bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifractal parameterization of a periodic surface microrelief formed at the face milling. 2. Distribution of elements volume of surface relief
Authors: Balytska N. , Penter L. , Kryzhanivskyy V. , Melnyk O. , Polonsky L. , Shadura V. , Ihlenfeldt S. , Moskvin P.
Published: December 2023

This study represents the first application of multifractal analysis to characterize spatial microforms’ volumes resulting from face milling on flat surfaces, emphasizing its novelty. Photographs of samples of C35 steel and AA22024 aluminum alloy, subjected to various cutting conditions during milling, were utilized to apply the multifractal approach for describing the machined surface microrelief. Multifractal spectra and their key parameters were computed for the samples’ surfaces generated at various feed rates and cutting depths. It is demonstrated that the characteristic functions of the performed multifractal analysis align with their canonical forms. The results offer compelling evidence that machining results in the formation of a system exhibiting self-similarity and fractal symmetry properties on the specimen’s surface. The practical significance of this research lies in the establishment of quantitative dependences between the parameters of the multifractal spectrum of surface microforms generated during the face milling under varying cutting depths and feed rates. This facilitates the identification of technological and physical factors responsible for observed variations in surface fractal properties. The formation of the multifractal spectra from surface element volumes is discussed in connection with the underlying physical phenomena associated with cutting conditions.
Deceptive XAI: Typology, Creation and Detection
Authors: Schneider Johannes , Meske Christian , Vlachos Michalis
Published: December 2023

Providing rationales for decisions can enhance transparency and cultivate trust. Nevertheless, in light of economic incentives and other factors that may encourage manipulation, the reliability of such explanations comes into question. This manuscript builds upon a previous conference paper$$^*$$

∗

by introducing a conceptual framework for deceptive explanations and constructing a typology grounded in interdisciplinary literature. The focus of our work is on how AI models can generate and detect deceptive explanations. In our empirical evaluation, we focus on text classification and introduce modifications to the explanations generated by GradCAM, a well-established method for explaining neural networks. Through a user study comprising 200 participants, we demonstrate that these deceptive explanations have the potential to mislead individuals. However, we also demonstrate that machine learning (ML) techniques can discern even subtle deceptive tactics with an accuracy exceeding 80%, given sufficient domain expertise. Furthermore, even in the absence of domain knowledge, unsupervised learning can be employed to identify inconsistencies in the explanations, provided that fundamental information about the underlying predictive model is accessible.
Parasitic Egg Detection and Classification in Low-Cost Microscopic Images Using Transfer Learning
Authors: Suwannaphong Thanaphon , Chavana Sawaphob , Tongsom Sahapol , Palasuwan Duangdao , Chalidabhongse Thanarat H. , Anantrasirichai Nantheera
Published: December 2023

Intestinal parasitic infection leads to several morbidities in humans worldwide, especially in tropical countries. The traditional diagnosis usually relies on manual analysis from microscopic images which is prone to human error due to morphological similarity of different parasitic eggs and abundance of impurities in a sample. Many studies have developed automatic systems for parasite egg detection to reduce human workload. However, they work with high-quality microscopes, which unfortunately remain unaffordable in some rural areas. Our work thus exploits a benefit of a low-cost USB microscope. This instrument however provides poor quality images due to the limitation of magnification (10$$\times$$
×
), causing difficulty in parasite detection and species classification. In this paper, we propose a CNN-based technique using transfer learning strategy to enhance the efficiency of automatic parasite classification in poor-quality microscopic images. The patch-based technique with a sliding window is employed to search for the location of the eggs. Two networks, AlexNet and ResNet50, are examined with a trade-off between architecture size and classification performance. The results show that our proposed framework outperforms the state-of-the-art object recognition methods. Our system combined with the final decision from an expert may improve the real faecal examination with low-cost microscopes.
The Coronal Alignment of Lower Limbs in the Adolescent Football and Ice Hockey Players
Authors: Žlak Nik , Krajnc Zmago , Merčun Aljaž , Drobnič Matej , Kacin Alan
Published: December 2023

Background

To investigate the influence of sport-specific activities on coronal axial alignment of the lower limbs in adolescent football and ice hockey players.

Methods

This cross-sectional study targeted healthy adolescent male football and ice hockey players with at least 3 years of sports participation. 90 football and 38 ice hockey players aged 12–16 years were divided into five age-matched subgroups. Coronal alignment of the lower limbs was determined by measuring the players' intercondylar or intermalleolar (ICD-IMD) distance with a custom-made calliper. In addition, their sports history was recorded. An age-matched comparison between the two sports groups was performed using the two-way model ANOVA and a multiple regression model for ICD-IMD was constructed. Results were additionally compared with age-matched data from the general population published in recent literature.

Results

A statistically significant increase in ICD-IMD values (p < 0.05) was found between 12 (football 0 mm; ice hockey − 64 mm) and 16 years (football 340 mm; ice hockey 310 mm) in both sports groups. Results of regression analysis of pooled group data showed that ICD-IMD has low positive correlation (r = 0.407; r2 = 0.168; p < 0.05) with time of participation in sport, but no association with age of athletes at the start of their sport participation (r = − 0.018; r2 = 0.000; p > 0.05). There were no statistically significant differences between the two groups at any time point. Both sports groups showed a significant increase in ICD-IMD values (mean 198 mm) after the age of 14 compared to the general population.

Conclusions

Participation in football and ice hockey is associated with a similar increase in ICD-IMD in the adolescent years in male athletes. The observed increase was higher in both groups of athletes than in their peers who do not regularly participate in sports.

Level of Evidence

Level 4 (case series).
Merocyanines form bacteriorhodopsins with strongly bathochromic absorption maxima
Authors: Mackintosh Megan J. , Hoischen Dorothee , Martin Hans-Dieter , Schapiro Igor , Gärtner Wolfgang
Published: December 2023

There is a need to shift the absorbance of biomolecules to the optical transparency window of tissue for applications in optogenetics and photo-pharmacology. There are a few strategies to achieve the so-called red shift of the absorption maxima. Herein, a series of 11 merocyanine dyes were synthesized and employed as chromophores in place of retinal in bacteriorhodopsin (bR) to achieve a bathochromic shift of the absorption maxima relative to bR’s $${\lambda }_{\mathrm{max}}^{a}$$

λ

max

a

of 568 nm. Assembly with the apoprotein bacterioopsin (bO) led to stable, covalently bound chromoproteins with strongly bathochromic absorbance bands, except for three compounds. Maximal red shifts were observed for molecules 9, 2, and 8 in bR where the $${\lambda }_{\mathrm{max}}^{a}$$

λ

max

a

was 766, 755, and 736 nm, respectively. While these three merocyanines have different end groups, they share a similar structural feature, namely, a methyl group which is located at the retinal equivalent position 13 of the polyene chain. The absorption and fluorescence data are also presented for the retinal derivatives in their aldehyde, Schiff base (SB), and protonated SB (PSB) forms in solution. According to their hemicyanine character, the PSBs and their analogue bRs exhibited fluorescence quantum yields (Φf) several orders of magnitude greater than native bR (Φf 0.02 to 0.18 versus 1.5 × 10–5 in bR) while also exhibiting much smaller Stokes shifts than bR (400 to 1000 cm−1 versus 4030 cm−1 in bR). The experimental results are complemented by quantum chemical calculations where excellent agreement between the experimental $${\lambda }_{\mathrm{max}}^{a}$$

λ

max

a

and the calculated $${\lambda }_{\mathrm{max}}^{a}$$

λ

max

a

was achieved with the second-order algebraic-diagrammatic construction [ADC(2)] method. In addition, quantum mechanics/molecular mechanics (QM/MM) calculations were employed to shed light on the origin of the bathochromic shift of merocyanine 2 in bR compared with native bR.

Graphical abstract
Microbe Goo Could Help Guide the Search for Life on Mars
Authors: van Deelen Grace
Published: December 2023

Sticky substances secreted by microbes may help create landforms on Earth.
Snow Accumulation Variability at the South Pole From 1983 to 2020, Associated With Central Tropical Pacific Forcing
Authors: Zhai Zhaosheng , Wang Yetang , Lazzara Matthew A. , Keller Linda M. , Wu Qingli
Published: December 2023

Despite a variety of efforts made to measure snow accumulation at the South Pole (SP), snow accumulation changes and their mechanism have not yet been fully explained. Here, SP stake farm measurements, global sea surface temperature observations, and atmospheric circulation data from European Centre for Medium‐Range Weather Forecasts Reanalysis version 5 were used to investigate the annual and seasonal snow accumulation changes at the SP during 1983–2020, and their association with central tropical Pacific Sea surface temperature variations. SP annual snow accumulation decreased significantly for the 1983–2007 period at a rate of −39.7 ± 1.4 mm decade−1, but switched to a dramatically positive trend during 2008–2020 (108.7 ± 2.7 mm decade−1), with the strongest increase in the austral autumn. The switch to a dramatically upward trend can largely be attributed to a cyclonic anomaly over the South Atlantic and an anticyclonic anomaly over the Drake Passage, causing the enhanced advection of warm and wet air into the SP. These circulation patterns were generated by an atmospheric Rossby wave train forced by rapid warming in the central tropical Pacific during 2008–2020.
UV Reflectance of Spacecraft Materials and Analog Soils: Implications for Bioburden Reductions on the Undersides of Mars Rovers
Authors: Schuerger Andrew C. , Moores John E.
Published: December 2023

The Mars Sample Return mission architecture will utilize three spacecraft to collect, cache, recover, launch, and return to Earth a diversity of regolith and rock samples. However, no comprehensive Mars Microbial Survival (MMS) model currently exists. As an initial effort in building an MMS model, we examined the UV reflectance of 15 spacecraft materials and seven Mars analog soils within the context of the Perseverance mission. Data were used to predict the times required to achieve one lethal dose (syn., Sterility Assurance Level [SAL]; def. as a bioburden reduction of −12 logs). Results suggest that a single SAL dosage of UVC was achieved on exposed surfaces on the upper deck of Perseverance within a few hours to a few sols post‐landing at Jezero Crater. The overall average for UVC reflectance from spacecraft materials was approximately 10%. The overall UVC reflectance from Mars analog soils was measured at 1.3%. The Adaptive Caching Assembly (ACA) on Perseverance is located on the forward edge of the underbelly of the spacecraft. Modeling of the accumulated UVC dosage for the ACA yielded a prediction of reaching one SAL for downward facing surfaces at 93 sols that receive “single‐bounce” UVC photons from the local terrain. The SAL increases to 930 sols if an additional “bounce” of the solar UV irradiation is required to reach a partially protected site in the ACA hardware. The current study is the first to report the UVC reflectance from a diversity of spacecraft materials.
Time-sensitive healthcare guidelines for youth with chronic diseases in custody: gaps in care
Authors: Dickens Colin , Ramesh Ahalya , Adanlawo Temiloluwa , DeBaun Michael R.
Published: December 2023

Case study

On May 9th, 2023, a U.S. Border Patrol detained a family of five near Brownsville, TX. During processing, one of the family members, an eight-year-old girl, ADRA, was noted to have sickle cell anemia and a heart disease condition. Five days after they arrived at the Donna Facility, on May 14th, ADRA displayed symptoms, including abdominal pain and fever, and tested positive for Influenza A. She was administered medication and transferred to a designated isolation unit at the Harlingen Border Patrol Station. Despite her deteriorating condition and her mother’s urgent requests for medical intervention, there were no documented consultations with an on-call physician or considerations for her transfer to a local hospital. On May 17th, ADRA’s health critically declined, marked by multiple visits to the medical unit for vomiting and abdominal pain. An ambulance was dispatched only after ADRA experienced a seizure and became unresponsive, Fig. 1. Her subsequent death was deemed a “preventable tragedy” attributed to systemic failures in the Border Patrol’s medical care and decision-making processes in a juvenile care monitor’s report.1

Impact

This article adds to the existing literature by:

Summarizing the gap in age-specific guidelines for six chronic diseases that occur in children and adolescents held in custody.

Identifying the lack of adequate intervention strategies for acute management of chronic diseases for youth held in custody and strategies for improving health equity.
Lysosomes, caspase-mediated apoptosis, and cytoplasmic activation of P21, but not cell senescence, participate in a redundant fashion in embryonic morphogenetic cell death
Authors: Duarte-Olivenza Cristina , Moran Goretti , Hurle Juan M. , Lorda-Diez Carlos I. , Montero Juan A.
Published: December 2023

Micromass cultures of embryonic limb skeletal progenitors replicate the tissue remodelling processes observed during digit morphogenesis. Here, we have employed micromass cultures in an in vitro assay to study the nature of cell degeneration events associated with skeletogenesis. In the assay, “naive” progenitors obtained from the autopod aggregate to form chondrogenic nodules and those occupying the internodular spaces exhibit intense apoptosis and progressive accumulation of larger cells, showing intense SA-β-Gal histochemical labelling that strictly overlaps with the distribution of neutral red vital staining. qPCR analysis detected intense upregulation of the p21 gene, but P21 immunolabelling showed cytoplasmic rather than the nuclear distribution expected in senescent cells. Semithin sections and transmission electron microscopy confirmed the presence of canonical apoptotic cells, degenerated cell fragments in the process of phagocytic internalization by the neighbouring cells, and large vacuolated cells containing phagosomes. The immunohistochemical distribution of active caspase 3, cathepsin D, and β-galactosidase together with the reduction in cell death by chemical inhibition of caspases (Q-VAD) and lysosomal cathepsin D (Pepstatin A) supported a redundant implication of both pathways in the dying process. Chemical inhibition of P21 (UC2288) revealed a complementary role of this factor in the dying process. In contrast, treatment with the senolytic drug Navitoclax increased cell death without changing the number of cells positive for SA-β-Gal. We propose that this model of tissue remodelling involves the cooperative activation of multiple degradation routes and, most importantly, that positivity for SA-β-Gal reflects the occurrence of phagocytosis, supporting the rejection of cell senescence as a defining component of developmental tissue remodelling.
The aryl hydrocarbon receptor controls mesenchymal stromal cell-mediated immunomodulation via ubiquitination of eukaryotic elongation factor-2 kinase
Authors: Lkhagva-Yondon Enkhmaa , Seo Myeong Seong , Oh Yena , Jung Jonghun , Jeon Eunhae , Na Kwangmin , Yoo Hyun Seung , Kim Woo Chul , Esser Charlotte , Song Sun U. , Jeon Myung-Shin
Published: December 2023

Mesenchymal stem cells (MSCs) have great therapeutic advantages due to their immunosuppressive properties. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose signaling plays an important role in the immune system. AHR may be involved in the regulation of MSC-associated immunomodulatory functions. However, the mechanisms by which AHR controls the immunosuppressive functions of MSCs are not well understood. Here, we report that Ahr-deficient MSCs show decreased therapeutic efficacy against graft-versus-host disease (GVHD) compared to wild-type (WT)-MSCs. This was probably due to decreased iNOS protein expression, which is a key regulatory enzyme in MSC immunomodulation. The expression of eukaryotic elongation factor 2 kinase (eEF2K), which inhibits the elongation stage of protein synthesis, is significantly increased in the Ahr-deficient MSCs. Inhibition of eEF2K restored iNOS protein expression. AHR is known to act as an E3 ligase together with CUL4B. We observed constitutive binding of AHR to eEF2K. Consequently, ubiquitination and degradation of eEF2K were inhibited in Ahr-deficient MSCs and by the AHR antagonist CH223191 in WT-MSCs. In summary, AHR regulates the immunomodulatory functions of MSCs through ubiquitination of eEF2K, thereby controlling iNOS protein synthesis and its product, nitric oxide levels.
Blockade of DDR1/PYK2/ERK signaling suggesting SH2 superbinder as a novel autophagy inhibitor for pancreatic cancer
Authors: Xu Hui , Tan Ming , Hou Guo-Qing , Sang Ya-Zhou , Lin Li , Gan Xiao-Cai , Cao Xuan , Liu An-Dong
Published: December 2023

Pancreatic cancer is highly lethal, of which 90% is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 12%, lacking effective treatment options and late diagnosis. Furthermore, the tumors show an intense resistance to cytotoxic chemotherapies. As autophagy is elevated in PDAC, targeting the autophagic pathway is regarded as a promising strategy for cancer treatment. Immunofluorescence and transmission electron microscopy were utilized to assess the autophagic flux. Label-free quantitative phosphoproteomics was used to figure out critically altered tyrosine phosphorylation of the proteins. Tumor-bearing mice were used to validate that SH2 TrM-(Arg)9 restrained the growth of tumor cells. SH2 TrM-(Arg)9 inhibited collagen-induced autophagy via blocking the DDR1/PYK2/ERK signaling cascades. SH2 TrM-(Arg)9 improved the sensitivity of PANC-1/GEM cells to gemcitabine (GEM). Inhibition of autophagy by SH2 TrM-(Arg)9 may synergized with chemotherapy and robusted tumor suppression in pancreatic cancer xenografts. SH2 TrM-(Arg)9 could enter into PDAC cells and blockade autophagy through inhibiting DDR1/PYK2/ERK signaling and may be a new treatment strategy for targeted therapy of PDAC.
Personalized dietary management of advanced prostate cancer using nutrigenomics: a case report
Authors: Brinkman Maree , Green Hayden , Crofts Sam , Jones Bridget , Walsh Simone , Smith Margaret
Published: December 2023

While there are emerging reports in the scientific literature on potential associations between cholesterol/lipids and prostate cancer, information on the dietary management of these cancer patients is currently lacking. We report on a 57-year-old white Australian male diagnosed with advanced prostate cancer who had personalized dietary management in preparation for and following his medical treatment: radiation and radical prostatectomy. Dietary recommendations were based on his blood results and nutrigenomic tests which showed a history of and genetic predisposition to dyslipidemia. Nutritional analysis also confirmed the need for dietary modification of his fat intake. Eighteen months post medical and dietary intervention his PSA level was reported at 0.1 ug/L and all blood lipid levels were within reference ranges. At two years there was no detectable disease recurrence and androgen deprivation therapy (ADT) was not required. Personalized dietary recommendations could be a clinically beneficial addition to the multidisciplinary management of prostate cancer patients.
Highly scalable photoinduced synthesis of silanols via untraversed pathway for chlorine radical (Cl•) generation
Authors: Saha Argha , Ali Wajid , Werz Daniel B. , Maiti Debabrata
Published: December 2023

The emergence of visible light-mediated synthetic transformations has transpired as a promising approach to redefine traditional organic synthesis in a sustainable way. In this genre, transition metal-mediated photoredox catalysis has led the way and recreated a plethora of organic transformations. However, the use of photochemical energy solely to initiate the reaction is underexplored. With the direct utilization of photochemical energy herein, we have established a general and practical protocol for the synthesis of diversely functionalized organosilanols, silanediols, and polymeric siloxanol engaging a wide spectrum of hydrosilanes under ambient reaction conditions. Streamlined synthesis of bio-active silanols via late-stage functionalization underscores the importance of this sustainable protocol. Interestingly, this work also reveals photoinduced non-classical chlorine radical (Cl•) generation from a readily available chlorinated solvent under aerobic conditions. The intriguing factors of the proposed mechanism involving chlorine and silyl radicals as intermediates were supported by a series of mechanistic investigations.
The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria
Authors: Bryant Owain J. , Lastovka Filip , Powell Jessica , Chung Betty Y. -W.
Published: December 2023

Translational control in pathogenic bacteria is fundamental to gene expression and affects virulence and other infection phenotypes. We used an enhanced ribosome profiling protocol coupled with parallel transcriptomics to capture accurately the global translatome of two evolutionarily distant pathogenic bacteria—the Gram-negative bacterium Salmonella and the Gram-positive bacterium Listeria. We find that the two bacteria use different mechanisms to translationally regulate protein synthesis. In Salmonella, in addition to the expected correlation between translational efficiency and cis-regulatory features such as Shine–Dalgarno (SD) strength and RNA secondary structure around the initiation codon, our data reveal an effect of the 2nd and 3rd codons, where the presence of tandem lysine codons (AAA-AAA) enhances translation in both Salmonella and E. coli. Strikingly, none of these features are seen in efficiently translated Listeria transcripts. Instead, approximately 20% of efficiently translated Listeria genes exhibit 70 S footprints seven nt upstream of the authentic start codon, suggesting that these genes may be subject to a novel translational initiation mechanism. Our results show that SD strength is not a direct hallmark of translational efficiency in all bacteria. Instead, Listeria has evolved additional mechanisms to control gene expression level that are distinct from those utilised by Salmonella and E. coli.
Widespread PREMA in the upper mantle indicated by low-degree basaltic melts
Authors: Cai Ronghua , Liu Jingao , Pearson D. Graham , Giuliani Andrea , van Keken Peter E. , Oesch Senan
Published: December 2023

Studies of ocean island basalts have identified a Prevalent Mantle (PREMA) component as a fundamental feature of mantle geochemical arrays; however, its origin and distribution are highly controversial, including its potential link to plumes sourced in low-shear-wave velocity provinces (LLSVPs) above the core-mantle boundary. In this study, we interrogate the compositional systematics of ~ 3500 Cenozoic oceanic and continental sodic basalts to provide insights into the origin and distribution of PREMA. We find that low-degree basaltic melts with high Nb concentrations located away from deep-mantle plumes have PREMA-like Sr-Nd-Hf isotopic signatures, implying that PREMA is highly fusible and not exclusively associated with LLSVPs. Geochemical modelling and mantle convection simulations indicate that PREMA could have been generated soon after Earth accretion, experiencing only minimal melting or enrichment, and then scattered throughout the upper mantle, rather than being the result of mixing between depleted and enriched mantle components.
Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops
Authors: Bsteh Daniel , Moussa Hagar F. , Michlits Georg , Yelagandula Ramesh , Wang Jingkui , Elling Ulrich , Bell Oliver
Published: December 2023

Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional gene silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. Additionally, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we found that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of a subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not linked to loss of Polycomb chromatin domains. Instead, PDS5A removal causes aberrant cohesin activity leading to ectopic insulation sites, which disrupt the formation of ultra-long Polycomb loops. We show that these loops are important for robust silencing at a subset of PRC1/PRC2 target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.
Alkali metal reduction of alkali metal cations
Authors: Pearce Kyle G. , Liu Han-Ying , Neale Samuel E. , Goff Hattie M. , Mahon Mary F. , McMullin Claire L. , Hill Michael S.
Published: December 2023

Counter to synthetic convention and expectation provided by the relevant standard reduction potentials, the chloroberyllate, [{SiNDipp}BeClLi]2 [{SiNDipp} = {CH2SiMe2N(Dipp)}2; Dipp = 2,6-i-Pr2C6H3)], reacts with the group 1 elements (M = Na, K, Rb, Cs) to provide the respective heavier alkali metal analogues, [{SiNDipp}BeClM]2, through selective reduction of the Li+ cation. Whereas only [{SiNDipp}BeClRb]2 is amenable to reduction by potassium to its nearest lighter congener, these species may also be sequentially interconverted by treatment of [{SiNDipp}BeClM]2 by the successively heavier group 1 metal. A theoretical analysis combining density functional theory (DFT) with elemental thermochemistry is used to rationalise these observations, where consideration of the relevant enthalpies of atomisation of each alkali metal in its bulk metallic form proved crucial in accounting for experimental observations.
The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection
Authors: Tapryal Nisha , Chakraborty Anirban , Saha Kaushik , Islam Azharul , Pan Lang , Hosoki Koa , Sayed Ibrahim M. , Duran Jason M. , Alcantara Joshua , Castillo Vanessa , Tindle Courtney , Sarker Altaf H. , Wakamiya Maki , Cardenas Victor J. , Sharma Gulshan , Crotty Alexander Laura E. , Sur Sanjiv , Sahoo Debashis , Ghosh Gourisankar , Das Soumita , Ghosh Pradipta , Boldogh Istvan , Hazra Tapas K.
Published: December 2023

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5’-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.
Generation of three-dimensional meat-like tissue from stable pig epiblast stem cells
Authors: Zhu Gaoxiang , Gao Dengfeng , Li Linzi , Yao Yixuan , Wang Yingjie , Zhi Minglei , Zhang Jinying , Chen Xinze , Zhu Qianqian , Gao Jie , Chen Tianzhi , Zhang Xiaowei , Wang Tong , Cao Suying , Ma Aijin , Feng Xianchao , Han Jianyong
Published: December 2023

Cultured meat production has emerged as a breakthrough technology for the global food industry with the potential to reduce challenges associated with environmental sustainability, global public health, animal welfare, and competition for food between humans and animals. The muscle stem cell lines currently used for cultured meat cannot be passaged in vitro for extended periods of time. Here, we develop a directional differentiation system of porcine pre-gastrulation epiblast stem cells (pgEpiSCs) with stable cellular features and achieve serum-free myogenic differentiation of the pgEpiSCs. We show that the pgEpiSCs-derived skeletal muscle progenitor cells and skeletal muscle fibers have typical muscle cell characteristics and display skeletal muscle transcriptional features during myogenic differentiation. Importantly, we establish a three-dimensional differentiation system for shaping cultured tissue by screening plant-based edible scaffolds of non-animal origin, followed by the generation of pgEpiSCs-derived cultured meat. These advances provide a technical approach for the development of cultured meat.
Orbital topological edge states and phase transitions in one-dimensional acoustic resonator chains
Authors: Gao Feng , Xiang Xiao , Peng Yu-Gui , Ni Xiang , Sun Qi-Li , Yves Simon , Zhu Xue-Feng , Alù Andrea
Published: December 2023

Topological phases of matter have attracted significant attention in recent years, due to the unusual robustness of their response to defects and disorder. Various research efforts have been exploring classical and quantum topological wave phenomena in engineered materials, in which different degrees of freedom (DoFs) – for the most part based on broken crystal symmetries associated with pseudo-spins – induce synthetic gauge fields that support topological phases and unveil distinct forms of wave propagation. However, spin is not the only viable option to induce topological effects. Intrinsic orbital DoFs in spinless systems may offer a powerful alternative platform, mostly unexplored to date. Here we reveal orbital-selective wave-matter interactions in acoustic systems supporting multiple orbital DoFs, and report the experimental demonstration of disorder-immune orbital-induced topological edge states in a zigzag acoustic 1D spinless lattice. This work expands the study of topological phases based on orbitals, paving the way to explore other orbital-dependent phenomena in spinless systems.
The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis
Authors: Elhai Muriel , Micheroli Raphael , Houtman Miranda , Mirrahimi Masoumeh , Moser Larissa , Pauli Chantal , Bürki Kristina , Laimbacher Andrea , Kania Gabriela , Klein Kerstin , Schätzle Philipp , Frank Bertoncelj Mojca , Edalat Sam G. , Keusch Leandra , Khmelevskaya Alexandra , Toitou Melpomeni , Geiss Celina , Rauer Thomas , Sakkou Maria , Kollias George , Armaka Marietta , Distler Oliver , Ospelt Caroline
Published: December 2023

Although patients with rheumatoid arthritis (RA) typically exhibit symmetrical joint involvement, some patients develop alternative disease patterns in response to treatment, suggesting that different molecular mechanism may underlie disease progression depending on joint location. Here, we identify joint-specific changes in RA synovium and synovial fibroblasts (SF) between knee and hand joints. We show that the long non-coding RNA HOTAIR, which is only expressed in knee SF, regulates more than 50% of this site-specific gene expression in SF. HOTAIR is downregulated after stimulation with pro-inflammatory cytokines and is expressed at lower levels in knee samples from patients with RA, compared with osteoarthritis. Knockdown of HOTAIR in knee SF increases PI-Akt signalling and IL-6 production, but reduces Wnt signalling. Silencing HOTAIR inhibits the migratory function of SF, decreases SF-mediated osteoclastogenesis, and increases the recruitment of B cells by SF. We propose that HOTAIR is an important epigenetic factor in joint-specific gene expression in RA.
Tunable ferroelectricity in oxygen-deficient perovskites with Grenier structure
Authors: Shin Yongjin , Galli Giulia
Published: December 2023

Using first-principles calculations, we predict that tunable ferroelectricity can be realized in oxide perovskites with the Grenier structure and ordered oxygen vacancies. Specifically, we show that R1/3A2/3FeO2.67 solids (where R is a rare-earth ion and A an alkaline-earth cation) exhibit polar phases, with a spontaneous polarization tunable by an appropriate choice of R and A. We find that larger cations combined with small R elements lead to a maximum in the polarization and to a minimum in the energy barriers required to switch the sign of the polarization. Ferroelectricity arises from cooperative distortions of octahedral and tetrahedral units, where a combination of rotational and sliding modes controls the emergence of polarization within three-dimensional connected layers. Our results indicate that polar Grenier phases of oxide perovskites are promising materials for microelectronic applications and, in general, for the study of phenomena emerging from breaking inversion symmetry in solids.
Mechanical-electrical-chemical coupling study on the stabilization of a hafnia-based ferroelectric phase
Authors: Bai Fenyun , Liao Jiajia , Yang Jiangheng , Jiang Yanping , Tang Xingui , Liu Qiuxiang , Tang Zhenhua , Zhou Yichun
Published: December 2023

The metastable polar orthorhombic phase is believed to be the origin of the ferroelectricity of hafnia-based films. The adjustment of stain, oxygen vacancies and dopant during film deposition and the wake-up electric cycling are common strategies to induce the ferroelectricity in hafnia. However, none of them could independently render the ferroelectric phase to be the most stable phase from the theoretical calculation results. The exact external conditions to stabilize orthorhombic phase still remain elusive. In this paper, we investigate the effects of the type, distribution, concentration, and charge state characteristics of oxygen vacancies and the uniaxial strain on the crystal’ energy, dielectric constant and spontaneous polarization (Ps); In addition, the impact of the applied electric field parallel to the Ps on the crystal’ energy is explored by first-principles calculations. It is challenging to independently stabilize the ferroelectric phase of hafnia-based films by a single component owing to the rather strict conditions. Surprisingly, the ferroelectricity can be easily obtained when simultaneously considering the effects of oxygen vacancies, uniaxial strain, and applied electric fields, suggesting the extremely important mechanical-electrical-chemical coupling effects. This work provides an explanation for the typical wake-up phenomenon in hafnia and a guidance for film applications.
Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial
Authors: Al-Sawaf Othman , Ligtvoet Rudy , Robrecht Sandra , Stumpf Janina , Fink Anna-Maria , Tausch Eugen , Schneider Christof , Boettcher Sebastian , Mikusko Martin , Ritgen Matthias , Schetelig Johannes , von Tresckow Julia , Vehling-Kaiser Ursula , Gaska Tobias , Wendtner Clemens Martin , Chapuy Bjoern , Fischer Kirsten , Kreuzer Karl-Anton , Stilgenbauer Stephan , Staber Philipp , Niemann Carsten , Hallek Michael , Eichhorst Barbara
Published: December 2023

In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45–82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2–72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study’s primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8–16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4–91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956.
Haplotype-resolved genome of heterozygous African cassava cultivar TMEB117 (Manihot esculenta)
Authors: Landi Michael , Shah Trushar , Falquet Laurent , Niazi Adnan , Stavolone Livia , Bongcam-Rudloff Erik , Gisel Andreas
Published: December 2023

Cassava (Manihot esculenta Crantz) is a vital tropical root crop providing essential dietary energy to over 800 million people in tropical and subtropical regions. As a climate-resilient crop, its significance grows as the human population expands. However, yield improvement faces challenges from biotic and abiotic stress and limited breeding. Advanced sequencing and assembly techniques enabled the generation of a highly accurate, nearly complete, haplotype-resolved genome of the African cassava cultivar TMEB117. It is the most accurate cassava genome sequence to date with a base-level accuracy of QV > 64, N50 > 35 Mbp, and 98.9% BUSCO completeness. Over 60% of the genome comprises repetitive elements. We predicted over 45,000 gene models for both haplotypes. This achievement offers valuable insights into the heterozygosity genome organization of the cassava genome, with improved accuracy, completeness, and phased genomes. Due to its high susceptibility to African Cassava Mosaic Virus (ACMV) infections compared to other cassava varieties, TMEB117 provides an ideal reference for studying virus resistance mechanisms, including epigenetic variations and smallRNA expressions.
The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds
Authors: Prado Pavel , Medel Vicente , Gonzalez-Gomez Raul , Sainz-Ballesteros Agustín , Vidal Victor , Santamaría-García Hernando , Moguilner Sebastian , Mejia Jhony , Slachevsky Andrea , Behrens Maria Isabel , Aguillon David , Lopera Francisco , Parra Mario A. , Matallana Diana , Maito Marcelo Adrián , Garcia Adolfo M. , Custodio Nilton , Funes Alberto Ávila , Piña-Escudero Stefanie , Birba Agustina , Fittipaldi Sol , Legaz Agustina , Ibañez Agustín
Published: December 2023

The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer’s disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson’s disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21–89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.
Condition-dependent survival and movement behavior in an endangered endemic damselfly
Authors: Mahdjoub Hayat , Zebsa Rabah , Kahalerras Amin , Amari Hichem , Bensouilah Soufyane , Samways Michael J. , Khelifa Rassim
Published: December 2023

Movement is essential for the maintenance of populations in their natural habitats, particularly for threatened species living in fluctuating environments. Empirical evidence suggests that the probability and distance of movement in territorial species are context-dependent, often depending on population density and sex. Here, we investigate the movement behavior of the spring cohort of an endangered endemic damselfly Calopteryx exul in a lotic habitat of Northeast Algeria using capture-mark-recapture (CMR) of adults. By sampling 10 gridded river stretches across a 2 km section of the watercourse, we were able to estimate the distance of movement throughout individual lifespans and estimate movement probability for both males and females. We used multistate models to examine whether individual density and sex ratio influence survival and movement probability. We found that males and females had similar movement kernels with most individuals moving short distances (83% performing movements of < 100 m and only 1% > 1000 m). Of the 547 marked individuals, 63% were residents, and 37% were movers (moved at least 50 m from one sampling occasion to another). Survival probability showed higher estimates for females and was slightly density-dependent (i.e., lower survival probabilities were associated with high male densities). Survival probability did not show a marked difference between residents and movers. Movement probability and distances were positively correlated with individual density, but were not or slightly correlated with sex ratio, respectively. These results are not in line with the hypotheses of sex-biased movement and survival costs of movement. Our results suggest that the species performs mostly short-distance movements that are dependent on intraspecific interactions.
Gamma-glutamyl transferase and calculus of kidney incidence: a Mendelian randomization study
Authors: Li Peizhe , Pang Yuewen , He Shuang , Duan Junyao , Gong Huijie , Yan Yongji , Shi Jing
Published: December 2023

Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016–1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070–1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002–1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020–1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.
Distant entanglement via photon hopping in a coupled cavity magnomechanical system
Authors: Sohail Amjad , Peng Jia-Xin , Hidki Abdelkader , Khalid Mohammad , Singh S. K.
Published: December 2023

We theoretically propose a scheme to generate distant bipartite entanglement between various subsystems in coupled magnomechanical systems where both the microwave cavities are coupled through single photon hopping coupling strength Γ. Each cavity contains a magnon mode and phonon mode and this gives six excitation modes in our model Hamiltonian which are cavity-1 photons, cavity-2 photons, magnon and phonon in cavity-1, and magnon and phonon in cavity-2. We found that significant bipartite entanglement exists between indirectly coupled subsystems in coupled microwave cavities for an appropriate set of parameters regime. Moreover, we also obtain suitable cavity and magnon detuning parameters for a significant distant bipartite entanglement in different bipartitions. In addition, it can be seen that a single photon hopping parameter significantly affects both the degree as well as the transfer of quantum entanglement between various bipartitions. Hence, our present study related to coupled microwave cavity magnomechanical configuration will open new perspectives in coherent control of various quantum correlations including quantum state transfer among macroscopic quantum systems.