bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Temperature X-ray Microanalysis Sheds New Light on Mineral Nutrition Aspects of Insect Leaf Galling
Authors: Fernando Denise R , Green Peter T , Marshall Alan T 
Published: February 2024

Abstract
Manipulation of host plant physiology by leaf-galling insects is a multifaceted process. Among fundamental knowledge gaps surrounding this scientifically intriguing phenomenon is the appropriation of plant mineral nutrients and moisture for galling advantage. Small, soluble mineral ions and watery cell contents in dense gall tissues risk disruption during routine sample preparations. In this study, an X-ray microanalysis was applied to investigate gall mineral nutrition. Morphologically diverse leaf galls were sampled from three Australian rainforest tree species. Using cryo-analytical scanning electron microscopy, real-time X-ray analytical maps of cellular mineral nutrients and water were integrated with anatomical images of gall and leaf cross-sectional surfaces. A comparison of host-leaf and gall anatomies bore direct evidence of drastic changes to leaf cells through the galling process. Distinct “wet” and “dry” regions within galls were anatomically and/or chemically differentiated, suggesting specific functionality. “Wet” regions comprising hydrated cells including soft gall-cavity linings where larvae are known to feed contained soluble plant mineral nutrients, while C-rich “dry” tissues largely devoid of mineral nutrients likely contribute structural support. Mapping immobile nutrients such as Mn may provide a means of “matching” specific gall cell types to those in ungalled host-leaf tissues. The findings here provided otherwise inaccessible insights into leaf-gall mineral nutrition.
Association Analysis Provides Insights into Plant Mitonuclear Interactions
Authors: Lian Qun , Li Shuai , Kan Shenglong , Liao Xuezhu , Huang Sanwen , Sloan Daniel B , Wu Zhiqiang 
Published: February 2024

Abstract
Cytonuclear interaction refers to the complex and ongoing process of coevolution between nuclear and organelle genomes, which are responsible for cellular respiration, photosynthesis, lipid metabolism, etc. and play a significant role in adaptation and speciation. There have been a large number of studies to detect signatures of cytonuclear interactions. However, identification of the specific nuclear and organelle genetic polymorphisms that are involved in these interactions within a species remains relatively rare. The recent surge in whole genome sequencing has provided us an opportunity to explore cytonuclear interaction from a population perspective. In this study, we analyzed a total of 3,439 genomes from 7 species to identify signals of cytonuclear interactions by association (linkage disequilibrium) analysis of variants in both the mitochondrial and nuclear genomes across flowering plants. We also investigated examples of nuclear loci identified based on these association signals using subcellular localization assays, gene editing, and transcriptome sequencing. Our study provides a novel perspective on the investigation of cytonuclear coevolution, thereby enriching our understanding of plant fitness and offspring sterility.
The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage
Authors: Castaño Bryan A , Schorer Sabrina , Guo Yitian , Calzetta Nicolás L , Gottifredi Vanesa , Wiesmüller Lisa , Biber Stephanie 
Published: February 2024

Abstract
It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate. Given that the levels of p53 trigger non-binary rheostat-like functions in response to stress or during differentiation, we explore the relevance of the p53 levels for its DDT functions at the fork. We show that subtle changes in p53 levels modulate the contribution of some DDT factors including POLι, POLη, POLζ, REV1, PCNA, PRIMPOL, HLTF and ZRANB3 to the DNA replication rate. Our results suggest that the levels of p53 are central to coordinate the balance between DDT pathways including (i) fork-deceleration by the ZRANB3-mediated fork reversal factor, (ii) POLι-p53-mediated fork-slowing, (iii) POLι- and POLη-mediated TLS and (iv) PRIMPOL-mediated fork-acceleration. Collectively, our study reveals the relevance of p53 protein levels for the DDT pathway choice in replicating cells.
All exons are not created equal—exon vulnerability determines the effect of exonic mutations on splicing
Authors: Holm Lise L , Doktor Thomas K , Flugt Katharina K , Petersen Ulrika S S , Petersen Rikke , Andresen Brage S 
Published: February 2024

Abstract
It is now widely accepted that aberrant splicing of constitutive exons is often caused by mutations affecting cis-acting splicing regulatory elements (SREs), but there is a misconception that all exons have an equal dependency on SREs and thus a similar vulnerability to aberrant splicing. We demonstrate that some exons are more likely to be affected by exonic splicing mutations (ESMs) due to an inherent vulnerability, which is context dependent and influenced by the strength of exon definition. We have developed VulExMap, a tool which is based on empirical data that can designate whether a constitutive exon is vulnerable. Using VulExMap, we find that only 25% of all exons can be categorized as vulnerable, whereas two-thirds of 359 previously reported ESMs in 75 disease genes are located in vulnerable exons. Because VulExMap analysis is based on empirical data on splicing of exons in their endogenous context, it includes all features important in determining the vulnerability. We believe that VulExMap will be an important tool when assessing the effect of exonic mutations by pinpointing whether they are located in exons vulnerable to ESMs.
Performing highly parallelized and reproducible GWAS analysis on biobank-scale data
Authors: Schönherr Sebastian , Schachtl-Riess Johanna F , Di Maio Silvia , Filosi Michele , Mark Marvin , Lamina Claudia , Fuchsberger Christian , Kronenberg Florian , Forer Lukas 
Published: February 2024

Abstract
Genome-wide association studies (GWAS) are transforming genetic research and enable the detection of novel genotype-phenotype relationships. In the last two decades, over 60 000 genetic associations across thousands of traits have been discovered using a GWAS approach. Due to increasing sample sizes, researchers are increasingly faced with computational challenges. A reproducible, modular and extensible pipeline with a focus on parallelization is essential to simplify data analysis and to allow researchers to devote their time to other essential tasks. Here we present nf-gwas, a Nextflow pipeline to run biobank-scale GWAS analysis. The pipeline automatically performs numerous pre- and post-processing steps, integrates regression modeling from the REGENIE package and supports single-variant, gene-based and interaction testing. It includes an extensive reporting functionality that allows to inspect thousands of phenotypes and navigate interactive Manhattan plots directly in the web browser. The pipeline is tested using the unit-style testing framework nf-test, a crucial requirement in clinical and pharmaceutical settings. Furthermore, we validated the pipeline against published GWAS datasets and benchmarked the pipeline on high-performance computing and cloud infrastructures to provide cost estimations to end users. nf-gwas is a highly parallelized, scalable and well-tested Nextflow pipeline to perform GWAS analysis in a reproducible manner.
Covert cortical processing: a diagnosis in search of a definition
Authors: Young Michael J , Fecchio Matteo , Bodien Yelena G , Edlow Brian L 
Published: February 2024

Abstract
Historically, clinical evaluation of unresponsive patients following brain injury has relied principally on serial behavioral examination to search for emerging signs of consciousness and track recovery. Advances in neuroimaging and electrophysiologic techniques now enable clinicians to peer into residual brain functions even in the absence of overt behavioral signs. These advances have expanded clinicians’ ability to sub-stratify behaviorally unresponsive and seemingly unaware patients following brain injury by querying and classifying covert brain activity made evident through active or passive neuroimaging or electrophysiologic techniques, including functional MRI, electroencephalography (EEG), transcranial magnetic stimulation-EEG, and positron emission tomography. Clinical research has thus reciprocally influenced clinical practice, giving rise to new diagnostic categories including cognitive-motor dissociation (i.e. ‘covert consciousness’) and covert cortical processing (CCP). While covert consciousness has received extensive attention and study, CCP is relatively less understood. We describe that CCP is an emerging and clinically relevant state of consciousness marked by the presence of intact association cortex responses to environmental stimuli in the absence of behavioral evidence of stimulus processing. CCP is not a monotonic state but rather encapsulates a spectrum of possible association cortex responses from rudimentary to complex and to a range of possible stimuli. In constructing a roadmap for this evolving field, we emphasize that efforts to inform clinicians, philosophers, and researchers of this condition are crucial. Along with strategies to sensitize diagnostic criteria and disorders of consciousness nosology to these vital discoveries, democratizing access to the resources necessary for clinical identification of CCP is an emerging clinical and ethical imperative.
Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study
Authors: Tan Darrell H S , Pico Espinosa Oscar , Matelski John , Khera Shreya S , Qamar Attia , Persaud Reva , Hurst Jacklyn R , Ly Angel , Lam Jessica , Naghibosadat Maedeh , Christie Natasha , Hasso Maan , Gough Kevin , Taggart Linda R , Tan Charlie , Ostrowski Mario , Ma Huiting , Gray-Owen Scott D , Kozak Robert , Mishra Sharmistha 
Published: February 2024

Abstract

Background
Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce.

Methods
We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation.

Results
Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75–45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct &lt; 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0–47.9) and 22.4 (16.6–29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0–12.1) and 0 (0–0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P &gt; .05).

Conclusions
MPXV DNA detectability varies by specimen type and persists for over 3–4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.
A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma
Authors: Yu Shawn , Yu Menggang , Keane Barry , Mauro David M , Helft Paul R , Harris William P , Sanoff Hanna K , Johnson Matthew S , O’Neil Bert , McRee Autumn Jackson , Somasundaram Ashwin 
Published: February 2024

Abstract

Background
Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564).

Methods
Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability.

Results
Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6).

Conclusion
In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016).
p17/C18-ceramide–mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury
Authors: Karakaya Eda , Oleinik Natalia , Edwards Jazlyn , Tomberlin Jensen , Barker Randy Bent , Berber Burak , Ericsson Maria , Alsudani Habeeb , Ergul Adviye , Beyaz Semir , Lemasters John J , Ogretmen Besim , Albayram Onder 
Published: February 2024

Abstract
Repeat concussions (or repetitive mild traumatic brain injury [rmTBI]) are complex pathological processes consisting of a primary insult and long-term secondary complications and are also a prerequisite for chronic traumatic encephalopathy (CTE). Recent evidence implies a significant role of autophagy-mediated dysfunctional mitochondrial clearance, mitophagy, in the cascade of secondary deleterious events resulting from TBI. C18-ceramide, a bioactive sphingolipid produced in response to cell stress and damage, and its synthesizing enzyme (CerS1) are precursors to selective stress-mediated mitophagy. A transporter, p17, mediates the trafficking of CerS1, induces C18-ceramide synthesis in the mitochondrial membrane, and acts as an elimination signal in cell survival. Whether p17-mediated mitophagy occurs in the brain and plays a causal role in mitochondrial quality control in secondary disease development after rmTBI are unknown. Using a novel repetitive less-than-mild TBI (rlmTBI) injury paradigm, ablation of mitochondrial p17/C18-ceramide trafficking in p17 knockout (KO) mice results in a loss of C18-ceramide–induced mitophagy, which contributes to susceptibility and recovery from long-term secondary complications associated with rlmTBI. Using a ceramide analog with lipid-selenium conjugate drug, LCL768 restored mitophagy and reduced long-term secondary complications, improving cognitive deficits in rlmTBI-induced p17KO mice. We obtained a significant reduction of p17 expression and a considerable decrease of CerS1 and C18-ceramide levels in cortical mitochondria of CTE human brains compared with age-matched control brains. These data demonstrated that p17/C18-ceramide trafficking is an endogenous neuroprotective mitochondrial stress response following rlmTBI, thus suggesting a novel prospective strategy to interrupt the CTE consequences of concussive TBI.
Smelling things
Authors: Martina Giulia , Nudds Matthew 
Published: February 2024

Abstract
In this paper, we outline and defend a view on which in olfactory experience we can, and often do, smell ordinary things of various kinds—for instance, cookies, coffee, and cake burnings—and the olfactory properties they have. A challenge to this view are cases of smelling in the absence of the source of a smell, such as when a fishy smell lingers after the fish is gone. Such cases, many philosophers argue, show that what we perceive in olfactory experience are odour objects, and not ordinary things. On behalf of our opponent, we articulate a screening-off argument based on cases of lingering smells for the thesis that we do not smell ordinary things. We then develop an alternative account of these cases that is consistent with our view. In doing so, we call into question two claims that are typically built into the notion of an odour object.
Patient-reported outcome for physical function in idiopathic inflammatory myopathy
Authors: Keret Shiri , Lomanto Silva Raisa , Chandra Tanya , Sharma Akanksha , Moghadam-Kia Siamak , Oddis Chester V , Aggarwal Rohit 
Published: February 2024

Abstract

Objectives
There is an unmet need to develop patient-reported outcomes measures for idiopathic inflammatory myopathies (IIM). We aimed to investigate the feasibility, compliance and psychometric properties of the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large US IIM population.

Methods
‘Myositis Patient Centered Tele-Research’ (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits [centre-based cohort (CBC)], and remotely using smartphone- and web-based technology [tele-research cohort (TRC)]. The CBC was further randomly divided (1:1 ratio) into a traditional local subcohort and a remote subcohort. Data collected included patient-reported outcomes and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months.

Results
A total of 120 IIM patients were enrolled (82 TRC/38 CBC, mean ± s.d. age 55 ± 13.4 years, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as subcohorts. PROMIS PF-20 showed strong test–retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and creatine kinase, as well as with most symptoms, and function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size.

Conclusions
PROMIS PF-20 demonstrates favourable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.
Comparison of the performance of two thermoluminescent dosimetry systems for the personal dose-equivalent Hp(10) measurement
Authors: Lu Fengfan , Li Wei , Jin Jing , Li Kui , Zhou Jinghua 
Published: February 2024

Abstract
The performance of two thermoluminescent dosimetry systems (RGD-3D and RE2000) manufactured in China and Finland was compared. Both of these dosimetry systems demonstrated satisfactory results as their performance met the requirements of the standard. The two dosimetry systems showed similar performance in the energy response. The RGD-3D dosimetry system performed better in nonlinear response, minimum detectable level and blind sample tests, whereas the RE2000 dosimetry system showed better stability.
How self-disclosure of negative experiences shapes prosociality?
Authors: Cheng Xiaojun , Wang Shuqi , Guo Bing , Wang Qiao , Hu Yinying , Pan Yafeng 
Published: February 2024

AbstractPeople frequently share their negative experiences and feelings with others. Little is known, however, about the social outcomes of sharing negative experiences and the underlying neural mechanisms. We addressed this dearth of knowledge by leveraging functional near-infrared spectroscopy (fNIRS) hyperscanning: while dyad participants took turns to share their own (self-disclosure group) or a stranger’s (non-disclosure group) negative and neutral experiences, their respective brain activity was recorded simultaneously by fNIRS. We observed that sharing negative (relative to neutral) experiences enhanced greater mutual prosociality, emotional empathy and interpersonal neural synchronization (INS) at the left superior frontal cortex in the self-disclosure group compared to the non-disclosure group. Importantly, mediation analyses further revealed that in the self-disclosure (but not non-disclosure) group, the increased emotional empathy and INS elicited by sharing negative experiences relative to sharing neutral experiences promoted the enhanced prosociality through increasing interpersonal liking. These results indicate that self-disclosure of negative experiences can promote prosocial behaviors via social dynamics (defined as social affective and cognitive factors, including empathy and liking) and shared neural responses. Our findings suggest that when people express negative sentiments, they incline to follow up with positive actions.
Sexual effects of commonly used recreational psychostimulants in women and the female rat model
Authors: Mott Maggie N , Goeders Nicholas E 
Published: February 2024

Abstract

Introduction
Recreational psychostimulants have been associated with increased sexual activity or changes in sexual function in women, but every drug in this class has not shown consistent sexual effects in scientific studies. Further, some studies in female animal models may recapitulate the effects observed in humans, while others produce conflicting results. Overall, though, published studies on the sexual effects of recreational stimulants in women are lacking.

Objectives
The objective of this manuscript was to review the published sexual effects of prominent recreational psychostimulants in women and in the female rat model.

Methods
Literature searches for “any years” were performed through PubMed and Google Scholar. Keywords for the searches included “amphetamine,” “methamphetamine,” “MDMA,” “ecstasy,” “3,4-methylenedioxymethamphetamine,” “cocaine,” “caffeine,” “sex,” “sexual,” “female,” and “women.” Studies in humans and using animal models were included.

Results
Older studies have shown that amphetamine produces a positive sexual effect in women, but often the sample size was too small to draw generalizable conclusions. Methamphetamine also has a positive effect on several sexual domains in women, as well as on vaginal lubrication. 3,4-Methylenedioxymethamphetamine may have a negative or positive effect on sexual activity, but often enhances the sensual aspects of sex. Though low doses of cocaine may heighten the sexual experience, most women who use cocaine experience negative sexual effects. Caffeine has been shown to enhance a physiological measure of arousal, vaginal blood flow, but based on our searches, no studies have investigated the subjective sexual effects of the drug.

Conclusion
Different recreational psychostimulants produce varying effects on sexual behavior and responses in women and female animal models, but more research is needed to understand these effects better.