bluuebunny/crossref_metadata_2025 huggingface dataset:
Critically buried avalanche victims can develop severe hypothermia in less than 60 minutes
Authors: Rauch Simon , Kompatscher Julia , Clara Andreas , Öttl Iris , Strapazzon Giacomo , Kaufmann Marc
Published: April 2023

Background
A major challenge in the management of avalanche victims in cardiac arrest is differentiating hypothermic from non-hypothermic cardiac arrest, as management and prognosis differ. Duration of burial with a cutoff of 60 min is currently recommended by the resuscitation guidelines as a parameter to aid in this differentiation This, because the fastest cooling rate under the snow reported so far is 9.4°C per hour, suggesting that it would take >60 min to cool below 30°C, which is the temperature threshold below which a hypothermic cardiac arrest can occur.
Case presentation
We describe a case with a cooling rate of 14°C per hour, assessed on site with an oesophageal temperature probe. The patient was transported under continuous mechanical CPR to an ECLS facility and rewarmed with VA-ECMO, although his HOPE score was 3 % only. After three days he developed brain death and became an organ donor.
Conclusions
With this case we would like to underline three important aspects: first, whenever possible, core body temperature should be used instead of burial duration to make triage decisions. Second, the HOPE score, which is not well validated for avalanche victims, had a good discriminatory ability in our case. Third, although extracorporeal rewarming was futile for the patient, he donated his organs. Thus, even if the probability of survival of a hypothermic avalanche patient is low based on the HOPE score, ECLS should not be withheld by default and the possibility of organ donation should be considered.
The impact of Green Financial Policies on Carbon Emission Efficiency: Empirical Evidence from China
Authors: Lei Zhonghao , Wang Dongmei
Published: April 2023

Given the release of China's green financial policy, this paper constructs a quasi-natural experiment to investigate the impact of such policy on urban carbon emission efficiency and its impact mechanism. In 2016, seven ministries including the People's Bank of China jointly issued the Guidance on Building A Green Financial System, a milestone of the establishment of a more comprehensive green financial policy system in China. However, it is not a straight determinant of improved efficiency of carbon emissions. Based on the empirical panel data of 283 prefecture-level cities from 2011–2020, we adopted a DID model to examine the effect of green financial policies on urban carbon emission efficiency, where the treatment and control groups were divided according to their degrees of dependence on energy as influenced by green financial policies. The results indicated that green financial policies significantly and sustainably improved the carbon efficiency in these cities. Our mechanism further revealed that such improvement was achieved by technological innovation, accelerated industrial restructuring, and reduced energy consumption.
Uni-RXN: A Unified Framework Bridging the Gap between Chemical Reaction Pretraining and Conditional Molecule Generation
Authors: Qiang Bo , Zhou Yiran , Ding Yuheng , Liu Ningfeng , Song Song , Zhang Liangren , Huang Bo , Liu Zhenming
Published: April 2023

Chemical reactions are the fundamental building blocks of drug design and organic chemistry research. In recent years, there has been a growing need for a large-scale deep-learning framework that can efficiently capture the basic rules of chemical reactions. In this paper, we have proposed a unified framework that addresses both the reaction representation learning and molecule generation tasks, which allows for a more holistic approach. Inspired by the organic chemistry mechanism, we develop a novel pretraining framework that enables us to incorporate inductive biases into the model. Our framework achieves state-of-the-art results on challenging downstream tasks. By possessing chemical knowledge, this framework can be applied to reaction-based generative models, overcoming the limitations of current molecule generation models that rely on a small number of reaction templates. In the extensive experiments, our model generates synthesizable drug-like structures of high quality. Overall, our work presents a significant step toward a large-scale deep-learning framework for a variety of reaction-based applications.
The impact of an e-newsletter or animated video to disseminate outdoor free-play information in relation to COVID-19 Guidelines in New South Wales Early Childhood Education and Care services: a randomised controlled trial
Authors: Reilly Kathryn , Jackson Jacklyn , Lum Melanie , Pearson Nicole , Lecathelinais Christophe , Wolfenden Luke , Turon Heidi , Yoong Sze Lin
Published: April 2023

Background: State-based Guidelines were issued for Early Childhood Education and Care (ECEC) services recommending greater time outdoors and inclusion of indoor-outdoor programs to facilitate social distancing to reduce spread of COVID-19. The aim of this 3-arm randomised controlled trial (RCT) was to examine the impact of different dissemination strategies on increasing ECEC service intentions to adopt recommendations from the Guidelines.
Methods: This was a post-intervention only RCT. A sample of eligible ECEC services in New South Wales (n=1026) were randomly allocated to one of three groups; i) e-newsletter resource; ii) animated video resource; or iii) control (standard email). The intervention was designed to address key determinants of guideline adoption including awareness and knowledge. Following delivery of the intervention in September 2021, services were invited to participate in an online or telephone survey from October-December 2021. The primary trial outcome was the proportion of services intending to adopt the Guidelines, defined as intention to; (i) offer an indoor-outdoor program for the full day; or (ii) offer more outdoor play time. Secondary outcomes included awareness, reach, knowledge and implementation of the Guidelines. Barriers to Guideline implementation, cost of the dissemination strategies and analytic data to measure fidelity of intervention delivery were also captured.
Results: Of the 154 services that provided post-intervention data, 58 received the e-newsletter (37.7%), 50 received the animated video (32.5%), and 46 received the control (29.9%). Services who received the animated video had nearly five times the odds (OR: 4.91 [1.03, 23.34] p=0.046) than those in the control group, to report having intentions to adopt the Guidelines. There were no statistically significant differences in awareness or knowledge of the Guidelines between either intervention or control services. Development costs were greatest for the animated video. The extent to which the dissemination strategy was viewed in full, were similar for both the e-newsletter and animated video.
Conclusion: This study found potential for the inclusion of interactive strategies to disseminate policy and guideline information within the ECEC setting, in the context of the need for rapid communication. Further research should explore the added benefits of embedding such strategies within a multi-strategy intervention.
Trial registration: Retrospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 23/02/2023 (ACTRN 12623000198628).
A Multilevel Analysis of the Triple Burden of Malnutrition in Indonesia: Trends and Determinants From Repeated Cross-Sectional Surveys
Authors: Andriani Helen , Friska Erlin , Arsyi Miftahul , Sutrisno Alphyyanto Eko , Waits Alexander , Rahmawati Nurul Dina
Published: April 2023

Background Although child malnutrition has been reducing, the coexistence in mothers and children of various forms of malnutrition has continued to rise around the world. In the Indonesian context, a knowledge gap exists on the coexistence of multiple malnutrition burdens. This study examines trends in the coexistence of the triple burden of malnutrition (TBM) among mother–child pairs living in the same house and explores multilevel (individual, household, and community) factors associated with TBM in Indonesia.Methods We used data from the 2013 and 2018 Indonesia Basic Health Research, the nationally representative survey of the Indonesian population, as repeated cross-sectional surveys. The anthropometric measurements of the mother–child pairs and the hemoglobin levels of the children were collected. We employed a multilevel mixed-effects model to consider the hierarchical data structure. The model captured the role of cluster, district, provincial differences, and the individual, household, community-level, and TBM status characteristics.Results Of 3,891 mother–child pairs analyzed, 24.9% experienced TBM. Girls had 63% higher odds than boys of TBM (aOR: 1.63; 95% CI: 1.30 to 2.03). Significantly lower odds were found in children of mothers who had a gestational age lower than 37 weeks (aOR: 0.72; 95% CI: 0.55 to 0.94). At the household level, children with a father who had a high-school, primary-school, or no school education had significantly higher odds of TBM than children of fathers who had graduated from academy. Children of mothers who visited Antenatal Care (ANC) no more than 6 times had significantly lower odds (aOR: 0.65; 95% CI: 0.47 to 0.88). Children of mothers who consumed Iron and Folic Acid (IFA) supplements had significantly lower odds.Conclusion TBM is related to characteristics at not just the individual level but also the family and community levels. To achieve significant outcomes, integrated nutrition interventions in Indonesia should also consider family and community factors.
Reciprocal regulation of forkhead box C1 and L1 cell adhesion molecule contributes to triple-negative breast cancer progression
Authors: Zhang Fan , Xu Yue , Lin Jiediao , Pan Hongchao , Cui Yukun
Published: April 2023

Purpose: Forkhead box C1 (FOXC1) may act as a therapeutic target for triple-negative breast cancer (TNBC) but without a comprehensive understanding of its regulations, especially at the upstream. L1 cell adhesion molecule (L1CAM) is a transmembrane glycoprotein that may involve in brain metastasis. Indicated by a positive correlation between FOXC1 and L1CAM transcripts, this study aims to further examine their relation in the process of TNBC.
Methods: FOXC1 and L1CAM transcripts were downloaded fromtwo public datasets, and their proteins were examined in four TNBC cell lines. FOXC1 and L1CAM were separately knocked down in BT549 cells; L1CAM was overexpressed in BT549-shFOXC1, MDA-MB-231, and HCC1937 cells. CCK-8, transwell and wound healing assays were conducted in these cells, so was immunohistochemical staining in tumors.
Results: L1CAM and FOXC1 transcripts were positively correlated in public datasets. BT549-shFOXC1 cells showed a decreased L1CAM expression both at the transcriptional and protein levels. Intriguingly, BT549-siL1CAM cells displayed decreased FOXC1 proteins, but exerted little effect on FOXC1 transcripts. Conversely, overexpression of L1CAM resulted in upregulation of FOXC1 protein without substantial change in FOXC1 mRNA, that consistently observedin BT549-shFOXC1, MDA-MB-231-L1CAM and HCC1937-L1CAM cells. Additionally, decreased or increased capacities of cell proliferation, migration, and invasion were seen along with down- or up-regulation of FOXC1 or L1CAM. Finally, a positive correlation between L1CAM and FOXC1 proteins was observed in human TNBC tumors.
Conclusion:FOXC1 and L1CAM display coregulation at the protein level but not mRNA level to positively affect cell proliferation, migration and invasion in TNBC.
Quantifying digital health inequality across a national healthcare system
Authors: Zhang Joe , Gallifant Jack , Pierce Robin , Teo James , Celi Leo , Ashrafian Hutan
Published: April 2023

Differential digital health uptake at population level is not well-understood. Deployment of universal digital health interventions, including a national smartphone app and online primary care services, allows measurement of digital inequality across a nation. We analysed data for 6356 primary care providers across England, testing association of population characteristics with digital uptake during 2021/2022. We find association between deprivation and reduced uptake, concerning for technologically driven widening of healthcare inequalities.
Iodide Manipulation Using Zinc Additives for Efficient Perovskite Solar Minimodules
Authors: Huang Jinsong , Uddin Md Aslam , Rana Prem Jyoti Singh , Ni Zhenyi , Yang Guang , Li Mingze , Wang Mengru , Gu Hangyu , Zhang Hengkai , Dou Benjia Dak
Published: April 2023

Interstitial iodides are the most important type of defects in perovskite solar cells that limits efficiency and stability. They can be generated during solution, film, and device processing and further accelerate device degradation. Herein, we find that introducing a small amount of an organozinc compound- zinc trifluoromethanesulfinate (Zn(OOSCF3)2) in the perovskite solution can control the iodide defects in resultant perovskites ink and films. CF3SOŌ vigorously suppresses molecular iodine formation in the perovskites by reducing it to iodide, while zinc cations can precipitate out excess iodide by forming a Zn-Amine complex so that the iodide interstitials in the resultant perovskite films can be suppressed. The perovskite films using these additives show improved photoluminescence quantum efficiency and reduce deep trap density, despite that zinc cations reduce the perovskite grain size and iodide interstitials. The zinc additives facilitate the formation of more uniform perovskite films on large-area substrates (78-108 cm2) in the blade-coating process. Fabricated minimodules show power conversion efficiencies of 19.60% and 19.21% with aperture areas of 84 and 108 cm2, respectively, as certified by National Renewable Energy Laboratory (NREL), the highest efficiency certified for minimodules of these sizes.
A Cellular Senescence-Related Signature Predicts Cervical Cancer Patient Outcome and Immunotherapy Sensitivity
Authors: Shao Huijing , Li Xia , Wu Pengfei , Chen Zixi , Zhang Caihong , Gu Hang
Published: April 2023

Cervical cancer (CC) is among the most prevalent gynaecological malignancy. The rate of mortality and morbidity of patients with CC is high. Cellular senescence is involved in tumorigenesis as well as cancer progression. However, the involvement of cellular senescence in CC development is still unclear and requires further investigation. We retrieved data on cellular senescence-related genes (CSRGs) from the “CellAge” Database. We used TCGA-CESC and the CGCI-HTMCP-CC datasets as the training and validation sets, respectively. Eight CSRGs signatures based on the data extracted from these sets were constructed using “univariate” and “Least Absolute Shrinkage and Selection Operator Cox regression analyses”. Using this model, we calculated the risk scores of all patients in the training and validation cohort and categorised these patients into the low-risk group (LR-G) and the high-risk group (HR-G). Finally, compared to patients in the HR-G, CC patients in the LR-G demonstrated a more positive clinical prognosis; the expression of senescence-associated secretory phenotype (SASP) markers and immune cell infiltration was higher, and these patients had more active immune responses. In vitro studies showed increased SERPINE1 and IL-1α ((genes included in the signature) expression in CC cells and tissues. The eight-gene prognostic signatures could modulate the expression of SASP factors and the tumour immune micro-environment (TIME). It could be used as a reliable biomarker for predicting the patient’s prognosis and response to immunotherapy in CC.
Increases in Negative Affective Arousal Precede Lower Self-Esteem in Patients with Borderline Personality Disorder but not in Patients with Depressive Disorders: An Experience Sampling Approach
Authors: Heekerens Johannes Bodo , Schulze Lars , Enge Juliane , Renneberg Babette , Roepke Stefan
Published: April 2023

Background: Instability in self-esteem and instability in affect are core features of borderline personality disorder (BPD). For decades, researchers and theorists have been interested in the temporal dynamics between these constructs. Some hypothesize that changes in affective states should precede changes in self-esteem (Linehan, 1993), while others suggest that changes in self-esteem should precede changes in affective states (Kernberg, 1975).
Methods: In this study, we investigated the temporal relations between negative affective arousal states and current self-esteem in daily life. Patients with BPD (n = 42) or depressive disorders (DD; n = 40), and non-clinical controls (NCC; n = 40) were assessed every 15 min for 13 hours.
Results: As expected, dynamic structural equation modeling showed higher levels of average daily negative affective arousal and lower levels of average daily self-esteem in the BPD group compared with the NCC group, and scores in the DD group were in-between the BPD and the NCC groups. In line with predictions based on Linehan`s (1993) model of affective dysregulation in BPD, negative affective arousal (t) and subsequent self-esteem (t+1) were significantly linked only in the BPD group, implying that higher negative affective arousal is followed by lower current self-esteem in the next measurement (ca. 15 min later). Importantly, self-esteem (t) and subsequent negative affective arousal (t+1) were not significantly related (Kernberg, 1975).
Conclusions:Our findings suggest close dynamic temporal relations between affective instability and self-esteem instability in BPD, which highlights the importance of providing patients with means to effectively modulate high negative affective arousal states.
Sleep Duration and Amyloid β Among Cognitively Healthy Later-Life Adults: A Systematic Review and Meta-Analysis
Authors: Moon Chooza , Schneiner Aaron , Cho Young Eun , Zhang Meina , Dang Hellen , Vu Kelly
Published: April 2023

Background Amyloid β (Aβ) is a hallmark of Alzheimer’s disease (AD). Insufficient sleep duration and poor sleep quality have been found to be a risk factor of developing AD because sleep may involve regulating Aβ. However, the magnitude of the relationship between sleep duration and Aβ is still unclear. This systematic review examines the relationship between sleep duration and Aβ in later-life adults.Methods We screened 5,005 published articles searched from relevant electronic databases (i.e., PubMed, CINAHL, Embase, and PsycINFO) and reviewed 14 articles for the qualitative synthesis and 7 articles for the quantitative synthesis.Results Mean ages of the samples ranged from 63 to 76. Studies measured Aβ using cerebrospinal fluid, serum, and positron emission tomography scans with two tracers: Carbone 11-labeled Pittsburgh compound B or fluorine 18–labeled. Sleep duration was subjectively measured using interviews, questionnaires, or using objective measures such as polysomnography or actigraphy. The studies accounted for demographic and lifestyle factors in their analyses. Five of the 14 studies reported a statistically significant association between sleep duration and Aβ. Using seven eligible articles, our quantitative synthesis demonstrated that the average association between sleep duration and Aβ was not statistically significant (Fisher’s Z = -0.006, 95% CI= -0.065 ~ 0.054).Conclusion This review suggests that caution should be taken when considering sleep duration as the primary factor for Aβ levels. More studies are needed using a longitudinal design, comprehensive sleep metrics, and larger sample sizes to advance our understanding of the optimal sleep duration and AD prevention.
Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1 dependent regulation of lipid metabolism
Authors: Jakob Ursula , Oleson Bryndon , Bhattrai Janakraj , Zalubas Sarah , Kravchenko Tessa , Ji Yuanyuan , Jiang Emily , Lu Christine , Madden Ciara , Bazopoulou Daphne , Jones Jace
Published: April 2023

Recent studies revealed that early-in-life events can have highly beneficial long-term effects in animals. We now demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox sensitive H3K4me3 modifying COMPASS complex, and conferred by a substantial increase in the heat shock independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to dramatic rearrangements of the organismal lipid landscape, and a significant decrease in mitochondrial β-oxidation. Both of these activities appear to majorly contribute to HSF-1’s protective effects against amyloid toxicity. In summary, our study reveals previously unknown links between developmental changes in the histone landscape, HSF-1 activity and lipid metabolism and the protection against age-associated amyloid toxicities later in life.
Using machine learning algorithm to analyse the hypothyroidism complications caused by radiotherapy in patients with head and neck cancer
Authors: Lee Tsair-Fwu , Lee Shen-Hao , Tseng Chin-Dar , Lin Chih-Hsueh , Chiu Chi-Min , Lin Guang-Zhi , Yang Jack , Chang Liyun , Chiu Yu-Hao , Yeh Shyh-An
Published: April 2023

Using machine learning algorithms to analyze the odds and predictors of complications of thyroid damage after radiation therapy in patients with head and neck cancer. This study used decision tree (DT), random forest (RF), and support vector machine (SVM) algorithms to evaluate predictors for the data of 137 head and neck cancer patients. Candidate factors included gender, age, thyroid volume, minimum dose, average dose, maximum dose, number of treatments, and relative volume of the organ receiving X dose (X: 10, 20, 30, 40, 50, 60 Gy). The algorithm was optimized according to these factors and cross-validation was performed 10 times to analyze the state of thyroid damage and select the predictors of thyroid dysfunction. The importance of the predictors identified by the three machine learning algorithms was ranked: the top five predictors were age, thyroid volume, average dose, V50 and V60. Of these, age and volume were negatively correlated with thyroid damage, indicating that the greater the age and thyroid volume, the lower the risk of thyroid damage; the average dose, V50 and V60 were positively correlated with thyroid damage, indicating that the larger the average dose, V50 and V60, the higher the risk of thyroid damage. The RF algorithm was most accurate in predicting the probability of thyroid damage among the three algorithms optimized using the above factors. The AUC was 0.827 and the ACC was 0.824. This study found that five predictors (age, thyroid volume, mean dose, V50 and V60) are important factors affecting the chance that patients with head and neck cancer who received radiation therapy will develop hypothyroidism. Using these factors as the prediction basis of the algorithm and using RF to predict the occurrence of hypothyroidism had the highest accuracy, which was 82.4%. This algorithm can be used as a reference for predicting the probability of radiation therapy complications and assisting medical decision-making in the future.
RNA-binding Protein ZC3H18 Enhances Cell Proliferation and Metastasis in Lung Adenocarcinoma
Authors: Mi Ke , Chen Yang , Zeng Lizhong , Yang Shuanying
Published: April 2023

Background LUAD is a prevalent type of lung cancer that originates from the glandular cells of the lung. Despite improvements in diagnosis and treatment, it remains a leading cause of cancer-related deaths worldwide. Thus, there is a critical need to develop reliable biomarkers for early detection, diagnosis, and prognosis of LUAD.Methods We first revealed that the expression level of ZC3H18 in LUAD patients. And we analyzed the prognostic value of ZC3H18 using KM-Plotter. We analyzed the co-expressed genes of ZC3H18 and conducted KEGG pathway and GO enrichment analyses. Furthermore, we conducted PPI network analysis, identified 8 hub genes closely associated with ZC3H18 to gain a better understanding of its functions. We silenced ZC3H18 using small interfering RNA (siRNA) and investigated its function in LUAD using in vitro functional assays. We measured cell proliferation through CCK-8, clone formation, and EdU assays, and evaluated cell migration and invasion abilities using scratch, Transwell migration, and invasion assays.Results ZC3H18 is highly expressed in LUAD and indicates poor prognosis. We screened 309 co-expressed genes and identified 8 hub genes (NOC2L, DDX51, DDX54, DHX37, SURF6, MYBBP1A, RBM19, POLR1A) closely related to RNA processes through PPI network analysis. Most of the enriched KEGG pathways and GO biological processes were also related to RNA processes. In vitro cell experiments showed that silencing ZC3H18 reduced cell proliferation and migration ability in LUAD.Conclusion The RNA-binding protein ZC3H18 promotes the proliferation and metastasis of LUAD through facilitating RNA processes.
Use of laryngeal mask airway in transferred infants: a retrospective study
Authors: Cavallin Francesco , Brombin Laura , Turati Marialuisa , Sparaventi Chiara , Doglioni Nicoletta , Villani Paolo Ernesto , Trevisanuto Daniele
Published: April 2023

Background Laryngeal mask airway (LMA) may be considered by health care givers of level I-II hospitals for neonatal resuscitation in interhospital care, but literature provides little information on this aspect. This study reviewed the use of LMA in a large series of neonates who underwent postnatal transfer by an Italian regional transport service.Methods This is a retrospective study evaluating the use of LMA in infants who underwent emergency transport by the Eastern Veneto Neonatal Emergency Transport Service between January 2003 and December 2021. All data were obtained from transport registry, transport forms and hospital charts.Results 64/3,252 transferred neonates (2%) received ventilation with a LMA, with increasing trend over time (p = 0.001). Most neonates were transferred after birth (97%) due to a respiratory or neurologic disease (95%). LMA was used before the transport (n = 60), during the transport (n = 1) or both (n = 3). No device-related adverse effects were recorded. Sixty-one neonates (95%) survived and were discharged/transferred from the referral center.Conclusions In a large series of transferred neonates, LMA use was rare but increasing over time, and showed some heterogeneity among referring centers. However, LMA was safe and lifesaving in “cannot intubate, cannot oxygenate” situations. Future prospective, multicenter research may provide detailed insights on LMA use in neonates needing postnatal transport.
Integrated bioinformatics and wet-lab analysis revealed cell adhesion prominent genes CDC42, TAGLN and GSN as prognostic biomarkers in colonic-polyp lesions
Authors: Tabatabaei Elmira , Mazloomnejad Radman , Rejali Leili , Forouzesh Flora , Noukabadi Fatemeh , Khanabadi Binazir , Salehi Zahra , nazemalhosseini-mojarad ehsan
Published: April 2023

Background Colorectal cancers are derived from intestinal polyps. Normally, alterations in cell adhesion genes expression cause deviation from the normal cell cycle, leading to cancer development, progression, and invasion. The present study aimed to investigate the elusive expression pattern of CDC42, TAGLN, and GSN genes in patients with high and low-risk polyp samples, and also colorectal cancer patients and their adjacent normal tissues.Materials and methods In upcoming study, 40 biopsy samples from Taleghani Hospital (Tehran, Iran) were collected, consisting of 20 colon polyps and 20 paired adjacent normal tissues. The expression of the nominated genes CDC42, TAGLN, and GSN was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2-ΔΔCt method. ROC curve analysis was performed to compare high-risk and low-risk polyps for the investigated genes. The expression of adhesion molecule genes was also evaluated using TCGA data and the correlation between adhesion molecule gene expression and immunophenotype was analyzed. The role of mi-RNAs and lncRNAs in overexpression of adhesion molecule genes was studied. Lastly, GO and KEGG were performed to identify pathways related to adhesion molecule gene expression in healthy, normal adjacent, and COAD tissues.Results The results showed that the expression patterns of these genes were significantly elevated in high-risk adenomas compared to low-risk polyps and normal tissues and were associated with various clinicopathological characteristics. The estimated AUC for CDC42, TAGLN, and GSN were 0.87, 0.77, and 0.80, respectively. The study also analyzed COAD cancer patient data and found that the selected gene expression in cancer patients was significantly reduced compared to high-risk polyps and healthy tissues. Survival analysis showed that while the expression level of the GSN gene had no significant relationship with survival rate, the expression of CDC42 and TAGLN genes did have a meaningful relationship, but with opposite effects, suggesting the potential use of these genes as diagnostic or prognostic markers for colorectal cancer.Conclusion The present study's findings suggest that the expression pattern of CDC42, TAGLN, and GSN genes was significantly increased during the transformation of normal tissue to polyp lesions, indicating their potential as prognostic biomarkers for colorectal polyp development. Further
Minimizing shivering during targeted normothermia: Comparison between a Novel Trans-Nasal and Surface Temperature Modulating Devices
Authors: Arnold Shannon , Armahizer Michael , Torres Luis F. , Tripathi Hemantkumar , Tandri Harikrishna , Choi H Alex , Chang Jason J. , Badjatia Neeraj
Published: April 2023

Background: Shivering is a common adverse effect of achieving and maintaining normothermia in neurocritical care patients. We compared the burden of shivering and shivering-related interventions between a novel trans-nasal temperature modulating device(tnTMD) and surface cooling temperature modulating devices(sTMDs) during the first 24 hours of targeted normothermia in mechanically ventilated febrile neurocritical care patients.
Methods: This is a case: control study controlling for factors that impact shiver burden: age, sex, body surface area. All patients underwent transnasal cooling (COOLSTAT, KeyTech, Inc) as part of an ongoing multicenter clinical trial(NCT03360656). Patients undergoing treatment with sTMDs were selected from consecutively treated patients during the same time-period. Data collected included: core body temperature (every 2 hours), bedside shivering assessment scale(BSAS) score (every 2 hours), and administration of anti-shivering medication for BSAS>1.Time to normothermia(<=37.5 C), as well as temperature burden>37.5 C(C*hr) were compared between groups using student’s t-test for mean differences. Proportion of patients requiring interventions as well as number of interventions per patient were compared using Chi-Square test. Significance was determined based on a P value < 0.05.
Results: There were 10 tnTMD patients and 30 sTMD patients included in the analysis (mean age: 62+/-4, 30% women, BSA = 1.97+/-0.25). There were no differences between groups in temperature at cooling initiation (tnTMD: 38.5+/-0.2 C vs sTMD: 38.7+/-0.5 C, P=0.3), time to <=37.5 C (tnTMD: 1.8+/-1.5 hours vs. sTMD: 2.9+/-1.4 hours, P=0.1), or temperature burden >37.5 (tnTMD:: -0.4 +/- 1.13 C*hr vs. sTMD median (IQR): -0.57 +/- 0.58 C*hr, P=0.67). The number of tnTMD patients who received pharmacologic shivering interventions was lower than the controls (20%vs.67%,p=0.01). tnTMD patients also had fewer shivering interventions per patient (0 (range: 0-3)vs.4(range: 0 – 23 ), p<0.001).
Conclusion: A transnasal cooling approach achieved similar time to normothermia and temperature burden with less shivering than surface cooling. This approach may be a feasible option to consider for mechanically ventilated febrile neurocritical care patients.
Trial registration: Clinical trials.gov: NCT03360656. Registered December 4, 2017. https://clinicaltrials.gov/ct2/show/NCT03360656
Integrative multi-region molecular profiling of primary prostate cancer with synchronous lymph node metastasis to characterize the biologically dominant clone
Authors: Singhal Udit , Nallandhighal Srinivas , Tosoian Jeffrey , Pham Trinh , Stangl-Kremser Judith , Lui CJ , Karim Razeem , Plouffe Komal , Morgan Todd , Cieslik Marcin , Luciano Roberta , Shariat Shahrokh , Finocchio Nadia , Dambrosio Lucia , Doglioni Claudio , Chinnaiyan Arul , Tomlins Scott , Briganti Alberto , Palapattu Ganesh , Udager Aaron , Salami Simpa
Published: April 2023

Localized prostate cancer is composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing subclones that may drive the biological trajectory of the disease. Previous large scale sequencing efforts have focused on the evolutionary process of metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we performed multi-region, targeted DNA/RNA next generation sequencing (NGS) and constructed phylogenetic trees from 14 patients with LN metastasis (88 primary prostate cancer foci with 23 synchronous LN metastases) to better define the molecular features of primary disease most likely to spread to the LNs. Of eight primary prostate cancer cases with evidence of extra-prostatic extension (EPE), phylogenetic analysis supported this region as the likely source of LN metastasis in four cases. In two patients with organ-confined disease and LN metastasis, sub-clonal seeding and clonal evolution was observed, with LN metastasis likely arising from a Gleason Grade Group 5 focus. Cribriform pattern was observed in seven patients in both LNs and the primary tumor foci most clonally related. Driver alterations, either oncogenic gene fusions or somatic mutations (e.g., CDK12, FOXA1), were shared among primary tumor and LN metastatic foci. Collectively, we found that a combination of histopathologic and molecular factors, including tumor grade, EPE, cellular morphology (e.g., cribriform pattern), and oncogenic genomic alterations were associated with synchronous LN metastasis. More work is needed to better define the molecular features of primary prostate cancer foci most likely to give rise to metastasis to improve risk stratification, guide treatment allocation, and inform novel therapeutic strategies.
FEM analysis of a new three-way drainage and pressure reduction system for road tunnels
Authors: Teng Zhaolei , Liu Yuanming , Mei Shilong , Zhou Yuhang , He Guohua , Li Yingxiao , Du Bitao
Published: April 2023

For the water-rich area tunnel elevation arch in the high-water pressure often causes elevation arch cracking and leakage, bulging and other disasters. When the drainage system is not designed properly, such disasters occur more frequently, and conventional road tunnel drainage cannot effectively reduce the water pressure at the elevation arch. Therefore, this paper proposes a new concept of "three-way drainage". The three-way drainage system is based on the conventional drainage system with a new drainage inlet at the elevation arch. On this basis, a series of numerical simulation studies are conducted to verify the pressure-reducing performance of the three-way drainage system on the lining. After demonstration and analysis, the three-way drainage concept can not only effectively reduce the water pressure at the elevation arch of the tunnel, but also have a significant effect on the overall drainage effect of the tunnel. The factors affecting the performance of the three-way drainage system are discussed by varying the model parameters. It was found that the hydraulic conduction coefficient of the surrounding rock and initial support, the number of reverse diversion holes in the elevation arch, the change in head height and the change in secondary lining parameters all had a significant effect on the water pressure outside the tunnel.
Effects of museum-based art activities on older community dwellers’ physical activity: The A-health randomized controlled trial results
Authors: Planta Océane , Cami Margot , Matskiv Jacqueline , Plonka Alexandra , Gros Auriane , Beauchet Olivier
Published: April 2023

Purpose. Museum-based art activities have demonstrated health benefits in older adults. Few clinical trials, however, have examined physical health benefits. This randomized controlled trial (RCT) aims to compare changes in daily step count over a 3-month period in older adults participating in museum art-based activities and their control counterparts.
Methods. Using a subset of 53 participants recruited in the A-health RCT, the daily step count of 28 participants in the intervention group and 25 in the control group were recorded with a Fitbit Alta HR. Weekly art-based activities were carried out at the Montreal Museum of Fine Art (MMFA, Quebec, Canada) over a 3-month period. The outcomes were the mean step count per active hours (i.e., between noon and 6pm), inactive hours (i.e., between midnight and 6am) and full day (i.e., 24h), and the change of step count following the 3-month (M3) intervention of art activities at the MMFA (M3).
Results. The intervention group had greater daily step count compared to the control group at M3, regardless of the step parameters examined (P ≤ 0.026). The change in daily step count for active hours (P = 0.023) and full day (P = 0.011) increased significantly with the MMFA art-based activities.
Conclusion. MMFA-based art activities improved daily physical activity in older community-dwellers who participated in the RCT, confirming health benefits and suggesting a potential of museums in health promotion and prevention.
Transcriptome analysis of fresh-cut kiwifruit treated with slightly acidic electrolyzed water (SAEW) and 1-methylcyclopropene (1-MCP)
Authors: Xu Fangxu
Published: April 2023

Fresh-cut kiwifruit is difficult to store due to the characteristics of thin and juicy rind, which results in the great limitation of development and utilization. The aim of the study was to evaluate the effect of slightly acidic electrolyzed water (SAEW) combined with 1-methylcyclopropene (1-MCP) on shelf life quality of fresh-cut kiwifruit by transcriptome technology. The results showed that SAEW or 1-MCP treatment suppressed ethylene production, respiratory rate, soluble solid content (SSC), polyphenol oxidase (PPO) and improved titratable acid content (TAC), total phenols content (TPC), total chlorophyll content (TCC), peroxidase (POD) and phenylalanine ammonia lyase (PAL) activities comparing with the untreated samples. There were 2754 differentially expressed genes (DEGs) between the combined treatment and the control on day 6. GO function annotation results showed that the related genes involved in cell membrane composition in samples might be involved in protein phosphorylation under the action of protein kinase genes. KEGG enrichment analysis showed that 715 DEGs were significantly enriched in 111 metabolic pathways on day 6 after combined treatment. In ethylene signaling pathway, expression levels of ETR and ERF1 were down-regulated, which proved that 1-MCP inhibited ethylene reaction by binding to ethylene receptors. Genes expression levels of SnRK2, MPK3/6, and BAP31 related to MAPK signaling pathway and protein processing in endoplasmic reticulum pathway were up-regulated, and the combined treatment had a positive regulatory effect on fruit defense during storage. In plant-pathogen interaction pathway, genes expression levels of MKK45 were down-regulated that proved the production of ROS was suppressed by combined treatment, consequently improving disease resistance of fresh-cut kiwifruit. Hence, the combination treatment of SAEW and 1-MCP may be a proven and effective technology to retain higher quality and nutritive properties of fresh-cut kiwifruit.
Molecular characterization of a novel single-stranded RNA mycovirus infecting the plant pathogenic fungus Ustilaginoidea virens
Authors: Zeng Rui , He Zhenrui , Fan Yu , Huang Xiaotong , Yang Mei , Zhou Erxun
Published: April 2023

Mycovirus is a kind of virus that infects fungi and oomycetes and can replicate in them, which widespread in all major groups of plant-pathogenic fungi and oomycetes. To date, no positive-sense single-stranded RNA (+ ssRNA) virus has been reported to be associated with Ustilaginoidea virens, the notorious causal agent of rice false smut (RFS). Here, we report the molecular characterization of a novel + ssRNA mycovirus, Ustilaginoidea virens narnavirus 1 (UvNV1), isolated from U. virens strain Uv418. UvNV1 has a genome of 3,131 nt and possesses an open reading frame (ORF) predicted to encode an RNA-dependent RNA polymerase (RdRP) of 1,017 amino acids (aa) with a molecular mass of 116.6 kDa. BLASTp analysis revealed that the RdRP showed 50.34% aa similarity to that of the previously described Zhangzhou Narna tick virus 1. Phylogenetic analyses indicated that UvNV1 is highly similar to viruses taxonomically classified in the genus Narnavirus, family Narnaviridae. Taken together, these results clearly demonstrate that UvNV1 is the first + ssRNA virus known to infect U. virens.
Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors
Authors: Muangkram Yuttamol , Himeno Yukiko , Amano Akira
Published: April 2023

To date, no effective treatment has been established for photoreceptor loss due to energy imbalances, but numerous therapeutic approaches have reported some success in slowing photoreceptor degeneration by downregulating energy demand. However, the detailed mechanisms remain unclear. This study aimed to clarify the composition of ATP consumption factors in photoreceptors in darkness and in light. We introduced mathematical formulas for ionic current activities combined with a phototransduction model to form a new mathematical model for estimating the energy expenditure of each ionic current. The proposed model included various ionic currents identified in mouse rods using a gene expression database incorporating an available electrophysiological recording of each specific gene. ATP was mainly consumed by Na+/K+-ATPase and plasma membrane Ca2+-ATPase pumps to remove excess Na+ and Ca2+. The rod consumed 7x107 molecules of ATP s− 1, where 65% was used to remove ions from the cyclic nucleotide-gated channel and 20% from the hyperpolarization-activated current in darkness. Increased light intensity raised the energy requirements of the complex phototransduction cascade mechanisms. Nevertheless, the overall energy consumption was less than that in darkness due to the significant reduction in ATPase activities, where the hyperpolarization-activated current proportion increased to 83%. A better understanding of energy demand/supply may provide an effective tool for investigating retinal pathophysiological changes and analyzing novel therapeutic treatments related to the energy consumption of photoreceptors.
Epigenetic modifications regulate cultivar-specific root development and metabolic adaptation to nitrogen availability in wheat
Authors: Xiao Jun , Zhang Hao , Jin Zhiyuan , Cui Fa , Zhao Long , Zhang Xiaoyu , Chen Jinchao , Zhang Jing , Li Yanyan , Li Yongpeng , Niu Yanxiao , Zhang Wenli , Gao Caixia , Fu Xiangdong , Tong Yiping , Wang Lei , Ling HongQing , Li Junming
Published: April 2023

The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture. Despite its importance, the way in which epigenetic modifications regulate cultivar-specific responses to low nitrogen (LN) constraints is not yet well understood. Here, we analyzed the chromatin landscapes in the roots, leaves, and seeds of two wheat cultivars (KN9204 and J411) that differ radically in NUE under varied nitrogen conditions. The chromatin regions responsible for regulating gene transcription exhibited clear cultivar-specificity between the two cultivars, and the regulation of nitrogen metabolism genes (NMGs) was closely linked to variation in histone modification levels instead of differences in DNA sequence. We also found that cultivar-specific histone modification regions contribute to the genetic regulation of NUE-related traits, such as the QTL locus of maximum root length of qMRL-7B. Additionally, LN-induced H3K27ac and H3K27me3 dynamics enhanced root growth more significantly in KN9204, while strengthened the nitrogen uptake system remarkably in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of the H3K27me3 methyltransferase further showed that changes in epigenetic modifications can alter the strategy for root development and nitrogen uptake in response to LN constraint. Taken together, our data highlight the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.
Activated Partial Thromboplastin Time-based Clot Waveform Analysis: A Potential for Application in Acute Myocardial Infarction and Its Complications
Authors: Ng Chen Lin , Uy Felix Maverick , Cheong May Anne , Wong Wan Hui , Lau Yee How , Ng Heng Joo , Yeo Khung Keong , Tan Chuen Wen
Published: April 2023

Background: Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications.
Methods: This is a retrospective case-control study that included patients with AMI who underwent emergency cardiac catheterisation and control patients who underwent elective orthopaedic and urological procedures. The pre-procedural aPTT and CWA parameters – min1, min2 and max2 – of AMI patients were compared against those of controls.
Results: Compared to controls (N=109), patients with AMI (N=214) had shorter aPTT (26.7±3.3s vs 27.9±1.7s, P<0.001) and higher CWA parameters (min1: 6.11±1.40%/s vs 5.58±1.14%/s; min2: 0.98±0.23%/s2 vs 0.90±0.19%/s2; max2: 0.81±0.20%/s2 vs 0.74±0.16%/s2, all P≤0.001). Elevated CWA parameters, defined as having CWA values above their respective reference ranges, were associated with the occurrence of AMI, with odds ratio (OR) of 2.06 [95% confidence intervals (CI):1.10–3.86], 2.23 (95% CI:1.18–4.24) and 2.01 (95% CI:1.07–3.77) for min1, min2 and max2, respectively. Similarly, elevated min1 and min2 were both individually associated with the presence of adverse outcomes of AMI with ORs of 2.63 (95% CI:1.24–5.59).
Conclusions: Patients with AMI had significantly increased CWA parameters. Elevated aPTT-based CWA parameters are significantly associated with the occurrence of AMI and its complications. Potential utility of CWA as risk and prognostic markers for AMI warrants future works.