bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualification of Ventricular Flow in Patients With Precapillary Pulmonary Hypertension With 4-dimensional Flow Magnetic Resonance Imaging
Authors: Xu Wenqing , Deng Mei , Zhang Ling , Zhang Peiyao , Gao Qian , Tao Xincao , Zhen Yanan , Liu Xiaopeng , Jin Ning , Chen Wenhui , Xie Wanmu , Liu Min
Published: May 2023

Purpose:

Our goal was to study both right and left ventricular blood flow in patients with precapillary pulmonary hypertension (pre-PH) with 4-dimensional (4D) flow magnetic resonance imaging (MRI) and to analyze their correlation with cardiac functional metrics on cardiovascular magnetic resonance (CMR) and hemodynamics from right heart catheterization (RHC).

Materials and Methods:

129 patients (64 females, mean age 47 ± 13 y) including 105 patients with pre-PH (54 females, mean age 49 ± 13 y) and 24 patients without PH (10 females, mean age 40 ± 12 y) were retrospectively included. All patients underwent CMR and RHC within 48 hours. 4D flow MRI was acquired using a 3-dimensional retrospectively electrocardiograph-triggered, navigator-gated phase contrast sequence. Right and left ventricular flow components including the percentages of direct flow (PDF), retained inflow (PRI), delayed ejection flow (PDE), and residual volume (PRVo) were respectively quantified. The ventricular flow components between patients with pre-PH and non-PH were compared and correlations of flow components with CMR functional metrics and hemodynamics measured with RHC were analyzed. Biventricular flow components were compared between survivors and deceased patients during the perioperative period.

Results:

Right ventricular (RV) PDF and PDE significantly correlated with RVEDV and RV ejection fraction. RV PDF negatively correlated with pulmonary arterial pressure (PAP) and pulmonary vascular resistance. When the RV PDF was <11%, the sensitivity and specificity of RV PDF for predicting mean PAP ≥25 mm Hg were 88.6% and 98.7%, respectively, with an area under the curve value of 0.95 ± 0.02. When RV PRVo was more than 42%, the sensitivity and specificity of RV PRVo for predicting mean PAP ≥25 mm Hg were 85.7% and 98.5%, respectively, with an area under the curve value of 0.95 ± 0.01. Nine patients died during the perioperative period. Biventricular PDF, RV PDE, and PRI of survivors were higher than nonsurvivors whereas RV PRVo increased in deceased patients.

Conclusions:

Biventricular flow analysis with 4D flow MRI provides comprehensive information about the severity and cardiac remodeling of PH and may be a predictor of perioperative death of patients with pre-PH.
Implementing a Combined Phone and Mail Recall to Increase Screening Colonoscopy Rates in Adults With Chronic Ulcerative Colitis
Authors: Glover Gypsy
Published: May 2023

Colon cancer is the third leading cancer nationally. To prevent colon cancer and decrease healthcare costs, high-risk individuals such as adults with chronic ulcerative colitis are recommended to stay up-to-date on screening colonoscopies. Despite these recommendations, screening colonoscopy rates remain low both globally and locally. The purpose of this article is to increase surveillance colonoscopy rates among adult patients with chronic ulcerative colitis. Research supports increasing surveillance colonoscopy rates by implementing a combined phone and mail recall with included educational material on the risks of colon cancer. At a clinic for inflammatory bowel disease patients in Southeast Alabama, participants with chronic ulcerative colitis who were overdue for screening colonoscopies were issued two reminder phone calls and a reminder letter coupled with educational material. Both the calls and letters reminded participants that they were due for a surveillance colonoscopy and provided them with an option to schedule the procedure. A pre- and post-survey was used to evaluate screening colonoscopy rates before and after the intervention. The survey indicated whether a patient had scheduled a colonoscopy, intended to schedule a colonoscopy, or completed a colonoscopy within 3 months of project completion. Survey results revealed an 83% increase in screening colonoscopies post-intervention. A chart audit was also performed 3 months after project completion and results indicated a 70% increase in completed colonoscopy rates. The findings from this evidence-based practice project indicate that implementing a phone and mail recall is successful in increasing screening colonoscopy rates.
Comparison of hydroxocobalamin with other resuscitative fluids in volume-controlled and uncontrolled hemorrhage models in swine (Sus-scrofa)
Authors: Paredes R. Madelaine , Castaneda Maria , Mireles Allyson A. , Rodriguez Dylan , Maddry Joseph
Published: May 2023

BACKGROUND

Traumatic hemorrhage is the leading cause of preventable death in military environments. Treatment with resuscitative fluids and blood components is based on availability, thus, frequently unavailable in the prehospital setting, due to lack of resources and costs. Hydroxocobalamin (HOC), increases blood pressure via nitric oxide scavenging. We evaluated HOC as a resuscitation fluid, in two swine hemorrhage models. Our objectives were to (1) evaluate whether HOC treatment following hemorrhagic shock improves hemodynamic parameters and (2) determine whether those effects are comparable to whole blood (WB) and lactated ringers (LR).

METHODS

Yorkshire swine (Sus scrofa) (n = 72) were used in models of controlled hemorrhage (CH) (n = 36) and uncontrolled hemorrhage (UH) (n = 36). Randomized animals received treatment with 500 mL of either WB, LR, HOC (150 mg/kg), followed by a six-hour observation (n = 6 each group). Survival, hemodynamics, blood gases (ABGs) and chemistries were collected. Data reported as mean ± standard error of the mean and statistical analysis by ANOVA (p < 0.05).

RESULTS

Blood loss for CH was 41% ± 0.02 versus 33% ± 0.07 for UH. For CH, HOC treatment maintained higher systolic blood pressure (sBP, mm Hg) compared with WB and LR (72 ± 1.1; 60 ± 0.8; 58 ± 1.6; respectively). Heart rate (HR), cardiac output (CO), Sp
o
2
and vascular resistance were comparable with WB and LR. The ABG values were comparable between HOC and WB. For UH, HOC treatment maintained sBP levels comparable to WB and higher than LR (70 ± 0.9; 73 ± 0.5; 56 ± 1.2). HR, CO, Sp
o
2
, and systemic vascular resistance were comparable between HOC and WB. Survival, hemodynamics, blood gases were comparable between HOC and WB. No survival differences were found between cohorts.

CONCLUSION

Hydroxocobalamin treatment improved hemodynamic parameters and Ca2+ levels compared with LR and equivalent to WB, in both models. Hydroxocobalamin may be a viable alternative when WB is not available.
Pediatric Intraoperative Neurophysiological Monitoring and Long-Term Outcomes in a Developing Country
Authors: San-Juan Daniel , Vanegas Jenny Angelica Vicuña , López Raúl Aguilar , Jiménez Christian Ramos , Reyes Luis Adrián de la Cruz
Published: May 2023

Purpose:

Pediatric intraoperative neurophysiological monitoring (IONM) has been shown to be effective in preventing and reversing postoperative neurological deficits in developed countries. There are currently no published studies from developing countries that describe neurophysiological findings and postoperative outcomes. Our study aims to address these gaps in children undergoing neurosurgical procedures in a single center.

Methods:

We conducted a retrospective study of case series of children who underwent IONM (2014–2020) in the State of Mexico, Mexico. Sociodemographic characteristics, IONM modalities, changes during procedures, and short-term and long-term postoperative results were recorded. Descriptive statistics were used.

Results:

We included 35 patients (≤18 years of age), 57% (20/35) boys. A relative increase of up to 5 times in the use of IONM is observed from 2014 (5.7%) to 2020 (25.7%) in our center. The most frequent preoperative pathologies were located at the infratentorial cranium (40%), followed by the spine and spinal cord (37.1%). The IONM modalities were as follows: free-running EMG 94.3%, transcranial electrical stimulation motor-evoked potentials 91.4%, somatosensory-evoked potentials 85.7%, triggered EMG 28.6%, EEG 25.7%, and visual-evoked potentials 5.7%. Only in 8.3%, we did not obtain sufficient evoked potential baseline signals. At 24 hours postoperatively true negatives were 100%. Long-term follow-up was completed in 22/35 (63%) at 3 months, 12/35 (34.2%) at 6 months, and 5/35 (14.3%) at 12 months with progressive motor and sensory improvement.

Conclusions:

Pediatric multimodal IONM in neurosurgeries from a single center in a developing country is mainly used in pathologies of the posterior fossa, spine, and spinal cord, with true negatives in 100% of those monitored, preventing and avoiding postoperative sequelae.
Non-destructive quality prediction of domestic, commercial red pepper
powder using hyperspectral imaging
Authors: Kim Sang Seop , Choi Ji-Young , Lim Jeong Ho , Cho Jeong-Seok
Published: May 2023

We analyzed the major quality characteristics of red pepper powders from various
regions and predicted these characteristics nondestructively using shortwave
infrared hyperspectral imaging (HSI) technology. We conducted partial least
squares regression analysis on 70% (n=71) of the acquired
hyperspectral data of the red pepper powders to examine the major quality
characteristics. Rc2 values of >0.8 were obtained
for the ASTA color value (0.9263) and capsaicinoid content (0.8310). The
developed quality prediction model was validated using the remaining 30%
(n=35) of the hyperspectral data; the highest accuracy was achieved for
the ASTA color value (Rp2=0.8488), and similar
validity levels were achieved for the capsaicinoid and moisture contents. To
increase the accuracy of the quality prediction model, we conducted spectrum
preprocessing using SNV, MSC, SG-1, and SG-2, and the model’s accuracy
was verified. The results indicated that the accuracy of the model was most
significantly improved by the MSC method, and the prediction accuracy for the
ASTA color value was the highest for all the spectrum preprocessing methods. Our
findings suggest that the quality characteristics of red pepper powders, even
powders that do not conform to specific variables such as particle size and
moisture content, can be predicted via HSI.
Chemical profile and antioxidant activity of peel of
Yellowball, a novel citrus variety
Authors: Lee Sun , Jo Seong-Ho , An Ji-Hyun , Jeong Seong-man , Kim Dong-Shin , Kim Sang Suk , Park Suk Man , Yun Su Hyun , Han Seung-Gab , Kim Hyun-Jin
Published: May 2023

Yellowball (Citrus hybrid cv.
Yellowball ) is a new citrus hybrid between
Haruka (C. tamurana ×
natsudaidai ) and Kiyomi (C.
unshiu × sinensis) and is known to possess
strong antioxidant activity. However, detailed information on the antioxidant
components of its peel has not yet been reported. This study evaluated the
antioxidant activity of the peel and identified the antioxidant components by
fractionating a methanolic extract of Yellowball peels using
liquid-liquid extraction with n-hexane, ethyl ether (ether), ethyl acetate (EA),
butanol, and water. The phenolic contents and antioxidant activities of the
n-hexane, ether, and EA fractions were higher than those of the other fractions,
and these fractions were further separated by semi-preparative high-performance
liquid chromatography (HPLC). Four antioxidant peaks, EA1, EA2, EA3, and He1,
were isolated and analyzed using ultra-performance liquid
chromatography–quadrupole-time- of-flight mass spectrometry
(UPLC-Q-TOF MS). Sinapoyl glucoside and hesperidin were identified in EA2 and
EA3, respectively, and a polymethoxylated flavone (PMF) complex
(5-hydroxy-3,6,7,8,3’,4’-hexamethoxyflavone, natsudaidain,
tetrameth- oxyflavone, and tangeretin) was identified in He1. A compound
in EA1 with m/z 223.0246 [M-H] could not be identified and was named unknown2.
The antioxidant activity of unknown2 (IC50=69.17
μg/mL) was similar to that of Trolox, which was
noted as a major antioxidant in Yellowball peel. Further
studies on the antioxidant capacity of Yellowball peel are
required; however, these results provide a foundation for using
Yellowball peel as an antioxidant.
Vitamin contents and antioxidant characteristics of red and gold kimchi cabbages (Brassica rapa. L. ssp. pekinensis)
Authors: Lee Kang-Hee , Oh Seung-min , Hong Won-Ho , Chun Jiyeon
Published: May 2023

Kimchi cabbage is widely consumed in Korea, with the popularity of this pickled vegetable dish growing internationally due to its health benefits. In this study, the physical (size, color), functional (antioxidant activity, total polyphenol, and flavonoid content), and nutritional (water- and fat-soluble vitamins) characteristics of two new kimchi cabbage varieties, namely red and gold kimchi cabbages (RKC and GKC, respectively), were analyzed and compared with those of the common kimchi cabbage (CKC). There were no significant differences in the thickness or length of the three kimchi cabbages, although RKC had the narrowest outer leaves among the three varieties (11.94 cm). Regarding chromaticity, yellowness was highest in GKC (29.86), whereas redness was highest in RKC (9.31). Furthermore, RKC had the highest recorded vitamin B6 and B9 (1,288.5 μg/100 g and 776.7 μg dietary folate equivalent/100 g, respectively). On the other hand, the fat-soluble vitamins vitamin A (β-carotene) and K (Phylloquinone) were both highest in GKC (907.1 μg/100 g and 712.2 μg/100 g, respectively). Generally, all kimchi cabbage samples contained high levels of vitamin E (1.8-4.9 mg α-tocopherol equivalent/100 g). RKC attained the highest antioxidant activity and total polyphenol and total flavonoid contents among the three kimchi cabbages. These results show that gold and red kimchi cabbage can be used as raw materials in the food-processing industry.
Physicochemical properties of kombucha with fruit peels during fermentation
Authors: Lee Tae Yeon , Yi Young Hyoun
Published: May 2023

The study investigated the pH, acidity, soluble solids, total sugar, polyphenol, flavonoid, anthocyanin content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and color of kombucha with a variety of added fruit peels during the fermentation process. Pear, grape, plum, orange, apple, and golden kiwi peels were added during fermentation. The pH showed a decrease, while an increase in acidity was observed. An increase in soluble solids, which was higher in most experimental groups than the control group, was also observed. A decrease in total sugar was observed over time. However, an increase was observed in reducing sugar. On Day 0, higher total sugar and reducing sugar were detected in the peel addition group compared with the control group. The antioxidant capacity of polyphenol, flavonoid, anthocyanins, and DPPH radicals scavenging increased with fermentation and was higher in all addition groups, except for pear, compared with the control group. Except for grapes and plums containing high levels of anthocyanins, an increase in the L-value was observed over time, and an increase in the a-value of grapes and plums was also observed (p<0.05). The possible utilization of inedible fruit peel in kombucha was shown. Applying inedible fruit peels to kombucha is proposed to increase antioxidant content and modulate color and pH.
The antioxidant ability of nutmeg ethanolic extract in bulk oil and oil-in-water emulsion matrices
Authors: Kim Ji-Eun , Bae Ji-Yun , Kim Mi-Ja
Published: May 2023

The antioxidant ability of 80% ethanolic extract of nutmeg seed (NM80) was evaluated using in vitro assays and bulk oil and oil-in-water (O/W) emulsion matrices. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) cation radical scavenging, and oxygen radical antioxidant capacity (ORAC) in vitro assays were used to evaluate the antioxidant ability of the extract. The DPPH radical scavenging activities of 25, 50, 100, and 200 μg/mL NM80 were 12.5, 20.9, 35.1, and 62.8%, respectively, while the ABTS cation radical scavenging activities were 2.7, 6.5, 30.5, and 29.8%, respectively, demonstrating a dose-dependent effect. The ORAC value was significantly higher at an NM80 concentration of 25 μg/mL than the positive control (p<0.05). The conjugated dienoic acid (CDA), ρ-anisidine, and tertiary butyl alcohol values in 90-min-heated corn oil containing 200 ppm of NM80 were significantly reduced by 3.26, 16.94, and 17.34%, respectively, compared to those for the sample without NM80 (p<0.05). However, the headspace oxygen content and CDA value in the O/W emulsion containing 200 ppm of NM80 at 60°C had 6.29 and 82.85% lower values, respectively, than those for the sample without NM80 (p<0.05). The major volatile compounds of NM80 were allyl phenoxyacetate, eugenol acetate, and eugenol. NM80 could be an effective natural antioxidant in lipid-rich foods in bulk oil or O/W emulsion matrix.
Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors
Authors: Crawford McKenna C. , Tripu Deepika R. , Barritt Samuel A. , Jing Yihang , Gallimore Diamond , Kales Stephen C. , Bhanu Natarajan V. , Xiong Ying , Fang Yuhong , Butler Kamaria A. T. , LeClair Christopher A. , Coussens Nathan P. , Simeonov Anton , Garcia Benjamin A. , Dibble Christian C. , Meier Jordan L.
Published: May 2023

The human acetyltransferase paralogs EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge. To address this gap, here we present a comparative study of drug-like EP300/CREBBP acetyltransferase inhibitors. First, we determine the biochemical and biological potencies of A-485, iP300w, and CPI-1612, highlighting the increased potency of the latter two compounds at physiological acetyl-CoA concentrations. Cellular evaluation shows that inhibition of histone acetylation and cell growth closely aligns with the biochemical potencies of these molecules, consistent with an on-target mechanism. Finally, we demonstrate the utility of comparative pharmacology by using it to investigate the hypothesis that increased CoA synthesis caused by knockout of PANK4 can competitively antagonize binding of EP300/CREBBP inhibitors and demonstrate proof-of-concept photorelease of a potent inhibitor molecule. Overall, our study demonstrates how knowledge of relative inhibitor potency can guide the study of EP300/CREBBP-dependent mechanisms and suggests new approaches to target delivery, thus broadening the therapeutic window of these preclinical epigenetic drug candidates.
Beyond the Kidney: Extra-Renal Manifestations of Monogenic Nephrolithiasis and Their Significance
Authors: Badreddine Jad , Tay Kimberly , Lin Hsin-Ti Cindy , Rhodes Stephen , Schumacher Fredrick R. , Bodner Donald , Wu Chen-Han Wilfred
Published: May 2023

Objective

To explore the frequency of occurrence of extra-renal manifestations associated with monogenic kidney stone diseases.

Methods

A literature review was conducted to identify genes that are well-established monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) and Human Protein Atlas (HPA) databases were used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a single gene-associated phenotype (GAP) unit such that one GAP encompasses all related disease phenotypes for a specific gene. We measured the total number of GAPs involving each phenotype category and determined the median phenotype category. Phenotype categories were classified as overrepresented or underrepresented if the number of GAPs involving them was higher or lower than the median, respectively. A chi-square test was conducted to determine whether the number of GAPs affecting a given category significantly deviated from the median.

Results

Fifty-five genes were identified as monogenic causes of nephrolithiasis. All GAPs comprised at least one extra-renal phenotype category. The median phenotype category was part of 10 (18%) unique GAPs. A total of 6 significantly overrepresented (growth, skeletal, neurologic, abdomen/gastrointestinal, muscle, metabolic features) and 5 significantly underrepresented (mouth, voice, neck, immunology, neoplasia) phenotype categories were identified among our group of monogenic kidney stone diseases (p<0.05) with impaired growth being the most common manifestation.

Conclusion

Monogenic nephrolithiasis is a multi-system disorder. Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal prognosis in patients.
Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases
Authors: Karlsson Joakim , Sah Vasu R. , Olofsson Bagge Roger , Kuznetsova Irina , Iqbal Munir , Alsén Samuel , Stenqvist Sofia , Saxena Alka , Ny Lars , Nilsson Lisa M. , Nilsson Jonas A.
Published: May 2023

Uveal melanoma (UM) is a rare melanoma originating in the eye’s uvea, with 50% of patients experiencing metastasis predominantly in the liver. In contrast to cutaneous melanoma, there is only a limited effectiveness of combined immune checkpoint therapies, and half of patients succumb to recurrent disease after two years. This study aimed to provide a path towards enhancing immunotherapy efficacy by identifying and functionally validating tumor-reactive T cells in liver metastases of patients with UM. We employed single-cell RNA sequencing of biopsies and tumor-infiltrating lymphocytes (TILs) to identify potential tumor-reactive T cells. Patient-derived xenograft (PDX) models of UM metastases were created from patients, and tumor sphere cultures were generated from these models for co-culture with autologous or MART1-specific HLA-matched allogenic TILs. Activated T cells were subjected to TCR sequencing, and the TCRs were matched to those found in single-cell sequencing data from biopsies, expanded TILs and in livers or spleens of PDX models injected with TILs. Our findings revealed that tumor-reactive T cells resided not only among activated and exhausted subsets of T cells, but also in a subset of cytotoxic effector cells. In conclusion, combining single-cell sequencing and functional analysis provides valuable insights into which T cells in UM may be useful for cell therapy amplification and marker selection.
Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS)
Authors: Yin Zhengwei , Li Min , Niu Ce , Yu Mingkai , Xie Xinru , Haimiti Gulishati , Guo Wenhong , Shi Juan , He Yueyue , Ding Jianbing , Zhang Fengbo
Published: May 2023

Objective the dominant epitopes of T and B cells of VirB8 and VirB10 of Brucella type IV. Secretory systems were predicted and analyzed by bioinformatics, and then multi-epitope vaccines were constructed by reverse vaccination. Methods The amino acid sequences of VirB8 and VirB10 were obtained from the UniProt database, T and B cell dominant epitopes were selected and supplemented with adjuvants to construct a multi-epitope vaccine, SOPMA and RoseTTAFold were applied to predict secondary and tertiary structures respectively for immune simulations. Finally, molecular dynamics simulations of iMEV-TLR4 were then performed. Results one cytotoxic T lymphocyte (CTL) epitope, five helper T lymphocyte (HTL) epitopes, two linear B cell epitopes and three conformational B cell epitopes were obtained in VirB8. 1 cytotoxic T lymphocyte (CTL) epitope, 4 helper T lymphocyte (HTL) epitopes, 4 linear B cell epitopes, and 3 conformational B cell epitopes were obtained in VirB10. The resulting multiepitope vaccine is a protein with good antigenicity, hydrophilicity, and stability. Conclusion a novel brucella multiepitope vaccine was designed by reverse vaccination, and this study provides a theoretical basis for further research.
GraphCPLMQA: Assessing protein model quality based on deep graph coupled networks using protein language model
Authors: Liu Dong , Zhang Biao , Liu Jun , Li Hui , Song Le , Zhang Gui-Jun
Published: May 2023

Model quality evaluation is crucial part of protein structural biology. How to distinguish high-quality models from low-quality models, and to assess which high-quality models have relatively incorrect regions for improvement, are remain challenge. More importantly, the quality assessment of multimer models is a hot topic for structure predicton.In this work, we present GraphCPLMQA, a novel graph-coupled network that uses embeddings from protein language models to assess residue-level protein model quality. The GraphCPLMQA consists of a graph encoding module and a transform-based convolutional decoding module. In encoding module, the underlying relational representations of sequence and high-dimensional geometry structure are extracted by protein language models with Evolutionary Scale Modeling. In decoding module, the mapping connection between structure and quality are inferred by the representations and low-dimensional features. Specifically, the triangular location and residue level contact order features are designed to enhance the association between the local structure and the overall topology. Experimental results demonstrate that GraphCPLMQA using single-sequence embedding achieves the best performance compared to the CASP15 interface evaluation method in 9108 models of CASP15 multimer test set. In CAMEO blind test (2022-05-20∼2022-08-13), GraphCPLMQA ranked first compared to other servers. GraphCPLMQA also outperforms state-of-the-art methods on 19,035 models in CASP13 and CASP14 monomer test set. Finally, on AlphaFold2 datasets, GraphCPLMQA was superior to self-assessment of AlphaFold2 in MAE metric, and it was able to screen out better models than AlphaFold2.
CO-EXPRESSION OF DISTINCT COILED COILS CAN LEAD TO THEIR ENTANGLEMENT
Authors: Mizgier Nikola A. , Jones Charlie E. , Furano Anthony V.
Published: May 2023

L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ∼100 million years (Myr) of activity in primates. L1 replicates in early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2, a replicase, and ORF1, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors.
Identification of Novel Scaffold Proteins for Improved Endogenous Engineering of Extracellular Vesicles
Authors: Zheng Wenyi , Rädler Julia , Sork Helena , Niu Zheyu , Roudi Samantha , Bost Jeremy , Görgens André , Zhao Ying , Mamand Doste , Liang Xiuming , Wiklander Oscar , Lehto Taavi , Gupta Dhanu , Nordin Joel Z. , EL Andaloussi Samir
Published: May 2023

Extracellular vesicles (EVs) are gaining ground as next-generation drug delivery modalities. Genetic fusion of the protein of interest to a scaffold protein with high EV-sorting ability represents a robust cargo loading strategy. To address the paucity of such scaffold proteins we conducted a large-scale comparative study involving 244 candidate proteins. Their EV-sorting potential was evaluated using a simple but reliable assay that can distinguish intravesicular cargo proteins from surface and non-vesicular proteins. Notably, 24 proteins with conserved EV-sorting abilities across five types of producer cells were identified. Most of these are first to be reported including TSPAN2 and TSPAN3, which emerged as lead candidates, outperforming the well-known CD63 scaffold. Importantly, these engineered EVs show promise as delivery vehicles as demonstrated byin vitroandin vivointernalization studies with luminal cargo proteins as well as surface display of functional domains. The discovery of these novel scaffolds provides a new platform for EV-based engineering.
Precision Targeting of Na-K-2Cl cotransporter (NKCC1) RNA In Vitro with RfxCas13d
Authors: Sandoval Alfredo , Chen Bo
Published: May 2023

The Na-K-2Cl cotransporter (NKCC1) is considered an attractive drug target in the Central nervous system (CNS) for treating various CNS disorders. However, the specific role of NKCC1 in different types following injury within the CNS is not well understood due to its expression in multiple cell types. Additionally, there is a lack of a robust method for knocking down NKCC1 transcripts. In this study, we utilized Cas13 nucleases, a type of programmable RNA-targeting CRISPR enzyme, to effectively degrade NKCC1 mRNA in cultured cells. We developed a versatile pipeline for crRNA screening and validation in vitro and demonstrated the successful knockdown of NKCC1 using RfxCas13d. Our findings establish RfxCas13d as a powerful tool for targeting specific transcripts in vitro. By demonstrating the successful in vitro application of RfxCas13d-mediated NKCC1 RNA knockdown, we have laid the groundwork for future investigations into the therapeutic potential of NKCC1 modulation in CNS disorders.
The subjective amplitude of the diurnal rhythm matters - chronobiological insights for neuroimaging studies
Authors: Zareba Michal Rafal , Scislewska Patrycja , Fafrowicz Magdalena , Marek Tadeusz , Oginska Halszka , Szatkowska Iwona , Beldzik Ewa , Domagalik Aleksandra
Published: May 2023

Multiple aspects of human physiology, including mood and cognition, are subjected to diurnal rhythms. While the previous neuroimaging studies have focused solely on the morningness-eveningness (ME) preference dichotomy, i.e. the circadian phase, the second key dimension of the diurnal rhythms, i.e. the strength of these preferences (amplitude; AM), has been completely overlooked. Uncovering the neural correlates of AM is especially important considering its link with negative emotionality. Structural T1-weighted neuroimaging data from 79 early (EC) and 74 late (LC) chronotypes were analysed to compare grey matter (GM) volume and cortical thickness. The study aimed to elucidate whether the subjective AM and its interaction with ME was a significant predictor of individual brain structure. Both GM volume and cortical thickness of the left primary visual cortex was negatively correlated with AM scores across the entire sample. Furthermore, EC and LC differed in their association between AM scores and the GM volume in the right middle temporal gyrus, with the positive and negative correlations reported respectively in the two groups. The current study underlines the importance of the visual system in circadian rhythmicity and provides possible neural correlates for AM-related differences in negative affect processing. Furthermore, the presence of the opposite correlations between brain anatomy and AM in the two groups suggests that the behavioural and neuronal chronotype differences might become more pronounced in individuals with extreme diurnal differences in mood and cognition, highlighting the necessity to additionally account for AM in neuroimaging studies.

Highlights

Structure of primary visual cortex is linked to subjective diurnal rhythms amplitude

Middle temporal gyrus is sensitive to interaction of rhythm phase and distinctness

Distinctness of the diurnal rhythms may modulate results of the neuroimaging studies
Temperature affects viral kinetics and vectorial capacity ofAedes aegyptimosquitoes co-infected with Mayaro and Dengue viruses
Authors: Terradas Gerard , Manzano-Alvarez Jaime , Vanalli Chiara , Werling Kristine , Cattadori Isabella M , Rasgon Jason L
Published: May 2023

Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquitoAedes aegyptiis the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. Here, we examine single and co-infection of Mayaro virus (-D strain,Alphavirus) and dengue virus (serotype 2,Flavivirus) inAe. aegyptiadults and cell lines at two constant temperatures, moderate (27°C) and hot (32°C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes, with a tendency for higher titers in co-infected mosquitoes at both temperatures and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs single infections and was more evident at earlier timepoints (7 vs 14 days post infection). The temperature-dependent phenotype was confirmedin vitroby faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses, but further studies are necessary to clarify the role of co-infection at different and variable temperature regimes.

Author summary

Global warming is having devastating consequences for the environment, and a cause of concern is the increase in local abundance and geographic range of mosquitoes and the associated viruses they transmit. This study explores how temperature affects the mosquito’s ability to survive and potentially spread two viruses, Mayaro and dengue, in single or co-infections. We found that Mayaro virus was not clearly affected by temperature or the presence of dengue infection. In contrast, dengue virus showed higher infection and potential for higher transmission in mosquitoes kept at high temperatures, and this trend was stronger in co-infections compared to single infections. Mosquito survival consistently decreased at high temperatures. We hypothesize the differences observed for dengue virus are due to the faster growth and viral activity in the mosquito at hotter temperatures, a pattern not observed for Mayaro virus. More studies under different temperature regimes are needed to clarify the role of co-infection.
High-density exploration of activity states in a multi-area brain model
Authors: Aquilué-Llorens David , Goldman Jennifer S. , Destexhe Alain
Published: May 2023

Biophysically-grounded whole-brain models were built recently using tractography data to interconnect multiple mesoscopic models, which can simulate the dynamics of neuronal populations with only a few equations. Mean-field models of neural populations, specifically the Adapting AdEx mean-field, was used for this purpose because it can integrate key biophysical mechanisms such as spike-frequency adaptation and its regulation at cellular scales, to the emergence of brain-scale dynamics. Using this approach, with the Virtual Brain (TVB) environment, it has been possible to model the macroscopic transitions between brain states, described by variation in brain-scale dynamics between asynchronous and rapid dynamics during conscious brain states, and synchronized slow-waves, with Up-and-Down state dynamics during unconscious brain states, emerging from mechanisms at the cellular level. Transitions between brain states are driven by changes in neuromodulation that can be due to intrinsic regulation during sleep-wake cycles or extrinsic factors such as anesthetics, which, in turn, affect spike-frequency adaptation. Here, we perform a dense grid parameter exploration of the TVB-AdEx model, making use of High Performance Computing, to thoroughly explore the properties of this model. We find that there is a remarkable robustness of the effect of adaptation to induce synchronized slow-wave activity. Moreover, the occurrence of slow waves is often paralleled with a closer relation between functional and structural connectivity. We find that hyperpolarization can also generate unconscious-like synchronized Up and Down states, which may be a mechanism underlying the action of anesthetics. We conclude that the parameter space of the TVB-AdEx model reveals features identified experimentally in sleep and anesthesia.
Do psycho-entrepreneurial traits and social networks matter for innovativeness among Saudi female entrepreneurs?
Authors: Jaziri Raouf , Miralam Mohammad Saleh
Published: May 2023

Purpose

Psychological and entrepreneurial traits have been widely studied as explicative variables of encouraging entrepreneurial behavior, while their impact on innovative activity is less explored. This study examines whether, how and why psycho-entrepreneurial traits and social networks effect innovativeness among women firm owners.

Design/methodology/approach

Analysis of data collected from 304 Saudi women entrepreneurs accompanied by business accelerators provides a wide support with some notable exceptions. We use Structural Equation Modeling technique to estimate how different constructs interact with each other and jointly affect directly or indirectly women's innovativeness behavior in Saudi Arabia.

Findings

Findings point out that innovativeness is positively and significantly affected by emotional intelligence, internal locus of control, entrepreneurial alertness and entrepreneurial self-efficacy. The construct of entrepreneurial self-efficacy mediates the relationship between both business and personal networks and innovativeness. However, professional forums and mentors have no significant effect on innovativeness.

Research limitations/implications

The sample selection is limited to two entrepreneurial support structures especially business accelerator and business incubator. Expanding the context to other support structures can reinforce the implications and provide more valuable results.

Practical implications

The findings are likely to be of applicability for improving women entrepreneurship by entrepreneurial support structures.

Originality/value

This research is original in the sense that it investigated useful insights of innovativeness among Saudi female entrepreneurs.
Exploring intervention strategies to enhance face recognition abilities in adolescents with autism spectrum disorder: assessing the impact of verbalization and Navon tasks
Authors: Kim Minje , Chung Kyong-Mee , Chung Eun-Sun
Published: May 2023

Purpose

The purpose of this study is to examine the effectiveness of two intervention strategies – identifying the global letter of Navon letters and verbally describing a face – in improving face recognition abilities of adolescents with autism spectrum disorder (ASD).

Design/methodology/approach

A total of 15 adolescents with ASD and 15 typically developing (TD) adolescents participated in this study, which consisted of three experimental conditions: verbalization, Navon and control. Participants were presented with a target face for a short period of time, then completed a task specific to the condition in a counterbalanced order, followed by a face recognition task.

Findings

The results of this study showed no significant interaction effects between groups and conditions, either in accuracy or reaction time. However, TD adolescents performed better than ASD adolescents in terms of accuracy. In addition, the verbalization condition resulted in better performance with slower response times compared to the control condition.

Originality/value

These findings suggest that verbalization may be a useful strategy to enhance face recognition abilities in ASD and TD individuals.
Exploration of caregiver experience for children with ASD: an in-depth perspective
Authors: Gupta Neha , Khanna Manya , Garg Rashi , Sethi Vedantika , Khattar Shivangi , Tekkar Purva , Maria Shwetha , Gupta Muskan , Saxena Akash , Gupta Parul , Ann Schuchert Sara
Published: May 2023

Purpose

This study aims to examine the psycho-emotional and social experiences of caregivers of children with autism spectrum disorder. Various facets of the caregiving experience are explored, including the feelings and thoughts of the parents/caregivers, such as the resilience experienced in their journey, how they coped with the challenges and also their positive experiences.

Design/methodology/approach

In this study, these aspects of the caregiving experience are broadly probed using semi-structured interviews subjected to narrative analysis. Lastly, there is a focus on the role of therapist-led intervention, specifically, the Eye to I©intervention model and its contributions to the parent/caregiver experience.

Findings

Findings from this study indicate that parents benefit from interventions that bridge gaps in skills and interpersonal communication which parents/caregivers feel they encounter in their day-to-day activities. Additionally, support groups for parents and caregivers could further address these issues.

Originality/value

This exploration reveals insights about the roles of societal structures and the caregiving journey.
Competence or warmth: why do consumers pay for green advertising?
Authors: Shi Jiarong , Jiang Zihao
Published: May 2023

Purpose

This study aims to assess the impact of functional green advertising receptivity and emotional green advertising receptivity on consumers' green purchase intention. The authors then examine the mediating role of perceived competence and perceived warmth. Furthermore, the authors explore the moderating effect of power distance belief (PDB) on the relationships between green advertising receptivity with different appeals and consumers' perceived competence and perceived warmth respectively.

Design/methodology/approach

Based on the online survey platform, a total of 468 responses were obtained in China from January to March 2022. 408 valid replies were collected and analyzed in this study. The research hypotheses were empirically verified with bootstrap approach.

Findings

The empirical results indicate that both functional green advertisi\ng receptivity and emotional green advertising receptivity are significantly positively correlated with green purchase intention, and perceived competence and perceived warmth play the mediating role. Besides, PDB significantly strengthens the relationship between functional green advertising receptivity and perceived competence, but weakens the incentive effect of emotional green advertising receptivity on perceived warmth.

Originality/value

The psychological mechanism of the receptivity of green advertising with different appeals affecting green purchase intention remains unclear. This is one of the first studies to uncover how functional green advertising receptivity and emotional green advertising receptivity influence green purchase intention. Besides, the impact of PDB on the formation process of consumer perception is also a black box. By clarifying and comparing the moderating role of PDB on the relationships between advertising receptivity with different appeals and consumers' perceived competence and perceived warmth, this study contributes to the research on the effectiveness of green advertising.
A novel word-graph-based query rewriting method for question answering
Authors: Yan Rongen , Dang Depeng , Gao Hu , Wu Yan , Yu Wenhui
Published: May 2023

Purpose

Question answering (QA) answers the questions asked by people in the form of natural language. In the QA, due to the subjectivity of users, the questions they query have different expressions, which increases the difficulty of text retrieval. Therefore, the purpose of this paper is to explore new query rewriting method for QA that integrates multiple related questions (RQs) to form an optimal question. Moreover, it is important to generate a new dataset of the original query (OQ) with multiple RQs.

Design/methodology/approach

This study collects a new dataset SQuAD_extend by crawling the QA community and uses word-graph to model the collected OQs. Next, Beam search finds the best path to get the best question. To deeply represent the features of the question, pretrained model BERT is used to model sentences.

Findings

The experimental results show three outstanding findings. (1) The quality of the answers is better after adding the RQs of the OQs. (2) The word-graph that is used to model the problem and choose the optimal path is conducive to finding the best question. (3) Finally, BERT can deeply characterize the semantics of the exact problem.

Originality/value

The proposed method can use word-graph to construct multiple questions and select the optimal path for rewriting the question, and the quality of answers is better than the baseline. In practice, the research results can help guide users to clarify their query intentions and finally achieve the best answer.
Toward ecological environmental risk for spoil ground group management in mega projects
Authors: Li Yulong , Yao Ziwen , Wu Jing , Zeng Saixing , Wu Guobin
Published: May 2023

Purpose

The numerous spoil grounds brought about by mega transportation infrastructure projects which can be influenced by the ecological environment. To achieve better management of spoil grounds, this paper aims to assess their comprehensive risk levels and categorize them into different categories based on ecological environmental risks.

Design/methodology/approach

Based on analysis of the environmental characteristics of spoil grounds, this paper first comprehensively identified the ecological environmental risk factors and developed a risk assessment index system to quantitatively describe the comprehensive risk levels. Second, this paper proposed a comprehensive model to determine the risk assessment and categorization of spoil ground group in mega projects integrating improved projection pursuit clustering (PPC) method and K-means clustering algorithm. Finally, a case study of a spoil ground group (includes 50 spoil grounds) in a mega infrastructure project in western China is presented to demonstrate and validate the proposed method.

Findings

The results show that our proposed comprehensive model can efficiently assess and categorize the spoil grounds in the group based on their comprehensive ecological environmental risk. In addition, during the process of risk assessment and categorization of spoil grounds, it is necessary to distinguish between sensitive factors and nonsensitive factors. The differences between different categories of spoil grounds can be recognized based on nonsensitive factors, and high-risk spoil grounds which need to be focused more on can be identified according to sensitive factors.

Originality/value

This paper develops a comprehensive model of risk assessment and categorization of a group of spoil grounds based on their ecological environmental risks, which can provide a reference for the management of spoil grounds in mega projects.