-Based Mastery Learning Curriculum Development Workbook
Authors: McGaghie William C. , Barsuk Jeffrey H. , Salzman David H. 
Published: February 2025

Summary Statement
This Workbook and its Action Plans and Notes aim to equip health professions educators with the information and guidance needed to develop and implement a simulation-based mastery learning curriculum. The Workbook begins with an introductory statement about mastery learning curriculum developers and teachers and also about expected behavior of learners in a mastery context. The Workbook continues with 10 connected sections on simulation-based mastery learning curriculum development: (1) problem identification and needs assessment, (2) targeted needs assessment, (3) goals and objectives, (4) education strategies, (5) learner assessment goals and tools, (6) standard setting, (7) curriculum implementation, (8) feedback and debriefing, (9) unexpected collateral effects, and (10) program evaluation. These sections are modeled after the Thomas and Kern (Curriculum Development for Medical Education: A Six-Step Approach. 4th ed. Baltimore: Johns Hopkins University Press; 2022) steps for curriculum development and add several steps needed to incorporate simulation-based mastery learning goals. Curriculum development is an iterative process and each decision impacts preceding and subsequent steps. In addition, steps often change and evolve as a curriculum is developed and revised. Users are encouraged to record and refine their curriculum development plans as they move, back-and-forth, through the Workbook and Action Plans and Notes. References are provided throughout the document to amplify the text and provide detailed examples of the curriculum development steps and procedures. The intended outcome is a simulation-based mastery learning curriculum plan that can be implemented and used to educate learners to a very high standard of achievement.
Protein folding stability estimation with an explicit consideration of unfolded states
Authors: Lee Heechan , Park Hahnbeom 
Published: February 2025

AbstractThermal folding stability is a critical requirement for the vast majority of proteins. Computational methods suggested to date for the absolute folding stability (ΔG) prediction – including those driven from protein structure prediction AIs – show clear limitations on reproducing quantitative experimental values. Here we present IEFFEUM, a deep neural network that jointly estimates ΔGand the equilibrium ensemble of folded and unfolded states represented by their residue-pair distance probability distributions. This joint learning considerably enhances the ΔGprediction accuracy against the scenario where ΔGprediction was learned alone. To improve the model, we further extend the dataset compared to previous related works, which includes the Mega-scale small proteins and disordered proteins for training, as well as wild-type natural proteins with sizes up to 900 residues for thorough validation. We show that IEFFEUM is robust to various protein types and sizes, and can be applied to more general types of mutational effects such as sequence insertions or deletions.
Combing the haystacks: The search for highly pathogenic avian influenza virus using a combined clinical and research-developed testing strategy
Authors: Adams Gordon C. , Devlin Jamie E. , Klontz Erik , Laing Rachel A. , Branda John A. , Chowdhury Navid , Kwon SunYoung , Sabeti Pardis C. , Stachler Elyse , Thiriveedhi Vamsi , Shenoy Erica S. , Lemieux Jacob E , Turbett Sarah E 
Published: February 2025

AbstractBackgroundHighly pathogenic H5 avian influenza A has caused sporadic human infections, increasing the risk for potential human-to-human spread. In 2024, the U.S. experienced outbreaks among poultry and cattle, prompting enhanced surveillance.ObjectiveTo evaluate an H5 testing algorithm in subjects with respiratory symptoms presenting for routine care during low influenza A virus circulation.DesignObservational study using clinical- and research-developed nucleic acid amplification tests (NAATs) and pooled screening methods.SettingAcademic medical center in Boston, MA.Participants5,400 symptomatic individuals contributing 6,935 respiratory specimens from June 23 to August 28, 2024.MeasurementsSpecimens underwent initial respiratory pathogen testing per clinical protocols, which did not routinely include influenza due to low summer-month prevalence. Influenza A-positive specimens were subtyped using a clinical assay for H5 assessment. SARS-CoV-2-negative specimens not tested for influenza were screened in pooled batches. Positive pools were deconvoluted to individual specimens and screened for H5 using quantitative polymerase chain reaction.ResultsInfluenza A was detected in 40 of 6,935 specimens (0.6%), comprising 35 of 5,400 unique subjects (0.7%). No H5 infections were identified. Of the 35 influenza-positive individuals, 10 cases (29%) were found through research-specific screening of SARS-CoV-2–negative specimens. No deaths attributed to influenza were recorded.LimitationsSingle center design, convenience sampling, absence of ocular specimens, and minimal sampling in high-risk areas may limit generalizability.ConclusionExpanded influenza testing using pooled NAATs successfully identified low-prevalence influenza A and ruled out H5 in this cohort. These data support targeted influenza screening to enhance surveillance for emerging subtypes rather than a broad-based clinical testing strategy for influenza A testing.Primary Funding SourceSupported by institutional resources and Center for Disease Control and Prevention contracts.
Integrative Epigenomic Landscape of Alzheimer’s Disease Brains Reveals Oligodendrocyte Molecular Perturbations Associated with Tau
Authors: Oatman Stephanie R. , Reddy Joseph S. , Atashgaran Amin , Wang Xue , Min Yuhao , Quicksall Zachary , Vanelderen Floor , Carrasquillo Minerva M. , Liu Chia-Chen , Yamazaki Yu , Nguyen Thuy T. , Heckman Michael , Zhao Na , DeTure Michael , Murray Melissa E. , Bu Guojun , Kanekiyo Takahisa , Dickson Dennis W. , Allen Mariet , Ertekin-Taner Nilüfer 
Published: February 2025

AbstractAlzheimer’s disease (AD) brains are characterized by neuropathologic and biochemical changes that are highly variable across individuals. Capturing epigenetic factors that associate with this variability can reveal novel biological insights into AD pathophysiology. We conducted an epigenome-wide association study of DNA methylation (DNAm) in 472 AD brains with neuropathologic measures (Braak stage, Thal phase, and cerebral amyloid angiopathy score) and brain biochemical levels of five proteins (APOE, amyloid-β (Aβ)40, Aβ42, tau, and p-tau) core to AD pathogenesis. Using a novel regional methylation (rCpGm) approach, we identified 5,478 significant associations, 99.7% of which were with brain tau biochemical measures. Of the tau-associated rCpGms, 93 had concordant associations in external datasets comprising 1,337 brain samples. Integrative transcriptome-methylome analyses uncovered 535 significant gene expression associations for these 93 rCpGms. Genes with concurrent transcriptome-methylome perturbations were enriched in oligodendrocyte marker genes, including known AD risk genes such asBIN1, myelination genesMYRF, MBPandMAGpreviously implicated in AD, as well as novel genes likeLDB3. We further annotated the top oligodendrocyte genes in an additional 6 brain single cell and 2 bulk transcriptome datasets from AD and two other tauopathies, Pick’s disease and progressive supranuclear palsy (PSP). Our findings support consistent rCpGm and gene expression associations with these tauopathies and tau-related phenotypes in both bulk brain tissue and oligodendrocyte clusters. In summary, we uncover the integrative epigenomic landscape of AD and demonstrate tau-related oligodendrocyte gene perturbations as a common potential pathomechanism across different tauopathies.
Genomic tree scans identify loci underlying adaptive peaks inAntirrhinum
Authors: Richardson Daniel M. , Bradley Desmond , Copsey Lucy , Whibley Annabel , Burrus Monique , Andalo Christophe , Zhu Sihui , Field David L. , Xue Yongbiao , Coen Enrico 
Published: February 2025

AbstractSpecies can be considered to occupy different peaks in a fitness landscape, visualised as an undulating surface, with height corresponding to fitness and horizontal coordinates to genotype1. A key evolutionary problem is to understand how populations traverse fitness valleys to reach different peaks. Hypothetical solutions include shifting balance theory2, peak movements due to environmental changes1,3, or peak connectivity in high-dimensional fitness spaces4,5. However, testing hypotheses is not straightforward because identifying loci and epistatic interactions underlying fitness peaks remains challenging6. Here we analyse the genetic architecture of a fitness landscape by studying barrier loci that reduce gene flow between populations. We identify barrier loci in an unbiased way, by scanning the genome for regions with deep-rooted trees with a common topology. Applying this method to populations ofAntirrhinum, we identify seven barrier loci, all of which control flower colour. We propose these loci underlie two peaks in a fitness landscape, the heights and positions of which vary depending on genotype-environment interactions, allowing them to have been accessed without traversing a fitness valley. Our findings provide a model for how reproductive barriers between species can arise through populations taking diverse paths in fitness space.
Overcoming Cisplatin Resistance in TP53-null Colon Cancer Organoids
Authors: Khalili Sana , Heine Paige , Khazan Minou , Banister Carolyn E. , Morrison Sidney E. , Buckhaults Phillip J. 
Published: February 2025

AbstractCisplatin chemotherapy of colorectal cancer (CRC) is associated with dose-limiting side effects and the development of drug resistance, resulting in reduced therapeutic effectiveness. The resistant phenotype in colon cancer is primarily due to changes in p53-regulated DNA damage signaling and /or defects in the cellular mismatch-repair pathway. Therefore, enhancing the efficacy of cisplatin chemotherapy remains a significant challenge. In this study, we used a TP53-KO patient-derived colon tumor organoid model to perform a genome-wide CRISPR KO screen in the absence and presence of cisplatin and identified gene knockouts that re-sensitize cisplatin-resistant TP53-KO colon cancer organoids to cisplatin treatment. Knockout of genes in the DNA Repair pathways, including Fanconi Anemia (FA cause re-sensitization of TP53-KO colon cancer cells to cisplatin. Inhibition of genes ERCC6, FANCL, and BRIP1 enhances cisplatin-induced cell death in TP53-KO colon cancer organoids. These findings suggest that targeting these pathways could be an effective approach to overcome chemoresistance of TP53-muatnt colon cancer cells to cisplatin.
Phenotypic similarity of NAD(P)-Malic Enzymes in Tomato: Unveiling Patterns of Convergent and Parallel Evolution
Authors: Martinatto Andrea , Böhm Jonas M. , Bustamante Claudia A. , Pancaldi Francesco , Schranz Eric , Tronconi Marcos A. 
Published: February 2025

SUMMARYTheSolanum lycopersicum(tomato) genome encodes seven malic enzymes (MEs): three cytosolic NADP-ME isoforms (SlNADP-ME1, -2, and -3), two plastidic NADP-ME proteins (SlNADP-ME4a and -4b), and two mitochondrial NAD-dependent subunits (SlNAD-ME1 and -2) of a heteromeric enzyme. Except for SlNADP-ME3, which is almost exclusively expressed in the root, all the genes are active in the major tissues of flowering plants (leaf, stem, flower, and root), with SlNADP-ME2 and -4b transcripts accumulating at relative high levels. During the cell expansion and ripening phases of fruit development,SlNADP-ME3and-4bexpression increased in the pericarp and seeds whileSlNADP-ME2remained at a high level. In green fruit,SlNADP-ME3and-4bare down-regulated by ethylene, withSlNAD-ME1and-2being up-regulated. A correlation between SlNADP-ME4b accumulation and NADP-ME activity was observed from the early immature green to the mature green fruit stages, linking this plastidic isoform to starch and lipid biosynthesis.SlNADP-ME1and-4aexpression increase with temperature, suggesting involvement in defense mechanisms and supported bycis-elements composition in their promoters. Interesting, SlNADP-ME3 biochemical properties and its accumulation in seeds is part of an inherited and long-conserved genetic lineage in Angiosperms including Arabidopsis NADP-ME1, involved in normal seed germination. By analyzing the phylogeny and synteny ofSlNAD(P)-MEgenes and determining the biochemical properties of the recombinant proteins, we seek functional similarities to Arabidopsis NAD(P)-ME members. Our findings enhance the understanding of malate metabolism in tomatoes, which could inform strategies to improve fruit quality. Additionally, they prompt a re-evaluation of pre-existing notions regarding the functional orthology of enzymes based on phylogenetic relationships.SIGNIFICANCE STATEMENTEnzyme functional orthology among distant plant species cannot be inferred through phylogenetic analysis because of the large independent rearrangements of genomes during evolution. A comprehensive characterization of the tomato NAD(P)-ME family and their comparison with members from an unrelated plant species, such as Arabidopsis, allowed us to evaluate the impact of selective pressures on orthologous genes. This approach reveals that the phenotypic similarity of an entire enzyme family in different species is achieved through diverse evolutionary events such as ancestry, parallelism, and genetic convergence.