bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thoracic ultrasound influences physiotherapist’s clinical decision-making in respiratory management of critical care patients: a multicentre cohort study
Authors: Le Neindre Aymeric , Hansell Louise , Wormser Johan , Gomes Lopes Andreia , Diaz Lopez Carlos , Romanet Christophe , Choukroun Gerald , Nguyen Maxime , Philippart François , Guinot Pierre-Grégoire , Buscher Hergen , Bouhemad Bélaid , Ntoumenopoulos George 
Published: March 2022

BackgroundThe potential influence of thoracic ultrasound on clinical decision-making by physiotherapists has never been studied. The aim of this study was to assess the impact of thoracic ultrasound on clinical decision-making by physiotherapists for critical care patients.MethodsThis prospective, observational multicentre study was conducted between May 2017 and November 2020 in four intensive care units in France and Australia. All hypoxemic patients consecutively admitted were enrolled. The primary outcome was the net reclassification improvement (NRI), quantifying how well the new model (physiotherapist’s clinical decision-making including thoracic ultrasound) reclassifies subjects as compared with an old model (clinical assessment). Secondary outcomes were the factors associated with diagnostic concordance and physiotherapy treatment modification.ResultsA total of 151 patients were included in the analysis. The NRI for the modification of physiotherapist’s clinical decisions was—40% (95% CI (−56 to −22%), p=0.02). Among the cases in which treatment was changed after ultrasound, 41% of changes were major (n=38). Using a multivariate analysis, the physiotherapist’s confidence in their clinical diagnosis was associated with diagnostic concordance (adjusted OR=3.28 95% CI (1.30 to 8.71); p=0.014). Clinical diagnosis involving non-parenchymal conditions and clinical signs reflecting abolished lung ventilation were associated with diagnostic discordance (adjusted OR=0.06 95% CI (0.01 to 0.26), p<0.001; adjusted OR=0.26 95% CI (0.09 to 0.69), p=0.008; respectively).ConclusionThoracic ultrasound has a high impact on the clinical decision-making process by physiotherapists for critical care patients.Trial registration numberNCT02881814;https://clinicaltrials.gov.
Artificial neural network modelling of generalised parton distributions
Authors: Dutrieux H. , Grocholski O. , Moutarde H. , Sznajder P. 
Published: March 2022

AbstractWe discuss the use of machine learning techniques in effectively nonparametric modelling of generalised parton distributions (GPDs) in view of their future extraction from experimental data. Current parameterisations of GPDs suffer from model dependency that lessens their impact on phenomenology and brings unknown systematics to the estimation of quantities like Mellin moments. The new strategy presented in this study allows to describe GPDs in a way fulfilling theory-driven constraints, keeping model dependency to a minimum. Getting a better grip on the control of systematic effects, our work will help the GPD phenomenology to achieve its maturity in the precision era commenced by the new generation of experiments.
BERIS: An mBERT-based Emotion Recognition Algorithm from Indian Speech
Authors: Mehra Pramod , Verma Shashi Kant 
Published: March 2022

Emotions, the building blocks of the human intellect, play a vital role in Artificial Intelligence (AI). For a robust AI-based machine, it is important that the machine understands human emotions. COVID-19 has introduced the world to no-touch intelligent systems. With an influx of users, it is critical to create devices that can communicate in a local dialect. A multilingual system is required in countries like India, which has a large population and a diverse range of languages. Given the importance of multilingual emotion recognition, this research introduces BERIS, an Indian language emotion detection system. From the Indian sound recording, BERIS estimates both acoustic and textual characteristics. To extract the textual features, we used Multilingual Bidirectional Encoder Representations from Transformers. For acoustics, BERIS computes the Mel Frequency Cepstral Coefficients and Linear Prediction coefficients, and Pitch. The features extracted are merged in a linear array. Since the dialogues are of varied lengths, the data are normalized to have arrays of equal length. Finally, we split the data into training and validated set to construct a predictive model. The model can predict emotions from the new input. On all the datasets presented, quantitative and qualitative evaluations show that the proposed algorithm outperforms state-of-the-art approaches.
Differential Gain-of-Function Activity of Three p53 Hotspot Mutants In Vivo
Authors: Xiong Shunbin , Chachad Dhruv , Zhang Yun , Gencel-Augusto Jovanka , Sirito Mario , Pant Vinod , Yang Peirong , Sun Chang , Chau Gilda , Qi Yuan , Su Xiaoping , Whitley Elizabeth M. , El-Naggar Adel K. , Lozano Guillermina 
Published: March 2022

Abstract

The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance. To better understand the activities by which TP53 mutations, identified in Li–Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline Trp53R245W allele (contact mutation) and compared them with existing models with Trp53R172H (structural mutation) and Trp53R270H (contact mutation) alleles. Thymocytes from heterozygous mice showed that all three hotspot mutations exhibited similar inhibitory effects on wild-type p53 transcription in vivo, and tumors from these mice had similar levels of loss of heterozygosity. However, the overall survival of Trp53R245W/+ and Trp53R270H/+ mice, but not Trp53R172H/+ mice, was significantly shorter than that of Trp53+/− mice, providing strong evidence for p53-mutant–specific GOF contributions to tumor development. Furthermore, Trp53R245W/+ and Trp53R270H/+ mice had more osteosarcoma metastases than Trp53R172H/+ mice, suggesting that these two contact mutants have stronger GOF in driving osteosarcoma metastasis. Transcriptomic analyses using RNA sequencing data from Trp53R172H/+, Trp53R245W/+, and Trp53R270H/+ primary osteosarcomas in comparison with Trp53+/– indicated that GOF of the three mutants was mediated by distinct pathways. Thus, both the inhibitory effect of mutant over wild-type p53 and GOF activities of mutant p53 contributed to tumorigenesis in vivo. Targeting p53 mutant–specific pathways may be important for therapeutic outcomes in osteosarcoma.

Significance:
p53 hotspot mutants inhibit wild-type p53 similarly but differ in their GOF activities, with stronger tumor-promoting activity in contact mutants and distinct protein partners of each mutant driving tumorigenesis and metastasis.
Epigenetic and Transcriptional Regulation of Innate Immunity in Cancer
Authors: Chen Chuan , Man Na , Liu Fan , Martin Gloria Mas , Itonaga Hidehiro , Sun Jun , Nimer Stephen D. 
Published: March 2022

AbstractInnate immune cells participate in the detection of tumor cells via complex signaling pathways mediated by pattern-recognition receptors, such as Toll-like receptors and nucleotide-binding and oligomerization domain–like receptors. These pathways are finely tuned via multiple mechanisms, including epigenetic regulation. It is well established that hematopoietic progenitors generate innate immune cells that can regulate cancer cell behavior, and the disruption of normal hematopoiesis in pathologic states may lead to altered immunity and the development of cancer. In this review, we discuss the epigenetic and transcriptional mechanisms that underlie the initiation and amplification of innate immune signaling in cancer. We also discuss new targeting possibilities for cancer control that exploit innate immune cells and signaling molecules, potentially heralding the next generation of immunotherapy.
A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect
Authors: Wen Xuejun , Shi Changrong , Zeng Xinying , Zhao Liang , Yao Lanlin , Liu Zhida , Feng Lixia , Zhang Deliang , Huang Jinxiong , Li Yesen , Lin Qin , Chen Haojun , Zhuang Rongqiang , Chen Xiaoyuan , Zhang Xianzhong , Guo Zhide 
Published: March 2022

Abstract

Purpose:
Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.

Experimental Design:
We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti–PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.

Results:
PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from “cold” to “hot,” to make low immunoactivity tumors sensitive to ICB therapy.

Conclusions:
In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.
Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer
Authors: Rajurkar Mihir , Parikh Aparna R. , Solovyov Alexander , You Eunae , Kulkarni Anupriya S. , Chu Chong , Xu Katherine H. , Jaicks Christopher , Taylor Martin S. , Wu Connie , Alexander Katherine A. , Good Charly R. , Szabolcs Annamaria , Gerstberger Stefanie , Tran Antuan V. , Xu Nova , Ebright Richard Y. , Van Seventer Emily E. , Vo Kevin D. , Tai Eric C. , Lu Chenyue , Joseph-Chazan Jasmin , Raabe Michael J. , Nieman Linda T. , Desai Niyati , Arora Kshitij S. , Ligorio Matteo , Thapar Vishal , Cohen Limor , Garden Padric M. , Senussi Yasmeen , Zheng Hui , Allen Jill N. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Goyal Lipika , Wo Jennifer Y. , Ryan David P. , Corcoran Ryan B. , Deshpande Vikram , Rivera Miguel N. , Aryee Martin J. , Hong Theodore S. , Berger Shelley L. , Walt David R. , Burns Kathleen H. , Park Peter J. , Greenbaum Benjamin D. , Ting David T. 
Published: March 2022

AbstractAltered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.Significance:Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.This article is highlighted in the In This Issue feature, p. 1397
Ticagrelor With or Without Aspirin in Chinese Patients Undergoing Percutaneous Coronary Intervention: A TWILIGHT China Substudy
Authors: Han Yaling , Claessen Bimmer E. , Chen Shao-Liang , Chunguang Qiu , Zhou Yujie , Xu Yawei , Hailong Lin , Chen Jiyan , Qiang Wu , Zhang Ruiyan , Luo Suxin , Li Yongjun , Zhu Jianhua , Zhao Xianxian , Cheng Xiang , Wang Jian’an , Su Xi , Tao Jianhong , Sun Yingxian , Wang Geng , Li Yi , Bian Liya , Goel Ridhima , Sartori Samantha , Zhang Zhongjie , Angiolillo Dominick J. , Cohen David J. , Gibson C. Michael , Kastrati Adnan , Krucoff Mitchell , Mehta Shamir R. , Ohman E. Magnus , Steg Philippe Gabriel , Liu Yuqi , Dangas George , Sharma Samin , Baber Usman , Mehran Roxana 
Published: March 2022

Background:
The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts.

Methods:
The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.

Results:

Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31–0.99];
P
=0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33–1.46];
P
=0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points.

Conclusions:
Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02270242.
Ten-Second Heart Rate Variability, Its Changes Over Time, and the Development of Hypertension
Authors: Kang Jeonggyu , Chang Yoosoo , Kim Yejin , Shin Hocheol , Ryu Seungho 
Published: March 2022

Background:
The role of ultrashort-term heart rate variability (HRV) and its temporal changes in incident hypertension are unknown. We aimed to investigate the association between 10-second HRV, its changes, and incident hypertension in adults aged <40 years and older.

Methods:
This cohort study included 232 587 Koreans (mean age 37.6 years) without hypertension. Hypertension was defined according to the 2017 American College of Cardiology and American Heart Association hypertension guidelines. HRV, including the root mean square of successive R-R interval differences and the SD of normal-to-normal R-R intervals, was estimated using standard 12-lead, 10-second electrocardiography.

Results:
During a median follow-up of 3.8 years, 40 268 hypertension cases were identified (incidence rates: 36.1 and 67.9 per 1000 person-years for young and older participants, respectively). An inverse association was observed between HRV and hypertension risk, in a dose-dependent manner. The multivariable-adjusted hazard ratios (95% CIs) for hypertension comparing the first to the fifth quintiles of root mean square of successive R-R interval difference and SD of normal-to-normal R-R interval were 1.58 (1.52–1.63) and 1.35 (1.30–1.39), respectively. These associations were stronger in young adults than in older adults. In a subsample of 150 301 participants, compared with stable HRV, an increase in HRV over time was also inversely associated with incident hypertension.

Conclusions:
A higher HRV and its increase over time on a 10-second electrocardiography were associated with a lower risk of hypertension. Our findings indicate that autonomic function, estimated using 10-second standard electrocardiography, plays a role in predicting hypertension, with a stronger effect in young adults.
Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial
Authors: Zhang Jack Jiaqi , Bai Zhongfei , Fong Kenneth N.K. 
Published: March 2022

Background:
Intermittent theta burst stimulation (iTBS) creates a state with increased excitability that permits treatment modalities to induce neuroplasticity and motor learning. Continuous theta burst stimulation before iTBS may induce metaplasticity and boost the facilitatory effect of iTBS. This study investigated the effects of priming iTBS (ie, applying continuous theta burst stimulation before iTBS) on poststroke hemiparetic upper limb recovery.

Methods:
In this randomized controlled trial, 42 patients with chronic stroke were recruited and randomly allocated to 10 sessions of either priming iTBS, nonpriming iTBS, or sham stimulation to the ipsilesional motor cortex, immediately before robot-assisted training. Outcomes included Fugl-Meyer Assessment-Upper Extremity, Action Research Arm Test and mean movement velocity during each robot-assisted training session. Twenty-one patients were enrolled for measuring the sensorimotor beta event-related desynchronization induced by either mirror visual feedback or movement.

Results:

The Fugl-Meyer Assessment-Upper Extremity scores revealed a significant time-by-group interaction (
P
=0.011). Priming and nonpriming iTBS were both superior to sham stimulation in post hoc comparisons; however, the superiority was diminished at follow-up. Among patients with a higher functioning upper limb, priming iTBS yielded a significantly greater improvement in Fugl-Meyer Assessment-Upper Extremity scores than nonpriming iTBS (
P
=0.025) and sham stimulation (
P
=0.029) did. No significant interaction was found when analyzing the Action Research Arm Test and mean movement velocity. Priming iTBS enhanced the patients’ mirror visual feedback–induced high beta sensorimotor event-related desynchronization over their ipsilesional hemisphere.

Conclusions:
Priming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from robot-assisted training, and patients with a higher functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor learning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the mirror visual feedback.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04034069.
Multilingual Autoregressive Entity Linking
Authors: De Cao Nicola , Wu Ledell , Popat Kashyap , Artetxe Mikel , Goyal Naman , Plekhanov Mikhail , Zettlemoyer Luke , Cancedda Nicola , Riedel Sebastian , Petroni Fabio 
Published: March 2022

Abstract
We present mGENRE, a sequence-to- sequence system for the Multilingual Entity Linking (MEL) problem—the task of resolving language-specific mentions to a multilingual Knowledge Base (KB). For a mention in a given language, mGENRE predicts the name of the target entity left-to-right, token-by-token in an autoregressive fashion. The autoregressive formulation allows us to effectively cross-encode mention string and entity names to capture more interactions than the standard dot product between mention and entity vectors. It also enables fast search within a large KB even for mentions that do not appear in mention tables and with no need for large-scale vector indices. While prior MEL works use a single representation for each entity, we match against entity names of as many languages as possible, which allows exploiting language connections between source input and target name. Moreover, in a zero-shot setting on languages with no training data at all, mGENRE treats the target language as a latent variable that is marginalized at prediction time. This leads to over 50% improvements in average accuracy. We show the efficacy of our approach through extensive evaluation including experiments on three popular MEL benchmarks where we establish new state-of-the-art results. Source code available at https://github.com/facebookresearch/GENRE.
ByT5: Towards a Token-Free Future with Pre-trained Byte-to-Byte Models
Authors: Xue Linting , Barua Aditya , Constant Noah , Al-Rfou Rami , Narang Sharan , Kale Mihir , Roberts Adam , Raffel Colin 
Published: March 2022

Abstract
Most widely used pre-trained language models operate on sequences of tokens corresponding to word or subword units. By comparison, token-free models that operate directly on raw text (bytes or characters) have many benefits: They can process text in any language out of the box, they are more robust to noise, and they minimize technical debt by removing complex and error-prone text preprocessing pipelines. Because byte or character sequences are longer than token sequences, past work on token-free models has often introduced new model architectures designed to amortize the cost of operating directly on raw text. In this paper, we show that a standard Transformer architecture can be used with minimal modifications to process byte sequences. We characterize the trade-offs in terms of parameter count, training FLOPs, and inference speed, and show that byte-level models are competitive with their token-level counterparts. We also demonstrate that byte-level models are significantly more robust to noise and perform better on tasks that are sensitive to spelling and pronunciation. As part of our contribution, we release a new set of pre-trained byte-level Transformer models based on the T5 architecture, as well as all code and data used in our experiments.1
What Is Negative Disjunctivism?
Authors: de Bruijn David 
Published: March 2022

Abstract
Negative disjunctivists like Mike Martin and Bill Fish understand hallucinations in purely epistemic terms, and do not attribute phenomenal character to these visual misfires. However, the approaches by Martin and Fish are importantly different, and there has been little systematic work on how negative disjunctivism is motivated. In this paper, I argue for a version of negative disjunctivism that centers on the idea that perception involves the exercise of a fallible self-conscious capacity. I claim that this at once explains hallucinations in purely negative terms that are close to Martin’s approach, while at the same time providing negative disjunctivism with an explanatory basis that Fish attempts to provide and Martin’s view lacks.