bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics
Authors: Han Yeaeun , Kim Sung Young
Published: January 2023

Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.
TPX2 prompts mitotic survival via the induction of BCL2L1 through YAP1 protein stabilization in human embryonic stem cells
Authors: Kim Yun-Jeong , Go Young-Hyun , Jeong Ho-Chang , Kwon Eun-Ji , Kim Seong-Min , Cheong Hyun Sub , Kim Wantae , Shin Hyoung Doo , Lee Haeseung , Cha Hyuk-Jin
Published: January 2023

Genetic alterations have been reported for decades in most human embryonic stem cells (hESCs). Survival advantage, a typical trait acquired during long-term in vitro culture, results from the induction ofBCL2L1upon frequent copy number variation (CNV) at locus 20q11.21 and is one of the strongest candidates associated with genetic alterations that occur via escape from mitotic stress. However, the underlying mechanisms forBCL2L1induction remain unknown. Furthermore, abnormal mitosis and the survival advantage that frequently occur in late passage are associated with the expression ofBCL2L1, which is in locus 20q11.21. In this study, we demonstrated that the expression ofTPX2, a gene located in 20q11.21, led toBCL2L1induction and consequent survival traits under mitotic stress in isogenic pairs of hESCs and human induced pluripotent stem cells (iPSCs) with normal and 20q11.21 CNVs. High Aurora A kinase activity by TPX2 stabilized the YAP1 protein to induce YAP1-dependentBCL2L1expression. A chemical inhibitor of Aurora A kinase and knockdown of YAP/TAZ significantly abrogated the high tolerance to mitotic stress throughBCL2L1suppression. These results suggest that the collective expression ofTPX2andBCL2L1from CNV at loci 20q11.21 and a consequent increase in YAP1 signaling promote genome instability during long-term in vitro hESC culture.
Grave-to-cradle: human embryonic lineage tracing from the postmortem body
Authors: Choi Seock Hwan , Ku Eu Jeong , Choi Yujin Angelina , Oh Ji Won
Published: January 2023

Curiosity concerning the process of human creation has been around for a long time. Relevant questions seemed to be resolved with the knowledge of how cells divide after fertilization obtained through in vitro fertilization experiments. However, we still do not know how human life is created at the cellular level. Recently, the value of cadavers as a resource from which to obtain “normal” cells and tissues has been established, and human research using postmortem bodies has attracted growing scientific attention. As the human genome can be analyzed at the level of nucleotides through whole-genome sequencing, individual cells in a postmortem body can be traced back to determine what developmental processes have transpired from fertilization. These retrospective lineage tracing studies have answered several unsolved questions on how humans are created. This review covers the methodologies utilized in lineage tracing research in a historical context and the conceptual basis for reconstructing the division history of cells in a retrospective manner using postzygotic somatic variants in postmortem tissue. We further highlight answers that postmortem research could potentially address and discuss issues that wait to be solved in the future.
ADAR1-dependent miR-3144-3p editing simultaneously induces MSI2 expression and suppresses SLC38A4 expression in liver cancer
Authors: Kim Hyung Seok , Na Min Jeong , Son Keun Hong , Yang Hee Doo , Kim Sang Yean , Shin Eunbi , Ha Jin Woong , Jeon Soyoung , Kang Keunsoo , Moon Kiho , Park Won Sang , Nam Suk Woo
Published: January 2023

Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), has been implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are largely unknown. Our multistage hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 was the most profoundly dysregulated gene among RNA-editing enzyme family members in liver cancer. Targeted inactivation of ADAR1 inhibited the in vitro tumorigenesis of liver cancer cells. An integrative computational analyses of RNA-edited hotspots and the known editing frequency of miRNAs suggested that the miRNA miR-3144-3p was edited by ADAR1 during liver cancer progression. Specifically, ADAR1 promoted A-to-I editing of canonical miR-3144-3p to replace the adenosine at Position 3 in the seed region with a guanine (ED_miR-3144-3p(3_A < G)) in liver cancer cells. We then demonstrated that Musashi RNA-binding protein 2 (MSI2) was a specific target of miR-3144-3p and that MSI2 overexpression was due to excessive ADAR1-dependent over-editing of canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as a specific gene target of ED_miR-3144-3p(3_A < G). The ectopic expression of both ADAR1 and the ED_miR-3144-3p(3_A < G) mimic enhanced mitotic activities, and ADAR1 suppressed SLC38A4 expression in liver cancer cells. Treatments with mouse-specific ADAR1-, MSI2-siRNA-, or SLC38A4-expressing plasmids suppressed tumorigenesis and tumor growth in a mouse model of spontaneous liver cancer. Our findings suggest that the aberrant regulation of ADAR1 augments oncogenic MSI2 effects by excessively editing canonical miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesis.
Biomolecular condensate assembly of nArgBP2 tunes its functionality to manifest the structural plasticity of dendritic spines
Authors: Cho Eunji , Lee Sang-Eun , Lee Unghwi , Goh Yuna , Jeong Seonyoung , Choi Junyoung , Jeong Won-Ki , Chang Sunghoe
Published: January 2023

nArgBP2, a candidate gene for intellectual disability, is a postsynaptic protein critical for dendritic spine development and morphogenesis, and its knockdown (KD) in developing neurons severely impairs spine-bearing excitatory synapse formation. Surprisingly, nArgBP2 KD in mature neurons did not cause morphological defects in the existing spines at rest, raising questions of how it functions in mature neurons. We found that unlike its inaction at rest, nArgBP2 KD completely inhibited the enlargement of dendritic spines during chemically induced long-term potentiation (cLTP) in mature neurons. We further found that nArgBP2 forms condensates in dendritic spines and that these condensates are dispersed by cLTP, which spatiotemporally coincides with spine head enlargement. Condensates with CaMKII phosphorylation-deficient mutant or CaMKII inhibition are neither dispersed nor accompanied by spine enlargement during cLTP. We found that nArgBP2 condensates in spines exhibited liquid-like properties, and in heterologous and in vitro expression systems, nArgBP2 undergoes liquid-liquid phase separation via multivalent intermolecular interactions between SH3 domains and proline-rich domains. It also forms coacervates with CaMKIIα, which is rapidly dissembled by calcium/CaMKIIα-dependent phosphorylation. We further showed that the interaction between nArgBP2 and WAVE1 competes with nArgBP2 phase separation and that blocking the nArgBP2-WAVE1 interaction prevents spine enlargement during cLTP. Together, our results suggest that nArgBP2 at rest is confined to the condensates but is released by CaMKIIα-mediated phosphorylation during synaptic plasticity, which regulates its timely interaction with WAVE1 to induce spine head enlargement in mature neurons.
Recent developments in multifunctional neural probes for simultaneous neural recording and modulation
Authors: Li Hongbian , Wang Jinfen , Fang Ying
Published: January 2023

Neural probes are among the most widely applied tools for studying neural circuit functions and treating neurological disorders. Given the complexity of the nervous system, it is highly desirable to monitor and modulate neural activities simultaneously at the cellular scale. In this review, we provide an overview of recent developments in multifunctional neural probes that allow simultaneous neural activity recording and modulation through different modalities, including chemical, electrical, and optical stimulation. We will focus on the material and structural design of multifunctional neural probes and their interfaces with neural tissues. Finally, future challenges and prospects of multifunctional neural probes will be discussed.
Determinants of survival and retrospective comparisons of 183 clinical trial patients with myelofibrosis treated with momelotinib, ruxolitinib, fedratinib or BMS- 911543 JAK2 inhibitor
Authors: Gangat Naseema , Begna Kebede H. , Al-Kali Aref , Hogan William , Litzow Mark , Pardanani Animesh , Tefferi Ayalew
Published: January 2023

Between October 2007 and July 2013, 183 Mayo Clinic patients (median age 65 years; 58% males) with high/intermediate risk myelofibrosis (MF) were enrolled in consecutive phase 1/2 JAK2 inhibitor (JAKi) clinical trials with momelotinib (n = 79), ruxolitinib (n = 50), fedratinib (n = 23) and BMS-911543 (n = 31). Using conventional criteria, the respective response rates for spleen and “transfusion-dependent anemia” were 47%, 32%, 83%, 62% and 51%, 30%, 10%, 44%, respectively, favoring momelotinib for anemia response (p = 0.02) and fedratinib for spleen response (p < 0.01). All study patients were followed to death or 2022, during which time 177 (97%) drug discontinuations, 27 (15%) leukemic transformations, and 22 (12%) allogeneic stem cell transplants (ASCT) were recorded. 5/10-year survival rate for all 183 patients was 41%/16% and not significantly different across the four drug cohorts (p = 0.33). Multivariable analysis of pre-treatment variables identified age >65 years (HR 3.5), absence of type 1/like CALR mutation (HR 2.8), baseline transfusion need (HR 2.1), and presence of ASXL1/SRSF2 mutation (HR 1.6) as risk factors for overall survival; subsequent HR-based modeling segregated three risk categories with 5/10-year survival rates of 84%/60%, 44%/14%, and 21%/5% (p < 0.01). In addition, spleen (p < 0.01) and anemia (p = 0.01) responses were independently associated with improved short-term survival while long-term survival was secured only by ASCT (5/10-year survival rate 91%/45% vs 47%/19% in non-transplanted patients; p < 0.01). The current retrospective study suggests the value of specific pre-treatment variables in identifying long-lived MF patients receiving JAKi and also confirms recent observations on the favorable impact of treatment response on short-term and of ASCT on long-term survival.
Intermediate water circulation drives distribution of Pliocene Oxygen Minimum Zones
Authors: Davis Catherine V. , Sibert Elizabeth C. , Jacobs Peter H. , Burls Natalie , Hull Pincelli M.
Published: January 2023

Oxygen minimum zones (OMZs) play a critical role in global biogeochemical cycling and act as barriers to dispersal for marine organisms. OMZs are currently expanding and intensifying with climate change, however past distributions of OMZs are relatively unknown. Here we present evidence for widespread pelagic OMZs during the Pliocene (5.3-2.6 Ma), the most recent epoch with atmospheric CO2 analogous to modern (~400-450 ppm). The global distribution of OMZ-affiliated planktic foraminifer, Globorotaloides hexagonus, and Earth System and Species Distribution Models show that the Indian Ocean, Eastern Equatorial Pacific, eastern South Pacific, and eastern North Atlantic all supported OMZs in the Pliocene, as today. By contrast, low-oxygen waters were reduced in the North Pacific and expanded in the North Atlantic in the Pliocene. This spatially explicit perspective reveals that a warmer world can support both regionally expanded and contracted OMZs, with intermediate water circulation as a key driver.
A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers
Authors: Wang David , Quesnel-Vallieres Mathieu , Jewell San , Elzubeir Moein , Lynch Kristen , Thomas-Tikhonenko Andrei , Barash Yoseph
Published: January 2023

Identification of cancer sub-types is a pivotal step for developing personalized treatment. Specifically, sub-typing based on changes in RNA splicing has been motivated by several recent studies. We thus develop CHESSBOARD, an unsupervised algorithm tailored for RNA splicing data that captures “tiles” in the data, defined by a subset of unique splicing changes in a subset of patients. CHESSBOARD allows for a flexible number of tiles, accounts for uncertainty of splicing quantification, and is able to model missing values as additional signals. We first apply CHESSBOARD to synthetic data to assess its domain specific modeling advantages, followed by analysis of several leukemia datasets. We show detected tiles are reproducible in independent studies, investigate their possible regulatory drivers and probe their relation to known AML mutations. Finally, we demonstrate the potential clinical utility of CHESSBOARD by supplementing mutation based diagnostic assays with discovered splicing profiles to improve drug response correlation.
Insights into the GSDMB-mediated cellular lysis and its targeting by IpaH7.8
Authors: Yin Hang , Zheng Jian , He Qiuqiu , Zhang Xuan , Li Xuzichao , Ma Yongjian , Liang Xiao , Gao Jiaqi , Kocsis Benjamin L. , Li Zhuang , Liu Xiang , Alto Neal M. , Li Long , Zhang Heng
Published: January 2023

The multifunctional GSDMB protein is an important molecule in human immunity. The pyroptotic and bactericidal activity of GSDMB is a host response to infection by the bacterial pathogen Shigella flexneri, which employs the virulence effector IpaH7.8 to ubiquitinate and target GSDMB for proteasome-dependent degradation. Furthermore, IpaH7.8 selectively targets human but not mouse GSDMD, suggesting a non-canonical mechanism of substrate selection. Here, we report the crystal structure of GSDMB in complex with IpaH7.8. Together with biochemical and functional studies, we identify the potential membrane engagement sites of GSDMB, revealing general and unique features of gasdermin proteins in membrane recognition. We further illuminate how IpaH7.8 interacts with GSDMB, and delineate the mechanism by which IpaH7.8 ubiquitinates and suppresses GSDMB. Notably, guided by our structural model, we demonstrate that two residues in the α1-α2 loop make the mouse GSDMD invulnerable to IpaH7.8-mediated degradation. These findings provide insights into the versatile functions of GSDMB, which could open new avenues for therapeutic interventions for diseases, including cancers and bacterial infections.
High-strength and machinable load-bearing integrated electrochemical capacitors based on polymeric solid electrolyte
Authors: Zhang Jinmeng , Yan Jianlong , Zhao Yanan , Zhou Qiang , Ma Yinxing , Zi Yaxian , Zhou Anan , Lin Shumin , Liao Longhui , Hu Xiaolan , Bai Hua
Published: January 2023

Load bearing/energy storage integrated devices (LEIDs) allow using structural parts to store energy, and thus become a promising solution to boost the overall energy density of mobile energy storage systems, such as electric cars and drones. Herein, with a new high-strength solid electrolyte, we prepare a practical high-performance load-bearing/energy storage integrated electrochemical capacitors with excellent mechanical strength (flexural modulus: 18.1 GPa, flexural strength: 160.0 MPa) and high energy storage ability (specific capacitance: 32.4 mF cm−2, energy density: 0.13 Wh m−2, maximum power density: 1.3 W m−2). We design and compare two basic types of multilayered structures for LEID, which significantly enhance the practical bearing ability and working flexibility of the device. Besides, we also demonstrate the excellent processability of the LEID, by forming them into curved shapes, and secondarily machining and assembling them into complex structures without affecting their energy storage ability.
Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness
Authors: Panganiban Ronald Allan M. , Yang Zhiping , Sun Maoyun , Park Chan Young , Kasahara David I. , Schaible Niccole , Krishnan Ramaswamy , Kho Alvin T. , Israel Elliot , Hershenson Marc B. , Weiss Scott T. , Himes Blanca E. , Fredberg Jeffrey J. , Tantisira Kelan G. , Shore Stephanie A. , Lu Quan
Published: January 2023

Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin—a metabolic hormone best known for its role in signaling satiation and fat metabolism—is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity.
B cell analyses after SARS-CoV-2 mRNA third vaccination reveals a hybrid immunity like antibody response
Authors: Andreano Emanuele , Paciello Ida , Pierleoni Giulio , Piccini Giulia , Abbiento Valentina , Antonelli Giada , Pileri Piero , Manganaro Noemi , Pantano Elisa , Maccari Giuseppe , Marchese Silvia , Donnici Lorena , Benincasa Linda , Giglioli Ginevra , Leonardi Margherita , De Santi Concetta , Fabbiani Massimiliano , Rancan Ilaria , Tumbarello Mario , Montagnani Francesca , Sala Claudia , Medini Duccio , De Francesco Raffaele , Montomoli Emanuele , Rappuoli Rino
Published: January 2023

The continuous evolution of SARS-CoV-2 generated highly mutated variants able to escape natural and vaccine-induced primary immunity. The administration of a third mRNA vaccine dose induces a secondary response with increased protection. Here we investigate the longitudinal evolution of the neutralizing antibody response in four donors after three mRNA doses at single-cell level. We sorted 4100 spike protein specific memory B cells identifying 350 neutralizing antibodies. The third dose increases the antibody neutralization potency and breadth against all SARS-CoV-2 variants as observed with hybrid immunity. However, the B cell repertoire generating this response is different. The increases of neutralizing antibody responses is largely due to the expansion of B cell germlines poorly represented after two doses, and the reduction of germlines predominant after primary immunization. Our data show that different immunization regimens induce specific molecular signatures which should be considered while designing new vaccines and immunization strategies.
A super-efficient polyquaternium gel that can remove over-10-times masses of lignins from wastewater for resourcefulness
Authors: Hu Menghan , Xie Na , Gao Shan , Huang Yujia , Yu Yikai
Published: January 2023

To address the efficient resourcefulness of papermaking wastewater, this study designed a super-efficient gel material (SGPQG/SGPQ) that could remove over-10-times masses of lignins from wastewater, and subsequently realized the highly-efficient reuse of wastes. The mass of lignin removed by per unit mass of SGPQG/SGPQ was 10,157.71 mg•g-1, i.e., the mass of lignin removed was 10.16 times that of the mass of SGPQG/SGPQ itself, which was 1.23-50.55 times better than the existing similar materials, showing a super-efficient lignin removal ability. Meanwhile, the average lignin removal rate of SGPQG/SGPQ was 1.85-3.34 times higher than those of the pre-products. Moreover, the extended application of SGPQG/SGPQ in the purification of a complex wastewater and a real papermaking wastewater had been also successfully carried out. The mechanism investigations confirmed an integrated skeleton-space effect mechanism, which is the key factor for SGPQG/SGPQ to achieve the super-efficient lignin removal in the purification of papermaking wastewater. In addition, the SGPQG/SGPQ wastes after treating lignins, could be directly used for adsorption treatment of dyeing wastewater, and had 443.9 times adsorption capacity compared to the widely-used activated carbon, demonstrating an efficient resourcefulness reuse.
Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA
Authors: Dmytrenko Oleg , Neumann Gina C. , Hallmark Thomson , Keiser Dylan J. , Crowley Valerie M. , Vialetto Elena , Mougiakos Ioannis , Wandera Katharina G. , Domgaard Hannah , Weber Johannes , Gaudin Thomas , Metcalf Josie , Gray Benjamin N. , Begemann Matthew B. , Jackson Ryan N. , Beisel Chase L.
Published: January 2023

Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3–5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR–Cas systems and create additional opportunities for CRISPR technologies.
Impact of plasmapheresis on severe COVID-19
Authors: Fonseca-González G. , Alamilla-Sánchez M. , García-Macas V. , Herrera-Acevedo J. , Villalobos-Brito M. , Tapia-Rangel E. , Maldonado-Tapia D. , López-Mendoza M. , Cano-Cervantes J. H. , Orozco-Vázquez J. , Timarán-Montenegro D. , Cortés-Martínez S. , Escarela-Serrano M. , Muñoz-López S. , Montiel-López L. , Mondragón-Terán P. , Suárez-Cuenca J. A.
Published: January 2023

The clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071–0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO2/FiO2 indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.
The prevalence, presentation and outcome of colistin susceptible-only Acinetobacter Baumannii-associated pneumonia in intensive care unit: a multicenter observational study
Authors: Wang Sheng-Huei , Yang Kuang-Yao , Sheu Chau-Chyun , Lin Yu-Chao , Chan Ming-Cheng , Feng Jia-Yih , Chen Chia-Min , Chen Chih-Yu , Zheng Zhe-Rong , Chou Yu-Ching , Peng Chung-Kan
Published: January 2023

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.
A randomized trial of once daily versus twice daily dosing of oral iron in CKD
Authors: Sood Vivek , Kamboj Kajal , Bhatia Prateek , Sharma Vishal , Kundu Monica , Ghosh Arpita , Singh Sanjay Kumar , Sen Thakur , Kaur Prabhjot , Ramachandran Raja , Rathi Manish , Kohli Harbir Singh , Gupta Krishan Lal , Malhotra Samir , Yadav Ashok Kumar , Kumar Vivek , Jha Vivekanand
Published: January 2023

We investigated the effect of two dosing regimens of oral iron on iron status and hematological parameters in patients with CKD. In this single center, open label, randomized, active controlled clinical trial, stable adult patients with CKD stage G3–4 with percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml were eligible. Participants were randomized to receive either 100 mg of ferrous ascorbate once daily (OD group) or 100 mg of ferrous ascorbate twice daily (BD group, total daily dose 200 mg). The primary outcome was change in %TSAT between groups over 12 weeks. The secondary outcomes were changes in other iron status and hematological parameters, serum interleukin-6 (IL-6) and hepcidin. 80 participants were enrolled out of which 76 completed the study. Change in %TSAT was not significantly different between groups (β = − 1.43, 95% CI − 3.99 to 1.12, BD group as reference). The rise in serum ferritin was less in the OD group as compared to BD group (β = − 0.36, 95% CI − 0.61 to − 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (β = 0.37, 95% CI 0.067–0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD.
Molecular evidence of hookworms in public environment of Bangladesh
Authors: Nath Tilak Chandra , Eom Keeseon S. , Choe Seongjun , Park Hansol , Lee Dongmin
Published: January 2023

Accurate diagnosis by precise identification of causative agents is essential for the effectiveness of any control interventions. Despite high zoonotic potential, available literature on hookworms in Bangladesh is still scarce and nonspecific. The objective of this study was to determine the occurrence of hookworms in public locations across northeastern Bangladesh (Sylhet metropolitan area) using integrated parasitological and molecular assays. A total of 130 samples (80 soil and 50 environmental canine feces) were collected and examined using modified flotation technique and formalin-ether sedimentation methods. Modified plate culture was used to isolate larvae. The identification was made based on morphometric features and confirmed by amplifying the ITS region of the nuclear rDNA. Overall, 66.2% (86/130) of examined samples were positive for hookworms infection. Characteristic eggs (61–68 × 29–37 μm) and/or larvae of hookworms were observed in 73.8% (59/80) soils and 54.0% (27/50) environmental fecal samples. Rhabditiform larvae (0.48–0.54 × 0.04–0.07 mm) were observed in cultured samples. Genetic analysis of rDNA sequences revealed the presence of Ancylostoma caninum and Ancylostoma ceylanicum. In this study, hookworms' contamination of the public environment was substantial. To the best of our knowledge, this is the first molecular proof of A. caninum and A. ceylanicum observed in urban public environment in Bangladesh.
Quantitative estimation of closed cell porosity in low density ceramic composites using X-ray microtomography
Authors: Smith J. D. , Garcia C. , Rodriguez J. , Scharf T. W.
Published: January 2023

X-ray Microtomography is a proven tool for phase fraction analysis of multi-phase systems, provided that each phase is adequately partitioned by some means of data processing. For porosity in materials containing low-density ceramic phases, differentiation between pores and the low-density phase(s) can be intractable due to low scattering in the low-density phase, particularly if small pores necessitate low binning. We present a novel, combined methodology for accurate porosity analysis—despite these shortcomings. A 3-stage process is proposed, consisting of (1) Signal/noise enhancement using non-local means denoising, (2) Phase segmentation using a convolutional neural network, and (3) Quantitative analysis of the resulting 3D pore metrics. This particular combination of denoising and segmentation is robust against the fragmentation of common segmentation algorithms, while avoiding the volitional aspects of model selection associated with histogram fitting. We discuss the procedure applied to ternary phase SiC–TiC-diamond composites produced by reactive spark plasma sintering with porosity spanning 2–9 vol%.
On the contribution of work or heat in exchanged energy via interaction in open bipartite quantum systems
Authors: Ahmadi B. , Salimi S. , Khorashad A. S.
Published: January 2023

The question of with what we associate work and heat in a quantum thermodynamic process has been extensively discussed, mostly for systems with time-dependent Hamiltonians. In this paper, we aim to investigate the energy exchanged between two quantum systems through interaction where the Hamiltonian of the system is time-independent. An entropy-based re-definitions of heat and work are presented for these quantum thermodynamic systems therefore an entropy-based formalism of both the first and the second laws of thermodynamics are introduced. We will use the genuine reasoning based on which Clausius originally defined work and heat. The change in the energy which is accompanied by a change in the entropy is identified as heat, while any change in the energy which does not lead to a change in the entropy is known as work. It will be seen that quantum coherence does not allow all the energy exchanged between two quantum systems to be only of the heat form. Several examples will also be discussed. Finally, we will examine irreversibility from our entropy-based formalism of quantum thermodynamics.
Classification of static postures with wearable sensors mounted on loose clothing
Authors: Jayasinghe Udeni , Janko Balazs , Hwang Faustina , Harwin William S.
Published: January 2023

Inertial Measurement Units (IMUs) are a potential way to monitor the mobility of people outside clinical or laboratory settings at an acceptable cost. To increase accuracy, multiple IMUs can be used. By embedding multiple sensors into everyday clothing, it is possible to simplify having to put on individual sensors, ensuring sensors are correctly located and oriented. This research demonstrates how clothing-mounted IMU readings can be used to identify 4 common postures: standing, sitting, lying down and sitting on the floor. Data were collected from 5 healthy adults, with each providing 1–4 days of data with approximately 5 h each day. Each day, participants performed a fixed set of activities that were video-recorded to provide a ground truth. This is an analysis of accelerometry data from 3 sensors incorporated into right trouser-leg at the waist, thigh and ankle. Data were classified as static/ dynamic activities using a K-nearest neighbour (KNN) algorithm. For static activities, the inclination angles of the three sensors were estimated and used to train a second KNN classifier. For this highly-selected dataset (60000–70000 data points/posture), the static postures were classified with 100% accuracy, illustrating the potential for clothing-mounted sensors to be used in posture classification.
High throughput sequencing revealed enhanced cell cycle signaling in SLE patients
Authors: Yang Mingyue , Wang Peisong , Liu Tao , Zou Xiaojuan , Xia Ying , Li Chenxu , Wang Xiaosong
Published: January 2023

The multi-system involvement and high heterogeneity of systemic lupus erythematosus (SLE) pose great challenges to its diagnosis and treatment. The purpose of the current study is to identify genes and pathways involved in the pathogenesis of SLE. High throughput sequencing was performed on the PBMCs from SLE patients. We conducted differential gene analysis, gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) analysis, and quantitative real-time PCR (qRT-PCR) verification. Protein–protein interaction (PPI) analysis, alternative splicing analysis, and disease correlation analysis were conducted on some key pathogenic genes as well. Furthermore, si-CDC6 was used for transfection and cell proliferation was monitored using a cell counting kit-8 (CCK-8) assay. We identified 2495 differential genes (1494 upregulated and 1001 downregulated) in SLE patients compared with healthy controls. The significantly upregulated genes were enriched in the biological process-related GO terms of the cell cycle, response to stress, and chromosome organization. KEGG enrichment analysis revealed 7 significantly upregulated pathways including SLE, alcoholism, viral carcinogenesis, cell cycle, proteasome, malaria, and transcriptional misregulation in cancer. We successfully verified some differential genes on the SLE pathway and the cell cycle pathway. CDC6, a key gene in the cell cycle pathway, had remarkably higher MXE alternative splicing events in SLE patients than that in controls, which may explain its significant upregulation in SLE patients. We found that CDC6 participates in the pathogenesis of many proliferation-related diseases and its levels are positively correlated with the severity of SLE. Knockdown of CDC6 suppressed the proliferation of Hela cells and PBMCs from SLE patients in vitro. We identified SLE-related genes and their alternative splicing events. The cell cycle pathway and the cell cycle-related biological processes are over-activated in SLE patients. We revealed a higher incidence of MXE events of CDC6, which may lead to its high expression in SLE patients. Upregulated cell cycle signaling and CDC6 may be related to the hyperproliferation and pathogenesis of SLE.
Design of a special rigid wheel for traversing loose soil
Authors: Elsheikh Mogeeb A.
Published: January 2023

Wheels play an important role in mobile robotics, wheelchairs and vehicles and represent an ideal solution for traversing rigid ground due to higher efficiency. Through traversing loose soil, the rigid wheels lose traction because of sinking and higher slip ratios. Therefore, the study suggests a new rigid wheel with a distinguished perimeter to increase mobility demands to overcome the previous inevitable concerns and clarifies its full detailed design. The lateral undulation locomotion of snakes inspired the author to introduce a new simple and affordable wheel design. The optimum values of the limbless creature movement on the sand are reflected in the geometrical parameters of the wheel, amplitude to wavelength ratio. In addition, the experimental work assessed the traveling performance of the fabricated wheel on the rigid ground and the sandy soil. The attained net traction and slip ratios approach the values of more complicated, expensive and heavier wheels that were used in farming and planetary exploration. Consequently, the wheel enables the wheeled locomotive to do missions on sandy soil with no trouble.
Dysfunctional epigenetic protein-coding gene-related signature is associated with the prognosis of pancreatic cancer based on histone modification and transcriptome analysis
Authors: Yu Xiao , Wang Yun , Shi Xiaoyi , Wang Zhihui , Wen Peihao , He Yuting , Guo Wenzhi
Published: January 2023

Emerging evidence suggests that epigenetic alterations are responsible for the oncogenesis and progression of cancer. However, the role of epigenetic reprogramming in pancreatic cancer is still not clear. In this study, we used the limma R package to identify differentially expressed protein-coding genes (PCGs) between pancreatic cancer tissues and normal control tissues. The cell-type identification by the estimating relative subsets of RNA transcripts (CIBERSORT) package was used to quantify relative cell fractions in tumors. Prognostic molecular clusters were constructed using ConsensusClusterPlus analysis. Furthermore, the least absolute shrinkage and selection operator and stepAIC methods were used to construct a risk model. We identified 2351 differentially expressed PCGs between pancreatic cancer and normal control tissues in The cancer genome atlas dataset. Combined with histone modification data, we identified 363 epigenetic PCGs (epi-PCGs) and 19,010 non-epi-PCGs. Based on the epi-PCGs, we constructed three molecular clusters characterized by different expression levels of chemokines and immune checkpoint genes and distinct abundances of various immune cells. Furthermore, we generated a 9-gene model based on dysfunctional epi-PCGs. Additionally, we found that patients with high risk scores showed poorer prognoses than patients with low risk scores (p < 0.0001). Further analysis showed that the risk score was significantly related to survival and was an independent risk factor for pancreatic cancer patients. In conclusion, we constructed a 9-gene prognostic risk model based on epi-PCGs that might serve as an effective classifier to predict overall survival and the response to immunotherapy in pancreatic cancer patients.
Early influence of endotamponade on corneal biomechanical parameters, central corneal thickness and accuracy of intraocular pressure measurement
Authors: Pniakowska Zofia , Jurowski Piotr
Published: January 2023

To define the influence of air, SF6 gas and silicon oil 1000cs tamponade injection and oil tamponade removal on corneal biomechanics, central corneal thickness and intraocular pressure. 77 eyes referred to vitrectomy were divided into 4 groups: 19 to air tamponade, 21 to SF6 tamponade, 19 to oil tamponade, 18 to oil tamponade removal. Pre- and postoperative corneal hysteresis, corneal resistance factor, corneal thickness, Goldman intraocular pressure (GAT) and corneal compensated intraocular pressure (IOPcc) were analysed. GAT and IOPcc did not change after the air or SF6 tamponade. The oil tamponade injection caused increase in GAT and IOPcc, while the oil removal caused reduction in those parameters. In all groups, preoperative and postoperative values of GAT and IOPcc did not differ. There was no change in corneal thickness and biomechanics after air, SF6 or oil tamponade while after removal of oil those parameters are decreased. The air, SF6 and oil tamponade does not change the corneal thickness and corneal biomechanics. The removal of oil causes decrease in corneal thickness and biomechanics which can lead to bias in intraocular pressure measurement. GAT and IOPcc did not differ in eyes pre- and post-vitrectomy, being similarly reliable measure.
Toward a mechanistic understanding of adsorption behavior of phenol onto a novel activated carbon composite
Authors: Allahkarami Esmaeil , Dehghan Monfared Abolfazl , Silva Luis Felipe O. , Dotto Guilherme Luiz
Published: January 2023

In this research, the solid–liquid adsorption systems for MSAC (PbFe2O4 spinel-activated carbon)-phenol and pristine activated carbon-phenol were scrutinized from the thermodynamics and statistical physics (sta-phy) viewpoints. Experimental results indicated that MSAC composite outperformed pristine AC for the uptake of phenol from waste streams. By increasing the process temperature, the amount of phenol adsorbed onto both adsorbents, MSAC composite and pristine AC, decreased. Thermodynamic evaluations for MSAC demonstrated the spontaneous and exothermic characteristics of the adsorption process, while positive values of ΔG for pristine AC indicated a non-spontaneous process of phenol adsorption in all temperatures. In a mechanistic investigation, statistical physics modeling was applied to explore the responsible mechanism for phenol adsorption onto the MSAC composite and pristine AC. The single-layer model with one energy was the best model to describe the experimental data for both adsorbents. The adsorption energies of phenol onto both adsorbents were relatively smaller than 20 kJ/mol, indicating physical interactions. By increasing temperature from 298 to 358 K, the value of the absorbed amount of phenol onto the MSAC composite and pristine AC at saturation (Qsat) decreased from 158.94 and 138.91 to 115.23 and 112.34 mg/g, respectively. Mechanistic studies confirm the significant role of metallic hydroxides in MSAC to facilitate the removal of phenol through a strong interaction with phenol molecules, as compared with pristine activated carbon.
Profilin 1 deficiency drives mitotic defects and reduces genome stability
Authors: Scotto di Carlo Federica , Russo Sharon , Muyas Francesc , Mangini Maria , Garribba Lorenza , Pazzaglia Laura , Genesio Rita , Biamonte Flavia , De Luca Anna Chiara , Santaguida Stefano , Scotlandi Katia , Cortés-Ciriano Isidro , Gianfrancesco Fernando
Published: January 2023

Profilin 1—encoded by PFN1—is a small actin-binding protein with a tumour suppressive role in various adenocarcinomas and pagetic osteosarcomas. However, its contribution to tumour development is not fully understood. Using fix and live cell imaging, we report that Profilin 1 inactivation results in multiple mitotic defects, manifested prominently by anaphase bridges, multipolar spindles, misaligned and lagging chromosomes, and cytokinesis failures. Accordingly, next-generation sequencing technologies highlighted that Profilin 1 knock-out cells display extensive copy-number alterations, which are associated with complex genome rearrangements and chromothripsis events in primary pagetic osteosarcomas with Profilin 1 inactivation. Mechanistically, we show that Profilin 1 is recruited to the spindle midzone at anaphase, and its deficiency reduces the supply of actin filaments to the cleavage furrow during cytokinesis. The mitotic defects are also observed in mouse embryonic fibroblasts and mesenchymal cells deriving from a newly generated knock-in mouse model harbouring a Pfn1 loss-of-function mutation. Furthermore, nuclear atypia is also detected in histological sections of mutant femurs. Thus, our results indicate that Profilin 1 has a role in regulating cell division, and its inactivation triggers mitotic defects, one of the major mechanisms through which tumour cells acquire chromosomal instability.
Older magma at Aso caldera than at Unzen stratovolcano in south west Japan as recorded through helium isotopes
Authors: Sano Yuji , Kagoshima Takanori , Zhang Maoliang , Takahata Naoto , Onoue Tetsuji , Shibata Tomo , Nishio Yoshiro , Chen Ai-Ti , Lee Hyunwoo , Fischer Tobias P. , Zhao Dapeng
Published: January 2023

Stratovolcanoes form conical mountains by ejecta and lava, while caldera volcanoes have depressions caused by post caldera collapse. Few studies have investigated relationships between this morphology difference and discharged fluid geochemistry. Here we present helium isotope ratios of geothermal fluids and groundwater inside and outside the caldera of Mt. Aso, Japan, and compare these to helium ratios in groundwater at Mt. Unzen, a stratovolcano in the same tectonic field. We find that helium isotopes decrease in proportion to distance from the central part of the volcano. However, the helium isotopes of inferred magmas are lower in Mt. Aso relative to Mt. Unzen. We combine this result with seismic tomography data and suggest that Mt. Aso may not be receiving new mantle material to the magma reservoir. Thus, we conclude that the caldera volcano Mt Aso probably features older magma and more developed geothermal systems than the stratovolcano Mt. Unzen.
Quaternary rainfall variability is governed by insolation in northern China and ice-sheet forcing in the South
Authors: Zhao Debo , Lu Zhengyao , Wan Shiming , Cheng Hai , Shi Xuefa , Li Anchun
Published: January 2023

Quaternary Asian low-latitude hydroclimate cyclicity has long been attributed to insolation forcing, in contrast to the dominant ice-sheet and CO2 controls identified in mid-high-latitude regions. However, debates exist regarding these rainfall variations and forcings due to inconsistent reconstructions and simulations. Here, by combining rainfall proxy records with multi-model simulations, dominant 23 ka rainfall cycle in northern China and 100 ka rainfall cycle in southern China and Southeast Asia were found. We propose that rainfall mainly occurs in summer in the north, primarily driven by insolation. Rainfall in the south is largely forced by high-latitude ice sheets, with enhanced spring and autumn rainfall in southern China and weakened rainfall in western Maritime Continent during glacial periods. This study highlights the seasonal contributions to orbital-scale rainfall changes, and sheds light on the Asian hydroclimate conditions associated with high-low-latitude climate interactions.
A multifunctional polymeric additive with a synergistic effect for high-performance lithium-ion batteries
Authors: Zhang Yunfeng , Zhang Yi , Bao Wei , Wang Yaying , Huo Shikang , Wang Rui , Hu Zhenyuan , Chen Weijie , Wang Deli
Published: January 2023

Poly(ethylene phosphate acrylonitrile) is proposed as a new multifunctional polymeric additive for endowing the carbonate electrolyte with good flame-retardance, enhanced Li-ion dissociation/transportation behavior and a stable LiFePO4cathode electrolyte interphase layer.