bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of the Tibetan Plateau and Yunnan‐Guizhou Plateau in the Regional Extreme Precipitation Over Sichuan Basin in Summer: A Case Study
Authors: Xu Xiaoke , Huang Anning , Zhao Wei , Yang Ben , Xue Daokai , Zhang Yan
Published: February 2024

The roles of the Tibetan Plateau (TP) and Yunnan‐Guizhou Plateau (YGP) in regional precipitation extremes over the Sichuan Basin (SCB) in summer under specific circulation background remain unclear. This study quantifies the impact of TP or YGP on the regional extreme precipitation event (REPE) which occurred during 04:00 Beijing time (BJT) on 11 August to 03:00 BJT on 13 August 2020 with a rainfall center located in the western SCB based on numerical experiments. Results show that the accumulated precipitation regionally averaged over the western SCB during the REPE can be reduced by 84% (51%) when the TP (YGP) is absent, and the decreased precipitation is mainly caused by the reduced stratus precipitation. Mechanism analysis indicates that relative to the control experiment including the TP and YGP, the absence of TP or YGP leads to reduced temperature over the SCB induced by anomalous cold advection from the upstream regions where the terrains are removed, and further results in much more stable stratification and thereafter weakens the ascending motions and reduces the stratus precipitation over the western SCB. On the other hand, the absence of TP or YGP induces an anomalous anti‐cyclone at 850 hPa over SCB, which further weakens both the uplift effect of terrain on airflow along the windward slope and water vapor transport over the western SCB and thereafter reduces the precipitation over this region. This study deepens the understanding of the topographic effect on regional extreme precipitation over SCB in summer from the thermodynamic and dynamic processes.
Detection of Subsurface Density Structures of the Aristarchus Plateau by Gravity Inversion
Authors: Liang Feng , Amrouche Mohamed , Yan Jianguo , Saibi Hakim
Published: February 2024

The Aristarchus plateau, located at the center of Oceanus Procellarum, exhibits one of the most complex volcanic features on the Moon. To understand the subsurface three‐dimensional density distribution under the Aristarchus plateau, we performed gravity inversion using high‐resolution gravity data obtained from the Gravity Recovery and Interior Laboratory mission. Our inversion results indicate the presence of a strong lateral density differentiation, with some positive and negative density anomalies possibly exhibiting a correlation with the volcanic features observed on the surface. A linear high‐density anomaly near the Cobra Head magma source and an elliptical high‐density anomaly both exactly match the surface basaltic exposures observable in the remote sensing data. We executed the density separation to extract low‐density anomalies of the whole plateau and removed most of the density artifacts. The low‐density anomalies display elevated terrain evidence of multiple “semi‐ring” structures, suggesting the location of buried remnants of crater rims. The Aristarchus crater has a central low‐density anomaly in the exact size and shape of the later‐formed impact crater. This anomaly is consistent with the high crater porosity produced by extensive impact‐generated fracturing and dilatant bulking, though the observed gravity and density anomalies are greater in magnitude than expected for this process. The remote sensing data expose high‐silica material in the crater rim, implying that the young crater excavated an underlying layer containing both plagioclase and Si‐rich materials, and indicating that the local uplift of feldspathic and/or silicic materials also contributes to the high amplitude of the low‐density anomaly in the Aristarchus crater.
Seismic Monitoring and Geomorphic Impacts of the Catastrophic 2018 Baige Landslide Hazard Cascades in the Tibetan Plateau
Authors: Zhang Zhen , Tan Yen Joe , Walter Fabian , He Siming , Chmiel Małgorzata , Su Jinrong
Published: February 2024

Surface hazards can form hazard cascades which expand their reach. However, our understanding of their complex dynamics and ability to mitigate their impacts remain limited. In 2018, two landslides dammed the Jinsha River in the Tibetan plateau and formed landslide‐dammed lakes. Subsequent dam breaches prompted the evacuation of >120,000 people. An early warning system for floods using a regional seismic network has been proposed on the basis of catastrophic floods having been detected ∼100 km away, with seismic energy proportional to discharge. Surprisingly, we find that this catastrophic outburst flood was undetectable beyond a few kilometers, with peak seismic energy preceding peak discharge. We propose that river channel stability also controls seismic energy generation and should be considered for accurate monitoring of catastrophic floods. In contrast, we find that the various processes during dam breach can be well‐characterized seismically further away and provide warning ∼60 min before discharge exceeds monsoon flood levels. We also show that numerical modeling of dam breaches which typically lacks in situ measurements can benefit from incorporating seismic data as constraints. Finally, we show that this event drastically increased sediment fluxes ∼670 km downstream for years and may significantly reduce the capacity of hydropower plants. Our results reveal ways to improve early warning of catastrophic outburst floods and the need to consider surface hazards' long‐term impact when managing infrastructure in mountainous regions.
Bridging Gaps Between the Geosciences and National Security
Authors: Chirico Peter , Molnia Bruce , Nguy-Robertson Anthony , Opstal Dan
Published: February 2024

The geoscience community and national security agencies need effective, two-way communication to exchange information.
Synaptotagmin-4 induces anhedonic responses to chronic stress via BDNF signaling in the medial prefrontal cortex
Authors: Kim Jeongseop , Seol Sihwan , Kim Tae-Eun , Lee Joonhee , Koo Ja Wook , Kang Hyo Jung
Published: February 2024

Stressful circumstances are significant contributors to mental illnesses such as major depressive disorder. Anhedonia, defined as loss of the ability to enjoy pleasure in pleasurable situations, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we demonstrated that synaptotagmin-4 (SYT4), which is involved in the release of neurotransmitters and neurotrophic factors, is implicated in chronic stress-induced anhedonia. Employing chronic unpredictable stress (CUS), we evaluated two subpopulations of mice, susceptible (SUS, anhedonic) and resilient (RES, nonanhedonic), based on sucrose preference, which was strongly correlated with social reward. The FosTRAP (targeted recombination in active populations) system and optogenetic approach revealed that neural activity in the medial prefrontal cortex (mPFC) was significantly associated with CUS-induced anhedonic behavioral phenotypes. By conducting weighted gene coexpression network analysis of RNA sequencing data from the mPFC of SUS and RES mice, we identified Syt4 as a hub gene in a gene network that was unique to anhedonia. We also confirmed that Syt4 overexpression in the mPFC was pro-susceptible, while Syt4 knockdown was pro-resilient; the pro-susceptible effects of SYT4 were mediated through a reduction in brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the mPFC. These findings suggest that SYT4-BDNF interactions in the mPFC represent a crucial regulatory mechanism of anhedonic susceptibility to chronic stress.
Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases
Authors: Takegahara Noriko , Kim Hyunsoo , Choi Yongwon
Published: February 2024

Osteoclasts are the principal cells that efficiently resorb bone. Numerous studies have attempted to reveal the molecular pathways leading to the differentiation and activation of osteoclasts to improve the treatment and prevention of osteoporosis and other bone-destructive diseases. While the cumulative knowledge of osteoclast regulatory molecules, such as receptor activator of nuclear factor-kB ligand (RANKL) and nuclear factor of activated T cells 1 (NFATc1), contributes to the understanding of the developmental progression of osteoclasts, little is known about how the discrete steps of osteoclastogenesis modify osteoclast status but not the absolute number of osteoclasts. The regulatory mechanisms involved in osteoclast maturation but not those involved in differentiation deserve special attention due to their potential use in establishing a more effective treatment strategy: targeting late-phase differentiation while preserving coupled bone formation. Recent studies have shed light on the molecules that govern late-phase osteoclast differentiation and maturation, as well as the metabolic changes needed to adapt to shifting metabolic demands. This review outlines the current understanding of the regulation of osteoclast differentiation, as well as osteoclast metabolic adaptation as a differentiation control mechanism. Additionally, this review introduces molecules that regulate the late-phase osteoclast differentiation and thus minimally impact coupled bone formation.
Role of UPF1 in lncRNA-HEIH regulation for hepatocellular carcinoma therapy
Authors: Cha Hyunho , Kim Minwoo , Ahn Narae , Jeong Seong Dong , Ignatova Elizaveta , Chi Sung Wook , Kim Hyeon Ho , Hwang Jungwook
Published: February 2024

UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5. According to analysis of RNA-seq and public data on patients with liver cancer, the expression of lncRNA-HEIH increased the levels of miR-194-5p targets and was inversely correlated with miR-194-5p expression in HCC patients. Furthermore, UPF1 depletion upregulated lncRNA-HEIH, which acts as a decoy of miR-194-5p that targets GNA13, thereby promoting GNA13 expression and HCC proliferation. The UPF1/lncRNA-HEIH/miR-194-5p/GNA13 regulatory axis is suggested to play a crucial role in cell progression and may be a suitable target for HCC therapy.
Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment
Authors: Lin Jiang , Wang Chengshuo , Wang Xiangdong , Chen Faming , Zhang Wei , Sun Hongchen , Yan Fuhua , Pan Yaping , Zhu Dongdong , Yang Qintai , Ge Shaohua , Sun Yao , Wang Kuiji , Zhang Yuan , Xian Mu , Zheng Ming , Mo Anchun , Xu Xin , Wang Hanguo , Zhou Xuedong , Zhang Luo
Published: February 2024

Abstarct

Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
Time to blood pressure control and predictors among patients receiving integrated treatment for hypertension and HIV based on an adapted WHO HEARTS implementation strategy at a large urban HIV clinic in Uganda
Authors: Amutuhaire Willington , Semitala Fred Collins , Kimera Isaac Derick , Namugenyi Christabellah , Mulindwa Frank , Ssenyonjo Rebecca , Katwesigye Rodgers , Mugabe Frank , Mutungi Gerald , Ssinabulya Isaac , Schwartz Jeremy I. , Katahoire Anne R. , Musoke Lewis S. , Yendewa George A. , Longenecker Chris T. , Muddu Martin
Published: February 2024

In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged $$\ge$$
≥
18 years and initiated Amlodipine 5 mg mono-therapy for BP (140–159)/(90–99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637–0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126–1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings.
FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer
Authors: Li Haiyang , Zheng Na , Guo Anning , Tang Weiwei , Li Muxin , Cao Yuanyuan , Ma Xinhua , Cao Hongyong , Ma Yong , Wang Hanjin , Zhao Shuli
Published: February 2024

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354–406 amino acids) to suppress the latter’s ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.
ACOD1 deficiency offers protection in a mouse model of diet-induced obesity by maintaining a healthy gut microbiota
Authors: Eberhart Tanja , Stanley Federico Uchenna , Ricci Luisa , Chirico Tiziana , Ferrarese Roberto , Sisti Sofia , Scagliola Alessandra , Baj Andreina , Badurek Sylvia , Sommer Andreas , Culp-Hill Rachel , Dzieciatkowska Monika , Shokry Engy , Sumpton David , D’Alessandro Angelo , Clementi Nicola , Mancini Nicasio , Cardaci Simone
Published: February 2024

Aconitate decarboxylase 1 (ACOD1) is the enzyme synthesizing itaconate, an immuno-regulatory metabolite tuning host-pathogen interactions. Such functions are achieved by affecting metabolic pathways regulating inflammation and microbe survival. However, at the whole-body level, metabolic roles of itaconate remain largely unresolved. By using multiomics-integrated approaches, here we show that ACOD1 responds to high-fat diet consumption in mice by promoting gut microbiota alterations supporting metabolic disease. Genetic disruption of itaconate biosynthesis protects mice against obesity, alterations in glucose homeostasis and liver metabolic dysfunctions by decreasing meta-inflammatory responses to dietary lipid overload. Mechanistically, fecal metagenomics and microbiota transplantation experiments demonstrate such effects are dependent on an amelioration of the intestinal ecosystem composition, skewed by high-fat diet feeding towards obesogenic phenotype. In particular, unbiased fecal microbiota profiling and axenic culture experiments point towards a primary role for itaconate in inhibiting growth of Bacteroidaceae and Bacteroides, family and genus of Bacteroidetes phylum, the major gut microbial taxon associated with metabolic health. Specularly to the effects imposed by Acod1 deficiency on fecal microbiota, oral itaconate consumption enhances diet-induced gut dysbiosis and associated obesogenic responses in mice. Unveiling an unrecognized role of itaconate, either endogenously produced or exogenously administered, in supporting microbiota alterations underlying diet-induced obesity in mice, our study points ACOD1 as a target against inflammatory consequences of overnutrition.
Integrated energy storage and CO2 conversion using an aqueous battery with tamed asymmetric reactions
Authors: Liu Yumei , An Yun , Zhu Jiexin , Zhu Lujun , Li Xiaomei , Gao Peng , He Guanjie , Pang Quanquan
Published: February 2024

Developing a CO2-utilization and energy-storage integrated system possesses great advantages for carbon- and energy-intensive industries. Efforts have been made to developing the Zn-CO2 batteries, but access to long cycling life and low charging voltage remains a grand challenge. Here we unambiguously show such inefficiencies originate from the high-barrier oxygen evolution reaction on charge, and by recharging the battery via oxidation of reducing molecules, Faradaic efficiency-enhanced CO2 reduction and low-overpotential battery regeneration can be simultaneously achieved. Showcased by using hydrazine oxidation, our battery demonstrates a long life over 1000 hours with a charging voltage as low as 1.2 V. The low charging voltage and formation of gaseous product upon hydrazine oxidation are the key to stabilize the catalyst over cycling. Our findings suggest that by fundamentally taming the asymmetric reactions, aqueous batteries are viable tools to achieve integrated energy storage and CO2 conversion that is economical, highly energy efficient, and scalable.
Congenital heart disease detection by pediatric electrocardiogram based deep learning integrated with human concepts
Authors: Chen Jintai , Huang Shuai , Zhang Ying , Chang Qing , Zhang Yixiao , Li Dantong , Qiu Jia , Hu Lianting , Peng Xiaoting , Du Yunmei , Gao Yunfei , Chen Danny Z. , Bellou Abdelouahab , Wu Jian , Liang Huiying
Published: February 2024

Early detection is critical to achieving improved treatment outcomes for child patients with congenital heart diseases (CHDs). Therefore, developing effective CHD detection techniques using low-cost and non-invasive pediatric electrocardiogram are highly desirable. We propose a deep learning approach for CHD detection, CHDdECG, which automatically extracts features from pediatric electrocardiogram and wavelet transformation characteristics, and integrates them with key human-concept features. Developed on 65,869 cases, CHDdECG achieved ROC-AUC of 0.915 and specificity of 0.881 on a real-world test set covering 12,000 cases. Additionally, on two external test sets with 7137 and 8121 cases, the overall ROC-AUC were 0.917 and 0.907 while specificities were 0.937 and 0.907. Notably, CHDdECG surpassed cardiologists in CHD detection performance comparison, and feature importance scores suggested greater influence of automatically extracted electrocardiogram features on CHD detection compared with human-concept features, implying that CHDdECG may grasp some knowledge beyond human cognition. Our study directly impacts CHD detection with pediatric electrocardiogram and demonstrates the potential of pediatric electrocardiogram for broader benefits.
Neutral ceramidase regulates breast cancer progression by metabolic programming of TREM2-associated macrophages
Authors: Sun Rui , Lei Chao , Xu Zhishan , Gu Xuemei , Huang Liu , Chen Liang , Tan Yi , Peng Min , Yaddanapudi Kavitha , Siskind Leah , Kong Maiying , Mitchell Robert , Yan Jun , Deng Zhongbin
Published: February 2024

The tumor microenvironment is reprogrammed by cancer cells and participates in all stages of tumor progression. Neutral ceramidase is a key regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of neutral ceramidase to the reprogramming of the tumor microenvironment is not well understood. Here, we find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth. Our result show that Ly6C+CD39+ tumor-infiltrating CD8 T cells are enriched in the tumor microenvironment and display an exhausted phenotype. Deletion of myeloid neutral ceramidase in vivo and in vitro induces exhaustion in tumor-infiltrating Ly6C+CD39+CD8+ T cells. Mechanistically, myeloid neutral ceramidase is required for the generation of lipid droplets and for the induction of lipolysis, which generate fatty acids for fatty-acid oxidation and orchestrate macrophage metabolism. Metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion.
Durvalumab and guadecitabine in advanced clear cell renal cell carcinoma: results from the phase Ib/II study BTCRC-GU16-043
Authors: Zakharia Yousef , Singer Eric A. , Acharyya Satwik , Garje Rohan , Joshi Monika , Peace David , Baladandayuthapani Veera , Majumdar Annesha , Li Xiong , Lalancette Claudia , Kryczek Ilona , Zou Weiping , Alva Ajjai
Published: February 2024

Epigenetic modulation is well established in hematologic malignancies but to a lesser degree in solid tumors. Here we report the results of a phase Ib/II study of guadecitabine and durvalumab in advanced clear cell renal cell carcinoma (ccRCC; NCT03308396). Patients received guadecitabine (starting at 60 mg/m2 subcutaneously on days 1-5 with de-escalation to 45 mg/m2 in case of dose limiting toxicity) with durvalumab (1500 mg intravenously on day 8). The study enrolled 57 patients, 6 in phase Ib with safety being the primary objective and 51in phase II, comprising 2 cohorts: 36 patients in Cohort 1 were treatment naive to checkpoint inhibitors (CPI) with 0-1 prior therapies and 15 patients in Cohort 2 were treated with up to two prior systemic therapies including one CPI. The combination of guadecitabine 45 mg/m2 with durvalumab 1500 mg was deemed safe. The primary objective of overall response rate (ORR) in cohort 1 was 22%. Sixteen patients (44%) experienced stable disease (SD). Secondary objectives included overall survival (OS), duration of response, progression-free survival (PFS), clinical benefit rate, and safety as well as ORR for Cohort 2. Median PFS for cohort 1 and cohort 2 were 14.26 and 3.91 months respectively. Median OS was not reached. In cohort 2, one patient achieved a partial response and 60% achieved SD. Asymptomatic neutropenia was the most common adverse event. Even though the trial did not meet the primary objective in cohort 1, the tolerability and PFS signal in CPI naive patients are worth further investigation.
HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Authors: Chen Shihui , Phillips Carolyn M.
Published: February 2024

RNA interference (RNAi) is a conserved gene silencing process that exists in diverse organisms to protect genome integrity and regulate gene expression. In C. elegans, the majority of RNAi pathway proteins localize to perinuclear, phase-separated germ granules, which are comprised of sub-domains referred to as P granules, Mutator foci, Z granules, and SIMR foci. However, the protein components and function of the newly discovered SIMR foci are unknown. Here we demonstrate that HRDE-2 localizes to SIMR foci and interacts with the germline nuclear Argonaute HRDE-1 in its small RNA unbound state. In the absence of HRDE-2, HRDE-1 exclusively loads CSR-class 22G-RNAs rather than WAGO-class 22G-RNAs, resulting in inappropriate H3K9me3 deposition on CSR-target genes. Thus, our study demonstrates that the recruitment of unloaded HRDE-1 to germ granules, mediated by HRDE-2, is critical to ensure that the correct small RNAs are used to guide nuclear RNA silencing in the C. elegans germline.
Brain asymmetries from mid- to late life and hemispheric brain age
Authors: Korbmacher Max , van der Meer Dennis , Beck Dani , de Lange Ann-Marie G. , Eikefjord Eli , Lundervold Arvid , Andreassen Ole A. , Westlye Lars T. , Maximov Ivan I.
Published: February 2024

The human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evaluate age-related differences in brain asymmetry. Most regional grey and white matter metrics presented asymmetry, which were higher later in life. Informed by these results, we conducted hemispheric brain age (HBA) predictions from left/right multimodal MRI metrics. HBA was concordant to conventional brain age predictions, using metrics from both hemispheres, but offers a supplemental general marker of brain asymmetry when setting left/right HBA into relationship with each other. In contrast to WM brain asymmetries, left/right discrepancies in HBA are lower at higher ages. Our findings outline various sex-specific differences, particularly important for brain age estimates, and the value of further investigating the role of brain asymmetries in brain ageing and disease development.
Sustainability benefits of transitioning from current diets to plant-based alternatives or whole-food diets in Sweden
Authors: Bunge Anne Charlotte , Mazac Rachel , Clark Michael , Wood Amanda , Gordon Line
Published: February 2024

Plant-based alternatives (PBAs) are increasingly becoming part of diets. Here, we investigate the environmental, nutritional, and economic implications of replacing animal-source foods (ASFs) with PBAs or whole foods (WFs) in the Swedish diet. Utilising two functional units (mass and energy), we model vegan, vegetarian, and flexitarian scenarios, each based on PBAs or WFs. Our results demonstrate that PBA-rich diets substantially reduce greenhouse gas emissions (30–52%), land use (20–45%), and freshwater use (14–27%), with the vegan diet showing the highest reduction potential. We observe comparable environmental benefits when ASFs are replaced with WFs, underscoring the need to reduce ASF consumption. PBA scenarios meet most Nordic Nutrition Recommendations, except for vitamin B12, vitamin D and selenium, while enhancing iron, magnesium, folate, and fibre supply and decreasing saturated fat. Daily food expenditure slightly increases in the PBA scenarios (3–5%) and decreases in the WF scenarios (4–17%), with PBA diets being 10–20% more expensive than WF diets. Here we show, that replacing ASFs with PBAs can reduce the environmental impact of current Swedish diets while meeting most nutritional recommendations, but slightly increases food expenditure. We recommend prioritising ASF reduction and diversifying WFs and healthier PBAs to accommodate diverse consumer preferences during dietary transitions.
Production vulnerability to wheat blast disease under climate change
Authors: Pequeno Diego N. L. , Ferreira Thiago B. , Fernandes José M. C. , Singh Pawan K. , Pavan Willingthon , Sonder Kai , Robertson Richard , Krupnik Timothy J. , Erenstein Olaf , Asseng Senthold
Published: February 2024

Wheat blast is a devastating disease caused by the fungal pathogen Magnaporthe oryzae pathotype Triticum that has spread to both neighbouring and distant countries following its emergence in Brazil in the 1980s. Under climate change conditions, wheat blast is predicted to spread primarily in tropical regions. Here we coupled a wheat crop simulation model with a newly developed wheat blast model, to provide quantitative global estimates of wheat blast vulnerability under current and future climates. Under current climatic conditions, 6.4 million hectares of arable land is potentially vulnerable to wheat blast. A more humid and warmer climate in the future (Representative Concentration Pathway 8.5) is likely to increase the area suitable for wheat blast infection, particularly in the Southern Hemisphere, and reduce global wheat production by 69 million tons per year (13% decrease) by mid-century. Impacts of climate change could be further exacerbated and food security problems increased.
Integrating transcriptomics and metabolomics to elucidate the mechanism by which taurine protects against DOX-induced depression
Authors: Li Yanan , Li Luxi , Wei Shanshan , Yao Jia , Liang Benhui , Chu Xue , Wang Lei , Liu Hui , Liao Dehua , Liu Daotong , Jiang Pei
Published: February 2024

Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.
Minimum dietary diversity and associated determinants among children aged 6–23 months in Pakistan
Authors: Kumar Ramesh , Mahmood Tahir , Naeem Nawal , Khan Shahzad Ali , Hanif Mubashir , Pongpanich Sathirakorn
Published: February 2024

Pakistan is facing a high prevalence of malnutrition and Minimum Dietary Diversity (MDD) is one of the core indicators that remain below the recommended level. This study assesses MDD and its associated factors among children aged 6 to 23 months in Pakistan. The study uses a cross-sectional study using the dataset of the latest available Multiple Indicators Cluster Survey (MICS) for all provinces of Pakistan. Multistage sampling is used to select 18,699 children aged 6 to 23 months. The empirical method is the Logistic Regression Analysis and Chi-Square Test. The dataset is freely and publicly available with all identifier information removed, and no ethics approvals are required. About one-fifth (20%) of infants and young children aged 6 to 23 months had met MDD, this number varies from 17 to 29%, highest in Baluchistan and lowest in Punjab province of Pakistan. The age group (18–23) indicates a 2.45 times greater chance of having MDD. Age (< 0.001), diarrhea (0.01), prenatal care (0.06), mother’s education (< 0.001), computer access (< 0.001), wealth quantile (< 0.001), and residence (< 0.001) were significantly associated with meeting MDD. However, gender (0.6) and mother’s age (0.4) both were statistically insignificant in meeting MDD. Regarding mothers’ education, compared to no education, the chance of MDD is 1.45 times greater for highly educated mothers in the Punjab province. Dietary diversity among children aged 6 to 23 months in Pakistan is low. It is recommended that mothers should be aware and encouraged to use dietary diverse food for infants and younger children.
DNA demethylation and tri-methylation of H3K4 at the TACSTD2 promoter are complementary players for TROP2 regulation in colorectal cancer cells
Authors: Gehring A. , Huebner K. , Rani H. , Erlenbach-Wuensch K. , Merkel S. , Mahadevan V. , Grutzmann R. , Hartmann A. , Schneider-Stock R.
Published: February 2024

TROP2 is a powerful cancer driver in colorectal cancer cells. Divergent epigenetic regulation mechanisms for the corresponding TACSTD2 gene exist such as miRNAs or DNA methylation. However, the role of TACSTD2 promoter hypermethylation in colorectal cancer has not been investigated yet. In this study, TROP2 expression strongly correlated with promoter methylation in different colorectal tumor cell lines. Treatment with 5-Azacytidine, a DNMT1 inhibitor, led to demethylation of the TACSTD2 promoter accompanied by an increase in TROP2 protein expression. TROP2 expression correlated with promoter methylation in vivo in human colon tumor tissue, thereby verifying promoter methylation as an important factor in the regulation of TROP2 expression in colorectal cancer. When performing a ChIP-Seq analysis in HCT116 and HT29 cells, we found that TACSTD2 promoter demethylation was accompanied by tri-methylation of H3K4. In silico analysis of GSE156613 data set confirmed that a higher binding of histone mark H3K4me3 around the TACSTD2 promoter was found in TACSTD2 high expressing tumors of colon cancer patients compared to the corresponding adjacent tumor tissue. Moreover, the link between TROP2 and the H3K4me3 code was even evident in tumors showing high intratumoral heterogeneity for TROP2 staining. Our data provide novel evidence for promoter demethylation and simultaneous gains of the active histone mark H3K4me3 across CpG-rich sequences, both being complementary mechanisms in the transcriptional regulation of TACSTD2 in colon cancer. The functional consequences of TROP2 loss in colorectal cancer needs to be further investigated.
Impact of the COVID-19 pandemic on the incidence and type of infections in hospitalized patients with cirrhosis: a retrospective study
Authors: Cuyàs Berta , Huerta Anna , Poca Maria , Alvarado-Tapias Edilmar , Brujats Anna , Román Eva , Guarner Carlos , Escorsell Àngels , Soriano German
Published: February 2024

Infections are a major cause of morbidity and mortality in cirrhosis, especially those caused by multi-drug resistant bacteria. During the COVID-19 pandemic, the incidence and type of infection in these patients may have been influenced by the restrictive measures implemented. We aimed to compare the infections in patients with cirrhosis hospitalized before the COVID-19 pandemic versus those hospitalized during the pandemic. We retrospectively compared infections in patients with cirrhosis hospitalized in the hepatology unit during the pre-pandemic period (3/2019–2/2020) with infections in patients hospitalized during the pandemic (3/2020–2/2021). Baseline characteristics, type of infections, type of bacteria, antimicrobial resistance and mortality were evaluated. There were 251 hospitalizations in 170 patients during the pre-pandemic period and 169 hospitalizations in 114 patients during the pandemic period. One or more infections were identified in 40.6% of hospitalizations during the pre-pandemic period and 43.8% of hospitalizations during the pandemic, P = 0.52. We found 131 infections in the pre-pandemic period and 75 infections during the pandemic. The percentage of nosocomial infections decreased in the pandemic period (25.3% vs. 37.4% in the pre-pandemic period, P = 0.06). We found a non-significant trend to a higher incidence of infections by multi-drug resistant organisms (MDRO) in the pandemic period than in the pre-pandemic period (6.5% vs. 4%). The incidence of infections was similar in both periods. However, during the pandemic, we observed a trend to a lower incidence of nosocomial infections with a higher incidence of MDRO infections.
A Bronze Age lip-paint from southeastern Iran
Authors: Eskandari Nasir , De Carlo Eugenio , Zorzi Federico , Dall’Acqua Stefano , Furlan Claudio , Artioli Gilberto , Vidale Massimo
Published: February 2024

A small chlorite vial, discovered among numerous artifacts looted and recovered in the Jiroft region of Kerman province, southeastern Iran, contains a deep red cosmetic preparation that is likely a lip-coloring paint or paste. Through analytical research involving XRD (X-ray diffraction), SEM–EDS (scanning electron microscopy-energy-dispersive spectroscopy), and HPLC–MS (high-performance liquid chromatography-mass spectrometry) analyses, the mineral components of the reddish substance were identified as hematite, darkened with manganite and braunite, and traces of galena and anglesite, mixed with vegetal waxes and other organic substances. The mixture, thus observed, bears a striking resemblance to the recipes of contemporary lipsticks. We also report the first radiocarbon date ever obtained from a Bronze age cosmetic in the ancient Near East: results place the pigment in the early 2nd millennium BCE, a date compatible with several mentions of the powerful eastern-iranian civilization of Marḫaši in coeval cuneiform texts of Mesopotamia, as well as with its currently emerging archaeological picture.
Energy storage and catalytic behaviour of cmWave assisted BZT and flexible electrospun BZT fibers for energy harvesting applications
Authors: Thirumalasetty Avanish Babu , Pamula Siva , Krishnan Thiyagarajan , Khade Vaishnavi , Sharief Pathan , Kota Venkata Siva Kumar , Adiraj Srinivas , Wuppulluri Madhuri
Published: February 2024

High-performance lead-free Barium Zirconium Titanate (BZT) based ceramics have emerged as a potential candidate for applications in energy storage, catalysis for electro chemical energy conversion and energy harvesting devices as presented in this work. In the present study hybrid microwave sintered BZT are studied for dielectric, ferroelectric and phase transition properties. BZT ceramic exhibits tetragonal structure as confirmed by the Retvield refinement studies. XPS studies confirms the elemental composition of BZT and presence of Zr. Polarization versus electric field hysteresis loops confirms the ferroelectric behaviour of BZT ceramic. Encouragingly, the BZT showed a moderate energy storage efficiency of 30.7 % and relatively good electro chemical energy conversion (HER). Excellent catalytic activity observed for BZT electrode in acid medium with low Tafel slope 77 mV dec-1. Furthermore, electrospun nanofibers made of PVDF-HFP and BZT are used to make flexible piezoelectric nano generators (PENGs). FTIR studies show that the 16 wt% BZT composite ink exhibits a higher electroactive beta phase. The optimized open-circuit voltage and short circuit current of the flexible PENG exhibits 7Vpp and 750 nA under an applied force of 3N. Thus, flexible and self-powered BZT PENGs are alternative source of energy due to its reliability, affordability and environmental-friendly nature.
Design of modified reference phase modulation based boost chopper fed fifteen level stepped DC link hybrid converter
Authors: Uthirasamy R. , Kumar S. Vishnu , Ananth Christo , David Selvaraj , Aggarwal Shruti , Ansar Syed Anas , Mittal Nitin , Gupta Lipika , Gared Fikreselam
Published: February 2024

A new fifteen-level stepped DC to AC hybrid converter is proposed for Solar Photovoltaic (SPV) applications. A boost chopper circuit is designed and interfaced with the fifteen-level hybrid converters specific to Electric Vehicles’ Brushless DC Motor (BLDC) drive systems. In chopper units, the output of solar panels is regulated and stepped up to obtain the nominal output voltage. In the stepped DC-link hybrid converter configuration, fifteen-level DC-link voltage is achieved by the series-operated DC-link modules with reduced electrical energy compression. From the comprehensive structure, it is anecdotal that the proposed topology has achieved minimum switching and power loss. Elimination of end passive components highlights the merits of the proposed hybrid systems. The reduction of controlled power semiconductor switches and gate-firing circuits has made the system more reliable than other hybrid converters. From the extensive analysis, the experimental setup has reported that 7% reduction in harmonics and a 54% reduction in controlled power switches than the existing fifteen-level converter topologies. Mitigation of power quality issues in the voltage profile of a fifteen-level multilevel hybrid converter is achieved through the implementation of dsPIC digital-controller-based gate triggering circuits.
Stronger genetic differentiation among within-population genetic groups than among populations in Scots pine provides new insights into within-population genetic structuring
Authors: Danusevičius Darius , Rajora Om P. , Kavaliauskas Darius , Baliuckas Virgilijus , Augustaitis Algirdas
Published: February 2024

We investigated the presence of spatial genetic groups within forest tree populations and determined if the genetic divergence among these groups is greater than that between populations using Scots pine (Pinus sylvestris) as a model species. We genotyped 890 adult trees of Scots pine in six natural populations in Lithuania at 11 nuclear microsatellite loci. We used a Bayesian clustering approach to identify the within-population genetic groups within each of the six populations. We calculated the differentiation indexes among the genetic groups within each population and among the six populations by ignoring the genetic groups. The Bayesian clustering revealed 2 to 6 distinct genetic groups of varying size as the most likely genetic structures within populations. The genetic differentiation indexes among the genetic groups within populations were nearly tenfold greater (FST = 0.012–0.070) than those between the populations (FST = 0.003). We conclude on the existence of markedly stronger structuring of genetic variation within populations than between populations of Scots pine in large forest tracts of northern Europe. Such genetic structures serve as a contributing factor to large within population genetic diversity in northern conifers. We assume that within population mating in Scots pine is not completely random but rather is stratified into genetic clusters. Our study provides pioneering novel key insights into structuring of genetic variation within populations. Our findings have implications for examining within-population genetic diversity and genetic structure, conservation, and management of genetic resources.
Serum biomarkers in patients with hand-arm vibration injury and in controls
Authors: Tekavec Eva , Nilsson Tohr , Dahlin Lars B. , Huynh Elizabeth , Axmon Anna , Nordander Catarina , Riddar Jakob , Kåredal Monica
Published: February 2024

Hand-arm vibration injury is a well-known occupational disorder that affects many workers globally. The diagnosis is based mainly on quantitative psychophysical tests and medical history. Typical manifestations of hand-arm vibration injury entail episodes of finger blanching, Raynaud’s phenomenon (RP) and sensorineural symptoms from affected nerve fibres and mechanoreceptors in the skin. Differences in serum levels of 17 different biomarkers between 92 patients with hand-arm vibration injury and 51 controls were analysed. Patients with hand-arm vibration injury entailing RP and sensorineural manifestations showed elevated levels of biomarkers associated with endothelial injury or dysfunction, inflammation, vaso- or neuroprotective compensatory, or apoptotic mechanisms: intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1); thrombomodulin (TM), heat shock protein 27 (HSP27); von Willebrand factor, calcitonin gene-related peptide (CGRP) and caspase-3. This study adds important knowledge on pathophysiological mechanisms that can contribute to the implementation of a more objective method for diagnosis of hand-arm vibration injury.
Internal fibrinolysis of fibrin clots is driven by pore expansion
Authors: Risman Rebecca A. , Paynter Bradley , Percoco Victoria , Shroff Mitali , Bannish Brittany E. , Tutwiler Valerie
Published: February 2024

Blood clots, which are composed of blood cells and a stabilizing mesh of fibrin fibers, are critical in cessation of bleeding following injury. However, their action is transient and after performing their physiological function they must be resolved through a process known as fibrinolysis. Internal fibrinolysis is the degradation of fibrin by the endogenous or innate presence of lytic enzymes in the bloodstream; under healthy conditions, this process regulates hemostasis and prevents bleeding or clotting. Fibrin-bound tissue plasminogen activator (tPA) converts nearby plasminogen into active plasmin, which is bound to the fibrin network, breaking it down into fibrin degradation products and releasing the entrapped blood cells. It is poorly understood how changes in the fibrin structure and lytic protein ratios influence the biochemical regulation and behavior of internal fibrinolysis. We used turbidity kinetic tracking and microscopy paired with mathematical modeling to study fibrin structure and lytic protein ratios that restrict internal fibrinolysis. Analysis of simulations and experiments indicate that fibrinolysis is driven by pore expansion of the fibrin network. We show that this effect is strongly influenced by the ratio of fibrin:tPAwhen compared to absolute tPA concentration. Thus, it is essential to consider relative protein concentrations when studying internal fibrinolysis both experimentally and in the clinic. An improved understanding of effective internal lysis can aid in development of better therapeutics for the treatment of bleeding and thrombosis.