bluuebunny/crossref_metadata_2025 huggingface dataset:
COP26 Futures We Want - Jamaica Country Profile
Authors: Luke Sarah , Taylor Michael , Smith David , Reynolds Rajne , Shuckburgh Emily
Published: October 2021

This regional profile for Jamaica was developed in the context of the BEIS COP26 Futures We Want project. It has been developed with input from in-country academic experts Professor Michael Taylor (University of the West Indies, Jamaica), Dr David Smith (University of the West Indies, Jamaica) and Mr Rajne Reynolds (University of the West Indies). It sets out a synthesis of the available evidence base on regional challenges and opportunities for mitigation, adaptation, and resilience measures for Jamaica associated with climate change and a global transition to an inclusive, desirable, and resilient net-zero future.
Intervención psicológica como parte del tratamiento integral de pacientes con insuficiencia cardíaca: Efecto sobre la capacidad funcional
Authors: Peláez-Hernández Viridiana , Orea-Tejeda Arturo , Domínguez-Trejo Benjamín , Figueroa López Carlos Gonzalo , Alcocer Díaz-Barreiro Luis , Pablo Santiago Ruth , Martínez Rubio Claudia Ivonn
Published: October 2021

El objetivo del presente trabajo fue investigar el efecto de una intervención psicológica cognitivo-conductual en la capacidad funcional de los pacientes con insuficiencia cardiaca, medida a través de la prueba de caminata de seis minutos. Participaron 53 pacientes, clases funcionales I y II, asignados aleatoriamente a: 1) grupo control (tratamiento médico usual, n=27, edad media 61.07±15.96, 55.6% hombres), o 2) grupo experimental (tratamiento médico usual e intervención psicológica, n=26, edad media 58.42±16.42, 65.4% mujeres). Mediante la prueba de caminata de seis minutos se evalúo la distancia recorrida en metros, el nivel de cansancio físico y el nivel de esfuerzo reportado en la escala de Borg. Las evaluaciones se realizaron antes y al final del programa de intervención, además de un seguimiento a tres meses. El programa de intervención psicológica incluyó psicoeducación, respiración diafragmática, relajación muscular progresiva y entrenamiento en solución de problemas, en cuatro sesiones de 90 minutos cada una, diferidas semanalmente. Los resultados muestran que el grupo experimental incrementó (p=0.00) la distancia recorrida y disminuyó el nivel de cansancio físico (p=0.02) y nivel de esfuerzo reportados (ns), lo cual se traduce en un mejor pronóstico. El grupo control no mostró cambios significativos. Se concluye que la intervención propuesta se adapta a las necesidades de la población con un efecto positivo en su condición de salud, por lo que se sugiere la integración de equipos interdisciplinarios que incluyan programas de intervención psicológica para mejorar la salud cardiovascular y la calidad de vida de los pacientes.
Non-Destructive Spatial Mapping of Glycosaminoglycan Loss in Native and Degraded Articular Cartilage Using Confocal Raman Microspectroscopy
Authors: Gao Tianyu , Boys Alexander J. , Zhao Crystal , Chan Kiara , Estroff Lara A. , Bonassar Lawrence J.
Published: October 2021

Articular cartilage is a collagen-rich tissue that provides a smooth, lubricated surface for joints and is also responsible for load bearing during movements. The major components of cartilage are water, collagen, and proteoglycans. Osteoarthritis is a degenerative disease of articular cartilage, in which an early-stage indicator is the loss of proteoglycans from the collagen matrix. In this study, confocal Raman microspectroscopy was applied to study the degradation of articular cartilage, specifically focused on spatially mapping the loss of glycosaminoglycans (GAGs). Trypsin digestion was used as a model for cartilage degradation. Two different scanning geometries for confocal Raman mapping, cross-sectional and depth scans, were applied. The chondroitin sulfate coefficient maps derived from Raman spectra provide spatial distributions similar to histological staining for glycosaminoglycans. The depth scans, during which subsurface data were collected without sectioning the samples, can also generate spectra and GAG distributions consistent with Raman scans of the surface-to-bone cross sections. In native tissue, both scanning geometries demonstrated higher GAG content at the deeper zone beneath the articular surface and negligible GAG content after trypsin degradation. On partially digested samples, both scanning geometries detected an ∼100 μm layer of GAG depletion. Overall, this research provides a technique with high spatial resolution (25 μm pixel size) to measure cartilage degradation without tissue sections using confocal Raman microspectroscopy, laying a foundation for potential in vivo measurements and osteoarthritis diagnosis.
Chagas Disease Drug Discovery in Latin America—A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021
Authors: de Oliveira Ramon G. , Cruz Luiza R. , Mollo María C. , Dias Luiz C. , Kratz Jadel M.
Published: October 2021

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing.
Gene Expression Profiling of Early Acute Febrile Stage of Dengue Infection and Its Comparative Analysis With Streptococcus pneumoniae Infection
Authors: Bajrai Leena H. , Sohrab Sayed S. , Alandijany Thamir A. , Mobashir Mohammad , Reyaz Muddassir , Kamal Mohammad A. , Firoz Ahmad , Parveen Shabana , Azhar Esam I.
Published: October 2021

Infectious diseases are the disorders caused by organisms such as bacteria, viruses, fungi, or parasites. Although many of them are permentantly hazardous, a number of them live in and on our bodies and they are normally harmless or even helpful. Under certain circumstances, some organisms may cause diseases and these infectious diseases may be passed directly from person to person or via intermediate vectors including insects and other animals. Dengue virus and Streptococcus pneumoniae are the critical and common sources of infectious diseases. So, it is critical to understand the gene expression profiling and their inferred functions in comparison to the normal and virus infected conditions. Here, we have analyzed the gene expression profiling for dengue hemorrhagic fever, dengue fever, and normal human dataset. Similar to it, streptococcus pneumoniae infectious data were analyzed and both the outcomes were compared. Our study leads to the conclusion that the dengue hemorrhagic fever arises in result to potential change in the gene expression pattern, and the inferred functions obviously belong to the immune system, but also there are some additional potential pathways which are critical signaling pathways. In the case of pneumoniae infection, 19 pathways were enriched, almost all these pathways are associated with the immune system and 17 of the enriched pathways were common with dengue infection except platelet activation and antigen processing and presentation. In terms of the comparative study between dengue virus and Streptococcus pneumoniae infection, we conclude that cell adhesion molecules (CAMs), MAPK signaling pathway, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction are commonly enriched in all the three cases of dengue infection and Streptococcus pneumoniae infection, focal adhesion was enriched between classical dengue fever — dengue hemorrhagic fever, dengue hemorrhagic fever—normal samples, and SP, and antigen processing and presentation and Leukocyte transendothelial migration were enriched in classical dengue fever —normal samples, dengue hemorrhagic fever—normal samples, and Streptococcus pneumoniae infection.
In Vitro Activity of Auranofin in Combination With Aztreonam-Avibactam Against Metallo-β-lactamase (MBL)-Producing Enterobacterales
Authors: Wang Wen , Huang Shifeng , Zou Chunhong , Ding Yanhui , Wang Huijuan , Pu Shuli , Liao Yunfeng , Du Hong , Wang Deqiang , Chen Liang , Niu Siqiang
Published: October 2021

Objectives

To assess the efficacy of aztreonam-avibactam-auranofin (ATM-AVI-AUR) against a collection of 88 carbapenemase-producing Enterobacterales (CPE) clinical isolates and 6 in vitro selected ATM-AVI-resistant CPE with CMY-16 Tyr150Ser and Asn346His mutants or transformants.

Methods

MICs of imipenem, ceftazidime-avibact8am (CAZ-AVI), ATM-AVI, CAZ-AVI-AUR and ATM-AVI-AUR were determined via the broth microdilution method. Genetic background and carbapenemase genes were determined by PCR and Sanger sequencing.

Results

AUR alone showed little antibacterial activity with AUR MICs were greater than 64 μg/mL for all the 88 clinical CPE isolates. The addition of AUR (16 μg/mL) resulted in an 3-folding dilutions MIC reduction of ATM-AVI MIC50 (0.5 to 0.0625 μg/mL) and a 2-folding dilutions MIC reduction of MIC90 (1 to 0.25 μg/mL) against all 88 clinical CPE isolates, respectively. Notably, the reduced ATM-AVI MIC values were mainly found in MBL-producers, and the MIC50 and MIC90 reduced by 2-folding dilutions (0.25 to 0.0625 μg/mL) and 3-folding dilutions (2 to 0.25 μg/mL) respectively by AUR among the 51 MBL-producers. By contrast, the addition of AUR did not showed significant effects on ATM-AVI MIC50 (0.0625 μg/mL) and MIC90 (0.125 μg/mL) among single KPC-producers. Interestingly, the addition of AUR restored the ATM-AVI susceptibility against the 6 in vitro selected ATM-AVI-resistant CMY-16 Tyr150Ser and Asn346His mutants or transfromants, with the MICs reduced from ≥32 μg/mL (32->256 μg/mL) to ≤8 μg/mL (0.0625-8 μg/mL).

Conclusions

Our results demonstrated that AUR potentiated the activities of CAZ-AVI and ATM-AVI against MBL-producing isolates in vitro. Importantly, AUR restored the ATM-AVI activity against ATM-AVI resistant mutant strains. As a clinically approved drug, AUR might be repurposed in combination with ATM-AVI to treat infections caused by highly resistant MBL-producing Enterobacterales.
Magnetic Resonance Texture Analysis in Myocardial Infarction
Authors: Peng Fei , Zheng Tian , Tang Xiaoping , Liu Qiao , Sun Zijing , Feng Zhaofeng , Zhao Heng , Gong Lianggeng
Published: October 2021

Texture analysis (TA) is a newly arisen field that can detect the invisible MRI signal changes among image pixels. Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, becoming the primary cause of death and disability worldwide. In recent years, various TA studies have been performed in patients with MI and show a good clinical application prospect. This review briefly presents the main pathogenesis and pathophysiology of MI, introduces the overview and workflow of TA, and summarizes multiple magnetic resonance TA (MRTA) clinical applications in MI. We also discuss the facing challenges currently for clinical utilization and propose the prospect.
Impact of Renal Function on Effectiveness and Safety Associated With Low Dose Dabigatran in Non-valve Atrial Fibrillation Patients After Catheter Ablation
Authors: Li Xiaoye , Zuo Chengchun , Ji Qiuyi , Wang Zi , Lv Qianzhou
Published: October 2021

Aim: The purpose of this study is to compare the effectiveness and safety of 110 mg dabigatran in non-valve atrial fibrillation (NVAF) patients with different eGFRs.

Methods: We conducted a single-center retrospective cohort study to investigate the effectiveness and safety of 110 mg dabigatran for NVAF patients between January 2017 and December 2018 based on the eGFR category.

Results: A total of 560 NVAF patients who treated with 110 mg dabigatran were included for analysis. In 12 months, the Kaplan-Meier survival curves indicated that the lower eGFR subgroups were more likely to experience thrombosis, bleeding, and cumulative events earlier (P = 0.021 for thrombosis; P = 0.026 for bleeding; P = 0.001 for cumulative events). Gastrointestinal bleeding occurred more frequently in the moderate group than in other groups (6.94% in the moderate group vs. 1.54% in the mild group vs. 1.22% in the normal group, P = 0.028). By multivariate analysis, chronic kidney disease (P = 0.043; OR = 4.273, 95% CI 1.043–17.543) and diabetes mellitus (P = 0.023; OR = 2.194, 95% CI 1.114–4.323) were independent predictors of the composite endpoints. A positive linear relationship was observed between eGFR levels and occurrence rate of thrombosis and bleeding under anticoagulation patients with 110 mg dabigatran (R2 = 0.432 and R2 = 0.784, respectively).

Conclusions: Impaired renal function was associated with decreased safety and increased thrombosis risks in NVAF patients taking low dose dabigatran.
Hydroxamate-Based Histone Deacetylase Inhibitors as Potential Mediators to Induce Dentine Regeneration by Human Dental Pulp Cell
Authors: Sulistyowati Indrani , Sukpaita Teerawat , Limjeerajarus Chalida Nakalekha , Ampornaramveth Ruchanee Salingcarnboriboon
Published: October 2021

Human dental pulp cells (hDPCs) have shown their plasticity when treated with the hydroxamate-based histone deacetylase (HDAC) inhibitor members, Trichostatin A (TSA), and suberoylanilide hydroxamic acid (SAHA). However, a comparison of their potency to stimulate odontoblast-like differentiation and mineralization has not been reported. The aim of our study was to confirm and compare these TSA and SAHA effects. Primary hDPCs cultured with/without various TSA or SAHA concentrations were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), ALP activity, alizarin red staining, and scratch wound healing assays. The inhibitory effect of TSA and SAHA on inhibiting the activity of HDAC was evaluated by HDAC activity assay. Odontoblast-related gene expression was determined using RT-qPCR. The MTT assay indicated that TSA or SAHA did not affect hDPC viability. TSA or SAHA treatment-induced odontoblast-like differentiation as evidenced by a significant increase in alkaline phosphatase activity and mineral deposition after 400 nM TSA or 1 μM SAHA treatment. A significant increase in nuclear factor I C, kruppel like factor 4, dentin matrix acidic phosphoprotein 1, dentin sialophosphoprotein, collagen type I alpha 1 chain, alkaline phosphatase (ALPL), integrin-binding sialoprotein, bone gamma-carboxyglutamate protein, vascular endothelial growth factor A, and cyclin-dependent kinase inhibitor 1A gene expression analyzed by RT-qPCR, at 24, 72 h, 7, and 10 days of treatment. The activity of HDAC in hDPCs culture was significantly inhibited after 72 h TSA and SAHA treatment. The scratch wound healing assay displayed enhanced cell migration at 72 h after TSA or SAHA treatment. Our findings demonstrated that TSA and SAHA have similar stimulatory effects in inducing HDPC odontogenic differentiation and mineralization and propose another potential use of TSA and SAHA to promote dentin regeneration.
Differences in Self-Directed Learning: Middle-School Students’ Autonomous Outdoor Studying
Authors: Uus Õnne , Mettis Kadri , Väljataga Terje , Ley Tobias
Published: October 2021

The use of self-directed learning (SDL) is an increasingly widespread trend in schools, although its core—the student’s attentional capability for multi-level processing—to construct relevant concepts and at the same time to keep in mind the needed sub-items, while also directing one’s own learning, has not been thoroughly investigated. We examined autonomous learning outdoors in small groups with 122 school students aged 14–16 years (the period that, through the developmental peculiarities of puberty, causes variety in cognitive skills). To detect whether individual characteristics reflect in students’ SDL progress, we measured participants’ pre-knowledge, their problem-solving strategies, and post-knowledge. We also asked about their prior SDL experience. The results showed 1) relations between one’s pre-and post-knowledge levels; 2) the impact of gender in the SDL efficacy; 3) the difficulty to memorize in the course of complex tasks while learning on one’s own. Our work gives insight into the SDL-specific heightened cognitive demand: school students’ cognitive obstacles in heavy load conditions and their prolonged maturation of executive functions—especially in adolescence as this age group passes its normal biological spurts of the human developmental path—which may differ individually.
The California Environmental Flows Framework: Meeting the Challenges of Developing a Large-Scale Environmental Flows Program
Authors: Stein Eric D. , Zimmerman Julie , Yarnell Sarah M. , Stanford Bronwen , Lane Belize , Taniguchi-Quan Kristine T. , Obester Alyssa , Grantham Theodore E. , Lusardi Robert A. , Sandoval-Solis Samuel
Published: October 2021

Environmental flow programs aim to protect aquatic habitats and species while recognizing competing water demands. Often this is done at the local or watershed level because it is relatively easier to address technical and implementation challenges at these scales. However, a consequence of this approach is that ecological flow criteria are developed for only a few areas as dictated by funding and interest with many streams neglected. Here we discuss the collaborative development of the California Environmental Flows Framework (CEFF) as an example process for developing environmental flow recommendations at a statewide scale. CEFF uses a functional flows approach, which focuses on protecting a broad suite of ecological, geomorphic, and biogeochemical functions instead of specific species or habitats, and can be applied consistently across diverse stream types and spatial scales. CEFF adopts a tiered approach in which statewide models are used to estimate ecological flow needs based on natural functional flow ranges, i.e., metrics that quantify the required magnitude, timing, duration, frequency, and/or rate-of-change of functional flow components under reference hydrologic conditions, for every stream reach in the state. Initial flow needs can then be revised at regional, or watershed, scales based on local constraints, management objectives, and available data and resources. The third tier of CEFF provides a process for considering non-ecological flow needs to produce a final set of environmental flow recommendations that aim to balance of all desired water uses. CEFF was developed via a broad inclusive process that included technical experts across multiple disciplines, representatives from federal and state agencies, and stakeholders and potential end-users from across the state. The resulting framework is therefore not associated with any single agency or regulatory program but can be applied under different contexts, mandates and end-user priorities. The inclusive development of CEFF also allowed us to achieve consensus on the technical foundations and commitment to applying this approach in the future.
Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts
Authors: Ren Xiaohan , Chen Xinglin , Zhang Xu , Jiang Silin , Zhang Tongtong , Li Guangyao , Lu Zhongwen , Zhang Dong , Wang Shangqian , Qin Chao
Published: October 2021

Immune microenvironment of prostate cancer (PCa) is implicated in disease progression. However, previous studies have not fully explored PCa immune microenvironment. This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunotherapy response rate. Furthermore, consensus clustering was performed to separate the population into three IRSclusters with different clinical outcomes. Patients in IRScluster3 showed the worst prognosis and highest immunotherapy response rate. On the other hand, patients in IRScluster2 showed better prognosis and low immunotherapy response rate. In addition, VGLL3, ANPEP, CD38, CCK, DPYS, CST2, COMP, CRISP3, NKAIN1, and F5 genes were differentially expressed in the three IRSclusters. Furthermore, CMap analysis showed that five compounds targeted IRS signature, thioridazine, trifluoperazine, 0175029-0000, trichostatin A, and fluphenazine. In summary, immune characteristics of PCa tumor microenvironment was explored and an IRS signature was constructed based on 10 immune terms. Analysis showed that this signature is a useful tool for prognosis and prediction of immunotherapy response rate of PCa.
CTNNB1 Alternation Is a Potential Biomarker for Immunotherapy Prognosis in Patients With Hepatocellular Carcinoma
Authors: Chen Lin , Zhou Qiaodan , Liu Junjie , Zhang Wei
Published: October 2021

Background

The emergence of immune checkpoint inhibitors (ICIs) marks the beginning of a new era of immunotherapy for hepatocellular carcinoma (HCC), however, not all patients respond successfully to this treatment. A major challenge for HCC immunotherapy is the development of ways to screen for those patients that would benefit from this type of treatment and determine the optimal treatment plan for individual patients. Therefore, it is important to find a biomarker which allows for the stratification of HCC patients, which distinguishes responders from non-responders, thereby further improving the clinical benefits for those undergoing immunotherapy.

Methods

We used univariate and multivariate Cox risk proportional regression models to evaluate the relationship between non-synonymous mutations with a mutation frequency greater than 10%. We made a prognosis of an immunotherapy HCC cohort using mutation and prognosis data. An additional three HCC queues from the cbioportal webtool were used for further verification. The CIBERSORT, IPS, quanTIseq, and MCPcounter algorithms were used to evaluate the immune cells. PCA and z-score algorithm were used to calculate immune-related signature with published gene sets. Gene set enrichment analysis (GSEA) was used to compare the differences in the pathway-based enrichment scores of candidate genes between mutant and wild types.

Results

Univariate and multivariate Cox results showed that only CTNNB1-Mutant(CTNNB1-MUT) was associated with progression-free survival (PFS) of HCC patients in the immunotherapy cohort. After excluding the potential bias introduced by other clinical features, it was found that CTNNB1-MUT served as an independent predictor of the prognosis of HCC patients after immunotherapy (P < 0.05; HR > 1). The results of the tumor immune microenvironment (TIME) analysis showed that patients with CTNNB1-MUT had significantly reduced activated immune cells [such as T cells, B cells, M1-type macrophages, and dendritic cells (DCs)], significantly increased M2-type macrophages, a significantly decreased expression of immunostimulating molecules, low activity of the immune activation pathways (cytokine pathway, immune cell activation and recruitment) and highly active immune depletion pathways (fatty acid metabolism, cholesterol metabolism, and Wnt pathway).

Conclusions

In this study, we found CTNNB1-MUT to be a potential biomarker for HCC immunotherapy patients, because it identified those patients are less likely to benefit from ICIs.
The Reliability of Anamnestic Data in the Management of Clostridium Tetani Infection in Elderly
Authors: Savioli Gabriele , Ceresa Iride Francesca , Giordano Mauro , Ferrari Ilaria , Varesi Angelica , Floris Valentina , Esposito Ciro , Croesi Barbara , Ricevuti Giovanni , Calvi Monica , Bressan Maria Antonietta , Oddone Enrico
Published: October 2021

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population.

Aim: Assess, in both the geriatric population (>65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin).

Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data.

Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p < 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p < 0.001). There was a statistically significant discrepancy (p < 0.001) between the therapy based on anamnestic data and the TQS test results.

Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus.
Predictors of Mortality in Hospitalized COVID-19 Patients Complicated With Hypotension and Hypoxemia: A Retrospective Cohort Study
Authors: Sun Baoni , Wang Hai , Lv Junhua , Pei Honghong , Bai Zhenghai
Published: October 2021

Introduction: COVID-19 patients with hypotension and hypoxemia had a significantly worse outcome. The purpose of this research was to ascertain the risk factors affecting the prognoses of these patients and to develop appropriate prognostic prediction tools.

Methods: From March 1, 2020, to April 16, 2020, a retrospective cohort analysis of COVID-19 patients with hypotension and hypoxemia was performed. The univariate and multivariate analyses were performed to identify the associated risk factors influencing the prognosis of COVID-19 patients with hypotension and hypoxemia, and the selected variables were then utilized to construct and validate the prediction model for these patients.

Results: Three hundred and twenty-seven COVID-19 patients with hypotension and hypoxemia who met the inclusion and exclusion criteria were included in this study. Age, temperature, troponin, and blood glucose were related to mortality in COVID-19 patients with hypotension and hypoxemia in both univariate and multivariate analyses. The MFP model (multiple fractional polynomial model), full model, and stepwise model were utilized to build the prediction model, and their AUCs were, respectively, 0.902 (0.868, 0.936), 0.902 (0.868, 0.936), and 0.902 (0.868, 0.936). Because the sample size for this research was limited, we utilized bootstrapping for internal validation. The AUCs of Bootstrap full and Bootstrap stepwise were 0.902 (0.867, 0.936) and 0.902 (0.868, 0.936), respectively.

Conclusion: Age, temperature, troponin, and blood glucose levels were associated with mortality in COVID-19 patients with hypotension and hypoxemia. Additionally, the prediction model developed using the variables above showed a high predictive value for predicting the prognosis of these individuals.
The Disease Associated Tau35 Fragment has an Increased Propensity to Aggregate Compared to Full-Length Tau
Authors: Lyu Chen , Da Vela Stefano , Al-Hilaly Youssra , Marshall Karen E. , Thorogate Richard , Svergun Dmitri , Serpell Louise C. , Pastore Annalisa , Hanger Diane P.
Published: October 2021

Tau35 is a truncated form of tau found in human brain in a subset of tauopathies. Tau35 expression in mice recapitulates key features of human disease, including progressive increase in tau phosphorylation, along with cognitive and motor dysfunction. The appearance of aggregated tau suggests that Tau35 may have structural properties distinct from those of other tau species that could account for its pathological role in disease. To address this hypothesis, we performed a structural characterization of monomeric and aggregated Tau35 and compared the results to those of two longer isoforms, 2N3R and 2N4R tau. We used small angle X-ray scattering to show that Tau35, 2N3R and 2N4R tau all behave as disordered monomeric species but Tau35 exhibits higher rigidity. In the presence of the poly-anion heparin, Tau35 increases thioflavin T fluorescence significantly faster and to a greater extent than full-length tau, demonstrating a higher propensity to aggregate. By using atomic force microscopy, circular dichroism, transmission electron microscopy and X-ray fiber diffraction, we provide evidence that Tau35 aggregation is mechanistically and morphologically similar to previously reported tau fibrils but they are more densely packed. These data increase our understanding of the aggregation inducing properties of clinically relevant tau fragments and their potentially damaging role in the pathogenesis of human tauopathies.
Cross-Streams Through the Ventral Posteromedial Thalamic Nucleus to Convey Vibrissal Information
Authors: Zhang Huimin , Wang Xiaojun , Guo Wenyan , Li Anan , Chen Ruixi , Huang Fei , Liu Xiaoxiang , Chen Yijun , Li Ning , Liu Xiuli , Xu Tonghui , Xue Zheng , Zeng Shaoqun
Published: October 2021

Whisker detection is crucial to adapt to the environment for some animals, but how the nervous system processes and integrates whisker information is still an open question. It is well-known that two main parallel pathways through Ventral posteromedial thalamic nucleus (VPM) ascend to the barrel cortex, and classical theory suggests that the cross-talk from trigeminal nucleus interpolaris (Sp5i) to principal nucleus (Pr5) between the main parallel pathways contributes to the multi-whisker integration in barrel columns. Moreover, some studies suggest there are other cross-streams between the parallel pathways. To confirm their existence, in this study we used a dual-viral labeling strategy and high-resolution, large-volume light imaging to get the complete morphology of individual VPM neurons and trace their projections. We found some new thalamocortical projections from the ventral lateral part of VPM (VPMvl) to barrel columns. In addition, the retrograde-viral labeling and imaging results showed there were the large trigeminothalamic projections from Sp5i to the dorsomedial section of VPM (VPMdm). Our results reveal new cross-streams between the parallel pathways through VPM, which may involve the execution of multi-whisker integration in barrel columns.
Whole-Brain Mapping of the Expression Pattern of T1R2, a Subunit Specific to the Sweet Taste Receptor
Authors: Jang Jea Hwa , Kim Ha Kyeong , Seo Dong Woo , Ki Su Young , Park Soonhong , Choi Sang-Hyun , Kim Dong-Hoon , Moon Seok Jun , Jeong Yong Taek
Published: October 2021

Chemosensory receptors are expressed primarily in sensory organs, but their expression elsewhere can permit ligand detection in other contexts that contribute to survival. The ability of sweet taste receptors to detect natural sugars, sugar alcohols, and artificial sweeteners suggests sweet taste receptors are involved in metabolic regulation in both peripheral organs and in the central nervous system. Our limited knowledge of sweet taste receptor expression in the brain, however, has made it difficult to assess their contribution to metabolic regulation. We, therefore, decided to profile the expression pattern of T1R2, a subunit specific to the sweet taste receptor complex, at the whole-brain level. Using T1r2-Cre knock-in mice, we visualized the overall distribution of Cre-labeled cells in the brain. T1r2-Cre is expressed not only in various populations of neurons, but also in glial populations in the circumventricular organs and in vascular structures in the cortex, thalamus, and striatum. Using immunohistochemistry, we found that T1r2 is expressed in hypothalamic neurons expressing neuropeptide Y and proopiomelanocortin in arcuate nucleus. It is also co-expressed with a canonical taste signaling molecule in perivascular cells of the median eminence. Our findings indicate that sweet taste receptors have unidentified functions in the brain and suggest that they may be a novel therapeutic target in the central nervous system.
BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials
Authors: Li Shan , Tao Li , Dai Haiyun , Gong Xue , Zhuo Yuguo , Xiang Hui , Zhao Yueyang , Gao Qing , Deng Liang
Published: October 2021

Background

BRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers.

Methods

Pubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test.

Results

A total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (Pheterogeneity = 0.40, for interaction).

Conclusion

BRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.
A Novel c-Mesenchymal-Epithelial Transition Factor Intergenic Fusion Response to Crizotinib in a Chinese Patient With Lung Adenocarcinoma: A Case Report
Authors: Liang Hongge , Zhou Dexun , Dai Lin , Zhang Moqin , Gao Zhancheng , Mu Xinlin
Published: October 2021

Background

The c-mesenchymal–epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping.

Methods

In June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People’s Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient’s worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered.

Conclusion

This was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.
Inhibition of Wnt-β-Catenin Signaling by ICRT14 Drug Depends of Post-Transcriptional Regulation by HOTAIR in Human Cervical Cancer HeLa Cells
Authors: Trujano-Camacho Samuel , Cantú-de León David , Delgado-Waldo Izamary , Coronel-Hernández Jossimar , Millan-Catalan Oliver , Hernández-Sotelo Daniel , López-Camarillo César , Pérez-Plasencia Carlos , Campos-Parra Alma D.
Published: October 2021

Background

In Cervical cancer (CC), in addition to HPV infection, the most relevant alteration during CC initiation and progression is the aberrant activation of Wnt/β-catenin pathway. Several inhibitory drugs of this pathway are undergoing preclinical and clinical studies. Long non-coding RNAs (lncRNAs) are associated with resistance to treatments. In this regard, understanding the efficiency of drugs that block the Wnt/β-catenin pathway in CC is of relevance to eventually propose successful target therapies in patients with this disease.

Methods

We analyzed the levels of expression of 249 components of the Wnt/β-catenin pathway in a group of 109 CC patients. Three drugs that blocking specific elements of Wnt/β-catenin pathway (C59, NSC668036 and ICRT14) by TOP FLASH assays and qRT-PCR were tested in vitro in CC cells.

Results

137 genes of the Wnt/β-catenin pathway were up-regulated and 112 down-regulated in CC patient’s samples, demonstrating that this pathway is dysregulated. C59 was an efficient drug to inhibit Wnt/β-catenin pathway in CC cells. NSC668036, was not able to inhibit the transcriptional activity of the Wnt/β-catenin pathway. Strikingly, ICRT14 was neither able to inhibit this pathway in HeLa cells, due to HOTAIR interaction with β-catenin, maintaining the Wnt/β-catenin pathway activated.

Conclusions

These results demonstrate a mechanism by which HOTAIR evades the effect of ICRT14, a Wnt/β-catenin pathway inhibitory drug, in HeLa cell line. The emergence of these mechanisms reveals new scenarios in the design of target therapies used in cancer.
The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer
Authors: Ma Xueyou , Ying Yufan , Xie Haiyun , Liu Xiaoyan , Wang Xiao , Li Jiangfeng
Published: October 2021

TAR-DNA-binding protein-43 (TDP-43) is a member of hnRNP family and acts as both RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation in various diseases. Currently, emerging evidence gradually elucidates the crucial role of TDP-43 in human cancers like it is previously widely researched in neurodegeneration diseases. A series of RNA metabolism events, including mRNA alternative splicing, transport, stability, miRNA processing, and ncRNA regulation, are all confirmed to be closely involved in various carcinogenesis and tumor progressions, which are all partially regulated and interacted by TDP-43. Herein we conducted the first overall review about TDP-43 and cancers to systematically summarize the function and precise mechanism of TDP-43 in different human cancers. We hope it would provide basic knowledge and concepts for tumor target therapy and biomarker diagnosis in the future.
Management of the Unexpected Difficult Airway in Neonatal Resuscitation
Authors: Berisha Gazmend , Boldingh Anne Marthe , Blakstad Elin Wahl , Rønnestad Arild Erlend , Solevåg Anne Lee
Published: October 2021

A “difficult airway situation” arises whenever face mask ventilation, laryngoscopy, endotracheal intubation, or use of supraglottic device fail to secure ventilation. As bradycardia and cardiac arrest in the neonate are usually of respiratory origin, neonatal airway management remains a critical factor. Despite this, a well-defined in-house approach to the neonatal difficult airway is often lacking. While a recent guideline from the British Pediatric Society exists, and the Scottish NHS and Advanced Resuscitation of the Newborn Infant (ARNI) airway management algorithm was recently revised, there is no Norwegian national guideline for managing the unanticipated difficult airway in the delivery room (DR) and neonatal intensive care unit (NICU). Experience from anesthesiology is that a “difficult airway algorithm,” advance planning and routine practicing, prepares the resuscitation team to respond adequately to the technical and non-technical stress of a difficult airway situation. We learned from observing current approaches to advanced airway management in DR resuscitations in a university hospital and make recommendations on how the neonatal difficult airway may be managed through technical and non-technical approaches. Our recommendations mainly pertain to DR resuscitations but may be transferred to the NICU environment.
Effects of Mycorrhizal Colonization on Transcriptional Expression of the Responsive Factor JERF3 and Stress-Responsive Genes in Banana Plantlets in Response to Combined Biotic and Abiotic Stresses
Authors: Rashad Younes M. , Fekry Waleed M. E. , Sleem Mohamed M. , Elazab Nahla T.
Published: October 2021

Banana plants (Musa acuminataL.) are exposed to various biotic and abiotic stresses that affect their production worldwide. Banana plants respond to these stresses, but their responses to combined stresses are unique and differ from those to various individual stresses. This study reported the effects of the mycorrhizal colonization of banana roots and/or infection with root rot on the transcriptional expression of the responsive factorJERF3and stress-responsive genes (POD, PR1,CHI, andGLU) under different salinity levels. Different transcriptional levels were recorded in response to the individual, dual, or triple treatments. All the applied biotic and abiotic stresses triggered the transcriptional expression of the tested genes when individually applied, but they showed different influences varying from synergistic to antagonistic when applied in combinations. The salinity stress had the strongest effect when applied in combination with the biotic stress and/or mycorrhizal colonization, especially at high concentrations. Moreover, the salinity level differentially affects the banana responses under combined stresses and/or mycorrhizal colonization in addition, the mycorrhizal colonization of banana plantlets improved their growth, photosynthesis, and nutrient uptake, as well as greatly alleviated the detrimental effects of salt and infection stresses. In general, the obtained results indicated that the responses of banana plantlets under the combined stresses are more complicated and differed from those under the individual stresses depending on the crosstalks between the signaling pathways.
The Power of Social Attribution: Perspectives on the Healing Efficacy of Ayahuasca
Authors: Brabec de Mori Bernd
Published: October 2021

During the last decades, ayahuasca gained much popularity among non-Indigenous and out-of-Amazonia based populations. In popular culture, it has been advertised as a natural remedy that was discovered by Indigenous peoples ante millennia and that has been used for shamanic healing of all kinds of ailments. This “neo-shamanic,” and often recreational, use of ayahuasca, however, has to be distinguished from traditional Indigenous praxes on the one hand, and, on the other hand, from medical investigation in the modern world. The former, Indigenous use mainly understands ayahuasca as an amplifying power for interacting with non-human beings in the animal, plant, or spirit realms. Within this paradigm, efficacy is not dependent on the drug, but on the correct communication between the healer (or sorcerer) and the non-human powers that are considered real and powerful also without resorting to ayahuasca. The latter, modern mode of understanding, contrastingly treats the neurochemical processes of MAO inhibition and dimethyltryptamine activity as trigger mechanisms for a series of psychological as well as somatic responses, including positive outcomes in the treatment of various mental conditions. I argue that there is an ontological incommensurability occurring especially between the Indigenous and medicinal concepts of ayahuasca use (with recreational use in its widest understanding trying to make sense from both sides). Modern medical applications of ayahuasca are so fundamentally different from Indigenous concepts that the latter cannot be used to legitimate or confirm the former (and vice versa). Finally, the deep coloniality in the process of appropriation of the Indigenous by the modern has to be questioned and resolved in any case of ayahuasca application.
Audiovisual Learning in Dyslexic and Typical Adults: Modulating Influences of Location and Context Consistency
Authors: Calabrich Simone L. , Oppenheim Gary M. , Jones Manon W.
Published: October 2021

Learning to read involves efficient binding of visual to auditory information. Aberrant cross-modal binding skill has been observed in both children and adults with developmental dyslexia. Here, we examine the contribution of episodic memory to acquisition of novel cross-modal bindings in typical and dyslexic adult readers. Participants gradually learned arbitrary associations between unfamiliar Mandarin Chinese characters and English-like pseudowords over multiple exposures, simulating the early stages of letter-to-letter sound mapping. The novel cross-modal bindings were presented in consistent or varied locations (i.e., screen positions), and within consistent or varied contexts (i.e., co-occurring distractor items). Our goal was to examine the contribution, if any, of these episodic memory cues (i.e., the contextual and spatial properties of the stimuli) to binding acquisition, and investigate the extent to which readers with and without dyslexia would differ in their reliance on episodic memory during the learning process. Participants were tested on their ability to recognize and recall the bindings both during training and then in post-training tasks. We tracked participants’ eye movements remotely with their personal webcams to assess whether they would re-fixate relevant empty screen locations upon hearing an auditory cue—indicative of episodic memory retrieval—and the extent to which the so-called “looking-at-nothing behavior” would modulate recognition of the novel bindings. Readers with dyslexia both recognized and recalled significantly fewer bindings than typical readers, providing further evidence of their persistent difficulties with cross-modal binding. Looking-at-nothing behavior was generally associated with higher recognition error rates for both groups, a pattern that was particularly more evident in later blocks for bindings encoded in the inconsistent location condition. Our findings also show that whilst readers with and without dyslexia are capable of using stimulus consistencies in the input—both location and context—to assist in audiovisual learning, readers with dyslexia appear particularly reliant on consistent contextual information. Taken together, our results suggest that whilst readers with dyslexia fail to efficiently learn audiovisual binding as a function of stimulus frequency, they are able to use stimulus consistency—aided by episodic recall—to assist in the learning process.