bluuebunny/crossref_metadata_2025 huggingface dataset:
Long term results of a prospective multicenter observational study on the use of anti-human T-lymphocyte immunoglobulin (ATLG) in unrelated donor transplantation (ATOS study)
Authors: Finke Jürgen , Schmoor Claudia , Ayuk Francis , Hasenkamp Justin , Verbeek Mareike , Wagner Eva-Maria , Biersack Harald , Schäfer-Eckart Kerstin , Wolf Dominik , Stuhler Gernot , Reibke Roland , Schmid Christoph , Kaufmann Martin , Eder Matthias , Bertz Hartmut , Grishina Olga
Published: March 2024

ATOS is a prospective observational study evaluating the outcome of patients receiving anti-human T-lymphocyte immunoglobulin (ATLG) in unrelated donor transplantation. Primary endpoint was severe GvHD and relapse-free survival (SGRFS). GvHD prophylaxis consisted of ATLG and CSA/ MTX or MMF. Outcome was compared to the ATLG arm of our prospective randomized phase III multicenter trial trial (RCT) [1, 2]. 165 patients, median age 54 (18; 77) years, with haematological malignancies with early (45.5%), intermediate (17.6%), and advanced (37.0%) disease were included. ATLG dose differed between centers according to local practise (median total ATLG dose of 46 (IQR 32–60, range 15–91) mg/kg). Median follow-up was 70 months. Estimated probabilities at 5 years follow up were for SGRFS 0.27, OS 0.52, DFS 0.43, NRM 0.23, relapse 0.34, acute GvhD °III/IV 0.13, severe chronic GvHD 0.27. OS rates differed dependent on disease status. An effect of the given ATLG dose could not be separated from potential center effects. Despite higher age and more advanced disease in ATOS, outcome was similar to the ATLG arm of our RCT. This long-term, multicenter, experience in routine clinical practice confirms the GvHD-protective effect of ATLG without compromising relapse and non-relapse mortality rates.

Clinical Trial Registry: German clinical trials register DRKS00004581.
Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells
Authors: Hermosilla V. E. , Gyenis L. , Rabalski A. J. , Armijo M. E. , Sepúlveda P. , Duprat F. , Benítez-Riquelme D. , Fuentes-Villalobos F. , Quiroz A. , Hepp M. I. , Farkas C. , Mastel M. , González-Chavarría I. , Jackstadt R. , Litchfield D. W. , Castro A. F. , Pincheira R.
Published: March 2024

Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified (SALL1-4), and SALL2 is the family’s most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.
Tradeoffs in alignment and assembly-based methods for structural variant detection with long-read sequencing data
Authors: Liu Yichen Henry , Luo Can , Golding Staunton G. , Ioffe Jacob B. , Zhou Xin Maizie
Published: March 2024

Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development.
Structural phase transition, s±-wave pairing, and magnetic stripe order in bilayered superconductor La3Ni2O7 under pressure
Authors: Zhang Yang , Lin Ling-Fang , Moreo Adriana , Maier Thomas A. , Dagotto Elbio
Published: March 2024

Motivated by the recently discovered high-Tc superconductor La3Ni2O7, we comprehensively study this system using density functional theory and random phase approximation calculations. At low pressures, the Amam phase is stable, containing the Y2− mode distortion from the Fmmm phase, while the Fmmm phase is unstable. Because of small differences in enthalpy and a considerable Y2− mode amplitude, the two phases may coexist in the range between 10.6 and 14 GPa, beyond which the Fmmm phase dominates. In addition, the magnetic stripe-type spin order with wavevector (π, 0) was stable at the intermediate region. Pairing is induced in the s±-wave channel due to partial nesting between the M = (π, π) centered pockets and portions of the Fermi surface centered at the X = (π, 0) and Y = (0, π) points. This resembles results for iron-based superconductors but has a fundamental difference with iron pnictides and selenides. Moreover, our present efforts also suggest La3Ni2O7 is qualitatively different from infinite-layer nickelates and cuprate superconductors.
Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus
Authors: Lin Gu-Lung , Drysdale Simon B. , Snape Matthew D. , O’Connor Daniel , Brown Anthony , MacIntyre-Cockett George , Mellado-Gomez Esther , de Cesare Mariateresa , Ansari M. Azim , Bonsall David , Bray James E. , Jolley Keith A. , Bowden Rory , Aerssens Jeroen , Bont Louis , Openshaw Peter J. M. , Martinon-Torres Federico , Nair Harish , Golubchik Tanya , Pollard Andrew J. ,   RESCEU Consortium
Published: March 2024

Respiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity is known to be age-dependent and highest in young infants, but other correlates of severity, particularly the presence of additional respiratory pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts of RSV-positive infants <12 months in Spain, the UK, and the Netherlands during 2017–20. We show, using targeted metagenomic sequencing of >100 pathogens, including all common respiratory viruses and bacteria, from samples collected from 433 infants, that burden of additional viruses is common (111/433, 26%) but only modestly correlates with RSV disease severity. In contrast, there is strong evidence in both cohorts and across age groups that presence ofHaemophilusbacteria (194/433, 45%) is associated with higher severity, including much higher rates of hospitalisation (odds ratio 4.25, 95% CI 2.03–9.31). There is no evidence for association between higher severity and other detected bacteria, and no difference in severity between RSV genotypes. Our findings reveal the genomic diversity of additional pathogens during RSV infection in infants, and provide an evidence base for future causal investigations of the impact of co-infection on RSV disease severity.
2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels
Authors: Cui Qi , Shieh Meg , Pan Tony W. , Nishimura Akiyuki , Matsunaga Tetsuro , Kelly Shane S. , Xu Shi , Jung Minkyung , Ogata Seiryo , Morita Masanobu , Yoshitake Jun , Chen Xiaoyan , Robinson Jerome R. , Qian Wei-Jun , Nishida Motohiro , Akaike Takaaki , Xian Ming
Published: March 2024

Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.
Controlled dissolution of a single ion from a salt interface
Authors: Han Huijun , Park Yunjae , Kim Yohan , Ding Feng , Shin Hyung-Joon
Published: March 2024

Interactions between monatomic ions and water molecules are fundamental to understanding the hydration of complex polyatomic ions and ionic process. Among the simplest and well-established ion-related reactions is dissolution of salt in water, which is an endothermic process requiring an increase in entropy. Extensive efforts have been made to date; however, most studies at single-ion level have been limited to theoretical approaches. Here, we demonstrate the salt dissolution process by manipulating a single water molecule at an under-coordinated site of a sodium chloride film. Manipulation of molecule in a controlled manner enables us to understand ion–water interaction as well as dynamics of water molecules at NaCl interfaces, which are responsible for the selective dissolution of anions. The water dipole polarizes the anion in the NaCl ionic crystal, resulting in strong anion–water interaction and weakening of the ionic bonds. Our results provide insights into a simple but important elementary step of the single-ion chemistry, which may be useful in ion-related sciences and technologies.
Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids
Authors: Wei Jiankai , Zhang Wei , Jiang An , Peng Hongzhe , Zhang Quanyong , Li Yuting , Bi Jianqing , Wang Linting , Liu Penghui , Wang Jing , Ge Yonghang , Zhang Liya , Yu Haiyan , Li Lei , Wang Shi , Leng Liang , Chen Kai , Dong Bo
Published: March 2024

Zygotic genome activation (ZGA) is a universal process in early embryogenesis of metazoan, when the quiescent zygotic nucleus initiates global transcription. However, the mechanisms related to massive genome activation and allele-specific expression (ASE) remain not well understood. Here, we develop hybrids from two deeply diverged (120 Mya) ascidian species to symmetrically document the dynamics of ZGA. We identify two coordinated ZGA waves represent early developmental and housekeeping gene reactivation, respectively. Single-cell RNA sequencing reveals that the major expression wave exhibits spatial heterogeneity and significantly correlates with cell fate. Moreover, allele-specific expression occurs in a species- rather than parent-related manner, demonstrating the divergence of cis-regulatory elements between the two species. These findings provide insights into ZGA in chordates.
Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection
Authors: Bing Jian , Guan Zhangyue , Zheng Tianhong , Ennis Craig L. , Nobile Clarissa J. , Chen Changbin , Chu Haiqing , Huang Guanghua
Published: March 2024

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.
Fungal community composition predicts forest carbon storage at a continental scale
Authors: Anthony Mark A. , Tedersoo Leho , De Vos Bruno , Croisé Luc , Meesenburg Henning , Wagner Markus , Andreae Henning , Jacob Frank , Lech Paweł , Kowalska Anna , Greve Martin , Popova Genoveva , Frey Beat , Gessler Arthur , Schaub Marcus , Ferretti Marco , Waldner Peter , Calatayud Vicent , Canullo Roberto , Papitto Giancarlo , Marinšek Aleksander , Ingerslev Morten , Vesterdal Lars , Rautio Pasi , Meissner Helge , Timmermann Volkmar , Dettwiler Mike , Eickenscheidt Nadine , Schmitz Andreas , Van Tiel Nina , Crowther Thomas W. , Averill Colin
Published: March 2024

Forest soils harbor hyper-diverse microbial communities which fundamentally regulate carbon and nutrient cycling across the globe. Directly testing hypotheses on how microbiome diversity is linked to forest carbon storage has been difficult, due to a lack of paired data on microbiome diversity and in situ observations of forest carbon accumulation and storage. Here, we investigated the relationship between soil microbiomes and forest carbon across 238 forest inventory plots spanning 15 European countries. We show that the composition and diversity of fungal, but not bacterial, species is tightly coupled to both forest biotic conditions and a seven-fold variation in tree growth rates and biomass carbon stocks when controlling for the effects of dominant tree type, climate, and other environmental factors. This linkage is particularly strong for symbiotic endophytic and ectomycorrhizal fungi known to directly facilitate tree growth. Since tree growth rates in this system are closely and positively correlated with belowground soil carbon stocks, we conclude that fungal composition is a strong predictor of overall forest carbon storage across the European continent.
Wheat powdery mildew resistance gene Pm13 encodes a mixed lineage kinase domain-like protein
Authors: Li Huanhuan , Men Wenqiang , Ma Chao , Liu Qianwen , Dong Zhenjie , Tian Xiubin , Wang Chaoli , Liu Cheng , Gill Harsimardeep S. , Ma Pengtao , Zhang Zhibin , Liu Bao , Zhao Yue , Sehgal Sunish K. , Liu Wenxuan
Published: March 2024

Wheat powdery mildew is one of the most destructive diseases threatening global wheat production. The wild relatives of wheat constitute rich sources of diversity for powdery mildew resistance. Here, we report the map-based cloning of the powdery mildew resistance gene Pm13 from the wild wheat species Aegilops longissima. Pm13 encodes a mixed lineage kinase domain-like (MLKL) protein that contains an N-terminal-domain of MLKL (MLKL_NTD) domain in its N-terminus and a C-terminal serine/threonine kinase (STK) domain. The resistance function of Pm13 is validated by mutagenesis, gene silencing, transgenic assay, and allelic association analyses. The development of introgression lines with significantly reduced chromosome segments of Ae. longissima encompassing Pm13 enables widespread deployment of this gene into wheat cultivars. The cloning of Pm13 may provide valuable insights into the molecular mechanisms underlying Pm13-mediated powdery mildew resistance and highlight the important roles of kinase fusion proteins (KFPs) in wheat immunity.
NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection
Authors: Zhao Yan , Ma Changchun , Cai Rongzhi , Xin Lijing , Li Yongsheng , Ke Lixin , Ye Wei , Ouyang Ting , Liang Jiahao , Wu Renhua , Lin Yan
Published: March 2024

Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA. Aberrations in ‘alanine, aspartate and glutamate metabolism’ proved to be prevalent throughout the ESCC evolution, consistently identified by NMR and MS, and reflected in 16 serum and 10 urine metabolic signatures in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperform clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and are effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).
Electrically controlled nonvolatile switching of single-atom magnetism in a Dy@C84 single-molecule transistor
Authors: Wang Feng , Shen Wangqiang , Shui Yuan , Chen Jun , Wang Huaiqiang , Wang Rui , Qin Yuyuan , Wang Xuefeng , Wan Jianguo , Zhang Minhao , Lu Xing , Yang Tao , Song Fengqi
Published: March 2024

Single-atom magnetism switching is a key technique towards the ultimate data storage density of computer hard disks and has been conceptually realized by leveraging the spin bistability of a magnetic atom under a scanning tunnelling microscope. However, it has rarely been applied to solid-state transistors, an advancement that would be highly desirable for enabling various applications. Here, we demonstrate realization of the electrically controlled Zeeman effect in Dy@C84 single-molecule transistors, thus revealing a transition in the magnetic moment from 3.8 $${\mu }_{{{{{{\rm{B}}}}}}}$$

μ

B

to 5.1 $${\mu }_{{{{{{\rm{B}}}}}}}$$

μ

B

for the ground-state GN at an electric field strength of 3$$-$$
−
10 MV/cm. The consequent magnetoresistance significantly increases from 600% to 1100% at the resonant tunneling point. Density functional theory calculations further corroborate our realization of nonvolatile switching of single-atom magnetism, and the switching stability emanates from an energy barrier of 92 meV for atomic relaxation. These results highlight the potential of using endohedral metallofullerenes for high-temperature, high-stability, high-speed, and compact single-atom magnetic data storage.
Ginseng extracts improve circadian clock gene expression and reduce inflammation directly and indirectly through gut microbiota and PI3K signaling pathway
Authors: Zhang Xue-Ying , Khakisahneh Saeid , Han Song-Yi , Song Eun-Ji , Nam Young-Do , Kim Hojun
Published: March 2024

Despite the potential benefits of herbal medicines for therapeutic application in preventing and treating various metabolic disorders, the mechanisms of action were understood incompletely. Ginseng (Panax ginseng), a commonly employed plant as a dietary supplement, has been reported to play its hot property in increasing body temperature and improving gut health. However, a comprehensive understanding of the mechanisms by which ginseng regulates body temperature and gut health is still incomplete. This paper illustrates that intermittent supplementation with ginseng extracts improved body temperature rhythm and suppressed inflammatory responses in peripheral metabolic organs of propylthiouracil (PTU)-induced hypothermic rats. These effects were associated with changes in gut hormone secretion and the microbiota profile. The in-vitro studies in ICE-6 cells indicate that ginseng extracts can not only act directly on the cell to regulate the genes related to circadian clock and inflammation, but also may function through the gut microbiota and their byproducts such as lipopolysaccharide. Furthermore, administration of PI3K inhibitor blocked ginseng or microbiota-induced gene expression related with circadian clock and inflammation in vitro. These findings demonstrate that the hot property of ginseng may be mediated by improving circadian clock and suppressing inflammation directly or indirectly through the gut microbiota and PI3K-AKT signaling pathways.
Causal diagramming for assessing human system risk in spaceflight
Authors: Antonsen Erik , Reynolds Robert J. , Charvat Jacqueline , Connell Erin , Monti Avalon , Petersen Devan , Nartey Nicholas , Anton Wilma , Abukmail Ahmed , Marotta Kristina , Van Baalen Mary , Buckland Daniel M.
Published: March 2024

For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining—based on evaluation of the available evidence—when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk “silos” to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB’s pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches.
Corneal confocal microscopy may help to distinguish Multiple System Atrophy from Parkinson’s disease
Authors: Niu Xuebin , Yin Peixiao , Guan Chenyang , Shao Qiuyue , Cui Guiyun , Zan Kun , Xu Chuanying
Published: March 2024

Multiple system atrophy (MSA) and Parkinson’s disease (PD) have clinical overlapping symptoms, which makes differential diagnosis difficult. Our research aimed to distinguish MSA from PD using corneal confocal microscopy (CCM), a noninvasive and objective test. The study included 63 PD patients, 30 MSA patients, and 31 healthy controls (HC). When recruiting PD and MSA, questionnaires were conducted on motor and non-motor functions, such as autonomic and cognitive functions. Participants underwent CCM to quantify the corneal nerve fibers. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) values in MSA are lower than PD (MSA vs. PD: CNFD, 20.68 ± 6.70 vs. 24.64 ± 6.43 no./mm2, p < 0.05; CNFL, 12.01 ± 3.25 vs. 14.17 ± 3.52 no./mm2, p < 0.05). In MSA + PD (combined), there is a negative correlation between CNFD and the Orthostatic Grading Scale (OGS) (r = −0.284, p = 0.007). Similarly, CNFD in the only MSA group was negatively correlated with the Unified Multiple System Atrophy Rating Scale I and II (r = −0.391, p = 0.044; r = −0.382, p = 0.049). CNFD and CNFL were inversely associated with MSA (CNFD: β = −0.071; OR, 0.932; 95% CI, 0.872 ~ 0.996; p = 0.038; CNFL: β = −0.135; OR, 0.874; 95% CI, 0.768–0.994; p = 0.040). Furthermore, we found the area under the receiver operating characteristic curve (ROC) of CNFL was the largest, 72.01%. The CCM could be an objective and sensitive biomarker to distinguish MSA from PD. It visually reflects a more severe degeneration in MSA compared to PD.
The photocatalytic oxidation of As(III) on birnessite
Authors: Li Ping , Wang Yun , Wang Jingjing , Wang Wei , Ding Zhe , Liang Jianjun , Fan Qiaohui
Published: March 2024

Birnessite is regarded as an efficient oxidizing agent that would significantly influence the environmental fate of elements such as arsenic. This study compared the chemical and photocatalytic oxidation of As(III) over birnessite. During the chemical oxidation, As(III) was oxidized to As(V), while Mn(IV) was reduced to Mn(II), subsequently forming MnOOH. The coverage of the reactive sites by MnOOH inhibited the chemical oxidation of residual As(III). At pH 5.0, after 360 min of reaction, 61% of As(III) was oxidized to As(V), and the oxidation of As(III) decreased with an increase in pH. The photocatalytic oxidation of As(III), where almost all As(III) could be oxidized to As(V) over a pH range of 5.0–8.0 and 360 min, was much more efficient compared to chemical oxidation. In contrast to chemical oxidation, the formation of MnOOH slightly affected the photocatalytic performance of birnessite. It was demonstrated that •O2− radicals and holes (hvb+) played an important role in the photocatalytic oxidation of As(III) over birnessite. Our findings confirmed that light dramatically promoted the oxidation of As(III) by birnessite, broadening the understanding of the environmental behaviors of arsenic.
Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition
Authors: Chang Hao-Wei , Lee Evan M. , Wang Yi , Zhou Cyrus , Pruss Kali M. , Henrissat Suzanne , Chen Robert Y. , Kao Clara , Hibberd Matthew C. , Lynn Hannah M. , Webber Daniel M. , Crane Marie , Cheng Jiye , Rodionov Dmitry A. , Arzamasov Aleksandr A. , Castillo Juan J. , Couture Garret , Chen Ye , Balcazo Nikita P. , Lebrilla Carlito B. , Terrapon Nicolas , Henrissat Bernard , Ilkayeva Olga , Muehlbauer Michael J. , Newgard Christopher B. , Mostafa Ishita , Das Subhasish , Mahfuz Mustafa , Osterman Andrei L. , Barratt Michael J. , Ahmed Tahmeed , Gordon Jeffrey I.
Published: March 2024

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure–function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.
Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses
Authors: Kelly Ronan J. , Landon Blair V. , Zaidi Ali H. , Singh Dipika , Canzoniero Jenna V. , Balan Archana , Hales Russell K. , Voong K. Ranh , Battafarano Richard J. , Jobe Blair A. , Yang Stephen C. , Broderick Stephen , Ha Jinny , Marrone Kristen A. , Pereira Gavin , Rao Nisha , Borole Aryan , Karaindrou Katerina , Belcaid Zineb , White James R. , Ke Suqi , Amjad Ali I. , Weksler Benny , Shin Eun Ji , Thompson Elizabeth , Smith Kellie N. , Pardoll Drew M. , Hu Chen , Feliciano Josephine L. , Anagnostou Valsamo , Lam Vincent K.
Published: March 2024

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab–relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613.
A synthetic digital city dataset for robustness and generalisation of depth estimation models
Authors: Li Jihao , Hu Jincheng , Huang Yanjun , Chen Zheng , Gao Bingzhao , Jiang Jingjing , Zhang Yuanjian
Published: March 2024

Existing monocular depth estimation driving datasets are limited in the number of images and the diversity of driving conditions. The images of datasets are commonly in a low resolution and the depth maps are sparse. To overcome these limitations, we produce a Synthetic Digital City Dataset (SDCD) which was collected under 6 different weather driving conditions, and 6 common adverse perturbations caused by the data transmission. SDCD provides a total of 930 K high-resolution RGB images and corresponding perfect observed depth maps. The evaluation shows that depth estimation models which are trained on SDCD provide a clearer, smoother, and more precise long-range depth estimation compared to those trained on one of the best-known driving datasets KITTI. Moreover, we provide a benchmark to investigate the performance of depth estimation models in different adverse driving conditions. Instead of collecting data from the real world, we generate the SDCD under severe driving conditions with perfect observed data in the digital world, enhancing depth estimation for autonomous driving.
B-cell receptor signaling activity identifies patients with mantle cell lymphoma at higher risk of progression
Authors: Gambino Simona , Quaglia Francesca Maria , Galasso Marilisa , Cavallini Chiara , Chignola Roberto , Lovato Ornella , Giacobazzi Luca , Caligola Simone , Adamo Annalisa , Putta Santosh , Aparo Antonino , Ferrarini Isacco , Ugel Stefano , Giugno Rosalba , Donadelli Massimo , Dando Ilaria , Krampera Mauro , Visco Carlo , Scupoli Maria Teresa
Published: March 2024

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.
Chitosan combined with humic applications during sensitive growth stages to drought improves nutritional status and water relations of sweet potato
Authors: Elshamly Ayman M. S. , Iqbal Rashid , Elshikh Mohamed S. , Alwasel Yasmeen A. , Chaudhary Talha
Published: March 2024

The current decline in freshwater resources presents a significant global challenge to crop production, a situation expected to intensify with ongoing climate change. This underscores the need for extensive research to enhance crop yields under drought conditions, a priority for scientists given its vital role in global food security. Our study explores the effects of using humic and chitosan treatments to alleviate drought stress during critical growth phases and their impact on crop yield and water efficiency. We employed four different irrigation strategies: full irrigation, 70% irrigation at the early vine development stage, 70% irrigation during the storage root bulking stage, and 85% irrigation across both stages, complemented by full irrigation in other periods. The plants received either humic treatments through foliar spray or soil application, or chitosan foliar applications, with tap water serving as a control. Our findings highlight that the early vine development stage is particularly vulnerable to drought, with a 42.0% decrease in yield observed under such conditions. In normal growth scenarios, foliar application of humic substances significantly improved growth parameters, resulting in a substantial increase in yield and water efficiency by 66.9% and 68.4%, respectively, compared to the control treatment under full irrigation. For sweet potatoes irrigated with 70% water at the storage root bulking stage, ground application of humic substances outperformed both foliar applications of chitosan and humic in terms of yield results. The highest tuber yield and water efficiency were attained by combining chitosan and humic ground applications, regardless of whether 70% irrigation was used at the storage root bulking stage or 85% irrigation during both the early vine development and storage root bulking stages.
A remarkable assemblage of petroglyphs and dinosaur footprints in Northeast Brazil
Authors: Troiano Leonardo P. , dos Santos Heloísa B. , Aureliano Tito , Ghilardi Aline M.
Published: March 2024

The Serrote do Letreiro Site, found on the northwest periphery of the Sousa Basin, Brazil, presents a remarkable convergence of paleontological and archaeological elements. It is constituted of sub-horizontal "lajeiros", or rock outcrops, intermingled with endemic Caatinga vegetation. The three prominent outcrops feature fossilized footprints of theropod, sauropod, and iguanodontian dinosaurs from the Early Cretaceous Period. Adjacent to these dinosaur tracks, indigenous petroglyphs adorn the surface. The petroglyphs, mainly characterized by circular motifs, maintain a striking resemblance to other petroglyphs found in the states of Paraíba and Rio Grande do Norte. This study primarily endeavors to delineate the site's major characteristics while concentrating on the relationship between the dinosaur footprints and the petroglyphs. It concurrently assesses the preservation status of this invaluable record, shedding light on its implications for the realms of paleontology, archaeology, and cultural heritage studies.
Study on the characteristics of increased mechanical stiffness according to changes in LCP shape to reinforce clavicle fractures
Authors: Kim Soo Min , Kim Seong-tak , Han Dong-woon , Kim Dae-Geun
Published: March 2024

The clavicle has various anatomic shapes unique to each individual. Additionally, with the increase in high-energy traumas such as sports injuries and traffic accidents, the patterns of fractures become complex and complicated. Thus, there is a need for a variety of shapes of locking compression plates (LCP) to accommodate different types of fractures and facilitate quicker rehabilitation. The aim of this study is to present different types of LCP that secure fracture fragments and distribute stress evenly, in comparison to typical anatomical LCPs, for reinforcing clavicle fractures. Three models were compared in this study: the typical shape, the center hole removed shape, and the double-curved wing shape. The DICOM (Digital Imaging and Communications in Medicine) file obtained from the computed tomography scan of the patient’s clavicle was used to extract the three-dimensional (3D) clavicle structure. Finite element analysis (FEA) simulation was employed to analyze the structural changes of the LCP under external forces. A reinforced jig was used to apply the same type of external force to each LCP, and an experiment was conducted to analyze the mechanical impact of the LCP’s structural characteristics. When comparing the stress values at the fracture zone point, resulting from the FEA simulation with applied bending forces, it was calculated that the stress dispersion effect was approximately ten times greater when transitioning from a typical LCP shape to a double-curved partial wing structure. Moreover, the ultimate stress increased 3.33 times, from 241.322 to 804.057 N, as the LCP design changed under cantilever bending conditions. This double-curved wing LCP design reduces stress concentration at the fracture site and minimizes stress in the fracture area when subjected to cantilever bending forces. Consequently, this newly designed LCP has the potential to decrease complications related to the plate and accelerate rehabilitation protocols.
Hydraulic characterization and start-up of a novel circulating flow bio-carriers
Authors: Li Xingyu , Li Guang , Yu Yunyong , Jia Hongsheng , Ma Xiaoning , Yang Hong , Opoku Prince Atta
Published: March 2024

High-quality biofilm carriers are crucial for the formation of biofilm, but problems such as slow biofilm growth on the carrier surface have been troubling a large number of researchers. The addition of a carrier changes the flow state in the reactor, which in turn affects the microbial attachment and the quantity of microorganisms. Also, aerobic microorganisms need to use dissolved oxygen in the water to remove water pollutants. In this paper, a novel recirculating flow carrier with a hollow cylinder structure is proposed, with a certain number of hollow inverted circular plates placed at equal distances inside. In this paper, the hydraulic residence time, aeration volume, and the spacing of the inflow plates of the recirculating flow biofilm carrier, which are three important factors affecting the hydraulic characteristics of the reactor, are first investigated. At the same time, it was compared with the common combined carrier to find the optimal operating conditions for the hydraulic characteristics. Secondly, a reactor start-up study was carried out to confirm that the new recirculating flow biofilm carrier could accelerate the biofilm growth by changing the hydraulic characteristics. The results showed that under the same conditions, the hydraulic properties of the reactor were better with the addition of the recirculating flow carrier, with an effective volume ratio of 98% and a significant reduction in short flows and dead zones. The stabilized removal of COD, NH3-N, and TN in the reactor with the addition of the recirculating flow carrier reached about 94%, 99%, and 91% respectively, at the beginning of the 15th day, which effectively proved the feasibility of the recirculating flow carrier.
CPMI-ChatGLM: parameter-efficient fine-tuning ChatGLM with Chinese patent medicine instructions
Authors: Liu Can , Sun Kaijie , Zhou Qingqing , Duan Yuchen , Shu Jianhua , Kan Hongxing , Gu Zongyun , Hu Jili
Published: March 2024

Chinese patent medicine (CPM) is a typical type of traditional Chinese medicine (TCM) preparation that uses Chinese herbs as raw materials and is an important means of treating diseases in TCM. Chinese patent medicine instructions (CPMI) serve as a guide for patients to use drugs safely and effectively. In this study, we apply a pre-trained language model to the domain of CPM. We have meticulously assembled, processed, and released the first CPMI dataset and fine-tuned the ChatGLM-6B base model, resulting in the development of CPMI-ChatGLM. We employed consumer-grade graphics cards for parameter-efficient fine-tuning and investigated the impact of LoRA and P-Tuning v2, as well as different data scales and instruction data settings on model performance. We evaluated CPMI-ChatGLM using BLEU, ROUGE, and BARTScore metrics. Our model achieved scores of 0.7641, 0.8188, 0.7738, 0.8107, and − 2.4786 on the BLEU-4, ROUGE-1, ROUGE-2, ROUGE-L and BARTScore metrics, respectively. In comparison experiments and human evaluation with four large language models of similar parameter scales, CPMI-ChatGLM demonstrated state-of-the-art performance. CPMI-ChatGLM demonstrates commendable proficiency in CPM recommendations, making it a promising tool for auxiliary diagnosis and treatment. Furthermore, the various attributes in the CPMI dataset can be used for data mining and analysis, providing practical application value and research significance.
The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer
Authors: Hagi Takaomi , Vangveravong Suwanna , Takchi Rony , Gong Qingqing , Goedegebuure S. Peter , Tiriac Herve , Van Tine Brian A. , Powell Matthew A. , Hawkins William G. , Spitzer Dirk
Published: March 2024

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.
Fabrication of pore-filling cation-exchange membrane from waste polystyrene and Spunbond Meltblown Spunbond (SMS) non-woven polypropylene fabric as the substrate
Authors: Asgari Hadi , Ghavipanjeh Farideh , Sabour Mohammad Reza , Emadzadeh Daryoush
Published: March 2024

Commercial ion-exchange membranes are typically thick, possessing limited mechanical strength, and have relatively high fabrication costs. In this study, we utilize a three-layer polypropylene fabric known as Spunbond Meltblown Spunbond (SMS) as the substrate. This choice ensures that the resulting membrane exhibits high strength and low thickness. SMS substrates with various area densities, including 14.5, 15, 17, 20, 25, and 30 g/m2, were coated with different concentrations of waste polystyrene solution (ranging from 5 × 104 to 9 × 104 mg/l) before undergoing sulfonation using concentrated sulfuric acid. The physicochemical and mechanical properties of the membrane were characterized and compared with those of commercial Neosepta CMX and Nafion-117 cation-exchange membranes. Remarkably, the fabricated membrane exhibited good performance compared to commercial ones. The cation-exchange capacity (2.76 meq/g) and tensile strength (37.15 MPa) were higher, and the electrical resistance (3.603Ω) and the thickness (130 μm) were lower than the commercial membranes.