bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Natural Language Processing to Assess Social Support in Patients With Advanced Cancer
Authors: Bhatt Sunil , Johnson P Connor , Markovitz Netana H , Gray Tamryn , Nipp Ryan D , Ufere Nneka , Rice Julia , Reynolds Matthew J , Lavoie Mitchell W , Clay Madison A , Lindvall Charlotta , El-Jawahri Areej 
Published: November 2022

Abstract

Background
Data examining associations among social support, survival, and healthcare utilization are lacking in patients with advanced cancer.

Methods
We conducted a cross-sectional secondary analysis using data from a prospective longitudinal cohort study of 966 hospitalized patients with advanced cancer at Massachusetts General Hospital from 2014 through 2017. We used NLP to identify extent of patients’ social support (limited versus adequate as defined by NLP-aided review of the Electronic Health Record (EHR)). Two independent coders achieved a Kappa of 0.90 (95% CI: 0.84-1.00) using NLP. Using multivariable regression models, we examined associations of social support with: 1) OS; 2) death or readmission within 90 days of hospital discharge; 3) time to readmission within 90 days; and 4) hospital length of stay (LOS).

Results
Patients’ median age was 65 (range: 21-92) years, and a plurality had gastrointestinal (GI) cancer (34.3%) followed by lung cancer (19.5%). 6.2% (60/966) of patients had limited social support. In multivariable analyses, limited social support was not significantly associated with OS (HR = 1.13, P = 0.390), death or readmission (OR = 1.18, P = 0.578), time to readmission (HR = 0.92, P = 0.698), or LOS (β = −0.22, P = 0.726). We identified a potential interaction suggesting cancer type (GI cancer versus other) may be an effect modifier of the relationship between social support and OS (interaction term P = 0.053). In separate unadjusted analyses, limited social support was associated with lower OS (HR = 2.10, P = 0.008) in patients with GI cancer but not other cancer types (HR = 1.00, P = 0.991).

Conclusion
We used NLP to assess the extent of social support in patients with advanced cancer. We did not identify significant associations of social support with OS or healthcare utilization but found cancer type may be an effect modifier of the relationship between social support and OS. These findings underscore the potential utility of NLP for evaluating social support in patients with advanced cancer.
Natural variation in CRABS CLAW contributes to fruit length divergence in cucumber
Authors: Che Gen , Pan Yupeng , Liu Xiaofeng , Li Min , Zhao Jianyu , Yan Shuangshuang , He Yuting , Wang Zhongyi , Cheng Zhihua , Song Weiyuan , Zhou Zhaoyang , Wu Tao , Weng Yiqun , Zhang Xiaolan 
Published: November 2022

Abstract
Fruit length is a key domestication trait that affects crop yield and appearance. Cucumber (Cucumis sativus) fruits vary from 5 to 60 cm in length. Despite the identification of several regulators and multiple quantitative trait loci (QTLs) underlying fruit length, the natural variation, and molecular mechanisms underlying differences in fruit length are poorly understood. Through map-based cloning, we identified a nonsynonymous polymorphism (G to A) in CRABS CLAW (CsCRC) as underlying the major-effect fruit size/shape QTL FS5.2 in cucumber. The short-fruit allele CsCRCA is a rare allele that has only been found in round-fruited semi-wild Xishuangbanna cucumbers. A near-isogenic line (NIL) homozygous for CsCRCA exhibited a 34∼39% reduction in fruit length. Introducing CsCRCG into this NIL rescued the short-fruit phenotype, and knockdown of CsCRCG resulted in shorter fruit and smaller cells. In natural cucumber populations, CsCRCG expression was positively correlated with fruit length. Further, CsCRCG, but not CsCRCA, targets the downstream auxin-responsive protein gene CsARP1 to regulate its expression. Knockout of CsARP1 produced shorter fruit with smaller cells. Hence, our work suggests that CsCRCG positively regulates fruit elongation through transcriptional activation of CsARP1 and thus enhances cell expansion. Using different CsCRC alleles provides a strategy to manipulate fruit length in cucumber breeding.
Wheat TaSnRK2.10 phosphorylates TaERD15 and TaENO1 and confers drought tolerance when overexpressed in rice
Authors: Zhang Yanfei , Wang Jingyi , Li Yuying , Zhang Zihui , Yang Lili , Wang Min , Zhang Yining , Zhang Jie , Li Chaonan , Li Long , Reynolds Matthew P , Jing Ruilian , Wang Chenyang , Mao Xinguo 
Published: November 2022

AbstractWheat (Triticum aestivum) is particularly susceptible to water deficit at the jointing stage of its development. Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) acts as a signaling hub in the response to drought stress, but whether SnRK2 helps plants cope with water deficit via other mechanisms is largely unknown. Here, we cloned and characterized TaSnRK2.10, which was induced by multiple abiotic stresses and phytohormones. Ectopic expression of TaSnRK2.10 in rice (Oryza sativa) conferred drought tolerance, manifested by multiple improved physiological indices, including increased water content, cell membrane stability, and survival rates, as well as decreased water loss and accumulation of H2O2 and malonaldehyde. TaSnRK2.10 interacted with and phosphorylated early responsive to dehydration 15 (TaERD15) and enolase 1 (TaENO1) in vivo and in vitro. TaERD15 phosphorylated by TaSnRK2.10 was prone to degradation by the 26S proteasome, thereby mitigating its negative effects on drought tolerance. Phosphorylation of TaENO1 by TaSnRK2.10 may account for the substantially increased levels of phosphoenolpyruvate (PEP), a key metabolite of primary and secondary metabolism, in TaSnRK2.10-overexpressing rice, thereby enhancing its viability under drought stress. Our results demonstrate that TaSnRK2.10 not only regulated stomatal aperture and the expression of drought-responsive genes, but also enhanced PEP supply and promoted the degradation of TaERD15, all of which enhanced drought tolerance.
PICLN modulates alternative splicing and light/temperature responses in plants
Authors: Mateos Julieta L , Sanchez Sabrina E , Legris Martina , Esteve-Bruna David , Torchio Jeanette C , Petrillo Ezequiel , Goretti Daniela , Blanco-Touriñán Noel , Seymour Danelle K , Schmid Markus , Weigel Detlef , Alabadí David , Yanovsky Marcelo J 
Published: November 2022

Abstract
Plants undergo transcriptome reprograming to adapt to daily and seasonal fluctuations in light and temperature conditions. While most efforts have focused on the role of master transcription factors, the importance of splicing factors modulating these processes is now emerging. Efficient pre-mRNA splicing depends on proper spliceosome assembly, which in plants and animals requires the methylosome complex. Ion Chloride nucleotide-sensitive protein (PICLN) is part of the methylosome complex in both humans and Arabidopsis (Arabidopsis thaliana), and we show here that the human PICLN ortholog rescues phenotypes of Arabidopsis picln mutants. Altered photomorphogenic and photoperiodic responses in Arabidopsis picln mutants are associated with changes in pre-mRNA splicing that partially overlap with those in PROTEIN ARGININE METHYL TRANSFERASE5 (prmt5) mutants. Mammalian PICLN also acts in concert with the Survival Motor Neuron (SMN) complex component GEMIN2 to modulate the late steps of UsnRNP assembly, and many alternative splicing events regulated by PICLN but not PRMT5, the main protein of the methylosome, are controlled by Arabidopsis GEMIN2. As with GEMIN2 and SM PROTEIN E1/PORCUPINE (SME1/PCP), low temperature, which increases PICLN expression, aggravates morphological and molecular defects of picln mutants. Taken together, these results establish a key role for PICLN in the regulation of pre-mRNA splicing and in mediating plant adaptation to daily and seasonal fluctuations in environmental conditions.
Sequence patterns and signatures: Computational and experimental discovery of amyloid-forming peptides
Authors: Xiao Xingqing , Robang Alicia S , Sarma Sudeep , Le Justin V , Helmicki Michael E , Lambert Matthew J , Guerrero-Ferreira Ricardo , Arboleda-Echavarria Johana , Paravastu Anant K , Hall Carol K 
Published: November 2022

Abstract
Screening amino acid sequence space via experiments to discover peptides that self-assemble into amyloid fibrils is challenging. We have developed a computational peptide assembly design (PepAD) algorithm that enables the discovery of amyloid-forming peptides. Discontinuous molecular dynamics (DMD) simulation with the PRIME20 force field combined with the FoldAmyloid tool is used to examine the fibrilization kinetics of PepAD-generated peptides. PepAD screening of ∼10,000 7-mer peptides resulted in twelve top-scoring peptides with two distinct hydration properties. Our studies revealed that eight of the twelve in silico discovered peptides spontaneously form amyloid fibrils in the DMD simulations and that all eight have at least five residues that the FoldAmyloid tool classifies as being aggregation-prone. Based on these observations, we re-examined the PepAD-generated peptides in the sequence pool returned by PepAD and extracted five sequence patterns as well as associated sequence signatures for the 7-mer amyloid-forming peptides. Experimental results from Fourier transform infrared spectroscopy (FTIR), thioflavin T (ThT) fluorescence, circular dichroism (CD), and transmission electron microscopy (TEM) indicate that all the peptides predicted to assemble in silico assemble into antiparallel β-sheet nanofibers in a concentration-dependent manner. This is the first attempt to use a computational approach to search for amyloid-forming peptides based on customized settings. Our efforts facilitate the identification of β-sheet-based self-assembling peptides, and contribute insights towards answering a fundamental scientific question: “What does it take, sequence-wise, for a peptide to self-assemble?”
Reduced homotopic interhemispheric connectivity in psychiatric disorders: evidence for both transdiagnostic and disorder specific features
Authors: Yao Shuxia , Kendrick Keith M 
Published: November 2022

Abstract
There is considerable interest in the significance of structural and functional connections between the two brain hemispheres in terms of both normal function and in relation to psychiatric disorders. In recent years, many studies have used voxel mirrored homotopic connectivity analysis of resting state data to investigate the importance of connectivity between homotopic regions in the brain hemispheres in a range of neuropsychiatric disorders. The current review summarizes findings from these voxel mirrored homotopic connectivity studies in individuals with autism spectrum disorder, addiction, attention deficit hyperactivity disorder, anxiety and depression disorders, and schizophrenia, as well as disorders such as Alzheimer's disease, mild cognitive impairment, epilepsy, and insomnia. Overall, other than attention deficit hyperactivity disorder, studies across psychiatric disorders report decreased homotopic resting state functional connectivity in the default mode, attention, salience, sensorimotor, social cognition, visual recognition, primary visual processing, and reward networks, which are often associated with symptom severity and/or illness onset/duration. Decreased homotopic resting state functional connectivity may therefore represent a transdiagnostic marker for general psychopathology. In terms of disorder specificity, the extensive decreases in homotopic resting state functional connectivity in autism differ markedly from attention deficit hyperactivity disorder, despite both occurring during early childhood and showing extensive co-morbidity. A pattern of more posterior than anterior regions showing reductions in schizophrenia is also distinctive. Going forward, more studies are needed to elucidate the functions of these homotopic functional connections in both health and disorder and focusing on associations with general psychopathology, and not only on disorder specific symptoms.
Advances in neuroimaging studies of alcohol use disorder (AUD)
Authors: Xie Ji-Yu , Li Rui-Hua , Yuan Wei , Du Jiang , Zhou Dong-Sheng , Cheng Yu-Qi , Xu Xue-Ming , Liu Heng , Yuan Ti-Fei 
Published: November 2022

Abstract
Alcohol use disorder (AUD) is a worldwide problem and the most common substance use disorder. Chronic alcohol consumption may have negative effects on the body, the mind, the family, and even society. With the progress of current neuroimaging methods, an increasing number of imaging techniques are being used to objectively detect brain impairment induced by alcoholism and serve a vital role in the diagnosis, prognosis, and treatment assessment of AUD. This article organizes and analyzes the research on alcohol dependence concerning the main noninvasive neuroimaging methods, structural magnetic resonance imaging, functional magnetic resonance imaging, and electroencephalography, as well as the most common noninvasive brain stimulation – transcranial magnetic stimulation, and intersperses the article with joint intra- and intergroup studies, providing an outlook on future research directions.
Quantifying conjugacy separability in wreath products of groups
Authors: Ferov Michal , Pengitore Mark 
Published: November 2022

Abstract
We study generalizations of conjugacy separability in restricted wreath products of groups. We provide an effective upper bound for $\mathcal{C}$-conjugacy separability of a wreath product $A \wr B$ in terms of the $\mathcal{C}$-conjugacy separability of A and B, the growth of $\mathcal{C}$-cyclic subgroup separability of B and the $\mathcal{C}$-residual girth of $B.$ As an application, we provide a characterization of when $A \wr B$ is p-conjugacy separable. We use this characterization to provide for each prime p an example of a wreath product with infinite base group that is p-conjugacy separable. We also provide asymptotic upper bounds for conjugacy separability for wreath products of nilpotent groups, which include the lamplighter groups and provide asymptotic upper bounds for conjugacy separability of the free metabelian groups.
CLASSIC IL-6 SIGNALING IS ASSOCIATED WITH POOR OUTCOMES IN BURN PATIENTS
Authors: Rehou Sarah , Abdullahi Abdikarim , Jeschke Marc G. 
Published: November 2022

ABSTRACT

Background: Interleukin (IL)-6 is a multifunctional cytokine with both a proinflammatory and anti-inflammatory role. In many studies, IL-6 increases rapidly after burn injury and is associated with poor outcomes. However, there are two aspects to IL-6; it can signal via its soluble IL-6 receptor (sIL-6R), which is referred to as trans-signaling and is regarded as the proinflammatory pathway. The role of sIL-6R postburn injury has yet to be explored in its entirety. We hypothesized that patients with a lower ratio of IL-6 to sIL-6R would have worse outcomes. Methods: Patients admitted to our burn center within 7 days of injury were included in this study. Patients were divided into two groups based on IL-6 and sIL-6R levels measured within the first 7 days postburn injury. Patients were in the high ratio group if their IL-6/sIL-6R ratio was ≥0.185. Clinical outcomes included organ biomarkers, morbidities, and hospital length of stay. Groups were compared using Student's t test, Mann-Whitney U, and Fisher's exact test as appropriate; a P value of <0.05 was considered statistically significant. Results: We studied 86 patients with a median age of 50 years (36–66 years) and a median total body surface area burn of 18% (10–31). There were 40 patients categorized with a low IL-6/sIL-6R ratio and 46 patients with a high IL-6/sIL-6R ratio. Patients in the high IL-6/sIL-6R ratio group had a significantly greater total body surface area burn (P < 0.001) and a significantly greater proportion of patients with inhalation injury (P = 0.001). Levels of IL-6 were significantly higher in patients with a high IL-6/sIL-6R ratio (P < 0.0001). However, levels of sIL-6R were not significantly different among the low and high groups (P = 0.965). Mortality was significantly greater in the high IL-6/sIL-6R ratio group (3% vs. 26%; P = 0.002). Conclusions: Interestingly, patients with a higher ratio of IL-6/sIL-6R had significantly greater mortality. Using sIL-6R as a marker for the proinflammatory immune response, we expected patients with a lower IL-6/sIL-6R ratio to have poor outcomes, typically associated with a hyperinflammatory or exaggerated immune response. However, the absolute value of sIL-6R did not differ. This suggests that classical signaling of IL-6 via its membrane-bound receptor, with an anti-inflammatory function, is important.
POSTHEMORRHAGIC SHOCK MESENTERIC LYMPH IMPAIRS SPLENIC DENDRITIC CELL FUNCTION IN MICE
Authors: Liu Hua , Li Jian-Feng , Zhang Li-Min , Wang Huai-Huai , Wang Xu-Qing , Liu Gui-Qing , Du Hui-Bo , Jin Yu-Jie , Xing Li-Qiang , Zhao Zi-Gang , Niu Chun-Yu 
Published: November 2022

ABSTRACT
Dendritic cell (DC)–mediated immune dysfunction is involved in the process of severe hemorrhagic shock that leads to sepsis. Although post–hemorrhagic shock mesenteric lymph (PHSML) induces immune organs injuries and apoptosis, whether PHSML exerts adverse effects on splenic DCs remains unknown. In this study, we established a hemorrhagic shock model (40 ± 2 mm Hg for 60 min) followed by fluid resuscitation with the shed blood and equal Ringer's solution and drained the PHSML after resuscitation. At 3 h after resuscitation, we harvested the splenic tissue to isolate DCs using anti-CD11c immunomagnetic beads and then detected the necrotic and apoptotic rates in splenocytes and splenic DCs. We also detected the levels of TNF-α, IL-10, and IL-12 in the culture supernatants and surface marker expressions of MHC-II, CD80, and CD86 of splenic DCs following LPS stimulation for 24 h. Second, we purified the DCs from splenocytes of normal mice to investigate the effects of PHSML treatment on cytokine production and surface marker expression following LPS stimulation. The results showed that PHSML drainage attenuated LPS-induced cell death of splenocytes and DCs. Meanwhile, PHSML drainage enhanced the DC percentage in splenocytes and increased the TNF-α and IL-12 production by DCs and the expressions of CD80, CD86, and MHCII of DCs treated by LPS. Furthermore, PHSML treatment reduced the productions of TNF-α, IL-10, and IL-12 and the expressions of CD80 and CD86 in normal DCs after treatment with LPS. In summary, the current investigation demonstrated that PHSML inhibited the cytokine production and surface marker expressions of DCs stimulated by LPS, suggesting that PHSML plays an important role in hemorrhagic shock–induced immunosuppression through the impairment of DC function and maturation.
Predicting and Interpreting Protein Developability via Transfer of Convolutional Sequence Representation
Authors: Golinski Alexander W. , Schmitz Zachary D. , Nielsen Gregory H. , Johnson Bryce , Saha Diya , Appiah Sandhya , Hackel Benjamin J. , Martiniani Stefano 
Published: November 2022

AbstractEngineered proteins have emerged as novel diagnostics, therapeutics, and catalysts. Often, poor protein developability – quantified by expression, solubility, and stability – hinders utility. The ability to predict protein developability from amino acid sequence would reduce the experimental burden when selecting candidates. Recent advances in screening technologies enabled a high-throughput developability dataset for 105of 1020possible variants of protein ligand scaffold Gp2. In this work, we evaluate the ability of neural networks to learn a developability representation from a high-throughput dataset and transfer this knowledge to predict recombinant expression beyond observed sequences. The model convolves learned amino acid properties to predict expression levels 44% closer to the experimental variance compared to a non-embedded control. Analysis of learned amino acid embeddings highlights the uniqueness of cysteine, the importance of hydrophobicity and charge, and the unimportance of aromaticity, when aiming to improve the developability of small proteins. We identify clusters of similar sequences with increased developability through nonlinear dimensionality reduction and we explore the inferred developability landscape via nested sampling. The analysis enables the first direct visualization of the fitness landscape and highlights the existence of evolutionary bottlenecks in sequence space giving rise to competing subpopulations of sequences with different developability. The work advances applied protein engineering efforts by predicting and interpreting protein scaffold developability from a limited dataset. Furthermore, our statistical mechanical treatment of the problem advances foundational efforts to characterize the structure of the protein fitness landscape and the amino acid characteristics that influence protein developability.Significance statementProtein developability prediction and understanding constitutes a critical limiting step in biologic discovery and engineering due to limited experimental throughput. We demonstrate the ability of a machine learning model to learn sequence-developability relationships first through the use of high-throughput assay data, followed by the transfer of the learned developability representation to predict the true metric of interest, recombinant yield in bacterial production. Model performance is 44% better than a model not pre-trained using the high-throughput assays. Analysis of model behavior reveals the importance of cysteine, charge, and hydrophobicity to developability, as well as of an evolutionary bottleneck that greatly limited sequence diversity above 1.3 mg/L yield. Experimental characterization of model predicted candidates confirms the benefit of this transfer learning and in-silico evolution approach.
Enhancing Mitochondrial Functions by Optogenetic Clustering
Authors: Qiu Kangqiang , Zou Weiwei , Tian Zhiqi , Huang Taosheng , Tsai Nien-Pei , Zhang Kai , Diao Jiajie 
Published: November 2022

AbstractKnown as the powerhouses of cells, mitochondria and its dynamics are important for their functions in cells. Herein, an optogenetic method that controlling mitochondria to form the clusters was developed. The plasmid named CRY2PHR-mCherry-Miro1TM was designed for the optogenetic system. The photoactivable protein CRY2PHR was anchored to mitochondria, via the specific organelle-targeting transmembrane domain Miro1TM. Under blue light illumination, CRY2PHR can form the oligomerization, called puncta. With the illuminated time extended, the puncta can interact, and the mitochondria were found to form clustering with reversibility and spatiotemporal controllability. The mitochondrial functions were found to enhance after the formation of optogenetic mitochondrial clusters. This method presented here provides a way to control mitochondrial clustering and raise mitochondrial functions up.