bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating Food and Drug Administration Mandated Breast Implant Patient Literature
Authors: Boyd Louisa C. , Kareh Aurora M. , Rodby Katherine A. 
Published: October 2023

Objectives
In October 2021, the US Food and Drug Administration mandated patient decision checklists and new labeling for breast implants with the goal of improving the informed decision-making process for patients considering breast implantation. Given growing concerns over breast implant–associated anaplastic large cell lymphoma, breast implant–associated squamous cell carcinoma, and breast implant illness, patients should be able to easily review these resources to make a fully informed decision when considering surgery. This study seeks to elucidate the accessibility, and therefore the utility of the newly mandated literature for the average breast implant patient.

Methods
Patient decision checklists and breast implant boxed warnings were obtained from the most used breast implant manufacturers in the United States—Allergan, Mentor, and Sientra. Readability analysis of all Food and Drug Administration required documents was performed using the Flesch Reading Ease Score, Flesch Kincaid Grade Level, Gunning-Fog Index, Coleman-Liau Index, Simplified Measure of Gobbledygook, and Automated Readability Index.

Results
The overall readability of all Allergan, Mentor, and Sientra patient materials correlates with a college reading level. Documents from all 3 implant manufacturers were of a statistically significantly higher reading level than that recommended by the American Medical Association and US Department of Health and Human Services. No materials were found to be at or below the recommended sixth-grade level.

Conclusions
The newly mandated breast implant patient decision guides are written at a college reading level. These materials should be simplified to improve health literacy shared decision making.
A Retrospective Review of Laser Therapy for Treatment of Hidradenitis Suppurativa
Authors: Fortoul Marla C. , Macias Martinez Brian , Ventura Rodriguez Darisel , Dallara Marissa , Stelnicki Eric J. , Kamel George 
Published: October 2023

Purpose
Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful and foul-smelling cystic nodules and sinus tracts in the apocrine gland-bearing regions. The treatment options include topical, intralesional, systemic, and surgical modalities. Currently, the most novel therapy is laser therapy to provide localized treatment without systemic adverse effects. However, data regarding patient outcomes after laser treatment are limited because of the low prevalence of this disease. This study aimed to evaluate the efficacy of laser therapy as a treatment modality for patients with HS.

Methods
A retrospective review cohort analysis of patients with HS undergoing laser treatment between 2016 and 2021 was conducted. Patient demographics, lesion location(s), Hurley stage, age of onset and diagnosis, treatment length, type, outcomes, and complications were analyzed.

Results
Ninety-four patients met the inclusion criteria; on average, patients were treated with 5.8 laser sessions for 14.8 months with no complications and minor blood loss. Hidradenitis suppurativa progression commonly starts during puberty, with a median onset of 13.8 years and diagnosis of HS at 16.2 years. All patients (n = 94) showed an improvement in HS disease severity: 59.6% completed treatment, 12.0% are currently undergoing treatment, and 26.0% were lost to follow-up.

Conclusions
Laser therapy is an effective and safe therapy for HS leading to improved quality of life and should be considered in the treatment and management of HS.
Facial Masculinization Surgery
Authors: Hoffman Alexandra F. , Laspro Matteo , Verzella Alexandra N. , Tran David L. , Rodriguez Eduardo D. 
Published: October 2023

Introduction
Facial masculinization surgery (FMS) is increasingly popular among cisgender and transgender men. The benefits of FMS are focused on facial identity and have been proven to decrease gender dysphoria in this population. Previous research showed increasing interest in gender affirmation surgery and facial feminization surgery, but the prevalence of FMS has not been explored. It is difficult to find these data based on surgical records alone because institutions do not have standardized methods of reporting and lack publications in the field. Our study aimed to analyze public interest in FMS by using worldwide Google Trends to quantify these trends.

Methods
A worldwide Google Trends search was completed from January 1, 2008, to December 31, 2022, for terms focused on FMS. Then, search terms were analyzed for nonfacial masculinization procedures and were aggregated. Lastly, a PubMed search was conducted for the terms “transgender” and “facial masculinization” from January 1, 2008, to December 31st, 2022, to compare publication rates.

Results
Our data showed an increasing interest in FMS through Google search trends since the year 2008. A similar trend was demonstrated for non-FMS gender-affirming terms. PubMed analysis showed “transgender” medicine publishing rates were approximately 39.65 times greater than “facial masculinization” publishing rates, although “facial masculinization” medicine did produce a positive trend over the study period of approximately 4 publications per year. The medical literature on transgender surgeries rapidly outpaces publications specifically focusing on FMS.

Conclusion
Our study showed increasing interest in gender affirmation surgery over time, particularly FMS. These increasing trends should encourage greater scientific exploration of FMS and research to properly quantify and assess surgical outcomes in this special population. Additional educational interventions for both the general public and medical providers, to increase awareness of unique challenges that impact this community and highlight changes in health care coverage over time, should be created to keep pace with increasing patient demand and address the physical, systemic, and psychosocial issues faced by people who identify as transgender.
XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants
Authors: Poulakou Garyfallia , Royer Pierre-Joseph , Evgeniev Nikolai , Evanno Gwénaëlle , Shneiker Françoise , Vanhove Bernard , Duvaux Odile , Marot Stéphane , Calvez Vincent 
Published: October 2023

ABSTRACTBackgroundXAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessedin vitro.MethodsA phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial,NCT04928430). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay.ResultsPatients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 daysvs14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro.ConclusionsXAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies.
Insights into Drug Cardiotoxicity from Biological and Chemical Data: The First Public Classifiers for FDA DICTrank
Authors: Seal Srijit , Spjuth Ola , Hosseini-Gerami Layla , García-Ortegón Miguel , Singh Shantanu , Bender Andreas , Carpenter Anne E. 
Published: October 2023

AbstractDrug-induced cardiotoxicity (DICT) is a major concern in drug development, accounting for 10-14% of postmarket withdrawals. In this study, we explored the capabilities of various chemical and biological data to predict cardiotoxicity, using the recently released Drug-Induced Cardiotoxicity Rank (DICTrank) dataset from the United States FDA. We analyzed a diverse set of data sources, including physicochemical properties, annotated mechanisms of action (MOA), Cell Painting, Gene Expression, and more, to identify indications of cardiotoxicity. We found that such data, including protein targets, especially those related to ion channels (such as hERG), physicochemical properties (such as electrotopological state) as well as peak concentration in plasma offer strong predictive ability as well as valuable insights into DICT. We also found compounds annotated with particular mechanisms of action, such as cyclooxygenase inhibition, could distinguish between most-concern and no-concern DICT compounds. Cell Painting features related to ER stress discern the most-concern cardiotoxic compounds from non-toxic compounds. While models based on physicochemical properties currently provide substantial predictive accuracy (AUCPR = 0.93), this study also underscores the potential benefits of incorporating more comprehensive biological data in future DICT predictive models. With the availability of - omics data in the future, using biological data promises enhanced predictability and delivers deeper mechanistic insights, paving the way for safer therapeutic drug development. All models and data used in this study are publicly released athttps://broad.io/DICTrank_Predictor
Comparison of the effectiveness of different normalization methods for metagenomic cross-study phenotype prediction under heterogeneity
Authors: Wang Beibei , Sun Fengzhu , Luan Yihui 
Published: October 2023

AbstractThe human microbiome, comprising microorganisms residing within and on the human body, plays a crucial role in various physiological processes and has been linked to numerous diseases. To analyze microbiome data, it is essential to account for inherent heterogeneity and variability across samples. Normalization methods have been proposed to mitigate these variations and enhance comparability. However, the performance of these methods in predicting binary phenotypes remains understudied. This study systematically evaluates different normalization methods in microbiome data analysis and their impact on disease prediction. Our findings highlight the strengths and limitations of scaling, compositional data analysis, transformation, and batch correction methods. Scaling methods like TMM and RLE show consistent performance, while compositional data analysis methods exhibit mixed results. Transformation methods, such as Blom and NPN, demonstrate promise in capturing complex associations. Batch correction methods, including BMC and Limma, consistently outperform other approaches. However, the influence of normalization methods is constrained by population effects, disease effects, and batch effects. These results provide insights for selecting appropriate normalization approaches in microbiome research, improving predictive models, and advancing personalized medicine. Future research should explore larger and more diverse datasets and develop tailored normalization strategies for microbiome data analysis.
A procedure for solid phase extractions using metal oxide coated silica column in lipidomics
Authors: Takeda Hiroaki , Takeuchi Manami , Hasegawa Mayu , Miyamoto Junki , Tsugawa Hiroshi 
Published: October 2023

ABSTRACTLipid enrichment is indispensable for enhancing the coverage of targeted molecules in mass spectrometry (MS)-based lipidomics studies. In this study, we developed a simple stepwise fractionation method using a titanium- and zirconium-dioxide-coated solid-phase extraction (SPE) silica column that separates neutral lipids, phospholipids, and other lipids, including fatty acids (FAs) and glycolipids. Chloroform was used to dissolve the lipids, and neutral lipids, including steryl esters and di- and triacylglycerols, were collected in the loading fraction. Second, methanol with formic acid (99:1, v/v) was used to retrieve FAs, ceramides, and glycolipids, including glycosylated ceramides and glycosylated diacylglycerols, by competing for affinity with the Lewis acid sites on the metal oxide surface. Finally, phospholipids strongly retained via chemoaffinity interactions were eluted using a solution containing 5% ammonia and high water content (45:50 v/v, 2-propanol:water), which canceled the electrostatic and chelating interactions with the SPE column. High average reproducibility of <10% and coverage of ∼100% compared to those of the non-SPE samples were demonstrated by untargeted lipidomics of human plasma and mouse brain, testis, and feces. The advantage of our procedure was showcased by characterizing minor lipid subclasses, including dihexosylceramides containing very long-chain polyunsaturated FA in the testis, mono- and digalactosyl monoacylglycerols in feces, and acetylated and glycolylated derivatives of gangliosides in the brain that were not detected using conventional solvent extraction methods. Likewise, the value of our method in biology is maximized during glycolipidome profiling in the absence of neutral lipids and phospholipids that cover more than 80% of the chromatographic peaks.Table of Contents artwork
Development of a novel healthcare discrimination measure: PreDict
Authors: Oladele Carol R. , Gonzalez-Colaso Rosana , Schulze Arian , Rizzo Tara ,   The PreDict Writing Group, Nunez-Smith Marcella 
Published: October 2023

AbstractIntroductionPatient reported quality of care measures are widely recognized tools for healthcare system performance assessment. Yet, there are few existing patient reported quality of care measures regarding health equity, and none to specifically collect patient experiences of discrimination in health care.ObjectiveTo develop an item pool to measure patient experiences of healthcare discrimination-the Patient-Reported Experiences of Discrimination in Care Tool (PreDict).MethodsUtilizing a multistage, exploratory sequential mixed methods study design, we conducted qualitative interviews (n=73) and expert panel consensus analysis to develop items to capture patient experiences of discrimination. This process plus systematic literature review identified extant items and informedde novoitems for inclusion in the item pool. Items were developed in English and Spanish and were not represented by extant items. Following identification of the initial item pool (n=125), candidate items underwent cognitive interview testing with English (n=113) and Spanish (n=70) speaking participants to evaluate items for clarity and comprehensiveness. English and Spanish items were also evaluated by a bilingual expert panel to recommend pool items for inpatient field testing.ResultsOne hundred and three items underwent cognitive interview testing and fifty-nine items were retained. Lack of clarity was the most cited factor for removal or revision of items. Expert panel review resulted in the removal of one additional item and the revision of seven items.Fifty-eight candidate items were retained for inclusion in field testing and future analyses using item response theory modeling.ConclusionPreDict fills an important gap in measurement of discrimination, which is known to influence patient health outcomes. Development and testing to date demonstrate evidence of validity in characterizing the complex phenomenon of healthcare discrimination.
Identification and development of Tetra-ARMS PCR-based screening test for a genetic variant of OLA1 (Tyr254Cys) in the human failing heart
Authors: Dubey Praveen K , Dubey Shubham , Singh Sarojini , Bhat Purnima Devaki , Pogwizd Steven , Krishnamurthy Prasanna 
Published: October 2023

AbstractObg-like ATPase 1 (OLA1) protein has GTP and ATP hydrolyzing activities and is important for cellular growth and survival. The human OLA1 gene maps on chromosome 2, at the locus 1q31, close to the Titin (TTN) gene, which is associated with familial dilated cardiomyopathy (DCM). In this study, we found that expression of OLA1 was significantly downregulated in human failing heart tissue (HF) as compared to in non-failing heart tissues (NF). Moreover, using the Sanger sequencing method, we characterized the human OLA1 gene and screened genetic mutations in patients with heart-failing and non-failing. Among failing and non-failing heart patients, we found a total of 15 mutations, including two transversions, one substitution, one indel, and eleven transition mutations in theOLA1gene. All the mutations were intronic except for a non-synonymous mutation, 5144A>G, resulting in 254Tyr>Cys in exon 8 of theOLA1gene. Furthermore, haplotype analysis of these mutations revealed that these single nucleotide polymorphisms (SNPs) are linked to each other, resulting in disease-specific haplotypes. Additionally, to screen for the 254Tyr>Cys point mutation, we developed a cost-effective, rapid genetic screening PCR test that can differentiate between homozygous (AA and GG) and heterozygous (A/G) genotypes. Our results show that this test can be used as a genetic screening tool for human cardiomyopathy. These findings have important implications for the diagnosis and treatment of cardiomyopathy.Abstract Figure
Regional quantification of cardiac metabolism with hyperpolarized [1 -13C]-pyruvate MRI evaluated in an oral glucose challenge
Authors: Larson Peder E. Z. , Tang Shuyu , Liu Xiaoxi , Sinha Avantika , Dwork Nicholas , Sivalokanathan Sanjay , Liu Jing , Bok Robert , Ordovas Karen G. , Slater James , Gordon Jeremy W. , Abraham M. Roselle 
Published: October 2023

AbstractBackgroundThe heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP)13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.MethodsWe developed and applied methods for whole-heart imaging of13C-pyruvate,13C-lactate and13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).ResultsWe demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6×6×21 mm3(13C-pyruvate) and 12×12×21 mm3(13C-lactate,13C-bicarbonate).13C-pyruvate and13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial13C-pyruvate-SNR,13C-lactate-SNR,13C-bicarbonate-SNR,13C-lactate/pyruvate ratio,13C-pyruvate-to-lactate conversion rate, kPL, and13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.ConclusionsWe demonstrate first-in-human regional quantifications of cardiac metabolism by HP13C-pyruvate MRI that aims to reflect LDH and PDH activity.
A 2-Hydroxybutyrate- mediated feedback loop regulates muscular fatigue
Authors: Wadsworth Brennan J , Leiwe Marina , Minogue Eleanor A , Cunha Pedro P , Engman Viktor , Brombach Carolin , Asvestis Christos , Sah-Teli Shiv K , Marklund Emilia , Koivunen Peppi , Ruas Jorge L , Rundqvist Helene , Lanner Johanna T , Johnson Randall S 
Published: October 2023

SummaryThe metabolite 2-hydroxybutyrate (2HB) is produced by skeletal muscle acutely during exercise and persists for several hours in the blood post-exertion. We show here that 2HB directly inhibits branched- chain aminotransferase enzymes, and that this inhibition in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity bothin vitroandin vivo, with the latter mimicking the effects of exercise training on whole body metabolism. Thus, we show here that 2-HB production by skeletal muscle represents a novel mechanism for the modification of metabolism by exercise.
Simulated complexes formed from a set of postsynaptic proteins suggest a localised effect of a hypomorphic Shank mutation
Authors: Miski Marcell , Weber Áron , Fekete-Molnár Krisztina , Keömley-Horváth Bence Márk , Csikász-Nagy Attila , Gáspári Zoltán 
Published: October 2023

AbstractThe postsynaptic density is an elaborate protein network beneath the postsynaptic membrane built up from the same major proteins but differing between synapses in exact composition and organization. Mutations perturbing generally occurring protein:protein interactions in this network can lead to specific effects, and the translation of biochemical effects to the system level can be especially challenging. In this work we use systems biology-based modeling of protein complex distributions in a set of major postsynaptic proteins including either a wild-type or a hypomorphic PDZ mutant Shank protein. Our results suggest that the effect of such mutations is heavily dependent on the overall availability of the protein components of the whole network. We simulated protein complex formation based on experimental data of various cell types with diverse protein abundances. The simulations revealed that mutations interfering with a single protein interaction can lead to protein complex changes only in specific cell types and in specific complexes. Although our system is currently far from a comprehensive description of the PSD, the results suggest a way to interpret specific mutations within a complex framework.Graphical AbstractHighlightsEffect of mutations affecting protein:protein interactions can be modeled in contextChanges in emerging protein complexes upon mutations are dependent on the availability of the individual proteinsOur model provides conceptual explanation of confided phenotypic effects of a mutation