bluuebunny/crossref_metadata_2025_split huggingface dataset:
2015–2021 Industry Payments to Pediatric Orthopaedic Surgeons: Analysis of Trends and Characteristics of Top-earning Surgeons
Authors: Noe McKenna C. , Kaji Ellie , Thomas George , Warren Jonathan R. , Schwend Richard M. 
Published: December 2023

Background:
Analysis of industry payments to pediatric orthopaedic surgeons last occurred in 2017. We investigated payments to pediatric orthopaedic surgeons from 2015 to 2021 to understand surgeon characteristics associated with increased industry payments.

Methods:
Open Payments Database datasets from 2015 to 2021 were queried for nonresearch payments to pediatric orthopaedic surgeons. Annual aggregates and subcategories were recorded. For surgeons receiving payments in 2021, the Hirsch index (h-index), gender, and US census division were found using the Scopus database, Open Payments Database, and online hospital profiles, respectively. χ2, Fisher exact, Mann-Whitney U, and t tests were used to compare surgeons in the top 25%, 10%, and 5% payment percentiles to the bottom 75%, 90%, and 95%, respectively.

Results:
Payments rose 125% from 2015 to 2021. Education, royalties, and faculty/speaker increased most, while travel/lodging, honoraria, charitable contributions, and ownership interest decreased. Only royalties increased from 2019 to 2021. In 2021, of 419 pediatric orthopaedic surgeons receiving industry payments, men received greater median aggregate payments than women ($379.03 vs. $186.96, P=0.047). There were no differences in gender proportions between the top 75% and bottom 25% (P=0.054), top 10% and bottom 90% (P=0.235), and top 5% and bottom 95% (P=0.280) earning comparison groups. The h-index was weakly positively correlated with industry payments (r
s=0.203, P<0.001). Mean h-indices in the 75th (P<0.001, 95% CI: 2.62-7.65), 90th (P=0.001, 95% CI: 3.28-13.03), and 95th (P=0.005, 95% CI: 4.25-21.11) percentiles were significantly higher. Proportions of surgeons from the Middle Atlantic and West South Central in the 90th (P=0.025) and 95th percentiles (P=0.033), respectively, were significantly lower compared to all other regions. A higher proportion of surgeons from the Pacific were placed in the 90th (P=0.004) and 95th (P=0.024) percentiles.

Conclusions:
Industry payments to pediatric orthopaedic surgeons rose from 2015 to 2021. Most categories fell from 2019 to 2021, which may be related to the SARS-CoV-19 pandemic. In 2021, though gender was not related to aggregate payment percentile, location in select US census divisions and h-index was.

Level of Evidence:
Level II—Retrospective study.
Study Characteristics and Impact of Pediatric Orthopaedic Society of North America Annual Meeting’s “Best Papers” From 2009 to 2019
Authors: Marquez Guillermo , Granger Caroline , Cline Justin A. , Goldfarb Charles A. , Wall Lindley B. 
Published: December 2023

Objective:
Award-winning abstracts are selected every year at the Pediatric Orthopaedic Society of North America (POSNA) annual meeting as “best paper” or poster. It is unknown how many achieve publication in peer-reviewed journals and the impact they have. We sought to determine the characteristics, including the level of evidence (LoE), publication rates, and the impact of award-winning abstracts on pediatric orthopaedic surgery practice from 2009 to 2019.

Methods:
Award-winning abstracts or “best papers” from 2009 to 2019 were retrospectively reviewed from the POSNA website from abstract publication to manuscript publication. A search across Pubmed was used to match abstracts to their publications by comparing author names, titles, study design and methodology, results, and conclusions. Area of focus, abstract authors, institutions, publication status, LoE, time to publication, authors of publication, journals of publication, and the journal’s latest Hirsch Index and impact factor were recorded.

Results:
There have been 54 “best papers” at the POSNA annual meeting from 2009 to 2019. Of those, 39 have been published across 17 different journals for a publication rate of 72%. The average time from abstract presentation to publication was 21.2 months with a range of 0 to 121 months. Of the published award-winning abstracts, 64% (25) were published within 2 years, 87% (34) within 3 years, and 95% (37) within 4 years. Out of the published abstracts, 26% (10) were in the Journal of Pediatric Orthopaedics, 23% (9) were in the Journal of Bone and Joint Surgery, and 10% (4) were in the Journal of Child Orthopaedics. The median number of abstract authors was 4 and increased to a median of 6 authors once published. Most award-winning abstracts had a LoE of 3. The average journal impact factor for all publications was 4; the average Hirsch Index for the corresponding author was 29.9, and the average number of citations for a publication was 41 with a range of 0 to 270.

Conclusions:
The majority of the “best papers” presented at POSNA annual meetings from 2009 to 2019 were published in peer-reviewed journals within 2 years of presentation, with approximately half being published in the Journal of Pediatric Orthopaedics or Journal of Bone and Joint Surgery. The publication rate of “best papers” at the POSNA annual meeting was found to be higher than rates reported for abstracts presented at the annual meetings of POSNA, American Society for Surgery of the Hand and European Pediatric Orthopaedic Society, but similar to the rates observed for American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, and Orthopaedic Trauma Association. Most of the selected “best papers” at the POSNA annual meeting are published and have a substantial impact on pediatric orthopaedic surgery practice.

Level of Evidence:
Level IV.
A comprehensive map of the ageing blood methylome
Authors: Seale Kirsten , Teschendorff Andrew , Reiner Alexander P , Voisin Sarah , Eynon Nir 
Published: December 2023

AbstractDuring ageing, the human methylome exhibits both differential (i.e. change in mean) and variable (i.e. change in variance) shifts, along with a general rise in entropy. However, it remains unclear whether DNA methylation sites that increasingly diverge between people (i.e. variably methylated positions (VMPs)) are distinct from those undergoing changes in mean methylation levels (i.e. differentially methylated positions (DMPs)), which changes drive entropy, how they contribute to epigenetic age measured by epigenetic clocks, and whether cell type heterogeneity plays a role in these alterations. To address these questions, we conducted a comprehensive analysis using > 32,000 human blood methylomes from 56 datasets (age range = 6-101 years). Our findings revealed an unprecedented proportion of the blood methylome that is differentially methylated with age (48% DMPs; FDR< 0.005) and variably methylated with age (37% VMPs; FDR< 0.005), with many sites overlapping between the two groups (59% of DMPs are VMPs). We observed that bivalent and Polycomb regions become increasingly methylated and divergent between individuals, while quiescent regions lose methylation in a more homogeneous manner between individuals. Unexpectedly, both chronological and biological clocks, but not pace-of-aging clocks, show a strong enrichment for those CpGs that accrue both mean and variance changes during aging. Furthermore, we uncovered that it is the accumulation of DMPs shifting towards a methylation fraction of 50% that drive the increase in entropy, resulting in an overall smoothening of the epigenetic landscape. However, approximately a quarter of DMPs oppose this direction of change, exhibiting anti-entropic effects. While DMPs were mostly unaffected by changes in cell type composition, VMPs and entropy measurements showed moderate sensitivity to such alterations. This investigation represents the largest to date of genome-wide DNA methylation changes and ageing in a single tissue, offering valuable insights into primary molecular changes that hold meaning for chronological and biological ageing.
Cytotoxic chemotherapy potentiates the immune response and efficacy of combination CXCR4/PD-1 inhibition in models of pancreatic ductal adenocarcinoma
Authors: Raufi Alexander G. , Pellicciotta Ilenia , Palermo Carmine F. , Sastra Steven A. , Chen Andrew , Alouani Emily , Maurer H. Carlo , May Michael , Iuga Alina , Rabadan Raul , Olive Kenneth P. , Manji Gulam Abbas 
Published: December 2023

ABSTRACTPurposeThe CXCL12-CXCR4 chemokine axis plays a significant role in modulating T-cell infiltration into the pancreatic tumor microenvironment. Despite promising preclinical findings, clinical trials combining inhibitors of CXCR4 (AMD3100/BL-8040) and anti-programmed death 1/ligand1 (anti-PD1/PD-L1) have failed to improve outcomes.Experimental DesignWe utilized a novel ex vivo autologous patient-derived immune/organoid (PDIO) co-culture system using human peripheral blood mononuclear cells and patient derived tumor organoids, and in vivo the autochthonous LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) pancreatic cancer mouse model to interrogate the effects of either monotherapy or all combinations of gemcitabine, AMD3100, and anit-PD1 on CD8+ T cell activation and survival.ResultsWe demonstrate that disruption of the CXCL12-CXCR4 axis using AMD3100 leads to increased migration and activation of CD8+ T-cells. In addition, when combined with the cytotoxic chemotherapy gemcitabine, CXCR4 inhibition further potentiated CD8+ T-cell activation. We next tested the combination of gemcitabine, CXCR4 inhibition, and anti-PD1 in the KPC pancreatic cancer mouse model and demonstrate that this combination markedly impacted the tumor immune microenvironment by increasing infiltration of natural killer cells, the ratio of CD8+ to regulatory T-cells, and tumor cell death while decreasing tumor cell proliferation. Moreover, this combination extended survival in KPC mice.ConclusionsThese findings suggest that combining gemcitabine with CXCR4 inhibiting agents and anti-PD1 therapy controls tumor growth by reducing immunosuppression and potentiating immune cell activation and therefore may represent a novel approach to treating pancreatic cancer.
A neurotransmitter atlas ofC. elegansmales and hermaphrodites
Authors: Wang Chen , Vidal Berta , Sural Surojit , Loer Curtis , Aguilar G. Robert , Merritt Daniel M. , Toker Itai Antoine , Vogt Merly C. , Cros Cyril , Hobert Oliver 
Published: December 2023

ABSTRACTMapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In theC. elegansnervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevantcis-regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters inC. elegans(glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel neurons that uptake monoaminergic neurotransmitters. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification inC. elegans.
Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts
Authors: Wei Julong , Resztak Justyna , Ranjbaran Ali , Alazizi Adnan , Mair-Meijers Henriette E , Slatcher Richard , Zilioli Samuele , Wen Xiaoquan , Luca Francesca , Pique-Regi Roger 
Published: December 2023

AbstractCis-regulatory elements (CREs) control gene transcription dynamics across cell types and in response to the environment. In asthma, multiple immune cell types play an important role in the inflammatory process. Genetic variants in CREs can also affect gene expression response dynamics and contribute to asthma risk. However, the regulatory mechanisms underlying control of transcriptional dynamics across different environmental contexts and cell-types at single cell resolution remains to be elucidated. To resolve this question, we performed scATAC-seq in activated peripheral blood mononuclear cells (PBMC) from 16 children with asthma with phytohemagglutinin (PHA) or lipopolysaccharide (LPS), and treated with dexamethasone (DEX), an antiinflammatory glucocorticoid. We analyzed changes in chromatin accessibility, measured transcription factor motif activity, and identified treatment and cell-type specific transcription factors that drive changes in both gene expression mean and variability. We observed strong positive linear dependence between motif response and their target gene expression changes, but negative in variability changes. This result suggests that an increase of transcription factor binding tightens the variability of gene expression around the mean. We then annotated genetic variants in chromatin accessibility peaks and response motifs followed by computational fine-mapping of eQTL signals from a pediatric asthma cohort. We found that eQTLs were 5-fold enriched in peaks with response motifs and refined the credible set for 410 asthma risk genes, with 191 having the causal variant in response motifs. In conclusion, scATAC-seq enhances the understanding of molecular mechanisms for asthma risk variants mediated by gene expression.
The base media formulation impacts the efficiency of ex-vivo erythropoiesis of primary human hematopoietic stem cells
Authors: Peterson Nana Ansuah , Egan Elizabeth S. 
Published: December 2023

AbstractDuring the COVID-19 pandemic, there was a disruption in the supply of the widely used erythroid differentiation media product, Iscove’s Modified Dulbecco’s Medium, manufactured by Biochrom AG. IMDM is a critical component of ex vivo erythropoiesis protocols used to generate genetically modified red blood cells for the study of malaria host factors. Therefore, we set out to identify the best alternative IMDM product for efficient erythroid differentiation of hematopoietic stem cells into enucleated red blood cells for use in our research. We tested other IMDM products, including I2911 (from Millipore Sigma), P04-20450 (from Pan Biotech) and EP-CM-L0216 (from ElabScience Technologies) which are all marketed specifically as replacements for the Biochrom AG product. We found that while FG0465, I2911, and P04-20450 were all sufficient for ex-vivo erythropoiesis, FG0465 IMDM was superior to other products tested in supporting maximal erythroid cell proliferation and enucleation.
The mechanism of homologous chromosome recognition and pairing facilitated by chromosome-tethered protein-RNA condensates
Authors: Ding Da-Qiao , Okamasa Kasumi , Yoshimura Yuriko , Matsuda Atsushi , Yamamoto Takaharu G. , Hiraoka Yasushi , Nakayama Jun-ichi 
Published: December 2023

AbstractPairing of homologous chromosomes during meiosis is crucial for successful sexual reproduction. Previous studies have shown that the fission yeastsme2RNA, a meiosis-specific long noncoding RNA (lncRNA), accumulates at thesme2locus and plays a key role in mediating robust pairing during meiosis. Several RNA-binding proteins accumulate at thesme2and other lncRNA gene loci in conjunction with the lncRNAs transcribed from these loci. These lncRNA-protein complexes form condensates that exhibit phase separation properties on chromosomes and are necessary for robust pairing of homologous chromosomes. To further understand the mechanisms by which phase separation affects homologous chromosome pairing, we conducted anin vitrophase separation assay with thesme2RNA-associated proteins (Smps) and RNAs. Our research has revealed that one of the Smps, Seb1, exhibits phase separation, which is enhanced by the addition of another Smp, Rhn1, and significantly increased by the addition of purified RNAs. Additionally, we have found that RNAs protect Smp condensates from treatment with 1,6-hexanediol. The Smp condensates containing different types of RNA display distinct FRAP profiles, and the Smp condensates containing the same type of RNA tend to fuse together more efficiently than those containing different types of RNA. Taken together, these results indicate that the RNA species in condensates determine their physical properties and suggest that regional RNA-Smp condensates with distinct properties ensure the pairing of homologous chromosomes.
A snapshot of injecting drug consumption from the analysis of used syringes within the Medically Supervised Injecting Centre in Sydney, Australia
Authors: Fursman Harrison , Finch Eleanor , Xiao Linda , Lefrançois Elodie , Gupta Anjali , Bartlett Mark , Latimer Julie , Chadwick Scott , Roux Claude , Morelato Marie 
Published: December 2023

AbstractIntroductionThe administration of illicit drugs by injection is associated with considerable harm, including an increased risk of overdose. The chemical analysis of used syringes can enhance knowledge on injecting drug consumption beyond traditional data sources (self‐report surveys). This additional information may be useful during significant global events like the COVID‐19 pandemic. This study aimed to examine a snapshot of the drugs injected at the Medically Supervised Injecting Centre (MSIC) in Sydney, Australia, in 2019–2020.MethodsUsed syringes were collected from MSIC across three periods throughout 2019 and 2020 (February 2019, March—April 2020 and June—September 2020). Drug residues were extracted from used syringes using methanol before detection by gas chromatography—mass spectrometry and ultra‐performance liquid chromatography—tandem mass spectrometry. The chemical analysis results were compared to self‐report data obtained from MSIC clients.ResultsHeroin (46–53%), methamphetamine (24–34%) and pharmaceutical opioids (15–27%) were the most common drug residues detected. The chemically detected drugs had declining coherence with the drugs self‐reported by MSIC clients across the time periods examined.Discussion and ConclusionsThere was no significant change in the drugs injected (heroin, methamphetamine and pharmaceutical opioids) across the three periods collected throughout varying COVID‐19 lockdown restrictions. Changes in the frequency of other drugs injected and discrepancies between chemical analysis and self‐report were potentially related to regulatory changes, degradation or misinformed sales. Routine chemical analysis of used syringes has provided an alternative information source to promote awareness of current drug trends and aid harm reduction.
Elastography findings in acne scar patients who were treated with microneedling
Authors: Demir Gizem , Aksoy Furkan , Buğdaycı Onur , Kaptanoğlu Aslı F. 
Published: December 2023

AbstractBackgroundAcne scar (AS) is a frequent sequela in patients with acne. In addition to advanced treatment methods, microneedling (MN) is still used as an effective option in the treatment of AS. However, similar to most diseases in dermatology, there is no objective tool to determine the severity of AS and to evaluate the treatment outcome.ObjectivesIn the current study, we aimed to evaluate skin elasticity in AS patients who have undergone MN therapy. Furthermore, other purposes were to determine the relationships between the history of isotretinoin use, demographic data, and changes in skin elasticity.MethodsIn order to evaluate the skin elasticity of 20 patients with AS, shear wave elastography (SWE) was performed before and after MN treatment. The physician's clinical assessment was evaluated with quantitative AS severity scale. In order to show that SWE is a consistent method, three repeated measurements were performed on 24 healthy participants.ResultsA significant increase was found between the shear‐wave velocity (SWV) values that were measured baseline and after treatment in the patient group (P = 0.033). In the control group, there was no significant difference between the three repeated measurements (P > 0.05). A statistically significant decrease was also detected in the AS severity scores (P < 0.005).ConclusionsIn AS patients who underwent MN treatment, a significant increase was found in skin elasticity compared to the baseline. We argued that SWE is a method that can be useful to evaluate skin elasticity before and after similar cosmetic procedures and dermatological diseases.
Evaluation of antioxidant and ACE inhibitory peptides in rice bran protein hydrolysate using non‐targeted UHPLC‐QTOF‐IMS profiling, MALDI‐TOF‐TOF‐MS/MS, and molecular docking study
Authors: Kumar Ajay , Singh Narpinder , Joshi Robin 
Published: December 2023

SummaryIn the present study, rice bran protein (RBP) from the PB1121 variety was hydrolysed using trypsin and subjected to non‐targeted IMS profiling to identify antioxidant and antihypertensive amino acids in the resulting RBP hydrolysates. The hydrolysate was then separated into three fractions using ultrafiltration, and each fraction was tested for antioxidant and ACE inhibitory activities. The ACE activity was assessed using the tripeptide hippuryl‐histidyl‐leucine (HHL) as a model peptide via HPLC‐DAD. The fraction with the molecular weight (>3000 Da) displayed the strongest antioxidant and ACE inhibitory activity. This fraction was further divided into five fractions using gel Sephadex G‐25, and the greatest levels of antioxidant and ACE inhibitory activity were found in fraction F3B. Fraction F3B was then fractionated using HPLC, and the fraction with ACE inhibitory activity (IC50 of 43 mg mL−1) was analysed using MALDI‐TOF‐TOF mass spectrometry to determine its exact molecular mass and amino acid sequence. The amino acid sequence FMKSK (phe‐met‐lys‐ser‐lys) with a Mw of 655.376 Da was detected, and the molecular docking investigation revealed that FMKSK suppresses ACE by forming strong hydrogen bonds with the active pockets of human ACE. These findings suggest that rice bran contains bioactive peptides with antioxidant and ACE inhibitory effects, making it a promising raw material for the production of beneficial products.