bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Update on Selected High-grade Renal Cell Carcinomas of the Kidney: FH-deficient, ALK-rearranged, and Medullary Carcinomas
Authors: Chen Ying-Bei
Published: December 2023

High-grade renal cell carcinoma (RCC), often diagnosed at advanced stages, significantly contributes to renal cancer-related mortality. This review explores the progress in understanding specific subtypes of high-grade RCC, namely fumarate hydratase (FH)-deficient RCC, anaplastic lymphoma kinase (ALK)-rearranged RCC, and SMARCB1-deficient renal medullary carcinoma, all of which are now recognized as molecularly defined entities in the WHO classification system (2022). While these entities each exhibit a morphologic spectrum that overlaps with other high-grade RCC, ancillary tools developed based on their distinctive molecular alterations can help establish a specific diagnosis, underscoring the importance of integrating molecular findings into diagnostic paradigms. It is important to exclude these specific tumor types in cases with similar morphologic spectrum before rendering a diagnosis of high-grade papillary RCC, collecting duct carcinoma, or RCC, NOS. Several gray areas exist within the spectrum of high-grade uncommon types of RCC, necessitating continued research to enhance diagnostic precision and therapeutic options.
Characterization of Amyloidosis in the Gastrointestinal Tract With an Emphasis on Histologically Distinct Interstitial Patterns of Deposition and Misinterpretations
Authors: Harris Jaryse Carol , Zhang Qingzhou , Tondon Rashmi , Alipour Zahra , Stashek Kristen
Published: December 2023

Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195 biopsies) with amyloid involvement of the luminal tract were reviewed. Amyloid subtyping by mass spectrophotometry was available for 59 patients. Immunoglobulin light chain (AL) was the most commonly identified subtype (60%), followed by serum amyloid A (AA; 19%) and transthyretin (ATTR; 16%). 150/195 biopsies (77%) were positive for amyloid deposition, with an average of 2.4 positive biopsies per every 3.1 taken per patient. The sites with the highest yield were duodenum (37/37, 100%) and colon (63/74, 85%). Gastric biopsies were most likely to involve the lamina propria (41/45, 91%, P < 0.001), with the background mucosa showing reactive epithelial changes in almost half of the biopsies (20/45, 44%). Several distinct histologic patterns of interstitial deposition were identified, including muscularis mucosae deposition (n = 40, 27% of positive biopsies), peri-Brunner gland (n = 6, 17% of duodenal biopsies), mass-forming (n = 4, 2.7% of positive biopsies, including 3 suspected cases with localized involvement), collagenous colitis-like (n = 3, 4.8% of positive colonic biopsies), and globular (n = 19, 12.7% of positive biopsies). Congo Red was ordered in 81% of cases in which it was requested clinically, with a positivity rate of 30%. Of the 34 cases in which an amyloid workup was requested (but Congo Red was not performed), 14 were positive on reevaluation. Several missed cases had deposition in multiple biopsies, and almost half were missed by subspecialist GI pathologists. Nine misinterpretations were from the stomach, with seven initially diagnosed as chemical or reactive gastropathy. Additional discrepant cases were identified from the duodenum (n = 2) and colon (n = 3), with the vascular-only deposition pattern (n = 3), muscularis mucosae-only deposition (n = 3), and globular pattern (n = 1) identified. Given the challenges of identifying amyloid on hematoxylin and eosin staining, Congo Red ordering percentage should be 100% in clinically suspicious cases unless deposition is definitively seen on hematoxylin and eosin staining.
A comprehensive map of the ageing blood methylome
Authors: Seale Kirsten , Teschendorff Andrew , Reiner Alexander P , Voisin Sarah , Eynon Nir
Published: December 2023

During 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

Purpose

The 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 Design

We 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.

Results

We 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.

Conclusions

These 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

Mapping 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

Cis-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

During 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

Pairing 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.
CycPeptMP: Enhancing Membrane Permeability Prediction of Cyclic Peptides with Multi-Level Molecular Features and Data Augmentation
Authors: Li Jianan , Yanagisawa Keisuke , Akiyama Yutaka
Published: December 2023

Cyclic peptides are versatile therapeutic agents with many excellent properties, such as high binding affinity, minimal toxicity, and the potential to engage challenging protein targets. However, the pharmaceutical utilities of cyclic peptides are limited by their low membrane permeability—an essential indicator of oral bioavailability and intracellular targeting. Current machine learning-based models of cyclic peptide permeability show variable performance due to the limitations of experimental data. Furthermore, these methods use features derived from the whole molecule which are used to predict small molecules and ignore the unique structural properties of cyclic peptides. This study presents CycPeptMP: an accurate and efficient method for predicting the membrane permeability of cyclic peptides. We designed features for cyclic peptides at the atom-, monomer-, and peptide-levels, and seamlessly integrated these into a fusion model using state-of-the-art deep learning technology. Using the latest data, we applied various data augmentation techniques to enhance model training efficiency. The fusion model exhibited excellent prediction performance, with root mean squared error of 0.503 and correlation coefficient of 0.883. Ablation studies demonstrated that all feature levels were essential for predicting membrane permeability and confirmed the effectiveness of augmentation to improve prediction accuracy. A comparison with a molecular dynamics-based method showed that CycPeptMP accurately predicted the peptide permeability, which is otherwise difficult to predict using simulations.
Tree-based differential testing using inferential uncertainty for RNA-Seq
Authors: Singh Noor Pratap , Wu Euphy Y. , Fan Jason , Love Michael I. , Patro Rob
Published: December 2023

Identifying differentially expressed transcripts poses a crucial yet challenging problem in transcriptomics. Substantial uncertainty is associated with the abundance estimates of certain transcripts which, if ignored, can lead to the exaggeration of false positives and, if included, may lead to reduced power. Given a set of RNA-Seq samples,TreeTerminusarranges transcripts in a hierarchical tree structure that encodes different layers of resolution for interpretation of the abundance of transcriptional groups, with uncertainty generally decreasing as one ascends the tree from the leaves. We introducemehenDi, which utilizes the tree structure fromTreeTerminusfor differential testing. The nodes output bymehenDi, called the selected nodes are determined in a data-driven manner to maximize the signal that can be extracted from the data while controlling for the uncertainty associated with estimating the transcript abundances. The identified selected nodes can include transcripts and inner nodes, with no two nodes having an ancestor/descendant relationship. We evaluated our method on both simulated and experimental datasets, comparing its performance with other tree-based differential methods as well as with uncertainty-aware differential transcript/gene expression methods. Our method detects inner nodes that show a strong signal for differential expression, which would have been overlooked when analyzing the transcripts alone.
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

Introduction

The 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.

Methods

Used 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.

Results

Heroin (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 Conclusions

There 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

Background

Acne 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.

Objectives

In 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.

Methods

In 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.

Results

A 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).

Conclusions

In 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

In 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.
A comparison between erythrocytapheresis and venesection for the treatment of JAK2‐mutated polycythaemia
Authors: Ngo Trung Q. , Scott Matthew W. , Sirdesai Shreerang , Hempton Jennifer L. , Hodges Georgina S. , Campbell Philip J.
Published: December 2023

Background

JAK2‐mutated polycythaemia vera (PV) is associated with reduced survival because of thrombotic events and haematological disease transformation. Therapeutic venesection has traditionally been used to lower haematocrit, but the technique of erythrocytapheresis has emerged over the last decade.

Aim

To compare erythrocytapheresis with venesection as treatment for PV by assessing medical efficacy and financial viability.

Methods

One hundred sixteen patients with PV who received red cell depletion therapy at Barwon Health between 2014 and 2021 were identified. The haematocrit drop after each session, interval between treatment times and number of sessions required to achieve a haematocrit <0.45 were compared with an independent t test. Thrombosis rates were compared with Pearson's chi‐squared test. Cost‐funding analysis was done by assessing the Weighted Inlier Equivalent Separation and National Weighted Activity Unit funding models.

Results

Patients treated with erythrocytapheresis achieved a greater haematocrit drop each treatment session (0.075 vs 0.03, P < 0.01), required fewer sessions to achieve a haematocrit <0.45 (1 vs 4, P < 0.01) and experienced fewer thrombotic complications (8.7% vs 32.1%, P = 0.02) than those treated with venesection. Cost‐funding analysis demonstrated that erythrocytapheresis was more financially viable with a surplus of AU$297 per session compared to a deficit of AU$176 with venesection. Even if funding for venesection is increased, the cost of erythrocytapheresis may be mitigated by a lower number of procedures required per year (3.8 vs 5.3, P < 0.01).

Conclusions

Erythrocytapheresis is more efficacious than venesection for the treatment of PV and is accompanied by rapid reductions in haematocrit and reduced thrombotic complications.
The effect of Li/Ce co‐doping on structural and electrical properties of Sr2−x(Li, Ce)x/2Nb2O7 piezoelectric ceramics
Authors: Yang Xinji , Chen Ning , Wang Fei , Tang Manjing , Xing Jie , Zhu Jianguo
Published: December 2023

As a typical perovskite‐like layered structure (PLS) ceramic, Sr2Nb2O7 (SNO) possesses a high Curie temperature TC value above 1300°C, which is expected to work in higher temperature environment. However, pure SNO presents a piezoelectric constant d33 value of ∼ 1 pC/N. Hence, (Li, Ce) ions are doped in SNO ceramics, which increases the distortion of oxygen octahedrons and enhances the intrinsic contribution of piezoelectric properties. The increased domain size with large proportion of high response areas means that the extrinsic contribution is also improved. The introduction of (Li, Ce) ions can also promote ceramic's grain growth and reduce oxygen vacancies, leading to the improvement of electrical properties. The optimal component Sr1.96(Li, Ce)0.02Nb2O7 ceramics exhibit a d33 value of 3.1 pC/N, a higher resistivity of 1.65×106
Ω·cm at 700°C and an excellent thermal stability (a d33 value of 3.0 pC/N after annealing at 1200°C for 2 h). This work provides an effective approach with simple process and low cost for the application of PLS materials in high‐temperature environments.
Cultures of power and politics: Two cases of the limits of anti‐essentialism in the political anthropology of lowland South America
Authors: Tym Christian , Saturno Silvana
Published: December 2023

Post‐structuralism's focus on hegemonic power, subjection, and political opportunity remains pre‐eminent in political anthropology, but its appropriateness for the post‐neoliberal conjuncture is up for question. While the arrival of neoliberal multiculturalism brought contingent identities and strategic deployment of culture‐as‐product into focus, questions remain about how and why some groups mobilize to claim cultural rights while others decline to do so. For this reason, this article returns to an earlier concern in Latin American political anthropology with cultural differences in the conceptualization and execution of political organization and power. This argument is based on two ethnographic case studies—from the Venezuelan Pume and the Ecuadorian Shuar—that demonstrate the contemporary significance for indigenous politics of evolving autochthonous notions of power and their expression in conventional forms of social organization. These politico‐cultural qualities are already constituting the form and objectives of indigenous political action prior to their expression in the public fora whose terms and opportunities are often presented as driving indigenous people's politics. Such an approach is important for understanding the dilemmas of solidarity as indigenous groups become more empowered and diverse in their political orientations.
Risk factors for food contamination among children discharged from community management of acute malnutrition programmes in South Sudan: A cross‐sectional study and hazard analysis critical control point approach
Authors: Wells Joseph , Abugo David Gama , Angong John , Lamwaka Nancy Grace , Gallandat Karin , Hassan Jackson Lwate , Deng Lino , Save Dimple , Braun Laura , Gose Mesfin , Amanya Jacob , Ayoub Khamisa , King Sarah , Stobaugh Heather , Cumming Oliver , D'Mello‐Guyett Lauren
Published: December 2023

Children under‐5 years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross‐sectional study comprised a household survey with samples of child food (n = 382) and structured observations of food preparation (n = 197) among children aged 6–59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in South Sudan. We quantified Escherichia coli and total coliforms (TCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% (n = 164) of samples were contaminated with E. coli (43% >0 E. coli CFU/g, 95% CI 38%–48%), and 90% (n = 343) had >10 TCs (CFU/g) (>10 TC CFU/g, 95% CI 87%–93%). Risk factors associated (p < 0.05) with child food contamination included if the child fed themselves (9.05 RR, 95% CI [3.18, 31.16]) and exposure to animals (2.63 RR, 95% CI [1.33, 5.34]). This study highlights the risk factors and potential control strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to enteric pathogens.
Systematic mediastinal staging in non‐small cell lung cancer: Filling in the guideline evidence gap
Authors: Steinfort Daniel P.
Published: December 2023

See related article
When “Yes Means Yes”: Short-Term Effects of an Educational Video on Acceptance of Ideals Related to Affirmative Sexual Consent Among Young Adults
Authors: Beeler-Blackburn Kaitlynn M. , Wong Norman C. H.
Published: December 2023

Sexual violence is a prevalent problem impacting college students across the United States. One of the prevention efforts suggested to deal with this concern is to better educate young adults about the ideals of sexual consent. Specifically, many colleges and universities have focused their attention to promote the practice of an affirmative sexual consent standard. Using the theory of planned behavior as the theoretical framework, an experimental study was conducted to test the effectiveness of a short educational video on increasing participants’ acceptance of an affirmative consent standard related to sexual consent, as reflected in more positive attitudes, norms, and greater perceptions of behavioral control related to the enactment of affirmative consent within sexual interactions. Participants were also asked about their endorsement of an indirect approach to sexual consent following viewing of the educational video. Overall results found support for most of the hypotheses, as the findings have practical implications for college health practitioners interested in promoting healthier sexual beliefs, specifically the acceptance of an affirmative consent standard for sexual consent.
Current Trends in the Synthesis of Inorganic and Organoelement Phosphorus- and Sulfur-Containing Polymers. A Review
Authors: Tarasova N. P. , Krivoborodov E. G. , Mezhuev Ya. O.
Published: December 2023

An analysis of literature data on the set of reactions for the production of macromolecules with a high content of phosphorus and sulfur has been carried out, and basic approaches that allow the introduction of these elements into the composition of polymers and polymeric materials have been considered in compliance with the fundamental principles of green chemistry. Methods for synthesis of functional polymers under mild conditions that require minimal energy input from external sources, which can become new growth points for green industrial technologies, are considered. Particular attention focuses on the synthesis of polyphosphazenes and polyphosphoesters for biomedical purposes, as well as on the inverse vulcanization reaction to give polymers used in sorption wastewater treatment, the creation of current sources, and IR optics.
Effect of Dephasing on the Current through a Periodically Driven Quantum Point Contact
Authors: Ermakov I. , Lychkovskiy O.
Published: December 2023

We consider two one-dimensional quantum XX magnets linked by a periodically driven quantum point contact. If magnets are initially polarized in opposite directions, one expects that a spin current through the quantum point contact will establish. It has been shown recently [Phys. Rev. B 103, L041405 (2021)] that, in fact, when the driving frequency exceeds a critical value, the current halts completely, the quantum point contact being effectively insulating. Here we enquire how this picture is affected by quantum dephasing. Our findings reveal that any nonzero dephasing restores the current.
Peripheral nerve stimulation for saphenous neuralgia
Authors: McCullough Meghan , Kenney Deborah , Curtin Catherine , Ottestad Einar
Published: December 2023

Background

Injury to saphenous nerve branches is frequent during knee surgery and can result in chronic pain. This saphenous neuralgia remains challenging to treat. Peripheral nerve stimulation (PNS) is a new potential non-pharmacologic treatment option. We present our outcomes experience using this technology in 12 patients.

Methods

We retrospectively reviewed PNS placement for saphenous neuralgia between 2000 and 2022 at a single institution. Demographic information was collected as well as response to the device. Four-question short-form Patient-Reported Outcome Measurement Information System (PROMIS) Scores were collected before and 2 weeks, 6 weeks, and 6 months postprocedure. Specific scores included pain interference and behavior, functional mobility, depression, anxiety, and sleep impairment. Change in pain interference measured by the short-form PROMIS tool at 6 months was chosen as the primary outcome.

Results

Twelve patients met inclusion criteria, with 10 patients having the full 6-month follow-up. In these 10 patients, the mean change from baseline in the short-form adjusted pain interference score (greater difference means improved pain) at 6 months was 5.8 (SD 6.5). Among all patients, average follow-up was 11.5 months (range 3–35 months). Most patients’ symptoms developed after knee surgery (84%). Prior to PNS, patients underwent other treatments including cryoablation (8%), radiofrequency ablation (16%), saphenous neurectomy (16%), or surgical release of adjacent nerves (25%). Ten patients (83%) reported any improvement in symptoms while two reported no benefit. Complications occurred in four patients (33%). Two patients had the device removed and a third discontinued use. PROMIS Scores for pain, functional mobility, mood, and sleep impairment all improved.

Discussion

Limited effective treatments exist for saphenous neuralgia. Our case series demonstrates the potential of PNS as a treatment for saphenous neuralgia. Comparative effectiveness studies are warranted to assess whether our effect size is clinically relevant.
Learning to Branch: Generalization Guarantees and Limits of Data-Independent Discretization
Authors: Balcan Maria-Florina , Dick Travis , Sandholm Tuomas , Vitercik Ellen
Published: December 2023

Tree search algorithms, such as branch-and-bound, are the most widely used tools for solving combinatorial and non-convex problems. For example, they are the foremost method for solving (mixed) integer programs and constraint satisfaction problems. Tree search algorithms come with a variety of tunable parameters that are notoriously challenging to tune by hand. A growing body of research has demonstrated the power of using a data-driven approach to automatically optimize the parameters of tree search algorithms. These techniques use a
training set
of integer programs sampled from an application-specific instance distribution to find a parameter setting that has strong average performance over the training set. However, with too few samples, a parameter setting may have strong average performance on the training set but poor expected performance on future integer programs from the same application. Our main contribution is to provide the first
sample complexity guarantees
for tree search parameter tuning. These guarantees bound the number of samples sufficient to ensure that the average performance of tree search over the samples nearly matches its future expected performance on the unknown instance distribution. In particular, the parameters we analyze weight
scoring rules
used for variable selection. Proving these guarantees is challenging because tree size is a volatile function of these parameters: we prove that, for any discretization (uniform or not) of the parameter space, there exists a distribution over integer programs such that every parameter setting in the discretization results in a tree with exponential expected size, yet there exist parameter settings between the discretized points that result in trees of constant size. In addition, we provide data-dependent guarantees that depend on the volatility of these tree-size functions: our guarantees improve if the tree-size functions can be well approximated by simpler functions. Finally, via experiments, we illustrate that learning an optimal weighting of scoring rules reduces tree size.
A Concise Concurrent B
+
-Tree for Persistent Memory
Authors: Wei Yan , Xingjun Zhang
Published: December 2023

Persistent memory (PM) presents a unique opportunity for designing data management systems that offer improved performance, scalability, and instant restart capability. As a widely used data structure for managing data in such systems, B
+
-Tree must address the challenges presented by PM in both data consistency and device performance. However, existing studies suffer from significant performance degradation when maintaining data consistency on PM. To settle this problem, we propose a new concurrent B
+
-Tree, CC-Tree, optimized for PM. CC-Tree ensures data consistency while providing high concurrent performance, thanks to several technologies, including partitioned metadata, log-free split, and lock-free read. We conducted experiments using state-of-the-art indices, and the results demonstrate significant performance improvements, including approximately 1.2–1.6x search, 1.5–1.7x insertion, 1.5–2.8x update, 1.9–4x deletion, 0.9–10x range scan, and up to 1.55–1.82x in hybrid workloads.
ALKHB5-demethylated lncRNA SNHG15 promotes myeloma tumorigenicity by increasing chromatin accessibility and recruiting H3K36me3 modifier SETD2
Authors: Yao Lan , Li Tingting , Teng Yao , Guo Jingjing , Zhang Hongyong , Xia Linghui , Wu Qiuling
Published: December 2023

To our knowledge, this study first demonstrated the prognostic significance and biological function of long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in multiple myeloma (MM), and indicated a novel revelation on the effect of N6-methyladenosine (m6A)-regulated lncRNA on MM tumorigenicity. Moreover, the novel chromatin-regulatory mechanism of lncRNA by interacting with epigenetic modifiers including m6A demethylase ALKBH5 and H3K36me3 methyltransferase SETD2 in myeloma progression elucidated intricate mechanism of tumor pathogenesis.
Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia
Authors: Stapleton Emma M. , Thurman Andrew L. , Pezzulo Alejandro A. , Comellas Alejandro P. , Thornell Ian M.
Published: December 2023

It is unknown why calcitriol (active vitamin D) deficiency worsens pulmonary disease outcomes. Results from mRNA, immunoblot, Ussing chamber, and absorption experiments indicate that calcitriol deficiency increases ENaC activity in human airway epithelia, decreasing apical hydration. Given that epithelial hydration is required for mucociliary transport and airway innate immune function, the increased ENaC activity observed in calcitriol-deficient epithelia may contribute to respiratory pathology observed in vitamin D deficiency.
Cenicriviroc prevents dysregulation of astrocyte/endothelial cross talk induced by ischemia and HIV-1 via inhibiting the NLRP3 inflammasome and pyroptosis
Authors: Fattakhov Nikolai , Ngo Alex , Torices Silvia , Joseph Joelle-Ann , Okoro Adesuwa , Moore Cameron , Naranjo Oandy , Becker Sarah , Toborek Michal
Published: December 2023

The present study reveals the role of astrocytic NOD-like receptor protein-3 (NLRP3) inflammasome in dysfunctional astrocyte-endothelial cross interactions triggered in response to oxygen/glucose deprivation injury associated with human immunodeficiency virus type 1 (HIV-1) infection. Our results suggest that blocking NLRP3 inflammasome activation and pyroptosis-mediated inflammation with cenicriviroc (CVC) may constitute a potentially effective therapeutic strategy for blood-brain barrier (BBB) protection during HIV-1-associated ischemic stroke.
Human Cx50 Isoleucine177 prevents heterotypic docking and formation of functional gap junction channels with Cx43
Authors: Wong Robert S. , Chen Honghong , Li Yi X. , Esseltine Jessica L. , Stathopulos Peter B. , Bai Donglin
Published: December 2023

The human lens is an avascular organ, and its transparency is partially dependent on gap junction (GJ) network composed of Cx46, Cx50, and Cx43. We found that human Cx46 can dock and form functional heterotypic GJs with Cx50 and Cx43, but Cx50 is unable to form functional heterotypic GJs with Cx43. Through mutagenesis and patch-clamp study of several designed variants, we found that Cx50 I177L was sufficient to form functional heterotypic GJs with Cx43.
Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation
Authors: Gerber Lucie , Resseguier Julien , Helle-Valle Tellef , Farhat Elie , Nilsson Göran E. , Lefevre Sjannie
Published: December 2023

We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.
Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice
Authors: Ritter McKenzie L. , Wagner Valerie A. , Balapattabi Kirthikaa , Opichka Megan A. , Lu Ko-Ting , Wackman Kelsey K. , Reho John J. , Keen Henry L. , Kwitek Anne E. , Morselli Lisa L. , Geurts Aron M. , Sigmund Curt D. , Grobe Justin L.
Published: December 2023

In mice, three distinct isoforms of Agouti-related peptide are encoded via distinct first exons. In the arcuate nucleus of the hypothalamus, Krüppel-like factor 4 stimulates transcription of the dominant isoform in lean mice, but this mechanism is altered during diet-induced obesity.