bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Big Lie: discursive risk analysis and wildland firefighter safety in the Western United States
Authors: Durbin Trevor J , Bendixsen Casper G , Neely Amber A , Strauss Sarah 
Published: October 2023

Abstract
While increased length and intensity of wildfire seasons in many places have led to more concern about wildland firefighter safety, we believe ethnography has been underutilized as a method within this domain. In response, we begin building a shared idiom for ethnographic engagement with wildland firefighter safety and similar occupations. We draw on ethnographic approaches to late industrialism to develop a method called discursive risk analysis (DRA) as an initial stage in a broader collaborative and generative research practice. By collaborative, we mean cooperation among stakeholder, disciplinary, professional, and other groups. We use DRA to analyse ethnographic data and documentary sources relevant to discussions of ‘the Big Lie’ among firefighters and agency leadership. The Big Lie is a term that both firefighters and agency leaders used to suggest that wildland firefighters are being harmed by agency discourse that says firefighters will be kept safe despite the unavoidable danger of the job. It is important to the Big Lie discussion that this harm is conceptualized by firefighters as discursively driven, necessitating a research method attentive to discourse. Discursive Risk Analysis of the Big Lie discussion suggests two discursive gaps that may result in two discursive risks. The first gap, found in agency discourse, is that ‘everyone knows the job is dangerous’ but ‘zero fatalities is a reasonable goal.’ This gap is associated with a discursive risk, a possible decrease in trust among wildland firefighters in agency leadership. The second gap, observed in firefighter discourse, is that ‘the job is dangerous’ but ‘no one will get hurt today.’ This gap is associated with another discursive risk, the possibility of decreased situational awareness. Finally, we clarify each of these gaps and risks through two anthropological concepts (the Sapir–Whorf hypothesis and the public secret) that can bring new perspectives to discussions about institutional cultures of health and safety.
A practical assembly guideline for genomes with various levels of heterozygosity
Authors: Mochizuki Takako , Sakamoto Mika , Tanizawa Yasuhiro , Nakayama Takuro , Tanifuji Goro , Kamikawa Ryoma , Nakamura Yasukazu 
Published: October 2023

Abstract
Although current long-read sequencing technologies have a long-read length that facilitates assembly for genome reconstruction, they have high sequence errors. While various assemblers with different perspectives have been developed, no systematic evaluation of assemblers with long reads for diploid genomes with varying heterozygosity has been performed. Here, we evaluated a series of processes, including the estimation of genome characteristics such as genome size and heterozygosity, de novo assembly, polishing, and removal of allelic contigs, using six genomes with various heterozygosity levels. We evaluated five long-read-only assemblers (Canu, Flye, miniasm, NextDenovo and Redbean) and five hybrid assemblers that combine short and long reads (HASLR, MaSuRCA, Platanus-allee, SPAdes and WENGAN) and proposed a concrete guideline for the construction of haplotype representation according to the degree of heterozygosity, followed by polishing and purging haplotigs, using stable and high-performance assemblers: Redbean, Flye and MaSuRCA.
Interpretable modeling of time-resolved single-cell gene–protein expression with CrossmodalNet
Authors: Yang Yongjian , Lin Yu-Te , Li Guanxun , Zhong Yan , Xu Qian , Cai James J 
Published: October 2023

Abstract
Cell-surface proteins play a critical role in cell function and are primary targets for therapeutics. CITE-seq is a single-cell technique that enables simultaneous measurement of gene and surface protein expression. It is powerful but costly and technically challenging. Computational methods have been developed to predict surface protein expression using gene expression information such as from single-cell RNA sequencing (scRNA-seq) data. Existing methods however are computationally demanding and lack the interpretability to reveal underlying biological processes. We propose CrossmodalNet, an interpretable machine learning model, to predict surface protein expression from scRNA-seq data. Our model with a customized adaptive loss accurately predicts surface protein abundances. When samples from multiple time points are given, our model encodes temporal information into an easy-to-interpret time embedding to make prediction in a time-point-specific manner, and is able to uncover noise-free causal gene–protein relationships. Using three publicly available time-resolved CITE-seq data sets, we validate the performance of our model by comparing it with benchmarking methods and evaluate its interpretability. Together, we show that our method accurately and interpretably profiles surface protein expression using scRNA-seq data, thereby expanding the capacity of CITE-seq experiments for investigating molecular mechanisms involving surface proteins.
The state of play in invasive species policy: Insights from invasive species laws and regulations in 21 US states
Authors: Reed Emily M X , Cathey Sara , Braswell Cameron , Agarwal Prashasti , Barney Jacob N , Brown Bryan L , Heminger Ariel , Kianmehr Ayda , Salom Scott , Schenk Todd , Sharma Gourav , Haak David C 
Published: October 2023

Abstract
Despite knowing the threats posed by biological invasions, governments struggle to effectively prevent and control invasive species. To mitigate the negative impacts of invasive species, a coordinated response, grounded in the best available science and attentive to the dynamics of policymaking, is critical. To evaluate patterns in state policies, we conducted a comprehensive survey of invasion-related laws and regulations in 21 eastern US states. We identified 706 policy chapters and found that most were enacted after 1970. The policies on terrestrial invasions outnumbered those for aquatic habitats, although the states farther east generally had a higher proportion of aquatic policies. Across all of the chapters, we identified 1200 unique species, 523 of which are listed as introduced or invasive. The state policies were inconsistent in which invasive species they name, especially for invertebrate taxa. Our conclusions indicate that effective, coordinated actions on invasives require improving communication, collaboration, and data sharing within and across domains.
Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5
Authors: Franchino Camilla Aurora , Brughera Martina , Baderna Valentina , De Ritis Daniele , Rocco Alessandra , Seneca Sara , Regal Luc , Podini Paola , D’Antonio Maurizio , Toro Camilo , Quattrini Angelo , Scalais Emmanuel , Maltecca Francesca 
Published: October 2023

Abstract
AFG3L2 is a mitochondrial protease exerting protein quality control in the inner mitochondrial membrane. Heterozygous AFG3L2 mutations cause spinocerebellar ataxia type 28 (SCA28) or dominant optic atrophy type 12 (DOA12), while biallelic AFG3L2 mutations result in the rare and severe spastic ataxia type 5 (SPAX5). The clinical spectrum of SPAX5 includes childhood-onset cerebellar ataxia, spasticity, dystonia and myoclonic epilepsy.
We previously reported that the absence or mutation of AFG3L2 leads to the accumulation of mitochondria-encoded proteins, causing the overactivation of the stress-sensitive protease OMA1, which over-processes OPA1, leading to mitochondrial fragmentation.
Recently, OMA1 has been identified as the pivotal player communicating mitochondrial stress to the cytosol via a pathway involving the inner mitochondrial membrane protein DELE1 and the cytosolic kinase HRI, thus eliciting the integrated stress response. In general, the integrated stress response reduces global protein synthesis and drives the expression of cytoprotective genes that allow cells to endure proteotoxic stress. However, the relevance of the OMA1-DELE1-HRI axis in vivo, and especially in a human CNS disease context, has been poorly documented thus far.
In this work, we demonstrated that mitochondrial proteotoxicity in the absence/mutation of AFG3L2 activates the OMA1-DELE1-HRI pathway eliciting the integrated stress response. We found enhanced OMA1-dependent processing of DELE1 upon depletion of AFG3L2. Also, in both skin fibroblasts from SPAX5 patients (including a novel case) and in the cerebellum of Afg3l2−/− mice we detected increased phosphorylation of the α-subunit of the eukaryotic translation initiation factor 2 (eIF2α), increased levels of ATF4 and strong upregulation of its downstream targets (Chop, Chac1, Ppp1r15a and Ffg21). Silencing of DELE1 or HRI in SPAX5 fibroblasts (where OMA1 is overactivated at basal state) reduces eIF2α phosphorylation and affects cell growth. In agreement, pharmacological potentiation of integrated stress response via Sephin-1, a drug that selectively inhibits the stress-induced eIF2alpha phosphatase GADD34 (encoded by Ppp1r15a), improved cell growth of SPAX5 fibroblasts and cell survival and dendritic arborization ex vivo in primary Afg3l2−/− Purkinje neurons. Notably, Sephin-1 treatment in vivo extended the lifespan of Afg3l2−/− mice, improved Purkinje neuron morphology, mitochondrial ultrastructure and respiratory capacity.
These data indicate that activation of the OMA1-DELE1-HRI pathway is protective in the context of SPAX5. Pharmacological tuning of the integrated stress response may represent a future therapeutic strategy for SPAX5 and other cerebellar ataxias caused by impaired mitochondrial proteostasis.
Antisense oligonucleotides restore excitability, GABA signalling and sodium current density in a Dravet syndrome model
Authors: Yuan Yukun , Lopez-Santiago Luis , Denomme Nicholas , Chen Chunling , O'Malley Heather A , Hodges Samantha L , Ji Sophina , Han Zhou , Christiansen Anne , Isom Lori L 
Published: October 2023

Abstract
Dravet syndrome is an intractable developmental and epileptic encephalopathy caused by de novo variants in SCN1A resulting in haploinsufficiency of the voltage-gated sodium channel Nav1.1. We showed previously that administration of the antisense oligonucleotide STK-001, also called ASO-22, generated using targeted augmentation of nuclear gene output technology to prevent inclusion of the nonsense-mediated decay, or poison, exon 20N in human SCN1A, increased productive Scn1a transcript and Nav1.1 expression and reduced the incidence of electrographic seizures and sudden unexpected death in epilepsy in a mouse model of Dravet syndrome. Here, we investigated the mechanism of action of ASO-84, a surrogate for ASO-22 that also targets splicing of SCN1A exon 20N, in Scn1a+/− Dravet syndrome mouse brain.
Scn1a +/− Dravet syndrome and wild-type mice received a single intracerebroventricular injection of antisense oligonucleotide or vehicle at postnatal Day 2. We examined the electrophysiological properties of cortical pyramidal neurons and parvalbumin-positive fast-spiking interneurons in brain slices at postnatal Days 21–25 and measured sodium currents in parvalbumin-positive interneurons acutely dissociated from postnatal Day 21–25 brain slices. We show that, in untreated Dravet syndrome mice, intrinsic cortical pyramidal neuron excitability was unchanged while cortical parvalbumin-positive interneurons showed biphasic excitability with initial hyperexcitability followed by hypoexcitability and depolarization block. Dravet syndrome parvalbumin-positive interneuron sodium current density was decreased compared to wild-type. GABAergic signalling to cortical pyramidal neurons was reduced in Dravet syndrome mice, suggesting decreased GABA release from interneurons. ASO-84 treatment restored action potential firing, sodium current density and GABAergic signalling in Dravet syndrome parvalbumin-positive interneurons. Our work suggests that interneuron excitability is selectively affected by ASO-84.
This new work provides critical insights into the mechanism of action of this antisense oligonucleotide and supports the potential of antisense oligonucleotide-mediated upregulation of Nav1.1 as a successful strategy to treat Dravet syndrome.
Role of insula and its subregions in progression from recent onset to chronic idiopathic tinnitus
Authors: Chen Qian , Lv Han , Wang Zhaodi , Li Xiaoshuai , Wang Xinghao , Huang Yuyou , Zhao Pengfei , Yang Zhenghan , Gong Shusheng , Wang Zhenchang 
Published: October 2023

Abstract
We determined the structural and functional alterations in the insula and its subregions in patients with idiopathic tinnitus in order to identify the neural changes involved in the progression from recent onset to chronic tinnitus. We recruited 24 recent-onset tinnitus patients, 32 chronic tinnitus patients and 36 healthy controls. We measured the grey matter volume and fractional amplitude of low-frequency fluctuation of the insula and its subregions and the functional connectivity within the insula and between the insula and the rest of the brain. Relationships between MRI and clinical characteristics were estimated using partial correlation analysis. Both recent-onset and chronic tinnitus patients showed decreased fractional amplitude of low-frequency fluctuation in the insula and its subregions, but only chronic tinnitus patients showed bilateral grey matter atrophy in the ventral anterior insula. Abnormal functional connectivity was detected in recent-onset and chronic tinnitus patients relative to the healthy controls, but functional connectivity differences between recent-onset and chronic tinnitus patients were found in only the auditory-related cortex, frontal cortex and limbic system. Functional alterations (fractional amplitude of low-frequency fluctuation and functional connectivity of the left ventral anterior insula), but not structural changes, were correlated with clinical severity. Bilateral grey matter atrophy in the ventral anterior insula decreased regional activities in the left ventral anterior insula and left posterior insula, and abnormal functional connectivity of the insula subregions with auditory and non-auditory areas were implicated in the progression from recent onset to chronic tinnitus. This suggests that tinnitus generation and development occur in a dynamic manner and involve aberrant multi-structural and functional (regional brain activity and abnormal functional connectivity) reorganization of the insula.
The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial
Authors: Schuster Jennifer E , Hamdan Lubna , Dulek Daniel E , Kitko Carrie L , Batarseh Einas , Haddadin Zaid , Stewart Laura S , Stahl Anna , Potter Molly , Rahman Herdi , Kalams Spyros A , Bocchini Claire E , Moulton Elizabeth A , Coffin Susan E , Ardura Monica I , Wattier Rachel L , Maron Gabriela , Grimley Michael , Paulsen Grant , Harrison Christopher J , Freedman Jason L , Carpenter Paul A , Englund Janet A , Munoz Flor M , Danziger-Isakov Lara , Spieker Andrew J , Halasa Natasha B ,   for the Pediatric HCT Flu Study, Goyal Rakesh , Thurber Joanne , McHenry Rendie , Bender Margaret , Barto Shari , Russo Michael , Shoemaker Lauren , Truong Kenny , Dvorak Christopher , Allison Kim J , Naik Swati , Williams Christopher , Blum Samantha , Lacombe Kirsten , Smith Hannah 
Published: October 2023

Abstract

Background
Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown.

Methods
This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3–17 years old who were 3–35 months post-allogeneic HCT, with each formulation administered twice, 28–42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28–42 days following each dose, and 138–222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3–5 and 6–35 months post-HCT, respectively.

Results
During 3 influenza seasons (2016–2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14–4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60–6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01–3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59–1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68–2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56–2.03]).

Conclusions
Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season.

Clinical Trials Registration
NCT02860039.
Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus
Authors: Stier Elizabeth A , Jain Mayuri , Joshi Himanshu , Darragh Teresa M , Deshmukh Ashish A , Lee Jeannette , Einstein Mark H , Jay Naomi , Berry-Lawhorn J Michael , Palefsky Joel M , Wilkin Timothy , Ellsworth Grant , French Audrey L , Barroso Luis F , Levine Rebecca , Guiot Humberto M , Rezaei M Katayoon , Chiao Elizabeth 
Published: October 2023

Abstract

Background
Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined.

Methods
We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results.

Results
In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4–31.3] and 13.4/100py [95% CI 8.0–22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1–7.4] and 4.2 [95% CI, 1.8–10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%–75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0–16.0).

Conclusions
Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.
Functional Assessment of Vitamin D Status by a Novel Metabolic Approach: The Low Vitamin D Profile Concept
Authors: Herrmann Markus , Zelzer Sieglinde , Cavalier Etienne , Kleber Marcus , Drexler-Helmberg Camilla , Schlenke Peter , Curcic Pero , Keppel Martin H , Enko Dietmar , Scharnagl Hubert , Pilz Stefan , März Winfried 
Published: October 2023

Abstract

Background
Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone.

Methods
25(OH)D, 24,25(OH)2D, and the VMR were determined in participants of the DESIRE (Desirable Vitamin D Concentrations, n = 2010) and the LURIC (Ludwigshafen Risk and Cardiovascular Health, n = 2456) studies. A low vitamin D metabolite profile (vitamin D insufficiency) was defined by a 24,25(OH)2D concentration &lt;1.2 ng/mL (&lt;3 nmol/L) and a VMR &lt;4%. Parathyroid hormone (PTH) and bone turnover markers were measured in both cohorts, whereas 10-year mortality data was recorded in LURIC only.

Results
The median age in DESIRE and LURIC was 43.3 and 63.8 years, respectively. Median 25(OH)D concentrations were 27.2 ng/mL (68.0 nmol/L) and 15.5 ng/mL (38.8 nmol/L), respectively. Serum 25(OH)D deficiency, defined as &lt;20.2 ng/mL (&lt;50 nmol/L), was present in 483 (24.0%) and 1701 (69.3%) participants of DESIRE and LURIC, respectively. In contrast, only 77 (3.8%) and 521 (21.2%) participants had a low vitamin D metabolite profile. Regardless of the serum 25(OH)D concentration, a low vitamin D metabolite profile was associated with a significantly higher PTH, accelerated bone metabolism, and higher all-cause mortality than an unremarkable vitamin D metabolite profile.

Conclusions
The personalized assessment of vitamin D status using a functional approach better identifies patients with accelerated bone metabolism and increased mortality than the use of a fixed 25(OH)D cutoff of 20 ng/mL (50 nmol/L).
Percutaneous mitral and tricuspid edge-to-edge repair as a bridge therapy to heart transplantation in advanced heart failure secondary to human immunodeficiency virus: a case report
Authors: Aquino-Bruno Heberto , Andrade-Cuellar Elias Noel , Morales-Portano Julieta D , Alcántara-Meléndez Marco Antonio 
Published: October 2023

Abstract

Background
Patients with end-stage heart failure (HF) and severe pulmonary hypertension (PH) are not eligible for heart transplant due to high mortality risk. Percutaneous interventions as edge-to-edge repair of the mitral/tricuspid valves are a safe and effective therapy as a bridge for transplantation in patients who have contraindications to heart transplantations (HTs).

Case summary
A 44-year-old man with a previous diagnosis of infection by human immunodeficiency virus (HIV) was admitted at the emergency room for exertional dyspnoea. He was diagnosed with a decompensated heart failure with reduced ejection fraction (HFrEF), severe mitral and tricuspid regurgitation, and high probability of PH. He presented poor response to guided medical treatment, even after implantable cardiac resynchronization therapy defibrillator (CRT-D). He was listed for a cardiac transplant, but after right catheterization, he was not an ideal candidate for transplantation, so it was decided to undergo percutaneous mitral and tricuspid edge-to-edge repair as a bridge to transplantation. The post-operative course was uneventful, with significant improvement in New York Heart Association functional class. The patient underwent a successful heart transplant 10 months after the procedure.

Discussion
In patients with advanced HF due to HIV, HT is an adequate treatment option. When there are functional mitral and tricuspid regurgitation and severe PH, despite optimal treatment according to current guidelines, percutaneous mitral and tricuspid repair therapy appears to be safe and effective for control of severe PH as a bridge measure for cardiac transplantation.