bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective comparison of acupuncture with sham acupuncture to determine impact on sedation and analgesia in mechanically ventilated critically ill patients (PASSION study): protocol for a randomised controlled trial
Authors: Zhang Yuzhuo , Yang Guang , Wei Jinyi , Chen Fangliang , Zhang Min-Zhou , Mao Shuai 
Published: August 2022

IntroductionSedation and analgesia are recommended to be employed in the intensive care unit (ICU) to enhance patient comfort and safety, facilitate mechanical ventilation and reduce oxygen demands. However, the increasing evidence demonstrates that excessive sedation and analgesia might prolong mechanical ventilation and increase costs and mortality. Acupuncture is known to be able to attenuate pain, anxiety and agitation symptoms while avoiding excessive sedation and analgesia caused by drugs. Therefore, we present a protocol to investigate whether acupuncture, used for sedation and analgesia, can reduce the duration of mechanical ventilation, save medical resources and reduce the mortality of critically ill patients receiving mechanical ventilation.Methods and analysisProspective, randomised controlled trial is conducted on 180 adult medical/surgical ICU patients with mechanical ventilation needing sedation at 3 ICUs between 03 November 2021 and 16 August 2023. Patients will be treated with analgesia and sedation to achieve desired target sedation levels (Richmond Agitation Sedation Score of −2 to 1). Enrolled patients will be randomly assigned in a ratio of 1:1:1 to receive deep needle insertion with combined manual and alternating-mode electrical stimulation on acupoints (AC group), superficial needle insertion without manual stimulation and electrical stimulation on non-acupoints (SAC group), or no acupuncture intervention (NAC group). The primary outcome is the duration of mechanical ventilation from randomisation until patients are free of mechanical ventilation (including non-invasive) without reinstitution for the following 48 hours. Secondary endpoints include the dose of administered sedatives and analgesic at comparable sedation levels throughout the study, ICU length of stay, hospital length of stay. Additional outcomes include the prevalence and days of delirium in ICU, mortality in ICU and within 28 days after randomisation, and the number of ventilator free days in 28 days.Ethics and disseminationThis trial was approved by the ethics committee at Guangdong Provincial Hospital of Chinese Medicine. We will publish the study results.Trial registration numberChiCTR2100052650.
PALLIA 10 score in phase I cancer studies
Authors: Ouali Kaïssa , Mateus Christine , Laparra Arianne , Martin Romano Patricia , Sampetrean Anda , Vuagnat Perrine , Varga Andrea , Champiat Stephane , Verlingue Loic , Geraud Arthur , Marabelle Aurélien , Hollebecque Antoine , Gazzah Anas , Bahleda Rastilav , Postel Vinay Sophie , Michot Jean-Marie , Bernard-Tessier Alice , Bayle Arnaud , Ribrag Vincent , Soria Jean-Charles , Scotte Florian , Massard Christophe , Pavliuc Elena , Baldini Capucine 
Published: August 2022

ObjectivePhase I clinical trials usually include patients with advanced disease who have failed standard therapies and should benefit from early palliative care. We try to assess whether PALLIA 10, a score developed in France to help identify patients who might benefit from a palliative care referral, could be used in a phase I department trial.MethodsWe assessed PALLIA 10 score and other prognostic factors in patients enrolled in phase I trials at Gustave Roussy Cancer Center prospectively during two periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the PALLIA 10 score was done in C2 by a palliative care specialist and a nurse.ResultsFrom 1 July 2018 to 1 November 2018 (C1) and from 1 December 2020 to 16 April 2021 (C2), 86 patients were assessed in C1 and 302 in C2. Median PALLIA 10 was very low in both cohorts (median 1, range 1–5 in C1 and 1–8 in C2). On C1 and C2, 12% and 5% of patients had a dedicated palliative consultation. In C2, assessment of PALLIA 10 score was significantly different between palliative care physician (median 5, range 3–8), phase I physician (median 1, range 1–6) and phase I nurse (median 3, range 1–8) (p<0.001).ConclusionMedian PALLIA 10 score was low when assessed by the phase I physician, which suggests the need for a better tool and appropriate clinician’s education to implement early palliative care in clinical practice and trials.
Fermion masses and mixings and $$g-2$$ muon anomaly in a 3-3-1 model with $$D_4$$ family symmetry
Authors: Hernández A. E. Cárcamo , Long Hoang Ngoc , Mora-Urrutia M. L. , Thao N. H. , Vien V. V. 
Published: August 2022

AbstractWe propose a predictive model based on the $$SU(3)_C\times SU(3)_L\times U(1)_X$$

S
U

(
3
)

C

×
S
U

(
3
)

L

×
U

(
1
)

X

gauge symmetry, which is supplemented by the $$D_4$$

D
4

family symmetry and several auxiliary cyclic symmetries whose spontaneous breaking produces the observed SM fermion mass and mixing pattern. The masses of the light active neutrinos are produced by an inverse seesaw mechanism mediated by three right handed Majorana neutrinos. To the best of our knowledge the model corresponds to the first implementation of the $$D_4$$

D
4

family symmetry in a $$SU(3)_C\times SU(3)_L\times U(1)_X$$

S
U

(
3
)

C

×
S
U

(
3
)

L

×
U

(
1
)

X

theory with three right handed Majorana neutrinos and inverse seesaw mechanism. Our proposed model successfully accommodates the experimental values of the SM fermion mass and mixing parameters, the muon anomalous magnetic moment as well as the Higgs diphoton decay rate and meson oscillations constraints. The consistency of our model with the muon anomalous magnetic moment requires charged exotic vector like leptons at the TeV scale.
Studying folding $$\leftrightarrow $$ unfolding dynamics of solvated alanine polypeptides using molecular dynamics
Authors: Hungerland Jonathan , Frederiksen Anders , Gerhards Luca , Solov’yov Ilia A. 
Published: August 2022

Abstract
The atomistic description of the folding process of a structureless chain of amino acids to a functioning protein is still considered to be a challenge for computational biophysics. An in-depth understanding of protein-folding can be achieved through atomistic dynamics accounting for the solvent effects, combined with the theoretical description of conformational changes in shorter polypeptide chains. The present paper studies the folding transitions in short polypeptide chains consisting of 11 alanine residues in explicit solvent employing all-atom molecular dynamics. The multiple observed folding $$\leftrightarrow $$
↔
unfolding events of the peptide are interpreted as a dynamic process and rationalised through the analysis of the potential energy surface of the system. It is demonstrated that alanine polypeptide folding dynamics is governed by the backbone dihedral angles and involves the formation of spontaneously folded $$\alpha $$
α
-helices which emerge and live for ca. 1–20 picoseconds. The helical content within the polypeptide at different temperatures was quantified through a statistical mechanics approach, which showed a reasonable agreement with the results of molecular dynamics simulations and experiments performed for alanine-rich peptides.

Graphical abstract
An Efficient Deep Learning Mechanism for the Recognition of Olive Trees in Jouf Region
Authors: Alshammari Hamoud H. , Shahin Osama R. 
Published: August 2022

Olive trees grow all over the world in reasonably moderate and dry climates, making them fortunate and medicinal. Pesticides are required to improve crop quality and productivity. Olive trees have had important cultural and economic significance since the early pre-Roman era. In 2019, Al-Jouf region in a Kingdom of Saudi Arabia’s north achieved global prominence by breaking a Guinness World Record for having more number of olive trees in a world. Unmanned aerial systems (UAS) were increasingly being used in aerial sensing activities. However, sensing data must be processed further before it can be used. This processing necessitates a huge amount of computational power as well as the time until transmission. Accurately measuring the biovolume of trees is an initial step in monitoring their effectiveness in olive output and health. To overcome these issues, we initially formed a large scale of olive database for deep learning technology and applications. The collection comprises 250 RGB photos captured throughout Al-Jouf, KSA. This paper employs among the greatest efficient deep learning occurrence segmentation techniques (Mask Regional-CNN) with photos from unmanned aerial vehicles (UAVs) to calculate the biovolume of single olive trees. Then, using satellite imagery, we present an actual deep learning method (SwinTU-net) for identifying and counting of olive trees. SwinTU-net is a U-net-like network that includes encoding, decoding, and skipping links. SwinTU-net’s essential unit for learning locally and globally semantic features is the Swin Transformer blocks. Then, we tested the method on photos with several wavelength channels (red, greenish, blues, and infrared region) and vegetation indexes (NDVI and GNDVI). The effectiveness of RGB images is evaluated at the two spatial rulings:

3

cm

/pixel and

13

cm

/pixel, whereas NDVI and GNDV images have only been evaluated at 13 cm/pixel. As a result of integrating all datasets of GNDVI and NDVI, all generated mask regional-CNN-based systems performed well in segmenting tree crowns (F1-measure from 95.0 to 98.0 percent). Based on ground truth readings in a group of trees, a calculated biovolume was 82 percent accurate. These findings support all usage of NDVI and GNDVI spectrum indices in UAV pictures to accurately estimate the biovolume of distributed trees including olive trees.
Asialoglycoprotein Receptor 1 Functions as a Tumor Suppressor in Liver Cancer via Inhibition of STAT3
Authors: Zhu Xingxin , Song Guangyuan , Zhang Shiyu , Chen Jun , Hu Xiaoyi , Zhu Hai , Jia Xing , Li Zequn , Song Wenfeng , Chen Jian , Jin Cheng , Zhou Mengqiao , Zhao Yongchao , Xie Haiyang , Zheng Shusen , Song Penghong 
Published: August 2022

Abstract

Liver cancer is characterized by aggressive growth and high mortality. Asialoglycoprotein receptor 1 (ASGR1), which is expressed almost exclusively in liver cells, is reduced in liver cancer. However, the specific mechanism of ASGR1 function in liver cancer has not been fully elucidated. On the basis of database screening, we identified ASGR1 as a tumor suppressor regulated by DNA methylation. Expression of ASGR1 was downregulated in liver cancer and correlated with tumor size, grade, and survival. Functional gain and loss experiments showed that ASGR1 suppresses the progression of liver cancer in vivo and in vitro. RNA sequencing and mass spectrometry showed that ASGR1 inhibits tyrosine phosphorylation of STAT3 by interacting with Nemo-like kinase (NLK). NLK bound the SH2 domain of STAT3 in an ATP-dependent manner and competed with glycoprotein 130 (GP130), ultimately suppressing GP130/JAK1-mediated phosphorylation of STAT3. ASGR1 altered the binding strength of NLK and STAT3 by interacting with GP130. Furthermore, the domain region of NLK was crucial for binding STAT3 and curbing its phosphorylation. Collectively, these results confirm that ASGR1 suppresses the progression of liver cancer by promoting the binding of NLK to STAT3 and inhibiting STAT3 phosphorylation, suggesting that approaches to activate the ASGR1–NLK axis may be a potential therapeutic strategy in this disease.

Significance:
ASGR1 downregulation by DNA methylation facilitates liver tumorigenesis by increasing STAT3 phosphorylation.
Developmental Deconvolution for Classification of Cancer Origin
Authors: Moiso Enrico , Farahani Alexander , Marble Hetal D. , Hendricks Austin , Mildrum Samuel , Levine Stuart , Lennerz Jochen K. , Garg Salil 
Published: August 2022

Abstract

Cancer is partly a developmental disease, with malignancies named based on cell or tissue of origin. However, a systematic atlas of tumor origins is lacking. Here we map the single-cell organogenesis of 56 developmental trajectories to the transcriptomes of over 10,000 tumors across 33 cancer types. We deconvolute tumor transcriptomes into signals for individual developmental trajectories. Using these signals as inputs, we construct a developmental multilayer perceptron (D-MLP) classifier that outputs cancer origin. D-MLP (ROC-AUC: 0.974 for top prediction) outperforms benchmark classifiers. We analyze tumors from patients with cancer of unknown primary (CUP), selecting the most difficult cases in which extensive multimodal workup yielded no definitive tumor type. Interestingly, CUPs form groups distinguished by developmental trajectories, and classification reveals diagnosis for patient tumors. Our results provide an atlas of tumor developmental origins, provide a tool for diagnostic pathology, and suggest developmental classification may be a useful approach for patient tumors.

Significance:
Here we map the developmental trajectories of tumors. We deconvolute tumor transcriptomes into signals for mammalian developmental programs and use this information to construct a deep learning classifier that outputs tumor type. We apply the classifier to CUP and reveal the developmental origins of patient tumors.
See related commentary by Wang, p. 2498.
This article is highlighted in the In This Issue feature, p. 2483
Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and CITE-seq Analysis
Authors: Yao Lijun , Jayasinghe Reyka G. , Lee Brian H. , Bhasin Swati S. , Pilcher William , Doxie Deon Bryant , Gonzalez-Kozlova Edgar , Dasari Surendra , Fiala Mark A. , Pita-Juarez Yered , Strausbauch Michael , Kelly Geoffrey , Thomas Beena E. , Kumar Shaji K. , Cho Hearn Jay , Anderson Emilie , Wendl Michael C. , Dawson Travis , D'souza Darwin , Oh Stephen T. , Cheloni Giulia , Li Ying , DiPersio John F. , Rahman Adeeb H. , Dhodapkar Kavita M. , Kim-Schulze Seunghee , Vij Ravi , Vlachos Ioannis S. , Mehr Shaadi , Hamilton Mark , Auclair Daniel , Kourelis Taxiarchis , Avigan David , Dhodapkar Madhav V. , Gnjatic Sacha , Bhasin Manoj K. , Ding Li 
Published: August 2022

As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System stage 3 patients exhibited decreased CD4+ T/CD8+ T cells ratio. Moreover, we observed upregulation of RAC2 and PSMB9, in natural killer cells of fast progressors compared with those of nonprogressors, as revealed by both scRNA-seq and CITE-seq RNA measurement. This detailed examination of the immune microenvironment in multiple myeloma using multiple single-cell technologies revealed markers associated with multiple myeloma rapid progression which will be further characterized by the full-scale immune atlas project.Significance:scRNA-seq, CyTOF, and CITE-seq are increasingly used for evaluating cellular heterogeneity. Understanding their concordances is of great interest. To date, this study is the most comprehensive examination of the measurement of the immune microenvironment in multiple myeloma using the three techniques. Moreover, we identified markers predicted to be significantly associated with multiple myeloma rapid progression.
Facções prisionais em dois territórios fronteriços
Authors: Dias Camila Nunes , Paiva Luiz Fábio S. 
Published: August 2022

O texto analisa de um ponto de vista comparativo as dinâmicas criminais que ocorrem em fronteiras caracterizadas pela presença de grupos brasileiros de base prisional na operacionalização do comércio transnacional de cocaína. Trata-se dos resultados de investimentos de pesquisa qualitativa desenvolvidos entre 2013 e 2018, na região da fronteira entre Brasil e Paraguai e da fronteira entre Brasil, Peru e Colômbia. As áreas estudadas são espaços alcançados por mercados ilegais e dinâmicas criminais transfronteiriças que têm sofrido importantes transformações, sobretudo em decorrência do protagonismo assumido por grupos brasileiros que aprenderam maneiras de atuar para a movimentação de mercados ilegais transnacionais, preservando estratégias que marcam sua história de base prisional e atuação em periferias urbanas.
Os significados de caipira
Authors: Guerra Luiz Antonio 
Published: August 2022

O presente artigo investiga a consolidação histórica da civilização caipira, o seu desmantelamento a partir de mudanças estruturais da sociedade brasileira e a resiliência de características de uma antiga cultura rural. O objetivo é acompanhar as mudanças nos usos do termo “caipira” para compreender o significado atribuído a ele hoje por aqueles que se identificam com tal cultura. Conclui-se que o conceito analisado sofreu um expressivo deslocamento semântico, devido às profundas transformações materiais e sociais pelas quais passou a população rural do centro-sul do Brasil tal como descrita pela Sociologia Rural paulista. Hoje, em vez do tipo humano característico dos bairros rurais, os elementos simbólicos e as referências identitárias tornam-se centrais para designar os indivíduos que se consideram herdeiros da matriz cultural caipira, ampliando-se, assim, os seus significados para tempos, espaços e experiências diversos.
L-2-Hydroxyglutarate Protects Against Cardiac Injury via Metabolic Remodeling
Authors: He Huamei , Mulhern Ryan M. , Oldham William M. , Xiao Wusheng , Lin Yi-Dong , Liao Ronglih , Loscalzo Joseph 
Published: August 2022

Background:
L-2-hydroxyglutarate (L2HG) couples mitochondrial and cytoplasmic energy metabolism to support cellular redox homeostasis. Under oxygen-limiting conditions, mammalian cells generate L2HG to counteract the adverse effects of reductive stress induced by hypoxia. Very little is known, however, about whether and how L2HG provides tissue protection from redox stress during low-flow ischemia (LFI) and ischemia-reperfusion injury. We examined the cardioprotective effects of L2HG accumulation against LFI and ischemia-reperfusion injury and its underlying mechanism using genetic mouse models.

Methods and Results:

L2HG accumulation was induced by homozygous (L2HGDH [L-2-hydroxyglutarate dehydrogenase]
–/–
) or heterozygous (L2HGDH
+/–
) deletion of the
L2HGDH
gene in mice. Hearts isolated from these mice and their wild-type littermates (L2HGDH
+/+
) were subjected to baseline perfusion and 90-minute LFI or 30-minute no-flow ischemia followed by 60- or 120-minute reperfusion. Using [
13
C]- and [
31
P]-NMR (nuclear magnetic resonance) spectroscopy, high-performance liquid chromatography, reverse transcription quantitative reverse transcription polymerase chain reaction, ELISA, triphenyltetrazolium staining, colorimetric/fluorometric spectroscopy, and echocardiography, we found that L2HGDH deletion induces L2HG accumulation at baseline and under stress conditions with significant functional consequences. In response to LFI or ischemia-reperfusion, L2HG accumulation shifts glucose flux from glycolysis towards the pentose phosphate pathway. These key metabolic changes were accompanied by enhanced cellular reducing potential, increased elimination of reactive oxygen species, attenuated oxidative injury and myocardial infarction, preserved cellular energy state, and improved cardiac function in both L2HGDH
–/–
and L2HGDH
+/–
hearts compared with L2HGDH
+/+
hearts under ischemic stress conditions.

Conclusion:
L2HGDH deletion-induced L2HG accumulation protects against myocardial injury during LFI and ischemia-reperfusion through a metabolic shift of glucose flux from glycolysis towards the pentose phosphate pathway. L2HG offers a novel mechanism for eliminating reactive oxygen species from myocardial tissue, mitigating redox stress, reducing myocardial infarct size, and preserving high-energy phosphates and cardiac function. Targeting L2HG levels through L2HGDH activity may serve as a new therapeutic strategy for cardiovascular diseases related to oxidative injury.
Tuberculosis and Risk of Ischemic Stroke: A Nationwide Cohort Study
Authors: Lee Han Rim , Yoo Jung Eun , Choi Hayoung , Han Kyungdo , Jung Jin Hyung , Park Jongkyu , Lee Hyun , Shin Dong Wook 
Published: August 2022

Background:
Conflicting results exist regarding the risk of ischemic stroke in tuberculosis survivors. We aimed to estimate the risk of ischemic stroke using a nationwide population-based retrospective cohort.

Methods:
We gathered data from the Korean National Health Insurance Service on tuberculosis survivors and 1:1 age- and sex-matched non-tuberculosis cases. Eligible participants were followed up from 1 year after tuberculosis diagnosis to the date of ischemic stroke event, date of death, or until the end of the study period (December 31, 2018), whichever came first. Cox proportional hazard regression and stratified analyses were performed to identify any related factors.

Results:
During follow-up periods of 3.8 years for patients with tuberculosis and matched non-tuberculosis cases, 1.3% of patients with tuberculosis (941/72 863) and 1.0% of matched non-tuberculosis cases (707/72 863) developed ischemic stroke. The overall risk of ischemic stroke was higher in tuberculosis patients (adjusted hazard ratio: 1.22 [95% CI, 1.10–1.36]) compared with the matched non-tuberculosis cases. A stratified analysis showed that patients with tuberculosis had increased risk of ischemic stroke regardless of age, sex, smoking status, alcohol consumption, physical activity, body mass index, and Charlson Comorbidity Index score.

Conclusions:
Tuberculosis survivors had a higher risk of ischemic stroke than their matched non-tuberculosis cases. The results of this study suggest that tuberculosis is a crucial infectious factor associated with increased incidence of ischemic stroke.