bluuebunny/crossref_metadata_2025 huggingface dataset:
Processing of corn-based dog foods through pelleting, baking and extrusion and their effect on apparent total tract digestibility and colonic health of adult dogs
Authors: Corsato Alvarenga Isabella , Lierz Ryan , Chen Youhan , Lu Andrea , Lu Nanyan , Aldrich Charles G
Published: March 2024

Different food processing parameters may alter starch granule structure and its cooking degree. With lower thermomechanical energy, more resistant starch (RS) is retained in the food, which may benefit gastrointestinal (GI) health. The objective of this study was to determine the effect of food processing on dietary utilization and dog gut health. Experimental diets containing 56% corn as the sole starch source were produced through pelleting, baking, and extrusion and compared to a baked control diet in which the corn was replaced with dextrose. The extruded diet resulted in the highest level (P < 0.05) of in vitro starch cook and lowest RS, while baked was intermediate and pelleted had the lowest starch cook and highest RS. To evaluate the in vivo effects of these treatments, 12 dogs were adapted to foods for 9 d, and feces were collected for 5 d in a replicated 4 × 4 Latin square design. Feces were scored for consistency using an ordinal scale, and parametric data included apparent digestibility (ATTD), parameters indicative of gut health, and the microbial composition, which was centered log-ratio transformed before operational taxonomic unit (OTU) analyses. Fecal scores were analyzed by ordinal logistic regression, and parametric data were analyzed as mixed models. Overall ATTD was greater (P < 0.05) in extruded, followed by baked and pelleted. Dogs fed the control had osmotic diarrhea, whereas dogs fed the other treatments had mostly acceptable fecal scores, with extrusion leading to the best fecal quality. The control also led to high fecal pH and low SCFAs, indicating dysbiosis. All corn foods had similar (P > 0.05) fecal SCFAs and extruded tended (P = 0.055) to promote higher fecal butyrate than baked and pelleted. The microbiome of dogs fed the corn foods had similar α diversity indices, and OTUs at the species and phyla levels were mostly alike and different from the control. In conclusion, the higher levels of in vitro RS did not translate into a better in vivo fermentation profile, and extruded kibble performed best regarding fecal quality, ATTD, and fecal SCFAs.
From Du Sommerard to Poldi Pezzoli
Authors: Froment Paul
Published: March 2024

During the Bourbon Restoration (1814–30), Alexandre Du Sommerard started collecting antiquarian objects, mainly dating from the medieval period. In 1833 he settled in the Hôtel de Cluny, where he displayed the collection in an imaginative way that aimed to recreate historical installations. Its success was such that, after the death of Du Sommerard in 1842, the hôtel and the collection of decorative arts were bought by the state and opened to the public as the Musée de Cluny in 1844. This new kind of museum offered an influential model for connoisseurs and collectors, among them Gian Giacomo Poldi Pezzoli.
Preferences of bereaved family members on communication with physicians when discontinuing anticancer treatment: referring to the concept of nudges
Authors: Yoshida Saran , Hirai Kei , Ohtake Fumio , Masukawa Kento , Morita Tatsuya , Kizawa Yoshiyuki , Tsuneto Satoru , Shima Yasuo , Miyashita Mitsunori
Published: March 2024

Background

This study aimed to clarify the situation and evaluate the communication on anticancer treatment discontinuation from the viewpoint of a bereaved family, in reference to the concept of nudges.

Methods

A multi-center questionnaire survey was conducted involving 350 bereaved families of patients with cancer admitted to palliative care units in Japan.

Results

The following explanations were rated as essential or very useful: (i) treatment would be a physical burden to the patient (42.9%), (ii) providing anticancer treatment was impossible (40.5%), (iii) specific disadvantages of receiving treatment (40.5%), (iv) not receiving treatment would be better for the patient (39.9%) and (v) specific advantages of not receiving treatment (39.6%). The factors associated with a high need for improvement of the physician’s explanation included lack of explanation on specific advantages of not receiving treatment (β = 0.228, P = 0.001), and lack of explanation of ‘If the patient’s condition improves, you may consider receiving the treatment again at that time.’ (β = 0.189, P = 0.008).

Conclusions

Explaining the disadvantages of receiving treatment and the advantages of not receiving treatment, and presenting treatment discontinuation as the default option were effective in helping patients’ families in making the decision to discontinue treatment. In particular, explanation regarding specific advantages of not receiving treatment was considered useful, as they caused a lower need for improvement of the physicians’ explanation.
The sovereign function test out of thin air? The status of the central bank determined behind the scenes in Certain Iranian Assets
Authors: Nakajima Kei , Okada Yohei , Nisugi Kento
Published: March 2024

On 30 March 2023, the International Court of Justice rendered its judgment on the merits of the case concerning Certain Iranian Assets, in which the Iranian central bank was not characterized as a company within the meaning of the Treaty of Amity. In so concluding, the Court relied upon the test focusing on the central bank’s sovereign functions and the purposes of the transaction at stake. Debate surrounds the origin and sources of inspiration of the sovereign function test, insofar as the majority’s minimum reasoning leaves an impression that it arose from thin air. This article explores the origin and the sources of inspiration of the test, concluding that the Court’s judgment affords the reading that the test was inspired, albeit clandestinely, by rules and practice specifically dedicated to the characterization of central bank activities, located in areas such as the laws of State immunity or responsibility, by judicial cross-referencing.
Empirical Effects of Resale Price Maintenance: Evidence from Fixed Book Price Policies in Europe
Authors: Williams Rhys J
Published: March 2024

This paper investigates the effects of Resale Price Maintenance (RPM) agreements in Europe by studying a legally permitted form of RPM in the book market. In particular, we study the effects of such agreements on prices and sales, finding that countries which have Fixed Book Prices policies witness higher book sales, relative to countries without such a policy, with no noticeable effect on the average price of books. We suggest that the mechanism for these findings is that FBP policies promote non-price competition and a diverse network of retailers, increasing quantity, whereas a change in bargaining power reduces double marginalisation, offsetting upward pricing pressure from RPM. While these results are limited to the book sector and are based on a limited number of countries changing policy, they nonetheless highlight that RPM agreements have the ability to confer positive competition effects and absolute prohibition of such agreements may not always be warranted.
New and Emerging Passive Immunization Strategies for the Prevention of RSV Infection During Infancy
Authors: Domachowske Joseph B
Published: March 2024

To date, safe and effective strategies to prevent medically attended respiratory syncytial virus (RSV) illness across the infant population have been limited to passive immunoprophylaxis for those at highest risk. While active vaccination strategies are finally available to protect adults 60 years and older from serious RSV infection, safe and effective vaccines for use in children have yet to emerge. In contrast, passive immunization strategies designed to protect all infants against RSV has finally met with success, with 2 new strategies approved by the US Food and Drug Administration during the second half of 2023. The first RSV passive immunization strategy to gain licensure for use in all infants is an extended half-life monoclonal antibody directed against an antigenic binding site on the RSV-F prefusion protein, a conformation not known to exist until 2013. The second novel passive immunization strategy approved during 2023 that has the potential to protect much of the infant population from RSV during young infancy centers on boosting preexisting RSV immunity during pregnancy using a prefusion RSV-F vaccine. The resulting boosted humoral immune response to RSV in the mother becomes part of the transplacental antibody endowment that is actively transported across the placenta to provide protection to those babies born at or near term. This review describes how and why these advances came to fruition seemingly “all at once” and provides insight into other passive immunization approaches that remain under development.
A comparative study of star-forming dwarf galaxies using the UVIT
Authors: Amrutha S , Das Mousumi , Yadav Jyoti
Published: March 2024

We present a far-ultraviolet (FUV) study of 16 star-forming dwarf galaxies (SFDGs) using the Ultra Violet Imaging Telescope. Morphologically, SFDGs are classified as dwarf spirals, dwarf irregulars, and blue compact dwarfs (BCDs). We extracted the star-forming complexes (SFCs) from the sample galaxies, derived their sizes, and estimated the FUV + 24 μm star-formation rates (SFRs). We also determined the approximate stellar disc mass associated with the SFCs using Infrared Array Camera 3.6 micron images. We derived the specific SFRs (sSFRs), as well as the SFR densities [Σ(SFR)] for the SFCs. We find that the lower Σ(SFR) for each type is different, with the dwarf irregulars having the lowest Σ(SFR) compared with others. However, the median size of the SFCs in the dwarf irregulars is the largest compared with the other two types when compared at roughly the same distance. We have derived the star-forming main sequence (SFMS) on the scale of SFCs for all three classes of SFDGs. We find that although all SFDGs approximately follow the global SFMS relation, i.e. SFR ∝ M*α (where globally α ≈ 1 for low-surface brightness galaxies and 0.9 for SFDGs), on the scale of SFCs the α value for each type is different. The α values for dwarf spirals, dwarf irregulars, and BCDs are found to be 0.74 ± 0.13, 0.87 ± 0.16, and 0.80 ± 0.19, respectively. However, the age of all SFCs approximately corresponds to 1 Gyr. Finally, we find that the outer SFCs in most galaxies except BCDs have a high sSFR, supporting the inside-out model of galaxy growth.
Spectroscopic diagnostics of lead stratification in hot subdwarf atmospheres
Authors: Scott L J A , Jeffery C S , Byrne C M , Dorsch M
Published: March 2024

Heavy metal subdwarfs are a class of hot subdwarfs with very high abundances of heavy elements, typically around 10 000 times solar. They include stars, which are strongly enhanced in either lead or zirconium, as well as other elements. Vertical stratification of the enhanced elements, where the element is concentrated in a thin layer of the atmosphere, has been proposed as a mechanism to explain the apparent high abundances. This paper explores the effects of the vertical stratification of lead on the theoretical spectra of hot subdwarfs. The concentration of lead in different regions of the model atmosphere is found to affect individual lines in a broadly wavelength-dependent manner, with the potential for lines to display modified profiles depending on the location of lead enhancement in the atmosphere. This wavelength dependence highlights the importance of observations in both the optical and the UV for determining whether stratification is present in real stars.
Swift
: a modern highly parallel gravity and smoothed particle hydrodynamics solver for astrophysical and cosmological applications
Authors: Schaller Matthieu , Borrow Josh , Draper Peter W , Ivkovic Mladen , McAlpine Stuart , Vandenbroucke Bert , Bahé Yannick , Chaikin Evgenii , Chalk Aidan B G , Chan Tsang Keung , Correa Camila , van Daalen Marcel , Elbers Willem , Gonnet Pedro , Hausammann Loïc , Helly John , Huško Filip , Kegerreis Jacob A , Nobels Folkert S J , Ploeckinger Sylvia , Revaz Yves , Roper William J , Ruiz-Bonilla Sergio , Sandnes Thomas D , Uyttenhove Yolan , Willis James S , Xiang Zhen
Published: March 2024

Numerical simulations have become one of the key tools used by theorists in all the fields of astrophysics and cosmology. The development of modern tools that target the largest existing computing systems and exploit state-of-the-art numerical methods and algorithms is thus crucial. In this paper, we introduce the fully open-source highly-parallel, versatile, and modular coupled hydrodynamics, gravity, cosmology, and galaxy-formation code Swift. The software package exploits hybrid shared- and distributed-memory task-based parallelism, asynchronous communications, and domain-decomposition algorithms based on balancing the workload, rather than the data, to efficiently exploit modern high-performance computing cluster architectures. Gravity is solved for using a fast-multipole-method, optionally coupled to a particle mesh solver in Fourier space to handle periodic volumes. For gas evolution, multiple modern flavours of Smoothed Particle Hydrodynamics are implemented. Swift also evolves neutrinos using a state-of-the-art particle-based method. Two complementary networks of sub-grid models for galaxy formation as well as extensions to simulate planetary physics are also released as part of the code. An extensive set of output options, including snapshots, light-cones, power spectra, and a coupling to structure finders are also included. We describe the overall code architecture, summarize the consistency and accuracy tests that were performed, and demonstrate the excellent weak-scaling performance of the code using a representative cosmological hydrodynamical problem with ≈300 billion particles. The code is released to the community alongside extensive documentation for both users and developers, a large selection of example test problems, and a suite of tools to aid in the analysis of large simulations run with Swift.
SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner
Authors: Geng Anke , Sun Jiahui , Tang Huanyin , Yu Yang , Wang Xiyue , Zhang Jingyuan , Wang Xiaona , Sun Xiaoxiang , Zhou Xiaofang , Gao Neng , Tan Rong , Xu Zhu , Jiang Ying , Mao Zhiyong
Published: March 2024

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.
Critical steps in the assembly process of the bacterial 50S ribosomal subunit
Authors: Seffouh Amal , Nikolay Rainer , Ortega Joaquin
Published: March 2024

During assembly, ribosomal particles in bacteria fold according to energy landscapes comprised of multiple parallel pathways. Cryo-electron microscopy studies have identified a critical maturation step that occurs during the late assembly stages of the 50S subunit in Bacillus subtilis. This step acts as a point of convergency for all the parallel assembly pathways of the subunit, where an assembly intermediate accumulates in a ‘locked’ state, causing maturation to pause. Assembly factors then act on this critical step to ‘unlock’ the last maturation steps involving the functional sites. Without these factors, the 50S subunit fails to complete its assembly, causing cells to die due to a lack of functional ribosomes to synthesize proteins. In this review, we analyze these findings in B. subtilis and examine other cryo-EM studies that have visualized assembly intermediates in different bacterial species, to determine if convergency points in the ribosome assembly process are a common theme among bacteria. There are still gaps in our knowledge, as these methodologies have not yet been applied to diverse species. However, identifying and characterizing these convergency points can reveal how different bacterial species implement unique mechanisms to regulate critical steps in the ribosome assembly process.
Defective transfer of parental histone decreases frequency of homologous recombination by increasing free histone pools in budding yeast
Authors: Karri Srinivasu , Yang Yi , Zhou Jiaqi , Dickinson Quinn , Jia Jing , Huang Yuxin , Wang Zhiquan , Gan Haiyun , Yu Chuanhe
Published: March 2024

Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging strands, respectively. Single Dpb3 deletion (dpb3Δ) or Mcm2 mutation (mcm2-3A), which each disrupts one parental histone transfer pathway, leads to the other's predominance. However, the biological impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeast Saccharomyces cerevisiae to determine the genetic and epigenetic outcomes from disruption of parental histone H3–H4 tetramer transfer. We found that a dpb3Δ mcm2-3A double mutant did not exhibit the asymmetric parental histone patterns caused by a single dpb3Δ or mcm2-3A mutation, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower in dpb3Δ, mcm2-3A and dpb3Δ mcm2-3A mutants, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones during DNA replication is essential for maintaining chromatin structure and that lower homologous recombination activity due to parental histone transfer defects is detrimental to cells.
SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer
Authors: Leppänen Noora , Kaljunen Heidi , Takala Eerika , Kaarijärvi Roosa , Mäkinen Petri I , Ylä-Herttuala Seppo , Paatero Ilkka , Paakinaho Ville , Ketola Kirsi
Published: March 2024

The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting in resistance to AR-targeted therapies. In this study, we examined the chromatin landscape of AR-positive prostate cancer cells post-exposure to the AR inhibitor enzalutamide. We identified a novel regulator of cell plasticity, the homeobox transcription factor SIX2, whose motif is enriched in accessible chromatin regions after treatment. Depletion of SIX2 in androgen-independent PC-3 prostate cancer cells induced a switch from a stem-like to an epithelial state, resulting in reduced cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects were mediated through the downregulation of the Wnt/β-catenin signalling pathway and subsequent reduction of nuclear β-catenin. Collectively, our findings provide compelling evidence that the depletion of SIX2 may represent a promising strategy for overcoming the cell plasticity mechanisms driving antiandrogen resistance in prostate cancer.
A phage nucleus-associated RNA-binding protein is required for jumbo phage infection
Authors: Enustun Eray , Armbruster Emily G , Lee Jina , Zhang Sitao , Yee Brian A , Malukhina Kseniya , Gu Yajie , Deep Amar , Naritomi Jack T , Liang Qishan , Aigner Stefan , Adler Benjamin A , Cress Brady F , Doudna Jennifer A , Chaikeeratisak Vorrapon , Cleveland Don W , Ghassemian Majid , Bintu Bogdan , Yeo Gene W , Pogliano Joe , Corbett Kevin D
Published: March 2024

Large-genome bacteriophages (jumbo phages) of the proposed family Chimalliviridae assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and DNA-targeting CRISPR-Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment for translation by host ribosomes, and transport of specific proteins into the nucleus-like compartment to support DNA replication and mRNA transcription. Here, we identify a conserved phage nuclear shell-associated protein that we term Chimallin C (ChmC), which adopts a nucleic acid-binding fold, binds RNA with high affinity in vitro, and binds phage mRNAs in infected cells. ChmC also forms phase-separated condensates with RNA in vitro. Targeted knockdown of ChmC using mRNA-targeting dCas13d results in accumulation of phage-encoded mRNAs in the phage nucleus, reduces phage protein production, and compromises virion assembly. Taken together, our data show that the conserved ChmC protein plays crucial roles in the viral life cycle, potentially by facilitating phage mRNA translocation through the nuclear shell to promote protein production and virion development.
Low Level Viremia Is Associated With Serious non-AIDS Events in People With HIV
Authors: Ganesan Anuradha , Hsieh Hsing-Chuan , Chu Xiuping , Colombo Rhonda E , Berjohn Catherine , Lalani Tahaniyat , Yabes Joseph , Joya Christie A , Blaylock Jason , Agan Brian K
Published: March 2024

Background

The consequences of low-level viremia in people with HIV are unclear. We used data from the US Military HIV Natural History Study to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs).

Methods

Included participants initiated antiretroviral therapy after 1996 and had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after antiretroviral therapy initiation. VLs were categorized as lower levels of LLV (51–199 copies/mL), higher level of low-level viremia (HLLV; 200–999 copies/mL), and (VF; ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS; ie, VL <50 copies/mL). Viral blips (ie, VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL) were analyzed in the VS category. Cox proportional hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% confidence intervals are presented.

Results

A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3 [1.2–1.4]), HLLV (1.6 [1.5–1.7]), and virologic failure (1.7 [1.7–1.8]).

Conclusions

The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.
Influence of egg sacs on the swimming performance of freshwater cyclopoid copepods
Authors: Svetlichny Leonid , Obertegger Ulrike
Published: March 2024

Female cyclopoid copepods carry their embryos in egg sacs that impact swimming performance until nauplii hatch. We studied kinematic parameters and mechanical energy of small routine jumps and large escape jumps of non-egg-carrying (NEC) and egg-carrying (EC) females of Mesocyclops leuckarti and Macrocyclops albidus. The drag and body acceleration costs for EC females of M. leuckarti and M. albidus during routine jumps were 28 and 40%, respectively, higher than those for NEC females moving at the same speed. Maintaining position in the water column by small jumps was more costly for EC females, requiring 2.2–2.3 times more jumps and energy. Consequently, the persistence of EC females was limited in the open water. In M. leuckarti and M. albidus, the average speed and distances of jumps were 5–6 and 1.5–2.2 times higher, respectively, and the duration of jumps was 2.2–2.5 times shorter during escape than routine swimming. The maximum jumping speeds of NEC females, 40.6 and 50.5 cm s−1, respectively, were 12–14% higher than those of EC females, whereas their power and cost of transport were 16 and 23% lower, respectively. These results clearly indicated that egg sacs impair swimming and increase energetic costs of movement.
Dysfunction of striatal parvalbumin interneurons drives motor stereotypies in Cntnap2−/− mouse model of autism spectrum disorders
Authors: Thabault Mathieu , Fernandes-Gomes Cloé , Huot Anne-Lise , Francheteau Maureen , Balbous-Gautier Anaïs , Fernagut Pierre-Olivier , Galvan Laurie
Published: March 2024

The involvement of parvalbumin (PV) interneurons in autism spectrum disorders (ASD) pathophysiology has been widely described without clearly elucidating how their dysfunctions could lead to ASD symptoms. The Cntnap2−/− mice, an ASD mouse model deficient for a major ASD susceptibility gene, display core ASD symptoms including motor stereotypies, which are directly linked to striatal dysfunction. This study reveals that striatal PV interneurons display hyperexcitability and hyperactivity in Cntnap2−/− mice, along with a reduced response in medium spiny neurons. We also provide evidence for a crucial role of striatal PV interneurons in motor stereotypies by demonstrating that their selective inhibition rescued a wild type-like phenotype. Our study identifies how PV interneuron dysfunctions disrupt striatal circuitry and drive the motor stereotypies in ASD.
The Labor Market Effects of Loan Guarantee Programs
Authors: Barrot Jean-Noël , Martin Thorsten , Sauvagnat Julien , Vallée Boris
Published: March 2024

We investigate the labor market effects of a loan guarantee program targeting French SMEs during the financial crisis. Exploiting differences in regional treatment intensity in a border discontinuity design, we uncover a central trade-off for such interventions. While the program has a positive impact on workers’ employment and earnings trajectories that translates into positive aggregate employment effects, it dampens the worker reallocation toward more productive firms that happens following recessions, and particularly so for high-skill workers. This labor allocation effect is economically significant and translates into a reduction in aggregate productivity.
Performance evaluation of computed tomography scanners in Indonesia: recommendation from a nation-wide study
Authors: Lubis Lukmanda Evan , Rafika Rafika , Noerwasana Adi Dradjat , Suryanti Rini , Soejoko Djarwani Soeharso
Published: March 2024

In this study, an evaluation of the compliance test data from 684 computed tomography (CT)-scanners in Indonesia for the 2019–22 test period was carried out. The study was aimed to describe the performance profile of CT-scanners in Indonesia and evaluate the testing protocol. A total of 87.8% of the CT-scanners unconditionally passed the tests, 8.8% passed the tests with conditions and 3.4% failed the tests. Of the devices conditionally passed the tests, the top two causes were water CT number accuracy (45.2%) and laser position accuracy (41.9%). Meanwhile, 75.0% of the failed devices were due to failing to meet the patient dose test criteria. The failure of the test for the water CT number accuracy parameter was caused by variations in the type of phantom used in the test, where several types of phantoms did not use water as material of the homogeneity module. Failures in laser position accuracy test were caused by the passing criteria that adjust to the minimum slice thickness, so that modern CT-scanner with small detector sizes and collimations tend not to pass. On the other hand, the failure on dose aspects was due to the frequent unavailability of baseline values for comparison. Of these top three failure causes, two of them, namely the CT number and dose test parameters, have been accommodated in the latest regulation (BAPETEN Regulation No. 2/2022) with a change in the evaluation method, while for the laser position accuracy test it is recommended to alter the passing criteria to an absolute value, namely 1 mm.
Study on the Extrapolability of Current Tumorgenicity Test With Mice by Comparing the Syngeneic or Allogeneic Mouse Transplantation Model
Authors: Tamura Takashi , Tahara Tsuyoshi , Inoue Michiko , Nanjo Ryota , Onoe Hirotaka , Yamamoto Takako , Kawamata Shin
Published: March 2024

The extrapolability of the current tumorigenicity test performed by transplanting human cell product into immunodeficient (NOG) mice was investigated. For this purpose, the susceptibility to form teratomas of NOG mice was assessed by transplanting undifferentiated human-induced pluripotent stem cells (hiPSCs) as positive control cells via the liver, striatum, or tail vein and evaluating the TPD50 value (dose required to form teratomas in half of the transplanted mice). This was then compared to the TPD50 of syngeneic or allogeneic mouse models. The TPD50 of C57/BL/6(B6)-iPSC or 129/Ola(129)-embryonic stem cell (ESC) transplanted into the liver of syngeneic mice was 4.08 × 105 and 4.64 × 104 cells, respectively, while the TPD50 of hiPSC administered into the liver of NOG mice was 4.64 × 104 cells. The TPD50 of B6-miPSC-synergic, 129-mESC-synergic, or 129-cell/B6 allogeneic transplantation into the striatum was 5.09 × 102, 1.0 × 104, and 3.73 × 104 cells, respectively, while that of hiPSC/NOG mice was 1.0 × 103 cells. The TPD50 for B6-miPSC or 129-mESC syngeneic tail vein infusion was 3.16 × 106 or 5.62 × 106 cells, respectively, while no incidence was observed from 1 × 107 B6-miPSCs in 129 mice or hiPSCs in NOG mice infusion study. Although the number of data sets was limited, these data indicate that the teratoma formation from transplanted undifferentiated hiPSCs via the liver or striatum in NOG mice is comparable to that in syngeneic or allogeneic mouse transplantation model, suggesting that the result of the current tumorigenicity test in NOG mice would provide useful information to infer the incidence of teratoma from residual undifferentiated hPSCs in hPSC-derived products after transplantation.
Chitosan and Grifola Frondosa nanoparticles insulate liver dysfunction in EAC-bearing mice
Authors: Radwan Aliaa M , Gebreel Doaa T , Allam Sahar , El-Atrash Afaf , Tousson Ehab
Published: March 2024

Background

Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and Grifola Frondosa have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice.

Methods

A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs.

Results

According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice.

Conclusions

Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.
Further draining of Discocyrtus to expand Neopachylinae (Opiliones, Gonyleptidae): absorption of taxa and establishment of new genera and species
Authors: Carvalho Rafael N , Kury Adriano B
Published: March 2024

The gonyleptids are one of the most diverse groups of harvestmen, exhibiting a vast range of sizes, shapes and behaviors. However, its internal classification, earlier based on meristic characters, particularly in larger groups such as Pachylinae and Discocyrtus, has been called into question by new proposals that consider morphological and molecular synapomorphies. Here, we aspire to evaluate the transfer of seven species currently classified under Discocyrtus sensu lato and the monotypic genus Oliverius from Pachylinae to Neopachylinae. Additionally, we propose the inclusion of two new species in Neopachylinae. To test our hypothesis, we expand upon previous cladistic analyses using maximum parsimony and incorporate 40 terminals representing Gonyleptoidea, including all existing members of Neopachylinae, and 116 morphological characters. Our results confirm the hypothesis of monophyly of Neopachylinae after the inclusion of the new and transferred taxa. To provide a comprehensive assessment of the results, we update some diagnoses at the genus and species-level within Neopachylinae. Furthermore, to accommodate the taxonomic changes resulting from this study, we propose 1) the establishment of two new genera, 2) the reassignment of five taxa at the generic level, and 3) the establishment of two new junior subjective synonymies at the species level.
Magnetic resonance imaging-based rim enhancement could effectually predict poor prognosis in hepatocellular carcinoma: a meta-analysis
Authors: Lu Yumin , Cen Yongyi , He Xin , Mo Xiaping , Luo Fang , Zhong Yubao
Published: March 2024

Recent studies have initially shown that MRI-based rim enhancement associates with poor prognosis in hepatocellular carcinoma (HCC) patients, but their sample sizes are small, leading to a necessary of comprehensive analyses to make a relatively solid statement. Thus, this meta-analysis aimed to summarize the correlation between MRI-based rim enhancement and prognosis in HCC patients. Until March 2023, a literature search was conducted on Web of Science, PubMed, EMBASE, Cochrane, CNKI, Wangfang, and CQVIP databases in order to identify studies that report the correlation between MRI-based rim enhancement and the prognosis of HCC patients. MRI-based rim enhancement and prognostic data were extracted and analyzed. In our study, eight studies containing 1816 HCC patients were analyzed. Generally, the presence of MRI-based rim enhancement was related to shortened disease-free survival (DFS) [hazard ratio (HR): 2.77, 95% confidence interval (CI): 2.11–3.62, P < 0.001], and worse overall survival (OS) (HR: 5.43, 95% CI: 2.14–13.79, P < 0.001). While no other prognostic data could be retrieved. Funnel plots, Begg’s test, and Egger’s test all indicated that no publication bias existed; and the risk score by Newcastle-Ottawa Scale criteria ranged from 7–9 points, suggesting a generally low risk of bias. Meanwhile, the sensitivity analysis showed that the significant findings did not change by omitting each study. Then, subgroup analyses revealed that no matter stratified by tumor size, treatment option, or sample size, rim enhancement was linked with unsatisfied DFS (all P < 0.05). Conclusively, MRI-based rim enhancement could effectually estimate poor survival in HCC patients, indicating its good prognostic value.
Prognostic analysis of sex and age in hepatocellular carcinoma: a SEER study
Authors: Chen Jun , Wang Xiao , Ye Wenyi
Published: March 2024

Objectives

This study aimed to explore the impact of sex on clinical features and survival among hepatocellular carcinoma (HCC) patients.

Methods

HCC case data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2010 to 2015 were selected for analysis. Kaplan–Meier curves displayed overall survival. Univariate cox regression examined the prognostic characteristics of individual features, and multivariate Cox regression assessed hazard ratios.

Results

This study comprised 3486 HCC patients, with 2682 males and 804 females. Across all age groups, there was a higher prevalence of males compared to females. Survival curves among female patients showed no significant differences across various age groups. However, among male patients, those under 60 demonstrated notably higher survival rates compared to those aged 60 and above. Regarding various ethnicities, TNM staging systems, tumor sizes, the presence of lung/bone/brain metastases, location in Purchased/Referred Care Delivery Areas, SEER historic stages, tumor grades, and individuals receiving chemotherapy, the proportion of male patients consistently exceeded that of female patients. Within the female patient group, individuals receiving chemotherapy exhibited significantly higher survival rates compared to those who did not. However, the administration of chemotherapy showed no significant impact on the survival rate of male patients. Multivariate Cox regression analysis revealed age, gender, and the administration of chemotherapy key factors influencing the overall survival prognosis.

Conclusion

Age, gender, and the administration of chemotherapy are influential factors in the prognosis of both male and female HCC patients.
Assessing Spns2-dependent S1P Transport as a Prospective Therapeutic Target
Authors: Kharel Y , Huang T , Dunnavant K , Foster D , Souza GMPR , Nimchuk KE , Merchak AR , Pavelec CM , Juskiewicz ZJ , Gaultier A , Abbott SBG , Shin J-B , Isakson BE , Xu W , Leitinger N , Santos WL , Lynch KR
Published: March 2024

S1P (sphingosine 1-phosphate) receptor modulator (SRM) drugs interfere with lymphocyte trafficking by downregulating lymphocyte S1P receptors. While the immunosuppressive activity of SRM drugs has proved useful in treating autoimmune diseases such as multiple sclerosis, that drug class is beset by on-target liabilities such as initial dose bradycardia. The S1P that binds to cell surface lymphocyte S1P receptors is provided by S1P transporters. Mice born deficient in one of these, spinster homolog 2 (Spns2), are lymphocytopenic and have low lymph S1P concentrations. Such observations suggest that inhibition of Spns2-mediated S1P transport might provide another therapeutically beneficial method to modulate immune cell positioning. We report here results using a novel S1P transport blocker (STB), SLF80821178, to investigate the consequences of S1P transport inhibition in rodents. We found that SLF80821178 is efficacious in a multiple sclerosis model but – unlike the SRM fingolimod – neither decreases heart rate nor compromises lung endothelial barrier function. Notably, although Spns2 null mice have a sensorineural hearing defect, mice treated chronically with SLF80821178 have normal hearing acuity. STBs such as SLF80821178 evoke a dose-dependent decrease in peripheral blood lymphocyte counts, which affords a reliable pharmacodynamic marker of target engagement. However, the maximal reduction in circulating lymphocyte counts in response to SLF80821178 is substantially less than the response to SRMs such as fingolimod (50% vs. 90%) due to a lesser effect on T lymphocyte sub-populations by SLF80821178. Finally, in contrast to results obtained with Spns2 deficient mice, lymph S1P concentrations were not significantly changed in response to administration of STBs at doses that evoke maximal lymphopenia, which indicates that current understanding of the mechanism of action of S1P transport inhibitors is incomplete.
Particulate matter constituents trigger the formation of extracellular amyloid β and Tau-containing plaques and neurite shorteningin vitro
Authors: Sebastijanović Aleksandar , Camassa Laura Maria Azzurra , Malmborg Vilhelm , Kralj Slavko , Pagels Joakim , Vogel Ulla , Zienolddiny-Narui Shan , Urbančič Iztok , Koklič Tilen , Štrancar Janez
Published: March 2024

Introduction

Air pollution is an environmental factor associated with Alzheimer’s disease, characterized by decreased cognitive abilities and memory. The limited models of sporadic Alzheimer’s disease fail to replicate all pathological hallmarks of the disease, making it challenging to uncover potential environmental causes. Environmentally driven models of Alzheimer’s disease are thus timely and necessary.

Methods

We used live-cell confocal fluorescent imaging combined with high-resolution stimulated emission depletion (STED) microscopy to follow the response of neuron-like cells to nanomaterial exposure. Here, we report that a high dose ratein vitroexposure of neuron-like cells to particulate matter constituents reproduces neurodegenerative phenotype, including extracellular amyloid-β containing plaques and decreased neurite length.

Results

Consistent with the existingin vivoresearch, we observed detrimental effects, specifically a substantial reduction in neurite length and formation of amyloid beta plaques, after exposure to iron oxide and diesel exhaust particles. Conversely, after exposure to engineered cerium oxide nanoparticles, the lengths of neurites were maintained, and almost no extracellular amyloid beta plaques were formed.

Discussion

Although the exact mechanism behind this effect remains to be explained, the high dose ratein vitromodel, comprising wild-type neuron-like cells, could serve as an alternative environmentally driven model of Alzheimer’s disease.

Abstract Figure

Graphical abstract

High dose ratein vitroexposure of neuron-like cells to particulate matter constituents, like diesel exhaust and iron oxide nanoparticles, reproduces neurodegenerative phenotype, including extracellular amyloid-β-containing plaques and reduction in neurite length and density.
Pitfalls and windfalls of detecting demographic declines using population genetics in long-lived species
Authors: Clark Meaghan I. , Fitzpatrick Sarah W. , Bradburd Gideon S.
Published: March 2024

Detecting recent demographic changes is a crucial component of species conservation and management, as many natural populations face declines due to anthropogenic habitat alteration and climate change. Genetic methods allow researchers to detect changes in effective population size (Ne) from sampling at a single timepoint. However, in species with long lifespans, there is a lag between the start of a decline in a population and the resulting decrease in genetic diversity. This lag slows the rate at which diversity is lost, and therefore makes it difficult to detect recent declines using genetic data. However, the genomes of old individuals can provide a window into the past, and can be compared to those of younger individuals, a contrast that may help reveal recent demographic declines. To test whether comparing the genomes of young and old individuals can help infer recent demographic bottlenecks, we use forward-time, individual-based simulations with varying mean individual lifespans and extents of generational overlap. We find that age information can be used to aid in the detection of demographic declines when the decline has been severe. When average lifespan is long, comparing young and old individuals from a single timepoint has greater power to detect a recent (within the last 50 years) bottleneck event than comparing individuals sampled at different points in time. Our results demonstrate how longevity and generational overlap can be both a hindrance and a boon to detecting recent demographic declines from population genomic data.
Beyond enumeration: Phenotype independent “labeling-capture-release” process enabling precise detection of circulating tumour cells and downstream applications
Authors: Lao Zhiqi , Ren Xiaoxue , Zhuang Dehua , Xie Lingxia , Zhang Yucong , Li Wei , Jiang Zhenyou , Chen Yue , Li Penghui , Tong Liping , Chu Paul K. , Wang Huaiyu
Published: March 2024

Although strategies for circulating tumor cells (CTCs) enrichment have been proposed, the practical effects of clinical CTCs detection are far from satisfactory. Generally, the methodologies for CTCs detection aim at naturally occurring targets, but misdetection/interferences are prevalent due to the diverse phenotypes and subpopulations of CTCs with high heterogeneity. Herein, a CTCs isolation system based on the “labeling-capture-release” process is demonstrated for precise and high-efficient enrichment of CTCs from clinical blood samples. The mechanism which is based on abnormal glyco-metabolism of tumor cells including CTCs can be utilized for the surface decoration of CTCs with artificial azido groups. With the aid of bio-orthogonal plates designed with DBCO- and disulfide groups and exploiting the anti-fouling effects, the cells labeled with azido groups can be capturedviaa copper-free click reaction and released in a non-destructive manner during subsequent disulfide reduction. The technique is demonstrated to label multiple different types of tumor cells with the EpCAM+/- phenotypes and adherent/suspended status, and all the epithelial/interstitial/hybrid phenotypes of CTCs can be separated from clinical blood samples from 25 patients with 10 different cancer types. Moreover, our strategy is superior to the clinically approved CTCs detection system from the perspective of broad-spectrum and accurate recognition of heterogeneous CTCs. The capturing efficiency of this isolation system is over 80% and the release efficiency exceeds 90%. Most of the released CTCs survive with maintained glycolytic activity thus boding well for downstream applications such as drug susceptibility tests using viable CTCs.
Network medicine informed multi-omics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis
Authors: Yu Mucen , Xu Jielin , Dutta Ranjan , Trapp Bruce , Pieper Andrew A. , Cheng Feixiong
Published: March 2024

Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. To date, the challenge to establishing effective treatment for ALS remains formidable, partly due to inadequate translation of existing human genetic findings into actionable ALS-specific pathobiology for subsequent therapeutic development. This study evaluates the feasibility of network medicine methodology via integrating human brain-specific multi-omics data to prioritize drug targets and repurposable treatments for ALS. Using human brain-specific genome-wide quantitative trait loci (x-QTLs) under a network-based deep learning framework, we identified 105 putative ALS-associated genes enriched in various known ALS pathobiological pathways, including regulation of T cell activation, monocyte differentiation, and lymphocyte proliferation. Specifically, we leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on brain-specific expression quantitative trait loci (QTL) (eQTL), protein QTLs (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL). Applying network proximity analysis of predicted ALS-associated gene-coding targets and existing drug-target networks under the human protein-protein interactome (PPI) model, we identified a set of potential repurposable drugs (including Diazoxide, Gefitinib, Paliperidone, and Dimethyltryptamine) for ALS. Subsequent validation established preclinical and clinical evidence for top-prioritized repurposable drugs. In summary, we presented a network-based multi-omics framework to identify potential drug targets and repurposable treatments for ALS and other neurodegenerative disease if broadly applied.