bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference genome for the California ribbed mussel,Mytilus californianus, an ecosystem engineer
Authors: Paggeot Lisa X , DeBiasse Melissa B , Escalona Merly , Fairbairn Colin , Marimuthu Mohan P A , Nguyen Oanh , Sahasrabudhe Ruta , Dawson Michael N 
Published: August 2022

AbstractThe California ribbed mussel, Mytilus californianus, is an ecosystem engineer crucial for the survival of many marine species inhabiting the intertidal zone of California. Here, we describe the first reference genome for M. californianus and compare it to previously published genomes from three other Mytilus species: M. edulis, M. coruscus, and M. galloprovincialis. The M. californianus reference genome is 1.65 Gb in length, with N50 sequence length of 118 Mb, and an estimated 86.0% complete single copy genes. Compared with the other three Mytilus species, the M. californianus genome assembly is the longest, has the highest N50 value, and the highest percentage complete single copy genes. This high-quality genome assembly provides a foundation for population genetic analyses that will give insight into future conservation work along the coast of California.
Neural correlates in functional brain mapping among breast cancer survivors receiving different chemotherapy regimens: a qEEG/HEG-based investigation
Authors: Vasaghi Gharamaleki Maryam , Mousavi Seyedeh Zahra , Owrangi Maryam , Gholamzadeh Mohammad Javad , Kamali Ali-Mohammad , Dehghani Mehdi , Chakrabarti Prasun , Nami Mohammad 
Published: August 2022

Abstract

Background
Post-chemotherapy cognitive impairment commonly known as ‘chemobrain’ or ‘chemofog’ is a well-established clinical disorder affecting various cognitive domains including attention, visuospatial working memory, executive function, etc. Although several studies have confirmed the chemobrain in recent years, scant experiments have evaluated the potential neurotoxicity of different chemotherapy regimens and agents. In this study, we aimed to evaluate the extent of attention deficits, one of the commonly affected cognitive domains, among breast cancer patients treated with different chemotherapy regimens through neuroimaging techniques.

Methods
Breast cancer patients treated with two commonly prescribed chemotherapy regimens, Adriamycin, Cyclophosphamide and Taxol and Taxotere, Adriamycin and Cyclophosphamide, and healthy volunteers were recruited. Near-infrared hemoencephalography and quantitative electroencephalography assessments were recorded for each participant at rest and during task performance to compare the functional cortical changes associated with each chemotherapy regimen.

Results
Although no differences were observed in hemoencephalography results across groups, the quantitative electroencephalography analysis revealed increased power of high alpha/low beta in left fronto-centro-parietal regions involved in dorsal and ventral attention networks in the Adriamycin, Cyclophosphamide and Taxol-treated group compared with the Taxotere, Adriamycin and Cyclophosphamide and control group. The Adriamycin, Cyclophosphamide and Taxol-treated cases had the highest current source density values in dorsal attention network and ventral attention network and ventral attention network-related centers in 10 and 15 Hz associated with the lowest Z-scored Fast Fourier Transform coherence in the mentioned regions.

Conclusions
The negatively affected neurocognitive profile in breast cancer patients treated with the Adriamycin, Cyclophosphamide and Taxol regimen proposes presumably neurotoxic sequelae of this chemotherapy regimen as compared with the Taxotere, Adriamycin and Cyclophosphamide regimen.
The oversight of autonomous artificial intelligence: lessons from nurse practitioners as physician extenders
Authors: Morrell Walker , Shachar Carmel , Weiss Anthony P 
Published: August 2022

Abstract
The development of autonomous artificial intelligence (A-AI) products in health care raises novel regulatory challenges, including how to ensure their safety and efficacy in real-world settings. Supplementing a device-centered regulatory scheme with a regulatory scheme that considers A-AI products as a ‘physician extender’ may improve the real-world monitoring of these technologies and produce other benefits, such as increased access to the services offered by these products. In this article, we review the three approaches to the oversight of nurse practitioners, one type of physician extender, in the USA and extrapolate these approaches to produce a framework for the oversight of A-AI products. Under the framework, the US Food and Drug Administration would evaluate A-AI products and determine whether they are allowed to operate independently of physician oversight; required to operate under some physician oversight via a ‘collaborative protocol’ model; or required to operate under direct physician oversight via a ‘supervisory protocol’ model.
Medication Burden Among Pediatric Cancer Survivors: Analysis of a Population-Wide Electronic Database in Hong Kong
Authors: Ewig Celeste Lom-Ying , Hui Ka Ho , Lee Samantha Lai Ka , Leung Alex Wing Kwan , Wong Grace Lai-Hung , Li Chi Kong , Cheung Yin Ting 
Published: August 2022

AbstractBackgroundFew studies have evaluated the medication burden borne by survivors of pediatric cancer. This study aimed to describe the drug utilization pattern of chronic medications in a cohort of young pediatric cancer survivors.MethodsThis was a population-based study of patients diagnosed with cancer at age 18 years or younger between 2000 and 2013 in Hong Kong and who had survived at least 5 years postdiagnosis. The primary outcome is the use of any chronic medication (medications that were prescribed for ≥30 consecutive days within a 6-month period). Multivariable log-binomial models were used to identify factors associated with chronic medication use. Kaplan-Meier analysis was used to present the cumulative proportion of survivors initiated on a chronic medication across time from cancer diagnosis.ResultsOf the 2444 survivors (median age = 22 years, interquartile range = 16-27 years), 669 (27.4%) required at least 1 chronic medication at least 5 years postdiagnosis. Survivors who developed a chronic health condition (CHC) had a 5.48 (95% confidence interval [CI] = 4.49 to 6.71) times higher risk of taking a chronic medication than those without CHC. At 10 years postdiagnosis, the cumulative proportion of survivors being initiated a chronic medication was 33.4% (95% CI = 31.1% to 35.6%) for the overall cohort. Higher cumulative proportions were observed in survivors with endocrine (74.6%, 95% CI = 68.4% to 79.6%), renal (68.8%, 95% CI = 54.2% to 78.7%), neurological (58.6%, 95% CI = 46.1% to 68.1%), and cardiovascular (54.7%, 95% CI = 44.0% to 63.4%) disorders.ConclusionSurvivors with certain CHCs had a higher risk of starting a prescription medication in the early phase of survivorship. Future studies include examining the impact of medication burden on survivors’ functional status.
Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer
Authors: McManus Jeffrey M , Vargas Roberto , Bazeley Peter S , Schumacher Fredrick R , Sharifi Nima 
Published: August 2022

Abstract

Background
The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes of castration-resistant prostate cancer and is associated with estrogen receptor positivity in postmenopausal breast cancer. Like breast cancer, endometrial cancer is another malignancy with hormone-dependent and hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate with hormone-independent cancer subtypes.

Methods
We employed a previously described classification of tumors in The Cancer Genome Atlas into genomic clusters. We determined HSD3B1 genotype frequencies by endometrial cancer genomic cluster and calculated the odds per adrenal-restrictive A allele for the largely hormone-independent copy-number (CN) high subtype vs other subtypes. An equivalent analysis was performed for the genomically similar, hormone-independent basal breast cancer subtype. Last, we performed survival analyses for UK Biobank participants with endometrial cancer by HSD3B1 genotype. All statistical tests were 2-sided.

Results
The adrenal-restrictive HSD3B1(1245A) allele was associated with the CN-high endometrial cancer subtype (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.14 to 2.32; P = .007). Similarly, HSD3B1(1245A) was associated with the basal breast cancer subtype (OR = 1.54, 95% CI = 1.13 to 2.08; P = .006). In the UK Biobank, endometrial cancer patients homozygous for HSD3B1(1245A) had worse overall (hazard ratio [HR] = 1.39, 95% CI = 1.16 to 1.68; P &lt; .001) and cancer-specific (HR = 1.39, 95% CI = 1.14 to 1.70; P = .001) survival, consistent with the A allele being enriched in the more aggressive CN-high subtype.

Conclusions
These findings suggest roles for adrenal-restrictive vs adrenal-permissive steroidogenesis, by way of rs1047303 genotype, in the development of and/or outcomes from at least 3 commonly hormone-associated types of cancer: prostate, breast, and endometrial.
Comparative functional RNA editomes of neural differentiation from human PSCs
Authors: Zhang Yu , Zhang Qu , Hou Yuhong , Wang Ran , Wang Yu 
Published: August 2022

Abstract
RNA editing is a fundamental mechanism that constitutes the epitranscriptomic complexity. A-to-G editing is the predominant type catalyzed by ADAR1 and ADAR2 in human. Using a CRISPR/Cas9 approach to knockout ADAR1/2, we identified a regulatory role of RNA editing in directed differentiation of human embryonic stem cells (hESCs) toward neural progenitor cells (NPCs). Genome-wide landscapes of A-to-G editing in hESCs and four derivative cell lineages representing all three germ layers and the extraembryonic cell fate were profiled, with a particular focus on neural differentiation. Furthermore, a bioinformatics-guided case study identified a potential functional editing event in ZYG11B 3ʹUTR that might play a role in regulation of NPC differentiation through gain of miR6089 targeting. Collectively, our study established the functional role of A-to-G RNA editing in neural lineage differentiation; illustrated the RNA editing landscapes of hESCs and NPC differentiation; and shed new light on molecular insights thereof.
Exploring metallicity-dependent rates of Type Ia supernovae and their impact on galaxy formation
Authors: Gandhi Pratik J , Wetzel Andrew , Hopkins Philip F , Shappee Benjamin J , Wheeler Coral , Faucher-Giguère Claude-André 
Published: August 2022

ABSTRACT
Type Ia supernovae are critical for feedback and elemental enrichment in galaxies. Recent surveys like the All-Sky Automated Survey for Supernova (ASAS-SN) and the Dark Energy Survey (DES) find that the specific supernova Ia rate at z ∼ 0 may be ≲20–50× higher in lower mass galaxies than at Milky Way-mass. Independently, observations show that the close-binary fraction of solar-type Milky Way stars is higher at lower metallicity. Motivated by these observations, we use the FIRE-2 cosmological zoom-in simulations to explore the impact of metallicity-dependent rate models on galaxies of $M_* \sim 10^7\!-\!10^{11}\, \rm {M}_{\odot }$. First, we benchmark our simulated star formation histories against observations, and show that the assumed stellar mass functions play a major role in determining the degree of tension between observations and metallicity-independent rate models, potentially causing ASAS-SN and DES observations to agree more than might appear. Models in which the supernova Ia rate increases with decreasing metallicity ($\propto Z^{-0.5 \,\, \rm {to} \,\, -1}$) provide significantly better agreement with observations. Encouragingly, these rate increases (≳10× in low-mass galaxies) do not significantly impact galaxy masses and morphologies, which remain largely unaffected except for our most extreme models. We explore implications for both [Fe/H] and [$\alpha /\rm {Fe}$] enrichment; metallicity-dependent rate models can improve agreement with the observed stellar mass–metallicity relations in low-mass galaxies. Our results demonstrate that a range of metallicity-dependent rate models are viable for galaxy formation and motivate future work.
Single base-pair resolution analysis of DNA binding motif with MoMotif reveals an oncogenic function of CTCF zinc-finger 1 mutation
Authors: Lebeau Benjamin , Zhao Kaiqiong , Jangal Maika , Zhao Tiejun , Guerra Maria , Greenwood Celia M T , Witcher Michael 
Published: August 2022

AbstractDefining the impact of missense mutations on the recognition of DNA motifs is highly dependent on bioinformatic tools that define DNA binding elements. However, classical motif analysis tools remain limited in their capacity to identify subtle changes in complex binding motifs between distinct conditions. To overcome this limitation, we developed a new tool, MoMotif, that facilitates a sensitive identification, at the single base-pair resolution, of complex, or subtle, alterations to core binding motifs, discerned from ChIP-seq data. We employed MoMotif to define the previously uncharacterized recognition motif of CTCF zinc-finger 1 (ZF1), and to further define the impact of CTCF ZF1 mutation on its association with chromatin. Mutations of CTCF ZF1 are exclusive to breast cancer and are associated with metastasis and therapeutic resistance, but the underlying mechanisms are unclear. Using MoMotif, we identified an extension of the CTCF core binding motif, necessitating a functional ZF1 to bind appropriately. Using a combination of ChIP-Seq and RNA-Seq, we discover that the inability to bind this extended motif drives an altered transcriptional program associated with the oncogenic phenotypes observed clinically. Our study demonstrates that MoMotif is a powerful new tool for comparative ChIP-seq analysis and characterising DNA-protein contacts.
Modeling splicing outcome by combining 5′ss strength and splicing regulatory elements
Authors: Müller Lisa , Ptok Johannes , Nisar Azlan , Antemann Jennifer , Grothmann Ramona , Hillebrand Frank , Brillen Anna-Lena , Ritchie Anastasia , Theiss Stephan , Schaal Heiner 
Published: August 2022

Abstract
Correct pre-mRNA processing in higher eukaryotes vastly depends on splice site recognition. Beyond conserved 5′ss and 3′ss motifs, splicing regulatory elements (SREs) play a pivotal role in this recognition process. Here, we present in silico designed sequences with arbitrary a priori prescribed splicing regulatory HEXplorer properties that can be concatenated to arbitrary length without changing their regulatory properties. We experimentally validated in silico predictions in a massively parallel splicing reporter assay on more than 3000 sequences and exemplarily identified some SRE binding proteins. Aiming at a unified ‘functional splice site strength’ encompassing both U1 snRNA complementarity and impact from neighboring SREs, we developed a novel RNA-seq based 5′ss usage landscape, mapping the competition of pairs of high confidence 5′ss and neighboring exonic GT sites along HBond and HEXplorer score coordinate axes on human fibroblast and endothelium transcriptome datasets. These RNA-seq data served as basis for a logistic 5′ss usage prediction model, which greatly improved discrimination between strong but unused exonic GT sites and annotated highly used 5′ss. Our 5′ss usage landscape offers a unified view on 5′ss and SRE neighborhood impact on splice site recognition, and may contribute to improved mutation assessment in human genetics.
Nonlinear manipulation and analysis of large DNA datasets
Authors: Cui Meiying , Zhao Xueping , Reddavide Francesco V , Gaillez Michelle Patino , Heiden Stephan , Mannocci Luca , Thompson Michael , Zhang Yixin 
Published: August 2022

AbstractInformation processing functions are essential for organisms to perceive and react to their complex environment, and for humans to analyze and rationalize them. While our brain is extraordinary at processing complex information, winner-take-all, as a type of biased competition is one of the simplest models of lateral inhibition and competition among biological neurons. It has been implemented as DNA-based neural networks, for example, to mimic pattern recognition. However, the utility of DNA-based computation in information processing for real biotechnological applications remains to be demonstrated. In this paper, a biased competition method for nonlinear manipulation and analysis of mixtures of DNA sequences was developed. Unlike conventional biological experiments, selected species were not directly subjected to analysis. Instead, parallel computation among a myriad of different DNA sequences was carried out to reduce the information entropy. The method could be used for various oligonucleotide-encoded libraries, as we have demonstrated its application in decoding and data analysis for selection experiments with DNA-encoded chemical libraries against protein targets.
A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics
Authors: Kumthekar Priya U , Avram Michael J , Lassman Andrew B , Lin Nancy U , Lee Eudocia , Grimm Sean A , Schwartz Margaret , Bell Burdett Kirsten L , Lukas Rimas V , Dixit Karan , Perron Isabella , Zhang Hui , Gradishar William J , Pentsova Elena I , Jeyapalan Suriya , Groves Morris D , Melisko Michelle , Raizer Jeffrey J 
Published: August 2022

AbstractBackgroundPatients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD).MethodsThis multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer.ResultsIntrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2–19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2–20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations.ConclusionThis study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes
Authors: Yuan Edith , Liu Kristie , Lee Justin , Tsung Kathleen , Chow Frances , Attenello Frank J 
Published: August 2022

AbstractGlioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 200 nucleotides that have been implicated to mediate various GBM pathologies, including chemoresistance. In this review, we aim to frame the TMZ response in GBM via exploration of the lncRNAs mediating three major mechanisms of TMZ resistance: (1) regulation of the DNA damage response, (2) maintenance of glioma stem cell identity, and (3) exploitation of hypoxia-associated responses.
Physician Payments from Pharmaceutical Companies Related to Cancer Drugs
Authors: Mitchell Aaron P , Mishra Meza Akriti , Trivedi Niti U , Bach Peter B , Gönen Mithat 
Published: August 2022

AbstractBackgroundDrug manufacturers claim that the purpose of financial payments to physicians is to facilitate education about new drugs. This claim suggests 2 testable hypotheses: payments should not be associated with drug revenue and payments for each drug should decline over time as physicians become educated.Materials and MethodsWe used open payments data on industry payments. We included payments for cancer drugs without generic/biosimilar competitors and used federal data sources to measure Medicare spending (a proxy for overall drug revenue) and a number of prescribers. We used generalized estimating equations (GEE) to model the drug-level association between industry payments and Medicare spending. Separately, we used GEE to estimate the change in payments with respect to the duration of time since initial FDA approval.ResultsThe sample included 89 drugs and 361 drug-year observations. The total value of industry payments for oncology drugs increased, from $53 333 854 in 2014 to $90 343 731 in 2018. There was no association between log-transformed mean, per-physician industry payments, and per-physician Medicare spending (estimate −0.001, 95%CI, −0.005 to 0.004). Payments for individual drugs decreased over time; estimated payments in the subsequent year for a drug with mean, per-physician payments of $1000 in the index year was: $681* for drugs 0-4 years since approval, $825 for 5-9 years, and $679* for ≥10 years (*P &lt; .05).ConclusionsAlthough industry-sponsored education may also serve marketing purposes, the absence of association between industry payments and Medicare spending and the decline in payments subsequent to approval are consistent with claims that industry payments function to facilitate physician education.