bluuebunny/crossref_metadata_2025 huggingface dataset:
Actin nucleators safeguard replication forks by limiting nascent strand degradation
Authors: Nieminuszczy Jadwiga , Martin Peter R , Broderick Ronan , Krwawicz Joanna , Kanellou Alexandra , Mocanu Camelia , Bousgouni Vicky , Smith Charlotte , Wen Kuo-Kuang , Woodward Beth L , Bakal Chris , Shackley Fiona , Aguilera Andrés , Stewart Grant S , Vyas Yatin M , Niedzwiedz Wojciech
Published: May 2023

Accurate genome replication is essential for all life and a key mechanism of disease prevention, underpinned by the ability of cells to respond to replicative stress (RS) and protect replication forks. These responses rely on the formation of Replication Protein A (RPA)-single stranded (ss) DNA complexes, yet this process remains largely uncharacterized. Here, we establish that actin nucleation-promoting factors (NPFs) associate with replication forks, promote efficient DNA replication and facilitate association of RPA with ssDNA at sites of RS. Accordingly, their loss leads to deprotection of ssDNA at perturbed forks, impaired ATR activation, global replication defects and fork collapse. Supplying an excess of RPA restores RPA foci formation and fork protection, suggesting a chaperoning role for actin nucleators (ANs) (i.e. Arp2/3, DIAPH1) and NPFs (i.e, WASp, N-WASp) in regulating RPA availability upon RS. We also discover that β-actin interacts with RPA directly in vitro, and in vivo a hyper-depolymerizing β-actin mutant displays a heightened association with RPA and the same dysfunctional replication phenotypes as loss of ANs/NPFs, which contrasts with the phenotype of a hyper-polymerizing β-actin mutant. Thus, we identify components of actin polymerization pathways that are essential for preventing ectopic nucleolytic degradation of perturbed forks by modulating RPA activity.
NBBC: a non-B DNA burden explorer in cancer
Authors: Xu Qi , Kowalski Jeanne
Published: May 2023

Alternate (non-B) DNA-forming structures, such as Z-DNA, G-quadruplex, triplex have demonstrated a potential role in cancer etiology. It has been found that non-B DNA-forming sequences can stimulate genetic instability in human cancer genomes, implicating them in the development of cancer and other genetic diseases. While there exist several non-B prediction tools and databases, they lack the ability to both analyze and visualize non-B data within a cancer context. Herein, we introduce NBBC, a non-B DNA burden explorer in cancer, that offers analyses and visualizations for non-B DNA forming motifs. To do so, we introduce ‘non-B burden’ as a metric to summarize the prevalence of non-B DNA motifs at the gene-, signature- and genomic site-levels. Using our non-B burden metric, we developed two analyses modules within a cancer context to assist in exploring both gene- and motif-level non-B type heterogeneity among gene signatures. NBBC is designed to serve as a new analysis and visualization platform for the exploration of non-B DNA, guided by non-B burden as a novel marker.
A conserved motif in the disordered linker of human MLH1 is vital for DNA mismatch repair and its function is diminished by a cancer family mutation
Authors: Wolf Karla , Kosinski Jan , Gibson Toby J , Wesch Nicole , Dötsch Volker , Genuardi Maurizio , Cordisco Emanuela Lucci , Zeuzem Stefan , Brieger Angela , Plotz Guido
Published: May 2023

DNA mismatch repair (MMR) is essential for correction of DNA replication errors. Germline mutations of the human MMR gene MLH1 are the major cause of Lynch syndrome, a heritable cancer predisposition. In the MLH1 protein, a non-conserved, intrinsically disordered region connects two conserved, catalytically active structured domains of MLH1. This region has as yet been regarded as a flexible spacer, and missense alterations in this region have been considered non-pathogenic. However, we have identified and investigated a small motif (ConMot) in this linker which is conserved in eukaryotes. Deletion of the ConMot or scrambling of the motif abolished mismatch repair activity. A mutation from a cancer family within the motif (p.Arg385Pro) also inactivated MMR, suggesting that ConMot alterations can be causative for Lynch syndrome. Intriguingly, the mismatch repair defect of the ConMot variants could be restored by addition of a ConMot peptide containing the deleted sequence. This is the first instance of a DNA mismatch repair defect conferred by a mutation that can be overcome by addition of a small molecule. Based on the experimental data and AlphaFold2 predictions, we suggest that the ConMot may bind close to the C-terminal MLH1-PMS2 endonuclease and modulate its activation during the MMR process.
STellaris: a web server for accurate spatial mapping of single cells based on spatial transcriptomics data
Authors: Li Xiangshang , Xiao Chunfu , Qi Juntian , Xue Weizhen , Xu Xinwei , Mu Zelin , Zhang Jie , Li Chuan-Yun , Ding Wanqiu
Published: May 2023

Single-cell RNA sequencing (scRNA-seq) provides insights into gene expression heterogeneities in diverse cell types underlying homeostasis, development and pathological states. However, the loss of spatial information hinders its applications in deciphering spatially related features, such as cell–cell interactions in a spatial context. Here, we present STellaris (https://spatial.rhesusbase.com), a web server aimed to rapidly assign spatial information to scRNA-seq data based on their transcriptomic similarity with public spatial transcriptomics (ST) data. STellaris is founded on 101 manually curated ST datasets comprising 823 sections across different organs, developmental stages and pathological states from humans and mice. STellaris accepts raw count matrix and cell type annotation of scRNA-seq data as the input, and maps single cells to spatial locations in the tissue architecture of properly matched ST section. Spatially resolved information for intercellular communications, such as spatial distance and ligand-receptor interactions (LRIs), are further characterized between annotated cell types. Moreover, we also expanded the application of STellaris in spatial annotation of multiple regulatory levels with single-cell multiomics data, using the transcriptome as a bridge. STellaris was applied to several case studies to showcase its utility of adding value to the ever-growing scRNA-seq data from a spatial perspective.
Confinement of ionomer for electrocatalytic CO2 reduction reaction via efficient mass transfer pathways
Authors: Du Xiaowei , Zhang Peng , Zhang Gong , Gao Hui , Zhang Lili , Zhang Mengmeng , Wang Tuo , Gong Jinlong
Published: May 2023

Gas diffusion electrodes (GDEs) mediate the transport of reactants, products and electrons for the electrocatalytic CO2 reduction reaction (CO2RR) in membrane electrode assemblies. The random distribution of ionomer, added by the traditional physical mixing method, in the catalyst layer of GDEs affects the transport of ions and CO2. Such a phenomenon results in elevated cell voltage and decaying selectivity at high current densities. This paper describes a pre-confinement method to construct GDEs with homogeneously distributed ionomer, which enhances mass transfer locally at the active centers. The optimized GDE exhibited comparatively low cell voltages and high CO Faradaic efficiencies (FE > 90%) at a wide range of current densities. It can also operate stably for over 220 h with the cell voltage staying almost unchanged. This good performance can be preserved even with diluted CO2 feeds, which is essential for pursuing a high single-pass conversion rate. This study provides a new approach to building efficient mass transfer pathways for ions and reactants in GDEs to promote the electrocatalytic CO2RR for practical applications.
More Risk, More Information: How Passive Ownership Can Improve Informational Efficiency
Authors: Buss Adrian , Sundaresan Savitar
Published: May 2023

We identify a novel economic mechanism through which passive ownership positively affects informational efficiency in the cross-section of firms. Passive investors’ inelastic demand lowers a firm’s cost-of-capital, inducing it to take more risk. The higher cash flow variance, in turn, incentivizes active investors to acquire more precise private information, pushing up price informativeness for firms with high passive ownership. High passive ownership also implies higher stock prices and higher stock-return variances. An increase in the aggregate size of passive investors amplifies these cross-sectional differences. We also document complementarities in firms’ real investment and investors’ information choices that can cause information crashes.

Received May 31, 2020; editorial decision January 4, 2023 by Editor Holger Mueller. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
Beyond the symptom: the biology of fatigue
Authors: Raizen David M , Mullington Janet , Anaclet Christelle , Clarke Gerard , Critchley Hugo , Dantzer Robert , Davis Ronald , Drew Kelly L , Fessel Josh , Fuller Patrick M , Gibson Erin M , Harrington Mary , Ian Lipkin W , Klerman Elizabeth B , Klimas Nancy , Komaroff Anthony L , Koroshetz Walter , Krupp Lauren , Kuppuswamy Anna , Lasselin Julie , Lewis Laura D , Magistretti Pierre J , Matos Heidi Y , Miaskowski Christine , Miller Andrew H , Nath Avindra , Nedergaard Maiken , Opp Mark R , Ritchie Marylyn D , Rogulja Dragana , Rolls Asya , Salamone John D , Saper Clifford , Whittemore Vicky , Wylie Glenn , Younger Jarred , Zee Phyllis C , Craig Heller H
Published: May 2023

A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.
Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement
Authors: Cooke Jessica A , Voigt Andrew P , Collingwood Michael A , Stone Nicholas E , Whitmore S Scott , DeLuca Adam P , Burnight Erin R , Anfinson Kristin R , Vakulskas Christopher A , Reutzel Austin J , Daggett Heather T , Andorf Jeaneen L , Stone Edwin M , Mullins Robert F , Tucker Budd A
Published: May 2023

Prior to use, newly generated induced pluripotent stem cells (iPSC) should be thoroughly validated. While excellent validation and release testing assays designed to evaluate potency, genetic integrity, and sterility exist, they do not have the ability to predict cell type-specific differentiation capacity. Selection of iPSC lines that have limited capacity to produce high-quality transplantable cells, places significant strain on valuable clinical manufacturing resources. The purpose of this study was to determine the degree and root cause of variability in retinal differentiation capacity between cGMP-derived patient iPSC lines. In turn, our goal was to develop a release testing assay that could be used to augment the widely used ScoreCard panel. IPSCs were generated from 15 patients (14-76 years old), differentiated into retinal organoids, and scored based on their retinal differentiation capacity. Despite significant differences in retinal differentiation propensity, RNA-sequencing revealed remarkable similarity between patient-derived iPSC lines prior to differentiation. At 7 days of differentiation, significant differences in gene expression could be detected. Ingenuity pathway analysis revealed perturbations in pathways associated with pluripotency and early cell fate commitment. For example, good and poor producers had noticeably different expressions of OCT4 and SOX2 effector genes. QPCR assays targeting genes identified via RNA sequencing were developed and validated in a masked fashion using iPSCs from 8 independent patients. A subset of 14 genes, which include the retinal cell fate markers RAX, LHX2, VSX2, and SIX6 (all elevated in the good producers), were found to be predictive of retinal differentiation propensity.
Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke
Authors: Nakagomi Takayuki , Nakano-Doi Akiko , Kubo Shuji , Sawano Toshinori , Kuramoto Yoji , Yamahara Kenichi , Matsuyama Tomohiro , Takagi Toshinori , Doe Nobutaka , Yoshimura Shinichi
Published: May 2023

We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.
The Fall of Roe v. Wade: The Addiction Specialist’s Role in Championing Reproductive Rights
Authors: Kurtz Theresa , Smid Marcela C.
Published: May 2023

Reproductive age-pregnant individuals who use substances are disproportionately impacted by the US Supreme Court reversal of Roe v. Wade. Because of historic and ongoing discrimination against pregnant individuals who use substances, this group is at high risk for inadequate pregnancy options counseling and lack of access to safe and legal abortions. Fetal rights laws set a concerning precedent that further criminalize and penalize substance use in pregnancy. As addiction specialists, we have the professional responsibility to champion the reproductive freedoms of pregnant individuals who use substances. There are several ways that addiction specialists can uphold the reproductive rights of patients on an individual, state, and federal level, including the following: incorporate reproductive healthcare into addiction practices, help those seeking abortion navigate barriers, partner with perinatal healthcare clinicians to provide evidence-based addiction treatment during pregnancy, and support decriminalization and destigmatization of substance use, especially in pregnancy.
Rehabilitation Interventions for Complex Regional Pain Syndrome: An Overview of Systematic Reviews
Authors: Shafiee Erfan , MacDermid Joy , Packham Tara , Grewal Ruby , Farzad Maryam , Bobos Pavlos , Walton David
Published: May 2023

Objectives:

An increasing number of systematic reviews have been conducted on various conservative management of complex regional pain syndrome (CRPS) targeting different rehabilitation interventions and objectives. The intent of this article was to summarize and critically appraise the body of evidence on conservative management of the CRPS and to provide an overall picture of the current state of the literature.

Methods:

This study was an overview of systematic reviews on conservative treatments for CRPS. We conducted a literature search from inception to January 2023 in the following databases: Embase, Medline, CINAHL, Google Scholar, Cochrane Library, and Physiotherapy Evidence Database (PEDro). Two independent reviewers conducted study screening, data extraction, and methodological quality assessment (using AMSTAR-2). Qualitative synthesis was the preferred method for reporting the findings of our review. We calculated the corrected covered area index to account for the proportion of overlapping primary studies that were included in multiple reviews.

Result:

We identified 214 articles, and a total of 9 systematic reviews of randomized controlled trials were eligible for inclusion. Pain and disability were the most common outcomes evaluated in the reviews. There were 6 (6/9; 66%) high-quality, 2 (2/9; 22%) moderate-quality, and 1 critically low-quality systematic review (1/9;11%), with the quality of the included trials ranging from very low to high. There was a large overlap across primary studies that were included in the systematic reviews (corrected covered area=23%). The findings of high-quality reviews support the effectiveness of mirror therapy (MT) and graded motor imagery (GMI) programs on pain and disability improvement in CRPS patients. The large effect size was reported for the effectiveness of MT on pain and disability (SMD:1.88 (95% CI: 0.73–3.02) and 1.30 (95% CI: 0.11–2.49), respectively) and the effectiveness of GMI program (GMIP) on pain and disability improvement (SMD: 1.36 (95% CI: 0.75–1.96) and 1.64 (95% CI: 0.53–2.74), respectively).

Discussion:

The evidence is in favor of adopting movement representation techniques, such as MT and GMI programs, for the treatment of pain and disability in patients with CRPS. However, this is based on a small body of primary evidence, and more research is required to generate conclusions. Overall, the evidence is not comprehensive or of sufficient quality to make definitive recommendations about the effectiveness of other rehabilitation interventions in improving pain and disability.
Individualized Positive End-expiratory Pressure Titration Strategies in Superobese Patients Undergoing Laparoscopic Surgery: Prospective and Nonrandomized Crossover Study
Authors: Boesing Christoph , Schaefer Laura , Hammel Marvin , Otto Mirko , Blank Susanne , Pelosi Paolo , Rocco Patricia R. M. , Luecke Thomas , Krebs Joerg
Published: May 2023

Background

Superobesity and laparoscopic surgery promote negative end-expiratory transpulmonary pressure that causes atelectasis formation and impaired respiratory mechanics. The authors hypothesized that end-expiratory transpulmonary pressure differs between fixed and individualized positive end-expiratory pressure (PEEP) strategies and mediates their effects on respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters in superobese patients.

Methods

In this prospective, nonrandomized crossover study including 40 superobese patients (body mass index 57.3 ± 6.4 kg/m2) undergoing laparoscopic bariatric surgery, PEEP was set according to (1) a fixed level of 8 cm H2O (PEEPEmpirical), (2) the highest respiratory system compliance (PEEPCompliance), or (3) an end-expiratory transpulmonary pressure targeting 0 cm H2O (PEEPTranspul) at different surgical positioning. The primary endpoint was end-expiratory transpulmonary pressure at different surgical positioning; secondary endpoints were respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters.

Results

Individualized PEEPCompliance compared to fixed PEEPEmpirical resulted in higher PEEP (supine, 17.2 ± 2.4 vs. 8.0 ± 0.0 cm H2O; supine with pneumoperitoneum, 21.5 ± 2.5 vs. 8.0 ± 0.0 cm H2O; and beach chair with pneumoperitoneum; 15.8 ± 2.5 vs. 8.0 ± 0.0 cm H2O; P < 0.001 each) and less negative end-expiratory transpulmonary pressure (supine, −2.9 ± 2.0 vs. −10.6 ± 2.6 cm H2O; supine with pneumoperitoneum, −2.9 ± 2.0 vs. −14.1 ± 3.7 cm H2O; and beach chair with pneumoperitoneum, −2.8 ± 2.2 vs. −9.2 ± 3.7 cm H2O; P < 0.001 each). Titrated PEEP, end-expiratory transpulmonary pressure, and lung volume were lower with PEEPCompliance compared to PEEPTranspul (P < 0.001 each). Respiratory system and transpulmonary driving pressure and mechanical power normalized to respiratory system compliance were reduced using PEEPCompliance compared to PEEPTranspul.

Conclusions

In superobese patients undergoing laparoscopic surgery, individualized PEEPCompliance may provide a feasible compromise regarding end-expiratory transpulmonary pressures compared to PEEPEmpirical and PEEPTranspul, because PEEPCompliance with slightly negative end-expiratory transpulmonary pressures improved respiratory mechanics, lung volumes, and oxygenation while preserving cardiac output.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Oral microbiome as a new research-target for supportive care and precision oncology
Authors: Bruno Julia Stephanie , Fregnani Eduardo Rodrigues
Published: May 2023

Purpose of review

A growing number of studies demonstrate the oral bacterial shift in cancer patients and the enrichment of oral bacteria in distant tumours. During the oncological treatment, opportunistic oral bacteria correlate with oral toxicities. This review focused on the most recent studies to identify which genera are the most mentioned and deserved further investigation.

Recent findings

This review evaluated bacterial changes in patients with head and neck, colorectal, lung and breast cancer. Greater composition of disease-related genera (e.g., Fusobacterium, Porphyromonas, Lactobacillus, Streptococcus, and Parvimonas) are present in the oral cavity of these groups of patients. The tumour specimen characterisation of head and neck, pancreatic and colorectal cancer also describes the presence of oral taxa. No evidence indicates that commensal oral bacteria have protective roles in distant tumours. Regardless, oral care is critical to prevent the growth of oral pathogens and reduce infection foci.

Recent evidence suggests that oral microbiota is a potential biomarker for oncological clinical outcomes and oral toxicities. Currently, the literature presents a remarkable methodological variety - from the sample collection site to the preference of the data analysis tools. For the oral microbiome to achieve the stage of being used as a clinical tool in the oncological context, more studies are necessary.
Advance care planning in oncology: a scoping review and some recommendations
Authors: Libert Yves , Choucroun Lisa , Razavi Darius , Merckaert Isabelle
Published: May 2023

Purpose of review

Cancer patients’ communication with their relatives and healthcare professionals (HCPs) is essential for advance care planning (ACP). The purpose of this scoping review was to synthesize recent research findings about factors enabling cancer patients’, their relatives’, and physicians’ communication about ACP, and to propose recommendations for future ACP implementation in cancer care.

Recent findings

This review confirmed the importance of aspects of the cancer care context (i.e., culture) as ACP uptake-predisposing and -enabling factors. It highlighted the difficulty of determining who should initiate ACP discussion, with which patients and at what time-points. It also highlighted a lack of consideration for socioemotional processes in the study of ACP uptake despite evidence that cancer patients’, relatives’ and physicians’ discomforts that arise from communication about end-of-life and the wish to safeguard each other are main obstacles to ACP implementation.

Based on these recent findings, we propose an ACP communication model, developed with the consideration of factors reported to influence ACP uptake and communication in healthcare, and integrating socioemotional processes. The testing of the model may yield suggestions for innovative interventions that can support communication about ACP and promote a better uptake in clinical practice.
New targeted treatments for advanced sarcomas
Authors: Li Chia-Chen , Chen Tom Wei-Wu
Published: May 2023

Purpose of review

The purpose of this review is to provide the rationale and results behind recent clinical trials regarding molecular-targeted agents for advanced sarcomas.

Recent findings

Tazemetostat, a first-in-class EZH2 inhibitor, was approved to treat advanced epithelioid sarcoma. In synovial sarcoma, the interaction between pathognomonic SS18-SSX fusion protein and the BAF complex has brought insight in using BRD9 inhibitors as a treatment based on synthetic lethality. MDM2 overexpression is an important mechanism to suppress p53 function, and MDM2 gene amplification is pathognomonic in well differentiated and dedifferentiated liposarcoma. Two MDM2 inhibitors, milademetan and BI907828, have both reached the optimal dosing and have shown promising efficacy in MDM2-amplified liposarcoma. Late-stage pivotal studies are ongoing for both of these MDM2 inhibitors. The co-amplification of CDK4 and MDM2 in liposarcoma also provided a rationale for CDK4/6 inhibitors as a potential therapy. Selinexor, an exportin-1 inhibitor, has shown single-agent activity in dedifferentiated liposarcoma and action in gastrointestinal stromal tumour in combination with imatinib. Lastly, a new formulation of mTOR inhibitor, nab-sirolimus, was recently approved for perivascular epithelioid cell tumour (PEComa).

Molecular-guided precision medicine holds a bright future in bringing more active treatments for advanced sarcoma patients.
Chemical features of melanoma tumor resident TRG CDR3s associated with better survival probabilities
Authors: Agnila Deo Rei L. , Huda Taha I. , Eakins Rachel A. , Patel Dhruv N. , Hsiang Monica , Chobrutskiy Andrea , Chobrutskiy Boris I. , Blanck George
Published: May 2023

We assessed the T-cell receptor gamma (TRG) recombination reads from the cancer genome atlas melanoma tumor exome files and the TRG recombination reads from an independent, melanoma exome file dataset, from the Moffitt Cancer Center. TRG complementarity determining region-3 (CDR3) amino acid (AA) sequences were assessed for chemical complementarity to cancer testis antigens, with such complementarity for FAM133A and CRISP2 associated with better survival probabilities for both datasets. These results, along with related TRG CDR3 AA chemical feature assessments provided in this report, have indicated opportunities for melanoma patient stratifications based on the recovery of TRG recombination reads from both tumor and blood samples, and the results may point towards novel, effective melanoma antigens.
Rising Inpatient Utilization and Costs of Cannabis Hyperemesis Syndrome Hospitalizations in Massachusetts After Cannabis Legalization
Authors: Marshall Allison , Fai Caitlin , Han John , Yule Amy M. , Jangi Sushrut
Published: May 2023

Goals:

We described the demographics, inpatient utilization, and cost of services among patients hospitalized for putative cannabinoid hyperemesis syndrome (CHS) predating and postdating cannabis legalization in Massachusetts.

Background:

As the recreational use of cannabis has been widely legalized nationally, the resulting shifts in clinical presentation, health care utilization, and estimated costs of CHS hospitalizations remain unclear in the postlegalization era.

Study:

We performed a retrospective cohort study among patients admitted to a large urban hospital between 2012 and 2021, before and after the date of cannabis legalization in Massachusetts (Dec 15, 2016). We examined the demographic and clinical characteristics of patients admitted for putative CHS, the utilization of hospital services, and estimated inpatient costs pre and postlegalization.

Results:

We identified a significant increase in putative CHS hospitalizations pre and post-cannabis legalization in Massachusetts (0.1% vs 0.02% of total admissions per time period, P < 0.05). Across 72 CHS hospitalizations, patient demographics were similar pre and postlegalization. Hospital resource utilization increased postlegalization, with increased length of stay (3 d vs 1 d, P < 0.005), and need for antiemetics (P < 0.05). Multivariate linear regression confirmed that postlegalization admissions were independently associated with increased length of stay (Β = 5.35, P < 0.05). The mean cost of hospitalization was significantly higher postlegalization ($18,714 vs $7460, P < 0.0005), even after adjusting for medical inflation ($18,714 vs $8520, P < 0.001) with intravenous fluid administration and endoscopy costs increased (P < 0.05). On multivariate linear regression, hospitalization for putative CHS during postlegalization predicted increased costs (Β = 10,131.25, P < 0.05).

Conclusions:

In the postlegalization era of cannabis in Massachusetts, we found increased putative CHS hospitalizations, with a concomitant increased length of hospital stay and total cost per hospitalization. As cannabis use increases, the recognition and costs of its deleterious effects are necessary to incorporate into future clinical practice strategies and health policy.
Feasibility of Accelerated Prostate Diffusion-Weighted Imaging on 0.55 T MRI Enabled With Random Matrix Theory Denoising
Authors: Lemberskiy Gregory , Chandarana Hersh , Bruno Mary , Ginocchio Luke A. , Huang Chenchan , Tong Angela , Keerthivasan Mahesh Bharath , Fieremans Els , Novikov Dmitry S.
Published: May 2023

Introduction

Prostate cancer diffusion weighted imaging (DWI) MRI is typically performed at high-field strength (3.0 T) in order to overcome low signal-to-noise ratio (SNR). In this study, we demonstrate the feasibility of prostate DWI at low field enabled by random matrix theory (RMT)-based denoising, relying on the MP-PCA algorithm applied during image reconstruction from multiple coils.

Methods

Twenty-one volunteers and 2 prostate cancer patients were imaged with a 6-channel pelvic surface array coil and an 18-channel spine array on a prototype 0.55 T system created by ramping down a commercial magnetic resonance imaging system (1.5 T MAGNETOM Aera Siemens Healthcare) with 45 mT/m gradients and 200 T/m/s slew rate. Diffusion-weighted images were acquired with 4 non-collinear directions, for which b = 50 s/mm2 was used with 8 averages and b = 1000 s/mm2 with 40 averages; 2 extra b = 50 s/mm2 were used as part of the dynamic field correction. Standard and RMT-based reconstructions were applied on DWI over different ranges of averages. Accuracy/precision was evaluated using the apparent diffusion coefficient (ADC), and image quality was evaluated over 5 separate reconstructions by 3 radiologists with a 5-point Likert scale. For the 2 patients, we compare image quality and lesion visibility of the RMT reconstruction versus the standard one on 0.55 T and on clinical 3.0 T.

Results

The RMT-based reconstruction in this study reduces the noise floor by a factor of 5.8, thereby alleviating the bias on prostate ADC. Moreover, the precision of the ADC in prostate tissue after RMT increases over a range of 30%–130%, with the increase in both signal-to-noise ratio and precision being more prominent for a low number of averages. Raters found that the images were consistently of moderate to good overall quality (3–4 on the Likert scale). Moreover, they determined that b = 1000 s/mm2 images from a 1:55-minute scan with the RMT-based reconstruction were on par with the corresponding images from a 14:20-minute scan with standard reconstruction. Prostate cancer was visible on ADC and calculated b = 1500 images even with the abbreviated 1:55-minute scan reconstructed with RMT.

Conclusions

Prostate imaging using DWI is feasible at low field and can be performed more rapidly with noninferior image quality compared with standard reconstruction.
Prediction of Bone Marrow Biopsy Results From MRI in Multiple Myeloma Patients Using Deep Learning and Radiomics
Authors: Wennmann Markus , Ming Wenlong , Bauer Fabian , Chmelik Jiri , Klein André , Uhlenbrock Charlotte , Grözinger Martin , Kahl Kim-Celine , Nonnenmacher Tobias , Debic Manuel , Hielscher Thomas , Thierjung Heidi , Rotkopf Lukas T. , Stanczyk Nikolas , Sauer Sandra , Jauch Anna , Götz Michael , Kurz Felix T. , Schlamp Kai , Horger Marius , Afat Saif , Besemer Britta , Hoffmann Martin , Hoffend Johannes , Kraemer Doris , Graeven Ullrich , Ringelstein Adrian , Bonekamp David , Kleesiek Jens , Floca Ralf O. , Hillengass Jens , Mai Elias K. , Weinhold Niels , Weber Tim F. , Goldschmidt Hartmut , Schlemmer Heinz-Peter , Maier-Hein Klaus , Delorme Stefan , Neher Peter
Published: May 2023

Objectives

In multiple myeloma and its precursor stages, plasma cell infiltration (PCI) and cytogenetic aberrations are important for staging, risk stratification, and response assessment. However, invasive bone marrow (BM) biopsies cannot be performed frequently and multifocally to assess the spatially heterogenous tumor tissue. Therefore, the goal of this study was to establish an automated framework to predict local BM biopsy results from magnetic resonance imaging (MRI).

Materials and Methods

This retrospective multicentric study used data from center 1 for algorithm training and internal testing, and data from center 2 to 8 for external testing. An nnU-Net was trained for automated segmentation of pelvic BM from T1-weighted whole-body MRI. Radiomics features were extracted from these segmentations, and random forest models were trained to predict PCI and the presence or absence of cytogenetic aberrations. Pearson correlation coefficient and the area under the receiver operating characteristic were used to evaluate the prediction performance for PCI and cytogenetic aberrations, respectively.

Results

A total of 672 MRIs from 512 patients (median age, 61 years; interquartile range, 53–67 years; 307 men) from 8 centers and 370 corresponding BM biopsies were included. The predicted PCI from the best model was significantly correlated (P≤ 0.01) to the actual PCI from biopsy in all internal and external test sets (internal test set:r= 0.71 [0.51, 0.83]; center 2, high-quality test set:r= 0.45 [0.12, 0.69]; center 2, other test set:r= 0.30 [0.07, 0.49]; multicenter test set:r= 0.57 [0.30, 0.76]). The areas under the receiver operating characteristic of the prediction models for the different cytogenetic aberrations ranged from 0.57 to 0.76 for the internal test set, but no model generalized well to all 3 external test sets.

Conclusions

The automated image analysis framework established in this study allows for noninvasive prediction of a surrogate parameter for PCI, which is significantly correlated to the actual PCI from BM biopsy.
Content of Telephone Consultations of Patients With Inflammatory Bowel Disease
Authors: Kawakami Aki , Tanaka Makoto , Sakagami Kayoko , Ito Hiroaki
Published: May 2023

This study aimed to analyze the specific contents of telephone consultations of patients with inflammatory bowel disease. A medical record survey was conducted at a clinic in Japan for 1 year. Telephone consultation sheets recorded by nurses for calls with the patients or their relatives were reviewed. Content analysis was used to summarize the telephone consultation content. Consultations were categorized into 8 categories. Coding was conducted by 2 independent researchers. Concordance rates were evaluated using kappa coefficients. We analyzed 476 sheets. A total of 229 participants consulted the clinic at least once. The mean number of consultations per person was 2.1. Of these patients, 96 (40.9%) had ulcerative colitis. The kappa coefficient was 0.89. The most frequent consultation was “Consultation on worsening health: Inflammatory bowel disease is likely to have worsened” (42.0%). The second most frequent response was “Consultation or progress report on a worsening health condition: The disease is unlikely to have worsened” (19.8%). For consultations related to worsening the disease, it would be useful to assess symptoms over the phone using a disease activity index to ascertain the degree of worsening and to develop a screening tool for determining whether patients can continue remote support or require face-to-face consultation.
Relative Change in Donor-Derived Cell-free DNA is Superior to Absolute Values for Diagnosis of Acute Lung Allograft Dysfunction
Authors: Trindade Anil J. , Chapin Kaitlyn C. , Gray Jennifer N. , Furuya Yuka , Mullican Amy , Hoy Haley , Demarest Caitlin T. , Robbins Ivan M. , Bacchetta Matthew , Erasmus David B. , Shaver Ciara M.
Published: May 2023

Background.

Donor-derived cell-free DNA (dd-cfDNA%) is a biomarker of early acute lung allograft dysfunction (ALAD), with a value of ≥1.0% indicating injury. Whether dd-cfDNA% is a useful biomarker in patients >2 y posttransplant is unknown. Our group previously demonstrated that median dd-cfDNA% in lung recipients ≥2 y posttransplant without ALAD was 0.45%. In that cohort, biologic variability of dd-cfDNA% was estimated by a reference change value (RCV) of 73%, suggesting that change exceeding 73% may be pathologic. In this study, we aimed to determine whether dd-cfDNA% variability or absolute thresholds are optimal for detecting ALAD.

Methods.

We prospectively measured plasma dd-cfDNA% every 3 to 4 mo in patients ≥2 y post–lung transplant. ALAD was defined as infection, acute cellular rejection, possible antibody-mediated rejection, or change in forced expiratory volume in 1 s >10%, and was adjudicated retrospectively. We analyzed area under the curve for RCV and absolute dd-cfDNA% and reported performance of RCV ≥73% versus absolute value >1% for discriminating ALAD.

Results.

Seventy-one patients had ≥2 baseline measurements of dd-cfDNA%; 30 developed ALAD. RCV of dd-cfDNA% at ALAD had a greater area under the receiver operator characteristic curve than absolute dd-cfDNA% values (0.87 versus 0.69, P = 0.018). Test characteristics of RCV >73% for ALAD diagnosis were sensitivity 87%, specificity 78%, positive predictive value 74%, and negative predictive value 89%. In contrast, dd-cfDNA% ≥1% had sensitivity 50%, specificity 78%, positive predictive value 63%, and negative predictive value 68%.

Conclusions.

Relative change in dd-cfDNA% has improved test characteristics for diagnosing ALAD compared with absolute values.
White matter volume and myelin oligodendrocyte glycoprotein (MOG) microsatellites in pediatric obsessive-compulsive disorder
Authors: Zai Gwyneth , Zai Clement C. , Arnold Paul D. , Richter Margaret A. , Hanna Gregory L. , Rosenberg David , Kennedy James L.
Published: May 2023

The myelin oligodendrocyte glycoprotein (MOG) gene plays an important role in myelination and has been implicated in the genetics of white matter changes in obsessive-compulsive disorder (OCD). We examined the association between variations of two microsatellite markers across MOG for association and total white matter volume as measured using volumetric MRI in 37 pediatric OCD patients 7–18 years. We compared white matter volumes between microsatellite allele groups using analysis of covariance with covariates of age, gender, and total intracranial volume. After controlling for multiple comparisons, a significant relationship was detected between MOG (TAAA)n and increased total white matter volume (P = 0.018–0.028). Although preliminary, our findings provide further support for the involvement of MOG in OCD.
Modelling animal contests based on spatio-temporal dynamics
Authors: Haluts Amir , Jordan Alex , Gov Nir S.
Published: May 2023

We present a general theoretical model for the spatio-temporal dynamics of animal contests. Inspired by interactions between physical particles, the model is formulated in terms of effective interaction potentials, which map typical elements of contest behaviour into empirically verifiable rules of contestant motion. This allows us to simulate the observable dynamics of contests in various realistic scenarios, notably in dyadic contests over a localized resource. Assessment strategies previously formulated in game-theoretic models, as well as the effects of fighting costs, can be described as variations in our model’s parameters. Furthermore, the trends of contest duration associated with these assessment strategies can be derived and understood within the model. Detailed description of the contestants’ motion enables the exploration of spatio-temporal properties of asymmetric contests, such as the emergence of chase dynamics. Overall, our framework aims to bridge the growing gap between empirical capabilities and theory in this widespread aspect of animal behaviour.
Eggshell composition and surface properties of avian brood-parasitic species compared with non-parasitic species
Authors: McClelland Stephanie C. , Attard Marie R. G. , Bowen James , Horrocks Nicholas P. C. , Jamie Gabriel A. , Dixit Tanmay , Spottiswoode Claire N. , Portugal Steven J.
Published: May 2023

The eggs of avian obligate brood-parasitic species have multiple adaptations to deceive hosts and optimize development in host nests. While the structure and composition of the eggshell in all birds is essential for embryo growth and protection from external threats, parasitic eggs may face specific challenges such as high microbial loads, rapid laying and ejection by the host parents. We set out to assess whether eggshells of avian brood-parasitic species have either (i) specialized structural properties, to meet the demands of a brood-parasitic strategy or (ii) similar structural properties to eggs of their hosts, due to the similar nest environment. We measured the surface topography (roughness), wettability (how well surfaces repel water) and calcium content of eggshells of a phylogenetically and geographically diverse range of brood-parasitic species (representing four of the seven independent lineages of avian brood-parasitic species), their hosts and close relatives of the parasites. These components of the eggshell structure have been demonstrated previously to influence such factors as the risk of microbial infection and overall shell strength. Within a phylogenetically controlled framework, we found no overall significant differences in eggshell roughness, wettability and calcium content between (i) parasitic and non-parasitic species, or (ii) parasitic species and their hosts. Both the wettability and calcium content of the eggs from brood-parasitic species were not more similar to those of their hosts' eggs than expected by chance. By contrast, the mean surface roughness of the eggs of brood-parasitic species was more similar to that of their hosts’ eggs than expected by chance, suggesting brood-parasitic species may have evolved to lay eggs that match the host nest environment for this trait. The lack of significant overall differences between parasitic and non-parasitic species, including hosts, in the traits we measured, suggests that phylogenetic signal, as well as general adaptations to the nest environment and for embryo development, outweigh any influence of a parasitic lifestyle on these eggshell properties.
Gender bias in video game dialogue
Authors: Rennick Stephanie , Clinton Melanie , Ioannidou Elena , Oh Liana , Clooney Charlotte , T. E. , Healy Edward , Roberts Seán G.
Published: May 2023

Gender biases in fictional dialogue are well documented in many media. In film, television and books, female characters tend to talk less than male characters, talk to each other less than male characters talk to each other, and have a more limited range of things to say. Identifying these biases is an important step towards addressing them. However, there is a lack of solid data for video games, now one of the major mass media which has the ability to shape conceptions of gender and gender roles. We present the
Video Game Dialogue Corpus
, the first large-scale, consistently coded corpus of video game dialogue, which makes it possible for the first time to measure and monitor gender representation in video game dialogue. It demonstrates that there is half as much dialogue from female characters as from male characters. Some of this is due to a lack of female characters, but there are also biases in who female characters speak to, and what they say. We make suggestions for how game developers can avoid these biases to make more inclusive games.
Interaction of the mechanosensitive microswimmer
Paramecium
with obstacles
Authors: Escoubet Nicolas , Brette Romain , Pontani Lea-Laetitia , Prevost Alexis Michel
Published: May 2023

In this work, we report investigations of the swimming behaviour of
Paramecium tetraurelia
, a unicellular microorganism, in micro-engineered pools that are decorated with thousands of cylindrical pillars. Two types of contact interactions are measured, either passive scattering of
Paramecium
along the obstacle or avoiding reactions (ARs), characterized by an initial backward swimming upon contact, followed by a reorientation before resuming forward motion. We find that ARs are only mechanically triggered approximately 10% of the time. In addition, we observe that only a third of all ARs triggered by contact are instantaneous while two-thirds are delayed by approximately 150 ms. These measurements are consistent with a simple electrophysiological model of mechanotransduction composed of a strong transient current followed by a persistent one upon prolonged contact. This is in apparent contrast with previous electrophysiological measurements where immobilized cells were stimulated with thin probes, which showed instantaneous behavioural responses and no persistent current. Our findings highlight the importance of ecologically relevant approaches to unravel the motility of mechanosensitive microorganisms in complex environments.
Modelling communication-enabled traffic interactions
Authors: Siebinga O. , Zgonnikov A. , Abbink D. A.
Published: May 2023

A major challenge for autonomous vehicles is handling interactions with human-driven vehicles—for example, in highway merging. A better understanding and computational modelling of human interactive behaviour could help address this challenge. However, existing modelling approaches predominantly neglect communication between drivers and assume that one modelled driver in the interaction responds to the other, but does not actively influence their behaviour. Here, we argue that addressing these two limitations is crucial for the accurate modelling of interactions. We propose a new computational framework addressing these limitations. Similar to game-theoretic approaches, we model a joint interactive system rather than an isolated driver who only responds to their environment. Contrary to game theory, our framework explicitly incorporates communication between two drivers and bounded rationality in each driver’s behaviours. We demonstrate our model’s potential in a simplified merging scenario of two vehicles, illustrating that it generates plausible interactive behaviour (e.g. aggressive and conservative merging). Furthermore, human-like gap-keeping behaviour emerged in a car-following scenario directly from risk perception without the explicit implementation of time or distance gaps in the model’s decision-making. These results suggest that our framework is a promising approach to interaction modelling that can support the development of interaction-aware autonomous vehicles.