bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of COVID-19 vaccines against severe COVID-19 among patients with cancer in Catalonia, Spain
Authors: Lazar Neto Felippe , Mercadé-Besora Núria , Raventós Berta , Pérez-Crespo Laura , Castro Junior Gilberto , Ranzani Otavio T. , Duarte-Salles Talita
Published: June 2024

Patients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%−61.1%) and 58.4% (95% CI 29.3%−75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%−84.2%) and 80.2% (95% CI 63.0%−89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.
C(sp3)–H sulfinylation of light hydrocarbons with sulfur dioxide via hydrogen atom transfer photocatalysis in flow
Authors: Nagornîi Dmitrii , Raymenants Fabian , Kaplaneris Nikolaos , Noël Timothy
Published: June 2024

Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO2 to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.
Birefringence-induced phase delay enables Brillouin mechanical imaging in turbid media
Authors: Antonacci Giuseppe , Vanna Renzo , Ventura Marco , Schiavone Maria Lucia , Sobacchi Cristina , Behrouzitabar Morteza , Polli Dario , Manzoni Cristian , Cerullo Giulio
Published: June 2024

Acoustic vibrations of matter convey fundamental viscoelastic information that can be optically retrieved by hyperfine spectral analysis of the inelastic Brillouin scattered light. Increasing evidence of the central role of the viscoelastic properties in biological processes has stimulated the rise of non-contact Brillouin microscopy, yet this method faces challenges in turbid samples due to overwhelming elastic background light. Here, we introduce a common-path Birefringence-Induced Phase Delay (BIPD) filter to disentangle the polarization states of the Brillouin and Rayleigh signals, enabling the rejection of the background light using a polarizer. We demonstrate a 65 dB extinction ratio in a single optical pass collecting Brillouin spectra in extremely scattering environments and across highly reflective interfaces. We further employ the BIPD filter to image bone tissues from a mouse model of osteopetrosis, highlighting altered biomechanical properties compared to the healthy control. Results herald new opportunities in mechanobiology where turbid biological samples remain poorly characterized.
A programmable seekRNA guides target selection by IS1111 and IS110 type insertion sequences
Authors: Siddiquee Rezwan , Pong Carol H. , Hall Ruth M. , Ataide Sandro F.
Published: June 2024

IS1111 and IS110 insertion sequence (IS) family members encode an unusual DEDD transposase type and exhibit specific target site selection. The IS1111 group include identifiable subterminal inverted repeats (sTIR) not found in the IS110 type1. IS in both families include a noncoding region (NCR) of significant length and, as each individual IS or group of closely related IS selects a different site, we had previously proposed that an NCR-derived RNA was involved in target selection2. Here, we find that the NCR is usually downstream of the transposase gene in IS1111 family IS and upstream in the IS110 type. Four IS1111 and one IS110 family members that target different sequences are used to demonstrate that the NCR determines a short seeker RNA (seekRNA) that co-purified with the transposase. The seekRNA is essential for transposition of the IS or a cargo flanked by IS ends from and to the preferred target. Short sequences matching both top and bottom strands of the target are present in the seekRNA but their order in IS1111 and IS110 family IS is reversed. Reprogramming the seekRNA and donor flank to target a different site is demonstrated, indicating future biotechnological potential for these systems.
Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2
Authors: Goradia Nishit , Werner Stefan , Mullapudi Edukondalu , Greimeier Sarah , Bergmann Lina , Lang Andras , Mertens Haydyn , Węglarz Aleksandra , Sander Simon , Chojnowski Grzegorz , Wikman Harriet , Ohlenschläger Oliver , von Amsberg Gunhild , Pantel Klaus , Wilmanns Matthias
Published: June 2024

While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.
Topological heavy fermions in magnetic field
Authors: Singh Keshav , Chew Aaron , Herzog-Arbeitman Jonah , Bernevig B. Andrei , Vafek Oskar
Published: June 2024

The recently introduced topological heavy fermion model (THFM) provides a means for interpreting the low-energy electronic degrees of freedom of the magic angle twisted bilayer graphene as hybridization amidst highly dispersing topological conduction and weakly dispersing localized heavy fermions. In order to understand the Landau quantization of the ensuing electronic spectrum, a generalization of THFM to include the magnetic field B is desired, but currently missing. Here we provide a systematic derivation of the THFM in B and solve the resulting model to obtain the interacting Hofstadter spectra for single particle charged excitations. While naive minimal substitution within THFM fails to correctly account for the total number of magnetic subbands within the narrow band i.e., its total Chern number, our method—based on projecting the light and heavy fermions onto the irreducible representations of the magnetic translation group— reproduces the correct total Chern number. Analytical results presented here offer an intuitive understanding of the nature of the (strongly interacting) Hofstadter bands.
Microenvironment regulation breaks the Faradaic efficiency-current density trade-off for electrocatalytic deuteration using D2O
Authors: He Meng , Li Rui , Cheng Chuanqi , Liu Cuibo , Zhang Bin
Published: June 2024

The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at −100 mA cm−2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at −100 mA cm−2 rationalizes the design concept.
Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals
Authors: Chen Anrong , Han Yang , Wu Rongfeng , Yang Bo , Zhu Lijuan , Zhu Feng
Published: June 2024

C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp2)-C(sp), C(sp2)-C(sp2), and C(sp2)-C(sp3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.
Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast
Authors: Gou Yuanwei , Li Dongfang , Zhao Minghui , Li Mengxin , Zhang Jiaojiao , Zhou Yilian , Xiao Feng , Liu Gaofei , Ding Haote , Sun Chenfan , Ye Cuifang , Dong Chang , Gao Jucan , Gao Di , Bao Zehua , Huang Lei , Xu Zhinan , Lian Jiazhang
Published: June 2024

While sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L−1. Additionally, our engineered strain enables the biosynthesis of fluorinated sanguinarine, showcasing the biotransformation of halogenated derivatives through more than 15 biocatalytic steps. This work serves as a blueprint for utilizing yeast as a scalable platform for biomanufacturing diverse benzylisoquinoline alkaloids and derivatives.
Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi
Authors: Lee Gi Young , Song Jeongmin
Published: June 2024

Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control Vi polymerization or acetylation is enough to result in different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper Vi capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo Vi capsule variants have primarily been identified in Africa, whereas the hyper Vi capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.
Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component Mios
Authors: Wilson Miranda L. , Romano Shannon N. , Khatri Nitya , Aharon Devora , Liu Yulong , Kaufman Odelya H. , Draper Bruce W. , Marlow Florence L.
Published: June 2024

Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
A prefrontal motor circuit initiates persistent movement
Authors: Wang Yihan , Sun Qian-Quan
Published: June 2024

Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.
Inter-continental variability in the relationship of oxidative potential and cytotoxicity with PM2.5 mass
Authors: Salana Sudheer , Yu Haoran , Dai Zhuying , Subramanian P. S. Ganesh , Puthussery Joseph V. , Wang Yixiang , Singh Ajit , Pope Francis D. , Leiva G. Manuel A. , Rastogi Neeraj , Tripathi Sachchida Nand , Weber Rodney J. , Verma Vishal
Published: June 2024

Most fine ambient particulate matter (PM2.5)-based epidemiological models use globalized concentration-response (CR) functions assuming that the toxicity of PM2.5 is solely mass-dependent without considering its chemical composition. Although oxidative potential (OP) has emerged as an alternate metric of PM2.5 toxicity, the association between PM2.5 mass and OP on a large spatial extent has not been investigated. In this study, we evaluate this relationship using 385 PM2.5 samples collected from 14 different sites across 4 different continents and using 5 different OP (and cytotoxicity) endpoints. Our results show that the relationship between PM2.5 mass vs. OP (and cytotoxicity) is largely non-linear due to significant differences in the intrinsic toxicity, resulting from a spatially heterogeneous chemical composition of PM2.5. These results emphasize the need to develop localized CR functions incorporating other measures of PM2.5 properties (e.g., OP) to better predict the PM2.5-attributed health burdens.
Biosynthesis of GMGT lipids by a radical SAM enzyme associated with anaerobic archaea and oxygen-deficient environments
Authors: Li Yanan , Yu Ting , Feng Xi , Zhao Bo , Chen Huahui , Yang Huan , Chen Xing , Zhang Xiao-Hua , Anderson Hayden R. , Burns Noah Z. , Zeng Fuxing , Tao Lizhi , Zeng Zhirui
Published: June 2024

Archaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs). The enzyme, which we name GMGT synthase (Gms), catalyzes the formation of a C(sp3)–C(sp3) linkage between the two isoprenoid chains of glycerol dialkyl glycerol tetraethers (GDGTs). This conclusion is supported by heterologous expression of gene gms from a GMGT-producing species in a methanogen, as well as demonstration of in vitro activity using purified Gms enzyme. Additionally, we show that genes encoding putative Gms homologs are present in obligate anaerobic archaea and in metagenomes obtained from oxygen-deficient environments, and appear to be absent in metagenomes from oxic settings.
Cross-feeding of bifidobacteria promotes intestinal homeostasis: a lifelong perspective on the host health
Authors: Xiao Meifang , Zhang Chuan , Duan Hui , Narbad Arjan , Zhao Jianxin , Chen Wei , Zhai Qixiao , Yu Leilei , Tian Fengwei
Published: June 2024

Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.
The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer
Authors: Johnson Kai C. C. , Ni Ai , Quiroga Dionisia , Pariser Ashley C. , Sudheendra Preeti K. , Williams Nicole O. , Sardesai Sagar D. , Cherian Mathew , Stover Daniel G. , Gatti-Mays Margaret , Ramaswamy Bhuvaneswari , Lustberg Maryam , Jhawar Sachin , Skoracki Roman , Wesolowski Robert
Published: June 2024

There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.
Structure and transcription of integrated HPV DNA in vulvar carcinomas
Authors: Van Arsdale Anne , Turker Lauren , Chang Yoke-Chen , Gould Joshua , Harmon Bryan , Maggi Elaine C. , Meshcheryakova Olga , Brown Maxwell P. , Luong Dana , Van Doorslaer Koenraad , Einstein Mark H. , Kuo Dennis Y. S. , Zheng Deyou , Haas Brian J. , Lenz Jack , Montagna Cristina
Published: June 2024

HPV infections are associated with a fraction of vulvar cancers. Through hybridization capture and DNA sequencing, HPV DNA was detected in five of thirteen vulvar cancers. HPV16 DNA was integrated into human DNA in three of the five. The insertions were in introns of human NCKAP1, C5orf67, and LRP1B. Integrations in NCKAP1 and C5orf67 were flanked by short direct repeats in the human DNA, consistent with HPV DNA insertions at sites of abortive, staggered, endonucleolytic incisions. The insertion in C5orf67 was present as a 36 kbp, human-HPV-hetero-catemeric DNA as either an extrachromosomal circle or a tandem repeat within the human genome. The human circularization/repeat junction was defined at single nucleotide resolution. The integrated viral DNA segments all retained an intact upstream regulatory region and the adjacent viral E6 and E7 oncogenes. RNA sequencing revealed that the only HPV genes consistently transcribed from the integrated viral DNAs were E7 and E6*I. The other two HPV DNA+ tumors had coinfections, but no evidence for integration. HPV-positive and HPV-negative vulvar cancers exhibited contrasting human, global gene expression patterns partially overlapping with previously observed differences between HPV-positive and HPV-negative cervical and oropharyngeal cancers. A substantial fraction of the differentially expressed genes involved immune system function. Thus, transcription and HPV DNA integration in vulvar cancers resemble those in other HPV-positive cancers. This study emphasizes the power of hybridization capture coupled with DNA and RNA sequencing to identify a broad spectrum of HPV types, determine human genome integration status of viral DNAs, and elucidate their structures.
Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice
Authors: Ogonczyk-Makowska Daniela , Brun Pauline , Vacher Clémence , Chupin Caroline , Droillard Clément , Carbonneau Julie , Laurent Emilie , Dulière Victoria , Traversier Aurélien , Terrier Olivier , Julien Thomas , Galloux Marie , Paul Stéphane , Eléouët Jean-François , Fouret Julien , Hamelin Marie-Eve , Pizzorno Andrés , Boivin Guy , Rosa-Calatrava Manuel , Dubois Julia
Published: June 2024

Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.
3D atlas of the human fetal chondrocranium in the middle trimester
Authors: Kaiser Markéta , Zikmund Tomáš , Vora Siddharth , Metscher Brian , Adameyko Igor , Richman Joy M. , Kaiser Jozef
Published: June 2024

The chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the  endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.
Identification of potential modulators for human GPD1 by docking-based virtual screening, molecular dynamics simulations, binding free energy calculations, and DeLA-drug analysis
Authors: Hu Anzheng , Chen Hongwei , Pang Wenwei , Pu Xiaojie , Qi Zhongquan , Chen Haiyan
Published: June 2024

Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington’s disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database (http://zinc.docking.org/) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development.
Assessing spatiotemporal population density dynamics from 2000 to 2020 in megacities using urban and rural morphologies
Authors: Xie Jing , Wei Nan , Gao Quan
Published: June 2024

Rapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban–rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban–rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.
Insights into polycrystalline microstructure of blood films with 3D Mueller matrix imaging approach
Authors: Ushenko Alexander G. , Sdobnov Anton , Soltys Irina V. , Ushenko Yuriy A. , Dubolazov Alexander V. , Sklyarchuk Valery M. , Olar Alexander V. , Trifonyuk Liliya , Doronin Alexander , Yan Wenjun , Bykov Alexander , Meglinski Igor
Published: June 2024

This study introduces a novel approach in the realm of liquid biopsies, employing a 3D Mueller-matrix (MM) image reconstruction technique to analyze dehydrated blood smear polycrystalline structures. Our research centers on exploiting the unique optical anisotropy properties of blood proteins, which undergo structural alterations at the quaternary and tertiary levels in the early stages of diseases such as cancer. These alterations manifest as distinct patterns in the polycrystalline microstructure of dried blood droplets, offering a minimally invasive yet highly effective method for early disease detection. We utilized a groundbreaking 3D MM mapping technique, integrated with digital holographic reconstruction, to perform a detailed layer-by-layer analysis of partially depolarizing dry blood smears. This method allows us to extract critical optical anisotropy parameters, enabling the differentiation of blood films from healthy individuals and prostate cancer patients. Our technique uniquely combines polarization-holographic and differential MM methodologies to spatially characterize the 3D polycrystalline structures within blood films. A key advancement in our study is the quantitative evaluation of optical anisotropy maps using statistical moments (first to fourth orders) of linear and circular birefringence and dichroism distributions. This analysis provides a comprehensive characterization of the mean, variance, skewness, and kurtosis of these distributions, crucial for identifying significant differences between healthy and cancerous samples. Our findings demonstrate an exceptional accuracy rate of over $$90\%$$

90
%

for the early diagnosis and staging of cancer, surpassing existing screening methods. This high level of precision and the non-invasive nature of our technique mark a significant advancement in the field of liquid biopsies. It holds immense potential for revolutionizing cancer diagnosis, early detection, patient stratification, and monitoring, thereby greatly enhancing patient care and treatment outcomes. In conclusion, our study contributes a pioneering technique to the liquid biopsy domain, aligning with the ongoing quest for non-invasive, reliable, and efficient diagnostic methods. It opens new avenues for cancer diagnosis and monitoring, representing a substantial leap forward in personalized medicine and oncology.
Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism
Authors: Silva-Pavez Eduardo , Mendoza Elizabeth , Morgado-Cáceres Pablo , Ahumada-Castro Ulises , Bustos Galdo , Kangme-Encalada Matías , de Arbina Amaia Lopez , Puebla-Huerta Andrea , Muñoz Felipe , Cereceda Lucas , Varas-Godoy Manuel , Hidalgo Yessia , Cardenas J. Cesar
Published: June 2024

Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserved their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway. Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated.
Investigation of metal concentration distribution and corresponding health exposure assessment of fabricated metal product manufacturers
Authors: Lan Cheng-Hang , Ou Lun-Chun , Liu Hung-Hsin , Peng Chiung-Yu
Published: June 2024

The fabricated metal product industries were identified as producers of variable and heterogeneous pollution. Workers in these manufacturing facilities are exposed to multiple pollutants present at variable concentrations. Specific known adverse health effects include bladder cancer associated with metalworking fluid exposure and lung cancer associated with electroplating processes. To reduce the incidence of these adverse effects, the main challenge is to identify the most hazardous pollutants within this complex exposure environment and evaluate the corresponding health potentials. In this study, exposure indices were formulated to assess multiple metal exposures with the ultimate goal of providing relevant information for exposure reduction and control measures. Fifteen plants, including metal mold manufacturing, metal casting, and surface treatment plants, were investigated in terms of total concentration, summation of corresponding ratio to threshold limit value (STLVr), hazard index (HI), and incremental cancer risk. The results revealed that emissions of aluminum, iron, and manganese were primarily found in the metal mold manufacturing/casting plants, while emissions of chromium, nickel, and zinc were found in surface treatment plants. STLVr and HI were more useful than the total concentration for identifying hazardous metals, which were chromium and nickel, and could specify the facilities that were in need of control measures. As for cancer risk, the metal mold manufacturing/casting plants had lower risk than the surface treatment plants, and the contributing metals for these two plant types were cobalt and chromium, respectively. This study established a useful procedure to evaluate health hazards and cancer risk. The resulting information is useful for prioritizing mitigation control of multiple metal exposures.
Longitudinal urinary neopterin is associated with hearing threshold change over time in independent older adults
Authors: Kidd Rachel L. , Agyemang-Prempeh Akosua , Sanderson Alan , Stuart Charlotte , Mahajan Sumeet , Verschuur Carl A. , Newman Tracey A.
Published: June 2024

Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65–75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch’s ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.
Domestic chickens solving mirror-mediated spatial location tasks uncovering their cognitive abilities
Authors: Hillemacher Sonja , Tiemann Inga
Published: June 2024

The increasing demand on adapting modern livestock farming to higher animal welfare standards requires a thorough understanding of a species’ cognitive abilities to determine their adaptability. With the chicken being the world’s most numerous birds in animal production, it is mandatory to identify its cognitive abilities and limitations in order to meet its needs. We investigated if chickens are able to use and understand the reflective properties of a mirror that is the correlation of reflections of food rewards and their real location. In total, 18 female chickens of two different breeds were tested in a mirror-mediated spatial location task. Eleven out of eighteen hens solved the task successfully and thus, possibly exploited the correlation between the reflection in the mirror and the real food reward. We found differences on a breed and on the individual level, with different amounts of time needed learning the association of reward and mirror image. The results imply sophisticated cognitive abilities in chickens, assuming they may be able to understand how mirror images represent objects in the real environment, and to make use of it during foraging. The chicken’s cognitive ability might lead to a new understanding and provision of animal welfare-compliant production environments.
Enhanced multi view 3D reconstruction with improved MVSNet
Authors: Li Guangchen , Li Kefeng , Zhang Guangyuan , Zhu Zhenfang , Wang Peng , Wang Zhenfei , Fu Chen
Published: June 2024

Although 3D reconstruction has been widely used in many fields as a key component of environment perception, existing technologies still have the potential for further improvement in 3D scene reconstruction. We propose an improved reconstruction algorithm based on the MVSNet network architecture. To glean richer pixel details from images, we suggest deploying a DE module integrated with a residual framework, which supplants the prevailing feature extraction mechanism. The DE module uses ECA-Net and dilated convolution to expand the receptive field range, performing feature splicing and fusion through the residual structure to retain the global information of the original image. Moreover, harnessing attention mechanisms refines the 3D cost volume's regularization process, bolstering the integration of information across multi-scale feature volumes, consequently enhancing depth estimation precision. When assessed our model using the DTU dataset, findings highlight the network's 3D reconstruction scoring a completeness (comp) of 0.411 mm and an overall quality of 0.418 mm. This performance is higher than that of traditional methods and other deep learning-based methods. Additionally, the visual representation of the point cloud model exhibits marked advancements. Trials on the Blended MVS dataset signify that our network exhibits commendable generalization prowess.
Improved sports image classification using deep neural network and novel tuna swarm optimization
Authors: Zhou Zetian , Zhang Heqing , Effatparvar Mehdi
Published: June 2024

Sports image classification is a complex undertaking that necessitates the utilization of precise and robust techniques to differentiate between various sports activities. This study introduces a novel approach that combines the deep neural network (DNN) with a modified metaheuristic algorithm known as novel tuna swarm optimization (NTSO) for the purpose of sports image classification. The DNN is a potent technique capable of extracting high-level features from raw images, while the NTSO algorithm optimizes the hyperparameters of the DNN, including the number of layers, neurons, and activation functions. Through the application of NTSO to the DNN, a finely-tuned network is developed, exhibiting exceptional performance in sports image classification. Rigorous experiments have been conducted on an extensive dataset of sports images, and the obtained results have been compared against other state-of-the-art methods, including Attention-based graph convolution-guided third-order hourglass network (AGTH-Net), particle swarm optimization algorithm (PSO), YOLOv5 backbone and SPD-Conv, and Depth Learning (DL). According to a fivefold cross-validation technique, the DNN/NTSO model provided remarkable precision, recall, and F1-score results: 97.665 ± 0.352%, 95.400 ± 0.374%, and 0.8787 ± 0.0031, respectively. Detailed comparisons reveal the DNN/NTSO model's superiority toward various performance metrics, solidifying its standing as a top choice for sports image classification tasks. Based on the practical dataset, the DNN/NTSO model has been successfully evaluated in real-world scenarios, showcasing its resilience and flexibility in various sports categories. Its capacity to uphold precision in dynamic settings, where elements like lighting, backdrop, and motion blur are prominent, highlights its utility. The model's scalability and efficiency in analyzing images from live sports competitions additionally validate its suitability for integration into real-time sports analytics and media platforms. This research not only confirms the theoretical superiority of the DNN/NTSO model but also its pragmatic effectiveness in a wide array of demanding sports image classification assignments.
Social and environmental stressors of cardiometabolic health
Authors: Bartoskova Polcrova Anna , Dalecka Andrea , Szabo Daniel , Gonzalez Rivas Juan Pablo , Bobak Martin , Pikhart Hynek
Published: June 2024

Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25–64 years) from the cross-sectional population-based study were analysed. The composite score of metabolic disorders (MS score) was calculated based on 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, triglycerides. The effects of social stressors (education level, income), environmental stressors (NO2, noise) and behavioural factors (unhealthy diet, smoking, alcohol consumption, sedentary behaviours) on MS score were assessed using a structural model. We observed a direct effect of education on MS score, as well as an indirect effect mediated via an unhealthy diet, smoking, and sedentary behaviours. We also observed a significant indirect effect of income via sedentary behaviours. The only environmental stressor predicting MS was noise, which also mediated the effect of education. In summary, the effect of social stressors on the development of cardiometabolic risk had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual’s unhealthy behaviour and might predispose individuals to higher levels of environmental stressors exposures.
Optimizing EEG ICA decomposition with data cleaning in stationary and mobile experiments
Authors: Klug M. , Berg T. , Gramann K.
Published: June 2024

Electroencephalography (EEG) studies increasingly utilize more mobile experimental protocols, leading to more and stronger artifacts in the recorded data. Independent Component Analysis (ICA) is commonly used to remove these artifacts. It is standard practice to remove artifactual samples before ICA to improve the decomposition, for example using automatic tools such as the sample rejection option of the AMICA algorithm. However, the effects of movement intensity and the strength of automatic sample rejection on ICA decomposition have not been systematically evaluated. We conducted AMICA decompositions on eight open-access datasets with varying degrees of motion intensity using varying sample rejection criteria. We evaluated decomposition quality using mutual information of the components, the proportion of brain, muscle, and 'other' components, residual variance, and an exemplary signal-to-noise ratio. Within individual studies, increased movement significantly decreased decomposition quality, though this effect was not found across different studies. Cleaning strength significantly improved the decomposition, but the effect was smaller than expected. Our results suggest that the AMICA algorithm is robust even with limited data cleaning. Moderate cleaning, such as 5 to 10 iterations of the AMICA sample rejection, is likely to improve the decomposition of most datasets, regardless of motion intensity.