bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in sequencing technologies for amyotrophic lateral sclerosis research
Authors: Udine Evan , Jain Angita , van Blitterswijk Marka
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is caused by upper and lower motor neuron loss and has a fairly rapid disease progression, leading to fatality in an average of 2-5 years after symptom onset. Numerous genes have been implicated in this disease; however, many cases remain unexplained. Several technologies are being used to identify regions of interest and investigate candidate genes. Initial approaches to detect ALS genes include, among others, linkage analysis, Sanger sequencing, and genome-wide association studies. More recently, next-generation sequencing methods, such as whole-exome and whole-genome sequencing, have been introduced. While those methods have been particularly useful in discovering new ALS-linked genes, methodological advances are becoming increasingly important, especially given the complex genetics of ALS. Novel sequencing technologies, like long-read sequencing, are beginning to be used to uncover the contribution of repeat expansions and other types of structural variation, which may help explain missing heritability in ALS. In this review, we discuss how popular and/or upcoming methods are being used to discover ALS genes, highlighting emerging long-read sequencing platforms and their role in aiding our understanding of this challenging disease.
STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent
Authors: Zhang Xilin , Chen Qiuqiang , He Ying , Shi Qian , Yin Chengyi , Xie Yanping , Yu Huanming , Bao Ying , Wang Xiang , Tang Chengwu , Dong Zhaohui
Published: January 2023

Background

Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown.

Methods

The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo.

Results

Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes.

Conclusions

Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.
The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?
Authors: Moreno Rui , Rhodes Andrew , Piquilloud Lise , Hernandez Glenn , Takala Jukka , Gershengorn Hayley B. , Tavares Miguel , Coopersmith Craig M. , Myatra Sheila N. , Singer Mervyn , Rezende Ederlon , Prescott Hallie C. , Soares Márcio , Timsit Jean-François , de Lange Dylan W. , Jung Christian , De Waele Jan J. , Martin Greg S. , Summers Charlotte , Azoulay Elie , Fujii Tomoko , McLean Anthony S. , Vincent Jean-Louis
Published: January 2023

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.
Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest
Authors: Kang Changshin , Min Jin Hong , Park Jung Soo , You Yeonho , Jeong Wonjoon , Ahn Hong Joon , In Yong Nam , Lee In Ho , Jeong Hye Seon , Lee Byung Kook , Jeong Jinwoo
Published: January 2023

Background

This study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest.

Methods

We conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1–2) or poor (CPC 3–5).

Results

Of the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38–69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0–4.0 h), and the PHSIon DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSIgroup had a good neurological outcome compared with 48 (75%) patients in the AHSIgroup. In the AHSIgroup, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4–30.7] ng/mL vs. 84.3 [32.4–167.0] ng/mL,P < 0.001). The area under the curve for PHSIon DW-MRI was 0.87 (95% confidence interval [CI] 0.80–0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%–100%) and 74.2% (95% CI 62.0–83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1–95.1%]; 100% specificity).

Conclusions

In this cohort study, PHSIfindings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.
Systematic optimization of Cas12a base editors in wheat and maize using the ITER platform
Authors: Gaillochet Christophe , Peña Fernández Alexandra , Goossens Vera , D’Halluin Katelijn , Drozdzecki Andrzej , Shafie Myriam , Van Duyse Julie , Van Isterdael Gert , Gonzalez Camila , Vermeersch Mattias , De Saeger Jonas , Develtere Ward , Audenaert Dominique , De Vleesschauwer David , Meulewaeter Frank , Jacobs Thomas B.
Published: January 2023

Background

Testing an ever-increasing number of CRISPR components is challenging when developing new genome engineering tools. Plant biotechnology has few high-throughput options to perform iterative design-build-test-learn cycles of gene-editing reagents. To bridge this gap, we develop ITER (Iterative Testing of Editing Reagents) based on 96-well arrayed protoplast transfections and high-content imaging.

Results

We validate ITER in wheat and maize protoplasts using Cas9 cytosine and adenine base editors (ABEs), allowing one optimization cycle — from design to results — within 3 weeks. Given that previous LbCas12a-ABEs have low or no activity in plants, we use ITER to develop an optimized LbCas12a-ABE. We show that sequential improvement of five components — NLS, crRNA, LbCas12a, adenine deaminase, and linker — leads to a remarkable increase in activity from almost undetectable levels to 40% on an extrachromosomal GFP reporter. We confirm the activity of LbCas12a-ABE at endogenous targets in protoplasts and obtain base-edited plants in up to 55% of stable wheat transformants and the edits are transmitted to T1 progeny. We leverage these improvements to develop a highly mutagenic LbCas12a nuclease and a LbCas12a-CBE demonstrating that the optimizations can be broadly applied to the Cas12a toolbox.

Conclusion

Our data show that ITER is a sensitive, versatile, and high-throughput platform that can be harnessed to accelerate the development of genome editing technologies in plants. We use ITER to create an efficient Cas12a-ABE by iteratively testing a large panel of vector components. ITER will likely be useful to create and optimize genome editing reagents in a wide range of plant species.
Efficient biosynthesis of (R)-mandelic acid from styrene oxide by an adaptive evolutionary Gluconobacter oxydans STA
Authors: Liu Fei , Zhou Junping , Hu Mengkai , Chen Yan , Han Jin , Pan Xuewei , You Jiajia , Xu Meijuan , Yang Taowei , Shao Minglong , Zhang Xian , Rao Zhiming
Published: January 2023

Background

(R)-mandelic acid (R-MA) is a highly valuable hydroxyl acid in the pharmaceutical industry. However, biosynthesis of optically pure R-MA remains significant challenges, including the lack of suitable catalysts and high toxicity to host strains. Adaptive laboratory evolution (ALE) was a promising and powerful strategy to obtain specially evolved strains.

Results

Herein, we report a new cell factory of the Gluconobacter oxydans to biocatalytic styrene oxide into R-MA by utilizing the G. oxydans endogenous efficiently incomplete oxidization and the epoxide hydrolase (SpEH) heterologous expressed in G. oxydans. With a new screened strong endogenous promoter P12780, the production of R-MA was improved to 10.26 g/L compared to 7.36 g/L of using Plac. As R-MA showed great inhibition for the reaction and toxicity to cell growth, adaptive laboratory evolution (ALE) strategy was introduced to improve the cellular R-MA tolerance. The adapted strain that can tolerate 6 g/L R-MA was isolated (named G. oxydans STA), while the wild-type strain cannot grow under this stress. The conversion rate was increased from 0.366 g/L/h of wild type to 0.703 g/L/h by the recombinant STA, and the final R-MA titer reached 14.06 g/L. Whole-genome sequencing revealed multiple gene-mutations in STA, in combination with transcriptome analysis under R-MA stress condition, we identified five critical genes that were associated with R-MA tolerance, among which AcrA overexpression could further improve R-MA titer to 15.70 g/L, the highest titer reported from bulk styrene oxide substrate.

Conclusions

The microbial engineering with systematic combination of static regulation, ALE, and transcriptome analysis strategy provides valuable solutions for high-efficient chemical biosynthesis, and our evolved G. oxydans would be better to serve as a chassis cell for hydroxyl acid production.
Effects of storage conditions and digestion time on DNA amplification of biting midge (Culicoides) blood meals
Authors: Bellekom Ben , Bailey Abigail , England Marion , Langlands Zoe , Lewis Owen T. , Hackett Talya D.
Published: January 2023

Background

Molecular analysis of blood meals is increasingly used to identify the hosts of biting insects such as midges and mosquitoes. Successful host identification depends on the availability of sufficient host DNA template for PCR amplification, making it important to understand how amplification success changes under different storage conditions and with different durations of blood meal digestion within the insect gut before being placed into the storage medium.

Method

We characterised and compared the digestion profile of two species of Culicoides over a 96-h period using a novel set of general vertebrate primers targeting the 16S rRNA gene. A set number of individuals from each species were killed over 13 time points post-blood feeding and preserved in 95% ethanol. Samples were stored either at ambient room temperature or in a − 20 °C freezer to examine the effect of storage condition on the PCR amplification success of host DNA.

Results

We found that amplification success across the 96-h sampling period post-feeding was reduced from 96 to 6% and 96% to 14% for Culicoides nubeculosus and Culicoides sonorensis, respectively. We found no effect of storage condition on PCR amplification success, and storage in 95% ethanol was sufficient to maintain high rates of amplifiable host DNA for at least 9 months, even at room temperature.

Conclusions

These findings highlight the limited time frame during which an individual may contain amplifiable host DNA and demonstrate the importance of timely sample capture and processing post-blood feeding. Moreover, storage in 95% ethanol alone is sufficient to limit host DNA degradation. These results are relevant to the design of studies investigating the biting behaviour and disease transmission potential of Culicoides and other biting Diptera.

Graphical Abstract
The first successful desensitization protocol in exenatide allergy: a case report
Authors: Yeğit Osman Ozan , Sarıbeyliler Göktuğ , Karadağ Pelin , Demir Semra , Gül Nurdan , Ünal Derya , Gelincik Akkor Aslı
Published: January 2023

Background

Glucagon-like peptide-1 (GLP-1) receptor agonists are important treatment options in obese patients with type 2 diabetes. To date, few immediate allergic reactions due to GLP-1 receptor agonists were reported. One report revealed that a patient with a level 1 anaphylaxis according to Brighton Criteria due to an exendin based GLP-1 receptor agonist was able to tolerate liraglutide (Human GLP-1 analogue), the alternative GLP-1 receptor agonist. Since exenatide is the only available GLP-1 receptor agonist covered by insurance in Turkey, a drug desensitization protocol, the only therapeutic method in hypersensitivity reactions used in case of absence of an alternative drug, was considered. Here, we report a successful desensitization protocol for the first time in two obese diabetic patients with an immediate hypersensitivity to exenatide.

Case presentation

The first patient was a 47 year-old female. She was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes after the last dose, following a week of an exenatide BID 5 mcg/20 mcl treatment. Although the reaction was sudden onset, it did not meet the Brighton Criteria of anaphylaxis. The second patient was a 46 year-old female. She had a large local immediate injection site reaction that appeared 15 min following an exenatide BID 5 mcg/20 mcl injection. The injection site reaction was not accompanied by a systemic allergic reaction. We performed desensitization with exenatide to two patients who need GLP-1 receptor agonist treatment. Protocol was completed in 7 steps in approximately 3 h, with the aim of reaching the daily dosage of exenatide. Throughout this process, we observed that both cases tolerated the protocol without any complaints or complications. Following the protocol, the patients safely tolerated the treatment for 3 months.

Conclusions

We present the first successful desensitization protocol to exenatide in both local and/or systemic immediate hypersensitivity reactions and indicate the importance of desensitization in patients who do not have alternative therapies.
Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling
Authors: Sui Liyan , Zhao Yinghua , Wang Wenfang , Chi Hongmiao , Tian Tian , Wu Ping , Zhang Jinlong , Zhao Yicheng , Wei Zheng-Kai , Hou Zhijun , Zhou Guoqiang , Wang Guoqing , Wang Zedong , Liu Quan
Published: January 2023

Background

Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive.

Results

We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus.

Conclusion

Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.
Pre-pregnancy body mass index has greater influence on newborn weight and perinatal outcome than weight control during pregnancy in obese women
Authors: Zhang Jin , Zhang Rui , Chi Jingjing , Li Ya , Bai Wenpei
Published: January 2023

Background

The pre-pregnancy weight and gestational weight gain (GWG) are closely related to perinatal maternal and infant complications, but the relationship between pre-pregnancy weight and GWG and the pattern of interaction have not been reported. This study investigated the influence of weight control during pregnancy on the perinatal maternal and infant outcomes.

Methods

A total of 835 singleton pregnant women who were hospitalized between January 2018 and December 2018 were retrospectively included in this study and divided into two groups: the diet guidance (DG) group (n = 167) and the control group (n = 668). The pre-pregnancy body mass index (BMI), GWG, and perinatal outcomes of the women and infants were determined in two groups.

Results

The dietary modification and reasonable exercise during pregnancy effectively reduced the GWG, and even some women with pre-pregnancy obesity achieved weight loss during pregnancy. The GWG in the DG group was significantly lower than in the control group, especially in the second and third trimesters. GWG was positively related to birth weight. The birth weight in the DG group was significantly lower than in the control group when their mothers had similar GWG. In women with pre-pregnancy obesity, GWG seemed to be negatively related to birth weight. However, after adjusting the mean BMI, the pre-pregnancy BMI and GWG were positively related to the birth weight. Compared with the control group, the incidences of dystocia, postpartum hemorrhage, macrosomia, small for gestational age infants and neonatal complications significantly reduced in the DG group, and the preterm birth rate was comparable between two groups. Some women with pre-pregnancy obesity lose weight during pregnancy, but there was no premature birth or small for gestational age infant. The incidences of macrosomia, postpartum hemorrhage, dystocia, cesarean section and gestational diabetes increased significantly with the increase of pre-pregnancy BMI.

Conclusion

For women with increased pre-pregnancy BMI, strict weight control is required to reduce obesity-related complications of the mother and infant. The weight control in the second and third trimesters is especially important and most likely to prevent GWG. Compared with GWG, pre-pregnancy BMI has greater influence on the birth weight and maternal and infant complications, and may even compromise the benefits of weight control during pregnancy. Thus, weight control is recommended before pregnancy.
Cherry fruit anthocyanins cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside protect against blue light-induced cytotoxicity in HaCaT cells
Authors: Lee Hyang-Yeol , Kim Jun-Sub
Published: January 2023

Blue light derived from multiple sources, including sunlight, generates reactive oxygen species (ROS) and negatively affects the skin in a manner similar to that of ultraviolet light. Cyanidin-3-O-glucoside (C3OG) and cyanidin-3-O-rutinoside (C3OR) are anthocyanin antioxidants that have protective effects on various tissues and cell types. However, the effects of anthocyanins on blue light-mediated changes remain unconfirmed. In this study, we determined the protective effects of C3OG and C3OR isolated and purified from waste cherry fruits (Prunus serrulata L. var. tomentella Nakai) against the blue light-induced ROS formation and inflammatory responses in HaCaT cells. It is showed that the treatment of C3OG and C3OR significantly reduced the blue light-induced cytotoxicity and ROS production in a dose dependent manner. Furthermore, we found that focal adhesion kinase (FAK) is a major upstream of blue light-induced expression of inflammatory cytokines (TNF-α, IL-6 and IL-8), and these effects were attenuated by C3OG or C3OR treatment. In the initial reaction, blue lights increased the phosphorylation of inhibitory-κB Kinase α (IKKα), c-jun N-terminal kinase (JNK), and p38. The phosphorylation of these intracellular proteins was reduced via FAK inhibitor, NAC (ROS scavenger), and anthocyanin treatments. After 24 h of blue light irradiation, C3OG or C3OR treatment markedly inhibited caspase-3-mediated apoptosis and cleaved-FAK-mediated anoikis, which is cell detachment-induced apoptosis. Therefore, our results indicate that C3OG and C3OR effectively protected human keratinocytes from harmful blue light-induced cytotoxicity and inflammation.
Dynamics of the gut microbiome, IgA response, and plasma metabolome in the development of pediatric celiac disease
Authors: Girdhar Khyati , Dogru Yusuf Dogus , Huang Qian , Yang Yi , Tolstikov Vladimir , Raisingani Amol , Chrudinova Martina , Oh Jaewon , Kelley Kristina , Ludvigsson Jonas F. , Kiebish Michael A. , Palm Noah W. , Ludvigsson Johnny , Altindis Emrah
Published: January 2023

Background

Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. Almost all CD patients possess human leukocyte antigen (HLA) DQ2/DQ8 haplotypes; however, only a small subset of individuals carrying these alleles develop CD, indicating the role of environmental factors in CD pathogenesis. The main objective of this study was to determine the contributory role of gut microbiota and microbial metabolites in CD onset. To this end, we obtained fecal samples from a prospective cohort study (ABIS) at ages 2.5 and 5 years. Samples were collected from children who developed CD after the final sample collection (CD progressors) and healthy children matched by age, HLA genotype, breastfeeding duration, and gluten-exposure time (n=15–16). We first used 16S sequencing and immunoglobulin-A sequencing (IgA-seq) using fecal samples obtained from the same children (i) 16 controls and 15 CD progressors at age 2.5 and (ii) 13 controls and 9 CD progressors at age 5. We completed the cytokine profiling, and plasma metabolomics using plasma samples obtained at age 5 (n=7–9). We also determined the effects of one microbiota-derived metabolite, taurodeoxycholic acid (TDCA), on the small intestines and immune cell composition in vivo.

Results

CD progressors have a distinct gut microbiota composition, an increased IgA response, and unique IgA targets compared to healthy subjects. Notably, 26 plasma metabolites, five cytokines, and one chemokine were significantly altered in CD progressors at age 5. Among 26 metabolites, we identified a 2-fold increase in TDCA. TDCA treatment alone caused villous atrophy, increased CD4+ T cells, Natural Killer cells, and two important immunoregulatory proteins, Qa-1 and NKG2D expression on T cells while decreasing T-regulatory cells in intraepithelial lymphocytes (IELs) in C57BL/6J mice.

Conclusions

Pediatric CD progressors have a distinct gut microbiota composition, plasma metabolome, and cytokine profile before diagnosis. Furthermore, CD progressors have more IgA-coated bacteria and unique targets of IgA in their gut microbiota. TDCA feeding alone stimulates an inflammatory immune response in the small intestines of C57BJ/6 mice and causes villous atrophy, the hallmark of CD. Thus, a microbiota-derived metabolite, TDCA, enriched in CD progressors’ plasma, has the potential to drive inflammation in the small intestines and enhance CD pathogenesis.
The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder
Authors: Jiang Xinyue , Sultan Alysha A. , Dimick Mikaela K. , Zai Clement C. , Kennedy James L. , MacIntosh Bradley J. , Goldstein Benjamin I.
Published: January 2023

Background

CACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD.

Methods

Participants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13–20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race.

Results

We observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01).

Conclusion

This study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD.
Implementing ICT in classroom practice: what else matters besides the ICT infrastructure?
Authors: Lomos Catalina , Luyten J. W. , Tieck Sabine
Published: January 2023

Background

The large-scale International Computer and Information Literacy Study (2018) has an interesting finding concerning Luxembourg teachers. Luxembourg has one of the highest reported level of technology-related resources for teaching and learning, but a relatively lower reported use of ICT in classroom practice.

Methods

ICT innovation requires a high initial level of financial investment in technology, and Luxembourg has achieved this since 2015. Once the necessary financial investment in ICT technology has been made, the key question is what else matters to increase the use of ICT in teaching. To identify the relevant factors, we used the “Four in Balance” model, aimed explicitly at monitoring the implementation of ICT in schools.

Results

Using data for 420 teachers in Luxembourg, we identify that within such a technology-driven approach to digitalization, teachers’ vision of ICT use in teaching, level of expertise, and the use of digital learning materials in class are significant support factors. Leadership and collaboration, in the form of an explicit vision of setting ICT as a priority for teaching in the school, also prove to be important.

Conclusions

Through these findings, we show that the initial investment in school infrastructure for ICT needs to be associated in its implementation with teachers’ ICT-related beliefs, attitudes, and ICT expertise.
Significance of the high-pressure properties and structural evolution of gas hydrates for inferring the interior of icy bodies
Authors: Hirai Hisako , Kadobayashi Hirokazu
Published: January 2023

Hydrogen, methane, and water ice are among the most abundant materials in the universe. Based on experimental, theoretical, and spacecraft data, gas hydrates consisting of gas and water ice have been predicted to exist throughout the universe. This review discusses the high-pressure properties of two common gas hydrates (methane and hydrogen hydrates) at low and high temperatures based primarily on experimental results. Gas hydrates consist of a water molecule host and a gaseous guest. They have a clathrate structure at low pressure and a filled-ice structure at high pressure. The host encloses the guest, and a specific interaction occurs between the guest and host, resulting in unique physical properties. When subjected to pressure, gas hydrates undergo various phase changes. Based on pressure and guest size, a general rule for phase changes occurring in gas hydrates exists. Analysis of the phase-transition mechanism shows that some cages are maintained after the transition to the next clathrate structure, while others are recombined into different cages of the next structure. This is a novel mechanism that can be called “cage recombination mechanism.” Low-temperature and high-pressure experiments have revealed that as the pressure increases, the guest molecules undergo a stepwise progression of orientational ordering, i.e., restriction of free rotation, which induces structural changes that stabilize the structure at high pressure. Theoretical studies have predicted that hydrogen-bond symmetrization in the host occurs at even higher pressures, further stabilizing the structure. Thus, hydrates respond to environmental changes such as pressure to achieve self-organization by the orientational ordering of the guest and hydrogen-bond symmetrization of the host. Additionally, results of high-temperature and high-pressure experiments conducted at conditions comparable to those in Neptune’s ice mantle show that methane hydrate decomposes into solid methane and ice VII, both of which melt at further elevated temperatures. Then, the methane molecules undergo further molecular dissociation to form diamonds. These findings are valuable for modeling the interiors of icy planets and understanding how magnetic fields and heat are generated.
Phylogenomics of five Pseudanabaena cyanophages and evolutionary traces of horizontal gene transfer
Authors: Zhu Jie , Yang Feng , Du Kang , Wei Zi-Lu , Wu Qing-Fa , Chen Yuxing , Li Wei-Fang , Li Qiong , Zhou Cong-Zhao
Published: January 2023

Background

Along with the fast development and urbanization in developing countries, the waterbodies aside the growing cities become heavily polluted and highly eutrophic, thus leading to the seasonal outbreak of cyanobacterial bloom. Systematic isolation and characterization of freshwater cyanophages might provide a biological solution to control the awful blooms. However, genomic sequences and related investigations on the freshwater cyanophages remain very limited to date.

Results

Following our recently reported five cyanophages Pam1~Pam5 from Lake Chaohu in China, here we isolated another five cyanophages, termed Pan1~Pan5, which infect the cyanobacteriumPseudanabaenasp. Chao 1811. Whole-genome sequencing showed that they all contain a double-stranded DNA genome of 37.2 to 72.0 kb in length, with less than half of the putative open reading frames annotated with known functions. Remarkably, the siphophage Pan1 encodes an auxiliary metabolic genephoHand constitutes, together with the host, a complete queuosine modification pathway. Proteomic analyses revealed that although Pan1~Pan5 are distinct from each other in evolution, Pan1 and Pan3 are somewhat similar to our previously identified cyanophages Pam3 and Pam1 at the genomic level, respectively. Moreover, phylogenetic analyses suggested that Pan1 resembles theα-proteobacterial phage vB_DshS-R5C, revealing direct evidence for phage-mediated horizontal gene transfer between cyanobacteria andα-proteobacteria.

Conclusion

In addition to the previous reports of Pam1~Pam5, the present findings on Pan1~Pan5 largely enrich the library of reference freshwater cyanophages. The abundant genomic information provides a pool to identify novel genes and proteins of unknown function. Moreover, we found for the first time the evolutionary traces in the cyanophage that horizontal gene transfer might occur at the level of not only inter-species, but even inter-phylum. It indicates that the bacteriophage or cyanophage could be developed as a powerful tool for gene manipulation among various species or phyla.
Feasibility of electroacupuncture at Baihui (GV20) and Zusanli (ST36) on survival with a favorable neurological outcome in patients with postcardiac arrest syndrome after in-hospital cardiac arrest: study protocol for a pilot randomized controlled trial
Authors: Zeng Ruifeng , Lai Fang , Huang Manhua , Zhu Decai , Chen Baijian , Tao Lanting , Huang Wei , Lai Chengzhi , Ding Banghan
Published: January 2023

Background

At present, even the first-line medication epinephrine still shows no evidence of a favourable neurological outcome in patients with sudden cardiac arrest (SCA). The high mortality of patients with postcardiac arrest syndrome (PCAS) can be attributed to brain injury, myocardial dysfunction, systemic ischaemia/reperfusion response, and persistent precipitating pathology. Targeted temperature management, the only clinically proven method in the treatment of PCAS, is still associated with a series of problems that have not been completely resolved.

Acupuncture is a crucial therapy in traditional Chinese medicine. On the basis of the results of previous studies, we hypothesize that electroacupuncture (EA) might provide therapeutic benefits in the treatment of PCAS. This study will explore the feasibility of EA on SCA patients.

Methods

This is a prospective pilot, randomized controlled clinical trial. Eligible patients with PCAS after in-hospital cardiac arrest (IHCA) admitted to our department will be randomly allocated to the control group or the EA group. Both groups will receive standard therapy according to American Heart Association guidelines for cardiopulmonary resuscitation. However, the EA group will also receive acupuncture at the Baihui acupoint (GV20) and Zusanli acupoint (ST36) with EA stimulation for 30 min using a dense-dispersed wave at frequencies of 20 and 100 Hz, a current intensity of less than 10 mA, and a pulse width of 0.5 ms. EA treatment will be administered for up to 14 days (until either discharge or death). The primary endpoint is survival with a favourable neurological outcome. The secondary endpoints are neurological scores, cardiac function parameters, and other clinical parameters, including Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, on days 0 to 28.

Discussion

This study will provide crucial clinical evidence on the efficacy of EA in PCAS when used as an adjunctive treatment with AHA standard therapy.

Trial registration

chictr.org.cn: ChiCTR2000040040. Registered on 19 November 2020. Retrospectively registered. http://www.chictr.org.cn/.
Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma
Authors: Zhang Zhi-Cheng , Liu Yi-Fu , Xi Ping , Nie Ye-Chen , Sun Ting , Gong Bin-Bin
Published: January 2023

Background

The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored.

Methods

The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database.

Results

CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy.

Conclusions

The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.
Detection and characterization of difenoconazole resistance in Stagonosporopsis citrulli from watermelon and muskmelon in Zhejiang Province of China
Authors: Kong Zhangliang , Zhang Yu , Zhuang Chaojie , Mao Chenxin , Zhang Chuanqing
Published: January 2023

The watermelon and muskmelon productions are important agriculture pillar industries of Zhejiang Province in China. Difenoconazole is an imidazole-class sterol, 14-demethylase inhibitor (DMI), which has been in use for several years to control gummy stem blight (GSB) caused by Stagonosporopsis species. However, the detection and characterization of difenoconazole resistance in GSB have not been clarified. In this study, a total of 112 isolates were collected from samples of GSB on watermelon and muskmelon in five locations of Zhejiang Province, China. All of the isolates were identified as Stagonosporopsis citrulli through morphology and multiplex PCR analysis. The determination of their resistance to difenoconazole via the discriminatory dosage method showed that the total resistance frequency was 89.3%. Among the resistant sub-population, 36.6% had high-level resistance to difenoconazole (DifHR), while 46.4% and 6.3% had low- (DifLR) and moderate-level resistance (DifMR), respectively. Additionally, the difenoconazole showed a positive cross-resistance with four DMIs, i.e., tebuconazole, prochloraz, metconazole, and mefentrifluconazole, but not hexaconazole. The phenotypic analysis found that the difenoconazole resistant (DifR) isolates demonstrated attenuated ability in both the mycelial growth and sporulation compared with the difenoconazole sensitive (DifS) isolates, while there was no significant difference in pathogenicity on watermelon leaves between the DifR and DifS isolates. Further exploration of the mechanism related to difenoconazole resistance of S. citrulli isolates revealed that the resistance to difenoconazole involved four types of mutations in CYP51, i.e., G463S for DifLR, I444M, Y446H, and A464G for DifHR. No over-expression of the cyp51 gene was found in the tested DifR isolates. Furthermore, it was found that 5% of the DifR isolates were significantly more sensitive to difenoconazole after being treated with 20 μg/mL chlorpromazine hydrochloride, indicating that the efflux mechanism may be involved in these difenoconazole-resistant isolates. Together, our study results suggested that S. citrulli had a strong resistance to difenoconazole on watermelon and muskmelon, and the mutations in cyp51and changes in fungicide efflux were responsible for the emergence of difenoconazole resistance in S. citrulli.
Effects of regional air pollutants on respiratory diseases in the basin metropolitan area of central Taiwan
Authors: Liang Chen-Jui , Lin Ping-Yi , Chen Ying-Chieh , Liang Jeng-Jong
Published: January 2023

This study divided a basin metropolitan area with high air pollution into three subareas, namely urban, suburban, and rural, on the basis of population density for a systematic analysis of the effects of local air pollutants on respiratory diseases. A panel data regression model was used to estimate the annual incidence growth rates (AIGRs) of the four respiratory diseases, namely lung cancer, chronic obstructive pulmonary disease, asthma, and pneumonia, resulting from exposure to fine particulate matter (PM2.5, diameter of 2.5 μm or less), odd oxygen (ODO), or nonmethane hydrocarbon (NMHC). The results indicate that the prevailing wind direction is not a major factor determining the distribution of air pollutants. The spatial distributions of ODO and NMHC differed from that of PM2.5. Three air pollutants contributed to positive AIGRs of the four diseases in the study area, but PM2.5 which had a negative AIGR for asthma in the rural subarea. The pollutants with the strongest effects on AIGR, in descending order, were NMHC, PM2.5, and ODO. The effect of ambient NMHC was significant and nonnegligible, especially in the urban subarea. A dimensionless potential AIGR (PAIGR) formula was established to quantitatively compare the effects of different air pollutants on the four respiratory diseases. The results indicate that ambient NMHC had the strongest effect on the incidences of the respiratory diseases, followed by that of ambient PM2.5. The effect of ambient NMHC was significant and nonnegligible, especially in the urban subarea. The PAIGR ratio ranges of PM2.5 to ODO and NMHC to ODO for the four diseases in urban subsarea were from 3 to 19 and from 289 to 920, respectively. This study also applied multivariate regression to assess the association among 5 aspects, namely air quality, point source, line source, area source, and socioeconomic status, and the incidences of the four respiratory diseases. The results indicate that the model has favorable fit and can thus reflect the associations of the 15 factors of 5 aspects with the four respiratory diseases in each subarea.
Mendelian susceptibility to mycobacterial disease: an overview
Authors: Errami Abderrahmane , El Baghdadi Jamila , Ailal Fatima , Benhsaien Ibtihal , Ouazahrou Kaoutar , Abel Laurent , Casanova Jean-Laurent , Boisson-Dupuis Stephanie , Bustamante Jacinta , Bousfiha Ahmed Aziz
Published: January 2023

Background

Mycobacteria include ubiquitous species of varying virulence. However, environmental and individual-specific factors, particularly host genetics, play a crucial role in the outcome of exposure to mycobacteria. The first molecular evidence of a monogenic predisposition to mycobacteria came from the study of Mendelian susceptibility to mycobacterial disease (MSMD), a rare inborn error of IFN-γ immunity conferring a selective susceptibility to infections even with low virulent mycobacteria, in patients, mostly children, without recognizable immune defects in routine tests. This article provides a global and updated description of the most important molecular, cellular, and clinical features of all known monogenic defects of MSMD.

Results

Over the last 20 years, 19 genes were found to be mutated in MSMD patients (IFNGR1, IFNGR2, IFNG, IL12RB1, IL12RB2, IL23R, IL12B, ISG15, USP18, ZNFX1, TBX21, STAT1, TYK2, IRF8, CYBB, JAK1, RORC, NEMO, and SPPL2A), and the allelic heterogeneity at these loci has led to the definition of 35 different genetic defects. Despite the clinical and genetic heterogeneity, almost all genetic etiologies of MSMD alter the interferon gamma (IFN-γ)-mediated immunity, by impairing or abolishing IFN-γ production or the response to this cytokine or both. It was proven that the human IFN-γ level is a quantitative trait that defines the outcome of mycobacterial infection.

Conclusion

The study of these monogenic defects contributes to understanding the molecular mechanism of mycobacterial infections in humans and to the development of new diagnostic and therapeutic approaches to improve care and prognosis. These discoveries also bridge the gap between the simple Mendelian inheritance and complex human genetics.
A comprehensive survey on reduced switch count multilevel inverter topologies and modulation techniques
Authors: N. V. Vinay Kumar , T GowriManohar
Published: January 2023

Multilevel inverters (MLIs) are becoming commonly increasing in high- and medium-power applications. This is because MLI has various intrinsic advantages over conventional two-level inverters, including reduced device ratings, high-quality output, and so on. Most of the traditional topologies are still used in key applications, and there is an increased attentiveness to emerging multilevel topologies to minimize the number of gate drivers, power semiconductor devices, and/or isolated DC sources. Although MLIs have a promising future in industry-oriented applications, their commercial acceptance has been constrained by their size cost, excessive device count, and switch complexity. To convey the drawbacks of MLIs, academics are continually developing next-generation topologies known as reduced switch count (RSC) MLIs. For various reasons throughout the past 10 years, many MLIs with RSC topologies have been described. In this study, an overview of some of the more newly proposed multilevel inverter network topologies that achieve the legitimate goal is presented.
Lessons from COVID-19 outbreaks for spaces between buildings using tactical urbanism
Authors: Abdelkader Mai M. , Khalifa Marwa , Elshater Abeer
Published: January 2023

Several urban agendas related to different urban spaces in cities are documented in the global literature. This research explores social interactions in voids between buildings using tactical urbanism. As part of this study, we examine changes in perceptions of the use of spaces between buildings by comparing critical differentiation factors before and after the outbreak of COVID-19. We conducted an online survey for three months among residents in Egypt using a comparative method based on personal, residential, and district characteristics. The results revealed that during and after the COVID-19 pandemic, the spaces between buildings played a critical role. According to the conclusion, tactical urbanism, rapid and low-cost intervention, material availability, and small-scale pop-ups are essential for reducing the adverse effects of COVID-19. These findings confirmed that the longer the outbreak persisted, the more planning shifted to smaller public spaces within walking distance, resulting in long-term activities rather than large areas of land being planned.
Teaching Postsecondary Students to Use Analogies as a Cognitive Learning Strategy: An Intervention
Authors: Tise Joseph C. , Sperling Rayne A. , Dann Michael S. , Young Taylor M.
Published: January 2023

This intervention extends learning strategies research into authentic learning environments. It shows college biology students can learn to generate analogies as a learning strategy and get better at doing so. Finally, students’ generated-analogy quality predicts analogical reasoning and knowledge of cognition.