bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas
Authors: Galbraith Kristyn , Garcia Mekka , Wei Siyu , Chen Anna , Schroff Chanel , Serrano Jonathan , Pacione Donato , Placantonakis Dimitris G , William Christopher M , Faustin Arline , Zagzag David , Barbaro Marissa , Eibl Maria Del Pilar Guillermo Prieto , Shirahata Mitsuaki , Reuss David , Tran Quynh T , Alom Zahangir , von Deimling Andreas , Orr Brent A , Sulman Erik P , Golfinos John G , Orringer Daniel A , Jain Rajan , Lieberman Evan , Feng Yang , Snuderl Matija 
Published: January 2024

Abstract

Background
Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma.

Methods
We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts.

Results
There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534).

Conclusions
The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.
Phase 1 trial of TPI 287, a microtubule stabilizing agent, in combination with bevacizumab in adults with recurrent glioblastoma
Authors: Goldlust Samuel A , Nabors Louis B , Hsu Sigmund , Mohile Nimish , Duic Paul J , Benkers Tara , Singer Samuel , Rao Mayank , Cappello Lori , Silberman Sandra L , Farmer George 
Published: January 2024

Abstract

Background
Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.

Methods
GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140–220 mg/m2 every 3 weeks and BEV 10 mg/kg every 2 weeks during 6-week cycles. An MRI was performed after each cycle, and treatment continued until progression as determined via response assessment in neuro-oncology criteria.

Results
Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral neuropathy were the most common treatment emergent adverse events. Dose-limiting toxicity was not observed, thus the MTD was not determined. Twenty-three patients were evaluable for median and 6-month progression-free survival, which were 5.5 months (mo) and 40%, respectively. Median and 12-month overall survival were 13.4 mo and 64%, respectively. The optimal phase 2 dose was determined to be 200 mg/m2.

Conclusions
TPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination.
Plasma Oxidative State Induced by Exercise in Young Heat-Not-Burn Cigarette Users
Authors: Takagi Aoi , Hamada Hironobu , Sekikawa Kiyokazu , Ueoka Hatsumi , Namba Haruchi , Sato Yoshinobu M , Kanda Naoto , Miyazaki Ryosuke 
Published: January 2024

Abstract

Introduction
Oxidative state, a risk factor for several diseases, is increased by habitual conventional cigarette (CC) smoking. Reports have demonstrated that heat-not-burn cigarettes (HNBCs), which have recently become popular among smokers, generate less oxidative state than CC in smokers with a long smoking history. However, no previous study has examined oxidative state in young HNBC users. Previously, we reported that exercise induces a greater oxidative state in young CC smokers than in never-smokers of similar age, but there was no difference in resting oxidative state. This study aimed to clarify the resting and exercise-induced oxidative states in young HNBC users, compared with those in never-smokers and CC users of similar age.

Methods
Healthy young never-smokers, HNBC users, and CC users were recruited, and they underwent the Wingate anaerobic test. Blood samples were collected before and after exercise, and the plasma hydroperoxide concentration, a marker of oxidative state, was measured.

Results
No significant differences in pre-exercise plasma hydroperoxide concentrations were detected among never-smokers, HNBC users, and CC users (n = 10 each). Plasma hydroperoxide concentration was significantly increased after exercise in all participants. The exercise induced a significant increase in plasma hydroperoxide concentration in HNBC users compared with that in never-smokers (p &lt; .005), but it was significantly decreased compared with that in CC users (p &lt; .01).

Conclusions
The use of HNBC increased exercise-induced plasma oxidative state compared with that in never-smokers, indicating that HNBC may lead to the risk of oxidative damage.

Implications
This study, for the first time, reports exercise-induced oxidative state in young HNBC users compared with never-smokers and CC users. The exercise-induced oxidative state in HNBC users was higher than that in never-smokers and lower than that in CC users. Our study suggests that the use of HNBCs increases the risk of acute oxidative damage.
Utility of Low-Dose Duvelisib for Advanced Mycosis Fungoides: A Single-Institution Study
Authors: Bazewicz Christopher , Verardi Nicolena , Akilov Oleg 
Published: January 2024

Abstract
Duvelisib, a small-molecule phosphatidylinositol 3-kinase-δ,γ inhibitor, has shown efficacy for mycosis fungoides (MF) at dosage ranges of 25-100 mg twice daily (BID), but with significant toxicity. We conducted a retrospective cohort study of patients with advanced MF treated with low-dose duvelisib (15 mg every other day to BID), in an effort to minimize toxicity. A total of 7 patients were included. The overall response rate on duvelisib was 71%, with the remaining patients maintaining stable disease. Mean modified Severity Weighted Assessment Tool score improved by 57.4% and mean percent body surface area involved improved by 52%. Median progression-free survival was 10.3 months. Adverse events occurred in 4 of 7 patients, the most common being fatigue (2/7; grades 1-2), nausea (2/7; grades 1-2), and transaminitis (2/7; grade 3). Overall, low-dose duvelisib showed efficacy for advanced MF with less toxicity, providing a rationale for its use as monotherapy and potentially combinatorial therapy.
Ribociclib-Induced Cutaneous Adverse Events in Metastatic HR+/HER2− Breast Cancer: Incidence, Multidisciplinary Management, and Prognostic Implication
Authors: Borroni Riccardo Giovanni , Bartolini Michela , Gaudio Mariangela , Jacobs Flavia , Benvenuti Chiara , Gerosa Riccardo , Tiberio Paola , Manara Sofia Ada Assunta Maria , Solferino Alessandra , Santoro Armando , De Sanctis Rita 
Published: January 2024

Abstract

Background
Ribociclib is approved for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC) treatment, in combination with endocrine therapy. Hematological, hepatic, and cardiac adverse events (AEs) emerged from pivotal trials, but little is known about cutaneous adverse events (CAEs).

Patients and Methods
We report data from a retrospective cohort study of all patients with HR+/HER2− ABC treated with ribociclib at Humanitas Cancer Center between June 2017 and December 2022. We recorded clinical-pathological data, the incidence, and treatment of ribociclib-related CAEs. These were evaluated according to the NCI-CTCAE v5.0 classification. Progression-free survival (PFS) was estimated by Kaplan-Meier method and the log-rank test was used to analyze differences between groups.

Results
Thirteen of 91 patients (14.3%) experienced treatment-related CAEs (mean time to the occurrence: 3.9 months). The most frequent CAEs were eczematous dermatitis (53.8%) and maculo-papular reaction (15.4%). Itch was reported by all 13 patients. The grade was G3 in 8 cases, G2 in 4, and G1 in 1. An integrated approach based on ribociclib dose modulation and dermatological interventions (oral antihistamine, moisturized cream, topical, and/or systemic steroids) could prevent ribociclib discontinuation in most patients. At a median follow-up of 20 months, the median PFS was 13 months (range, 1-66) with a better PFS curves for patients experiencing CAEs (P = .04).

Conclusion
We mapped frequency and types of ribociclib-induced CAEs. An interdisciplinary management of CAEs incorporated into routine care may reduce the rate of drug discontinuation thus potentially contributing to better long-term outcomes.
SUPPRESSOR OF MAX2 1-LIKE (SMXL) homologs are MAX2-dependent repressors of Physcomitrium patens growth
Authors: Guillory Ambre , Lopez-Obando Mauricio , Bouchenine Khalissa , Le Bris Philippe , Lécureuil Alain , Pillot Jean-Paul , Steinmetz Vincent , Boyer François-Didier , Rameau Catherine , de Saint Germain Alexandre , Bonhomme Sandrine 
Published: January 2024

Abstract
SUPPRESSOR OF MAX2 (SMAX)1-LIKE (SMXL) proteins are a plant-specific clade of type I HSP100/Clp-ATPases. SMXL genes are present in virtually all land plant genomes. However, they have mainly been studied in angiosperms. In Arabidopsis (Arabidopsis thaliana), 3 functional SMXL subclades have been identified: SMAX1/SMXL2, SMXL345, and SMXL678. Of these, 2 subclades ensure endogenous phytohormone signal transduction. SMAX1/SMXL2 proteins are involved in KAI2 ligand (KL) signaling, while SMXL678 proteins are involved in strigolactone (SL) signaling. Many questions remain regarding the mode of action of these proteins, as well as their ancestral roles. We addressed these questions by investigating the functions of the 4 SMXL genes in the moss Physcomitrium patens. We demonstrate that PpSMXL proteins are involved in the conserved ancestral MAX2-dependent KL signaling pathway and negatively regulate growth. However, PpSMXL proteins expressed in Arabidopsis cannot replace SMAX1 or SMXL2 function in KL signaling, whereas they can functionally replace SMXL4 and SMXL5 and restore root growth. Therefore, the molecular functions of SMXL proteins are conserved, but their interaction networks are not. Moreover, the PpSMXLC/D clade positively regulates SL signal transduction in P. patens. Overall, our data reveal that SMXL proteins in moss mediate crosstalk between the SL and KL signaling pathways.
Degradation of FATTY ACID EXPORT PROTEIN1 by RHOMBOID-LIKE PROTEASE11 contributes to cold tolerance in Arabidopsis
Authors: John Annalisa , Krämer Moritz , Lehmann Martin , Kunz Hans-Henning , Aarabi Fayezeh , Alseekh Saleh , Fernie Alisdair , Sommer Frederik , Schroda Michael , Zimmer David , Mühlhaus Timo , Peisker Helga , Gutbrod Katharina , Dörmann Peter , Neunzig Jens , Philippar Katrin , Neuhaus Horst Ekkehard 
Published: January 2024

Abstract
Plants need to acclimate to different stresses to optimize growth under unfavorable conditions. In Arabidopsis (Arabidopsis thaliana), the abundance of the chloroplast envelope protein FATTY ACID EXPORT PROTEIN1 (FAX1) decreases after the onset of low temperatures. However, how FAX1 degradation occurs and whether altered FAX1 abundance contributes to cold tolerance in plants remains unclear. The rapid cold-induced increase in RHOMBOID-LIKE PROTEASE11 (RBL11) transcript levels, the physical interaction of RBL11 with FAX1, the specific FAX1 degradation after RBL11 expression, and the absence of cold-induced FAX1 degradation in rbl11 loss-of-function mutants suggest that this enzyme is responsible for FAX1 degradation. Proteomic analyses showed that rbl11 mutants have higher levels of FAX1 and other proteins involved in membrane lipid homeostasis, suggesting that RBL11 is a key element in the remodeling of membrane properties during cold conditions. Consequently, in the cold, rbl11 mutants show a shift in lipid biosynthesis toward the eukaryotic pathway, which coincides with impaired cold tolerance. To test whether cold sensitivity is due to increased FAX1 levels, we analyzed FAX1 overexpressors. The rbl11 mutants and FAX1 overexpressor lines show superimposable phenotypic defects upon exposure to cold temperatures. Our re­sults show that the cold-induced degradation of FAX1 by RBL11 is critical for Arabidop­sis to survive cold and freezing periods.
Heritable, multinucleotide deletions in plants using viral delivery of a repair exonuclease and guide RNAs
Authors: Liu Degao , Myers Erik A , Xuan Shuya , Prichard Lynn E , Donahue Lilee I , Ellison Evan E , Starker Colby G , Voytas Daniel F 
Published: January 2024

Abstract
CRISPR/Cas9-mediated mutagenesis typically results in short insertion/deletion mutations, which are often too small to disrupt the function of cis-acting regulatory elements. Here, we describe a highly efficient in planta gene editing approach called VirTREX2-HLDel that achieves heritable multinucleotide deletions in both protein-coding genes and noncoding DNA regulatory elements. VirTREX2-HLDel uses RNA viruses to deliver both the 3 prime repair exonuclease 2 (TREX2) and single-guide RNAs. Our method enables recovery of multiplexed heritable deletions and increases the heritable gene editing frequency at poorly edited sites. We identified functional conservation and divergence of MICRORNA164 (miR164) in Nicotiana benthamiana and tomato (Solanum lycopersicum) using VirTREX2-HLDel and observed previously uncharacterized phenotypes in plants with large deletions at this locus. Our viral delivery method reduces the need for tissue culture and will accelerate the understanding of protein-coding and regulatory regions in plants.
Valsa mali effector Vm_04797 interacts with adaptor protein MdAP-2β to manipulate host autophagy
Authors: Sun Yubo , Luo Danyan , Liu Yuerong , Tu Wenyan , Che Runmin , Feng Hao , Huang Lili , Ma Fengwang , Liu Changhai 
Published: January 2024

Abstract
Apple Valsa canker, caused by the ascomycete fungus Valsa mali, employs virulence effectors to disturb host immunity and poses a substantial threat to the apple industry. However, our understanding of how V. mali effectors regulate host defense responses remains limited. Here, we identified the V. mali effector Vm_04797, which was upregulated during the early infection stage. Vm_04797, a secreted protein, suppressed Inverted formin 1 (INF1)-triggered cell death in Nicotiana benthamiana and performed virulence functions inside plant cells. Vm_04797 deletion mutants showed substantially reduced virulence toward apple. The adaptor protein MdAP-2β positively regulated apple Valsa canker resistance and was targeted and degraded by Vm_04797 via the ubiquitination pathway. The in vitro analysis suggested that Vm_04797 possesses E3 ubiquitin ligase activity. Further analysis revealed that MdAP-2β is involved in autophagy by interacting with Malus domestica autophagy protein 16 MdATG16 and promoting its accumulation. By degrading MdAP-2β, Vm_04797 inhibited autophagic flux, thereby disrupting the defense response mediated by autophagy. Our findings provide insights into the molecular mechanisms employed by the effectors of E3 ubiquitin ligase activity in ascomycete fungi to regulate host immunity.
ELONGATED HYPOTCOTYL5 and SPINE BASE SIZE1 together mediate light-regulated spine expansion in cucumber
Authors: Zhao Lijun , Fan Pengfei , Wang Yueling , Xu Nana , Zhang Minjuan , Chen Mingyue , Zhang Mengyao , Dou Junling , Liu Dongming , Niu Huanhuan , Zhu Huayu , Hu Jianbin , Sun Shouru , Yang Luming , Yang Sen 
Published: January 2024

Abstract
Plant trichome development is influenced by diverse developmental and environmental signals, but the molecular mechanisms involved are not well understood in most plant species. Fruit spines (trichomes) are an important trait in cucumber (Cucumis sativus L.), as they affect both fruit smoothness and commercial quality. Spine Base Size1 (CsSBS1) has been identified as essential for regulating fruit spine size in cucumber. Here, we discovered that CsSBS1 controls a season-dependent phenotype of spine base size in wild-type plants. Decreased light intensity led to reduced expression of CsSBS1 and smaller spine base size in wild-type plants, but not in the mutants with CsSBS1 deletion. Additionally, knockout of CsSBS1 resulted in smaller fruit spine base size and eliminated the light-induced expansion of spines. Overexpression of CsSBS1 increased spine base size and rescued the decrease in spine base size under low light conditions. Further analysis revealed that ELONGATED HYPOTCOTYL5 (HY5), a major transcription factor involved in light signaling pathways, directly binds to the promoter of CsSBS1 and activates its expression. Knockout of CsHY5 led to smaller fruit spine base size and abolished the light-induced expansion of spines. Taken together, our study findings have clarified a CsHY5–CsSBS1 regulatory module that mediates light-regulated spine expansion in cucumber. This finding offers a strategy for cucumber breeders to develop fruit with stable appearance quality under changing light conditions.
Perceptual integration of bodily and facial emotion cues in chimpanzees and humans
Authors: Heesen Raphaela , Kim Yena , Kret Mariska E , Clay Zanna 
Published: January 2024

Abstract
For highly visual species like primates, facial and bodily emotion expressions play a crucial role in emotion perception. However, most research focuses on facial expressions, while the perception of bodily cues is still poorly understood. Using a novel comparative priming eye-tracking design, we examined whether our close primate relatives, the chimpanzees (Pan troglodytes), and humans infer emotions from bodily cues through subsequent perceptual integration with facial expressions. In experiment 1, we primed chimpanzees with videos of bodily movements of unfamiliar conspecifics engaged in social activities of opposite valence (play and fear) against neutral control scenes to examine attentional bias toward succeeding congruent or incongruent facial expressions. In experiment 2, we assessed the same attentional bias in humans yet using stimuli showing unfamiliar humans. In experiment 3, humans watched the chimpanzee stimuli of experiment 1, to examine cross-species emotion perception. Chimpanzees exhibited a persistent fear-related attention bias but did not associate bodily with congruent facial cues. In contrast, humans prioritized conspecifics' congruent facial expressions (matching bodily scenes) over incongruent ones (mismatching). Nevertheless, humans exhibited no congruency effect when viewing chimpanzee stimuli, suggesting difficulty in cross-species emotion perception. These results highlight differences in emotion perception, with humans being greatly affected by fearful and playful bodily cues and chimpanzees being strongly drawn toward fearful expressions, regardless of the preceding bodily priming cue. These data advance our understanding of the evolution of emotion signaling and the presence of distinct perceptual patterns in hominids.
Detecting Artificial Intelligence-Generated Personal Statements in Professional Physical Therapist Education Program Applications: A Lexical Analysis
Authors: Hollman John H , Cloud-Biebl Beth A , Krause David A , Calley Darren Q 
Published: January 2024

Abstract

Objective
The objective of this study was to compare the lexical sophistication of personal statements submitted by professional physical therapist education program applicants with those generated by OpenAI’s Chat Generative Pretrained Transformer (ChatGPT).

Methods
Personal statements from 152 applicants and 20 generated by ChatGPT were collected, all in response to a standardized prompt. These statements were coded numerically, then analyzed with recurrence quantification analyses (RQAs). RQA indices including recurrence, determinism, max line, mean line, and entropy were compared with t-tests. A receiver operating characteristic curve analysis was used to examine discriminative validity of RQA indices to distinguish between ChatGPT and human-generated personal statements.

Results
ChatGPT-generated personal statements exhibited higher recurrence, determinism, mean line, and entropy values than did human-generated personal statements. The strongest discriminator was a 13.04% determinism rate, which differentiated ChatGPT from human-generated writing samples with 70% sensitivity and 91.4% specificity (positive likelihood ratio = 8.14). Personal statements with determinism rates exceeding 13% were 8 times more likely to have been ChatGPT than human generated.

Conclusion
Although RQA can distinguish artificial intelligence (AI)-generated text from human-generated text, it is not absolute. Thus, AI introduces additional challenges to the authenticity and utility of personal statements. Admissions committees along with organizations providing guidelines in professional physical therapist education program admissions should reevaluate the role of personal statements in applications.

Impact
As AI-driven chatbots like ChatGPT complicate the evaluation of personal statements, RQA emerges as a potential tool for admissions committees to detect AI-generated statements.