bluuebunny/crossref_metadata_2025 huggingface dataset:
New method of using a convolutional neural network for 2D intraprostatic tumor segmentation from PET images
Authors: Rainio Oona , Lahti Jari , Anttinen Mikael , Ettala Otto , Seppänen Marko , Boström Peter , Kemppainen Jukka , Klén Riku
Published: October 2023

Purpose

A new method of using a convolutional neural network (CNN) to perform automatic tumor segmentation from two-dimensional transaxial slices of positron emission tomography (PET) images of high-risk primary prostate cancer patients is introduced.

Methods

We compare three different methods including (1) usual image segmentation with a CNN whose continuous output is converted to binary labels with a constant threshold, (2) our new technique of choosing separate thresholds for each image PET slice with a CNN to label the pixels directly from the PET slices, and (3) the combination of the two former methods based on using the second CNN to choose the optimal thresholds to convert the output of the first CNN. The CNNs are trained and tested multiple times by using a data set of 864 slices from the PET images of 78 prostate cancer patients.

Results

According to our results, the Dice scores computed from the predictions of the second method are statistically higher than those of the typical image segmentation (p-value<0.002).

Conclusion

The new method of choosing unique thresholds to convert the pixels of the PET slices directly into binary tumor masks is not only faster and more computationally efficient but also yields better results.
Cardiovascular safety of psychedelic medicine: current status and future directions
Authors: Wsół Agnieszka
Published: October 2023

Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number of recent studies, due to the indisputable resurgence of serotonergic hallucinogens, have shown their efficacy in alleviating depression, anxiety, substance abuse therapies, and existential distress treatment in patients facing life-threatening illness. Psychedelics are generally considered to be physiologically safe with low toxicity and low addictive potential. However, their agonism at serotonergic receptors should be considered in the context of possible serotonin-related cardiotoxicity (5-HT2A/2B and 5-HT4 receptors), influence on platelet aggregation (5-HT2A receptor), and their proarrhythmic potential. The use of psychedelics has also been associated with significant sympathomimetic effects in both experimental and clinical studies. Therefore, the present review aims to provide a critical discussion of the cardiovascular safety of psilocybin, d-lysergic acid diethylamide (LSD), N,N-dimethyltryptamine, ayahuasca, and mescaline, based on the results of experimental research and clinical trials in humans. Experimental studies provide inconsistent information on the potential cardiovascular effects and toxicity of psychedelics. Data from clinical trials point to the relative cardiovascular safety of psychedelic-assisted therapies in the population of “healthy” volunteers. However, there is insufficient evidence from therapies carried out with microdoses of psychedelics, and there is still a lack of data on the safety of psychedelics in the population of patients with cardiovascular disease. Therefore, the exact determination of the cardiovascular safety of psychedelic therapies (especially long-term therapies) requires further research.
Responsiveness to Coethnics and Cominorities: Evidence from an Audit Experiment of State Legislators
Authors: Rivera-Burgos Viviana , Rubio Julia María
Published: October 2023

How do legislators respond to coethnic and cominority constituents? We conduct an audit study of all state legislators to explore white legislators’ responsiveness to different minority groups and minority group legislators’ responsiveness to each other. Black and Latino Americans currently make up about one-third of the overall U.S. population and an even larger share of some state populations. In light of this growing diversification of the American electorate, legislators may have incentives to appeal to a broad racial constituency. In our experiment, state legislators are randomly assigned to receive an email from a white, Black, or Latino constituent. Our findings suggest a lack of legislators’ discrimination, on average, against Black relative to white constituents. Instead, we find that all legislators, on average, respond more to both white and Black constituents relative to Latinos. The evidence suggests that Black legislators do not exhibit coethnic solidarity toward their Black constituents or cominority solidarity toward their Latino constituents; however, Latinos do exhibit coethnic and cominority solidarity (though there are too few Latino legislators to definitively establish this claim). We also estimate effects among white legislators by party and racial composition of districts in order to provide suggestive evidence for white legislators’ intrinsic vs. strategic motivations.
Photography, Film and Storytelling of Posthuman Crises in Blade Runner
Authors: He Kanjing
Published: October 2023

Blade Runner (1982), directed by Ridley Scott and adapted from Philip K. Dick’s Do Androids Dream of Electric Sheep? (1968), incorporates the media of film and photography and utilizes various filmmaking techniques, including cinematography, sound effects, and dialogues, to reflect on the complex relationship between humans, technology and power. Through cinematographic techniques such as light and dark contrast, shifting eye-level and high camera angles, as well as geometric patterns, the film portrays a technologically-advanced futuristic city and its underlying issues of power struggles and social hierarchy. The portrayal of replicants, through static and moving images and sound effects, emphasizes their close resemblance to humans, particularly their performance of emotions, and how technology alters the fundamental concept of humanity. Photography, as a medium, captures an unreliable and incomplete moment of childhood to expose the dystopian nightmare of memory manipulation that severs the connection between memory and identity. This article analyses Blade Runner as an intermedial narrative that highlights the tension between the deceptive appearance of a futuristic city, with flying cars, replicants, and other technologies created for human convenience, and the harsh reality of posthuman crises such as social hierarchy, technological dominance, memory manipulation, and replicant rebellion.
The immigrant versus the state: The marginal contribution of tribunal judges to administrative justice
Authors: Tomkinson Sule , Paquet Mireille , Robert Laurence
Published: October 2023

Administrative tribunal judges determine rights and entitlements regarding bureaucratic decisions. In immigration appeal cases, they review negative decisions of permanent residency acquisition and family reunification. Based on an analysis of all immigration appeal decisions in Canada’s Quebec province over a period of twenty-three years, we find that tribunal judges confirm the bureaucratic decision in the vast majority of cases, noting the migrants’ inability to meet the annual income requirements, and rarely reverse the decision in favour of migrants. Documenting the marginal contribution of tribunal judges to promoting administrative justice, this article contributes to the debate on whether and how courts can advance immigrants’ rights.
Highly sensitive flexible heat flux sensor based on a microhole array for ultralow to high temperatures
Authors: Li Le , Tian Bian , Zhang Zhongkai , Shi Meng , Liu Jiangjiang , Liu Zhaojun , Lei Jiaming , Li Shuimin , Lin Qijing , Zhao Libo , Jiang Zhuangde
Published: October 2023

With the growing demand for thermal management of electronic devices, cooling of high-precision instruments, and biological cryopreservation, heat flux measurement of complex surfaces and at ultralow temperatures has become highly imperative. However, current heat flux sensors (HFSs) are commonly used in high-temperature scenarios and have problems when applied in low-temperature conditions, such as low sensitivity and embrittlement. In this study, we developed a flexible and highly sensitive HFS that can operate at ultralow to high temperatures, ranging from −196 °C to 273 °C. The sensitivities of HFSs with thicknesses of 0.2 mm and 0.3 mm, which are efficiently manufactured by the screen-printing method, reach 11.21 μV/(W/m2) and 13.43 μV/(W/m2), respectively. The experimental results show that there is a less than 3% resistance change from bending to stretching. Additionally, the HFS can measure heat flux in both exothermic and absorptive cases and can measure heat flux up to 25 kW/m2. Additionally, we demonstrate the application of the HFS to the measurement of minuscule heat flux, such as heat dissipation of human skin and cold water. This technology is expected to be used in heat flux measurements at ultralow temperatures or on complex surfaces, which has great importance in the superconductor and cryobiology field.
Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: results from the phase 3 CORAL study
Authors: Parikh Sagar V. , Aaronson Scott T. , Mathew Sanjay J. , Alva Gustavo , DeBattista Charles , Kanes Stephen , Lasser Robert , Bullock Amy , Kotecha Mona , Jung JungAh , Forrestal Fiona , Jonas Jeff , Vera Theresa , Leclair Bridgette , Doherty James
Published: October 2023

Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized 1:1 to once-daily, blinded zuranolone+ADT or placebo+ADT for 14 days, then continued open-label SOC ADT for 28 more days. The primary endpoint was change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 3. Among 425 patients in the full analysis set, CFB in HAMD-17 total score at Day 3 was significantly improved with zuranolone+ADT vs placebo+ADT (least squares mean [standard error], −8.9 [0.39] vs −7.0 [0.38]; p = 0.0004). The majority of patients receiving zuranolone+ADT that experienced treatment-emergent adverse events (TEAEs) reported mild or moderate events. The most common TEAEs present in ≥10% of patients in either zuranolone+ADT or placebo+ADT groups were somnolence, dizziness, headache, and nausea. These results demonstrate that zuranolone+ADT provided more rapid improvement in depressive symptoms compared with placebo+ADT in patients with MDD, with a safety profile consistent with previous studies. Clinical trial registration: ClinicalTrials.gov identifier: NCT04476030.
PTEN-regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression
Authors: Miller Karina A. , Degan Seamus , Wang Yanqing , Cohen Joseph , Ku Sheng Yu , Goodrich David W. , Gelman Irwin H.
Published: October 2023

PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/RbPE:−/− mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:−/− mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110β and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4, a known PC metastasis suppressor. In contrast, PTEN expression, which dampened these oncogenic behaviors, correlated with greater dependence on p110α plus AKT1. Our data suggest that metastatic PC aggressiveness is controlled by specific PI3K/AKT isoform combinations influenced by divergent Src activation or PTEN-loss pathways.
Long-term immune response to SARS-CoV-2 infection and vaccination in children and adolescents
Authors: Messiah Sarah E. , Talebi Yashar , Swartz Michael D. , Sabharwal Rachit , Han Haoting , Bergqvist Emma , Kohl Harold W. , Valerio-Shewmaker Melissa , DeSantis Stacia M. , Yaseen Ashraf , Kelder Steven H. , Ross Jessica , Padilla Lindsay N. , Gonzalez Michael O. , Wu Leqing , Lakey David , Shuford Jennifer A. , Pont Stephen J. , Boerwinkle Eric
Published: October 2023

Background

This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents.

Methods

Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed.

Results

N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20).

Conclusions

This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules.

Impact

This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection.

Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti–SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months.

This information can inform future SARS-CoV-2 vaccination schedules in this age group.
DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation
Authors: Zhang Qun , Feng Ping , Zhu Xun-Hua , Zhou Shi-Qing , Ye Ming-Liang , Yang Xiao-Jing , Gong Sha , Huang Sheng-Yan , Tan Xi-Rong , He Shi-Wei , Li Ying-Qing
Published: October 2023

Emerging evidence indicates that DNA methylation plays an important role in the initiation and progression of nasopharyngeal carcinoma (NPC). DNAJA4 is hypermethylated in NPC, while its role in regulating NPC progression remains unclear. Here, we revealed that the promoter of DNAJA4 was hypermethylated and its expression was downregulated in NPC tissues and cells. Overexpression of DNAJA4 significantly suppressed NPC cell migration, invasion, and EMT in vitro, and markedly inhibited the inguinal lymph node metastasis and lung metastatic colonization in vivo, while it did not affect NPC cell viability and proliferation capability. Mechanistically, DNAJA4 facilitated MYH9 protein degradation via the ubiquitin-proteasome pathway by recruiting PSMD2. Furthermore, the suppressive effects of DNAJA4 on NPC cell migration, invasion, and EMT were reversed by overexpression of MYH9 in NPC cells. Clinically, a low level of DNAJA4 indicated poor prognosis and an increased probability of distant metastasis in NPC patients. Collectively, DNAJA4 serves as a crucial driver for NPC invasion and metastasis, and the DNAJA4-PSMD2-MYH9 axis might contain potential targets for NPC treatments.
Enhanced adhesion of PEDOT:PSS to substrates using polydopamine as a primer
Authors: Carter Joseph L. , Kelly Catherine A. , Jenkins Mike J.
Published: October 2023

Utilization of the conducting polymer PEDOT:PSS in flexible optoelectronic devices is hindered by poor adhesion to flexible, polymer-based substrates. In this communication, the ability of poly(dopamine) (PDA) to act as a primer and improve adhesion is probed. The presence of hydrophilic PDA on the surface of the substrate increased the wettability of polypropylene (PP); however, it was reduced for poly(ethylene terephthalate) (PET). Despite this, PDA was established as an effective primer to improve the quality and adhesion of pristine PEDOT:PSS and PEDOT:PSS/Tween 80 films on glass, PP and PET substrates. In addition, PDA did not negatively impact the sheet resistance of the PEDOT:PSS/Tween 80 films, indicating its suitability as a primer in flexible optoelectronic devices.
Enhanced brain structure-function tethering in transmodal cortex revealed by high-frequency eigenmodes
Authors: Yang Yaqian , Zheng Zhiming , Liu Longzhao , Zheng Hongwei , Zhen Yi , Zheng Yi , Wang Xin , Tang Shaoting
Published: October 2023

While the link between brain structure and function remains an ongoing challenge, the prevailing hypothesis is that the structure-function relationship may itself be gradually decoupling from unimodal to transmodal cortex. However, this hypothesis is constrained by the underlying models which may neglect requisite information. Here we relate structural and functional connectivity derived from diffusion and functional MRI through orthogonal eigenmodes governing frequency-specific diffusion patterns. We find that low-frequency eigenmodes contribute little to functional interactions in transmodal cortex, resulting in divergent structure-function relationships. Conversely, high-frequency eigenmodes predominantly support neuronal coactivation patterns in these areas, inducing structure-function convergence along a unimodal-transmodal hierarchy. High-frequency information, although weak and scattered, could enhance the structure-function tethering, especially in transmodal association cortices. Our findings suggest that the structure-function decoupling may not be an intrinsic property of brain organization, but can be narrowed through multiplexed and regionally specialized spatiotemporal propagation regimes.
An ancient river landscape preserved beneath the East Antarctic Ice Sheet
Authors: Jamieson Stewart S. R. , Ross Neil , Paxman Guy J. G. , Clubb Fiona J. , Young Duncan A. , Yan Shuai , Greenbaum Jamin , Blankenship Donald D. , Siegert Martin J.
Published: October 2023

The East Antarctic Ice Sheet (EAIS) has its origins ca. 34 million years ago. Since then, the impact of climate change and past fluctuations in the EAIS margin has been reflected in periods of extensive vs. restricted ice cover and the modification of much of the Antarctic landscape. Resolving processes of landscape evolution is therefore critical for establishing ice sheet history, but it is rare to find unmodified landscapes that record past ice conditions. Here, we discover an extensive relic pre-glacial landscape preserved beneath the central EAIS despite millions of years of ice cover. The landscape was formed by rivers prior to ice sheet build-up but later modified by local glaciation before being dissected by outlet glaciers at the margin of a restricted ice sheet. Preservation of the relic surfaces indicates an absence of significant warm-based ice throughout their history, suggesting any transitions between restricted and expanded ice were rapid.
Invasive Californian death caps develop mushrooms unisexually and bisexually
Authors: Wang Yen-Wen , McKeon Megan C. , Elmore Holly , Hess Jaqueline , Golan Jacob , Gage Hunter , Mao William , Harrow Lynn , Gonçalves Susana C. , Hull Christina M. , Pringle Anne
Published: October 2023

Canonical sexual reproduction among basidiomycete fungi involves the fusion of two haploid individuals of different mating types, resulting in a heterokaryotic mycelial body made up of genetically different nuclei. Using population genomics data and experiments, we discover mushrooms of the invasive and deadlyAmanita phalloidescan also be homokaryotic; evidence of sexual reproduction by single, unmated individuals. In California, genotypes of homokaryotic mushrooms are also found in heterokaryotic mushrooms, implying nuclei of homokaryotic mycelia are also involved in outcrossing. We find death cap mating is controlled by a single mating type locus, but the development of homokaryotic mushrooms appears to bypass mating type gene control. Ultimately, sporulation is enabled by nuclei able to reproduce alone as well as with others, and nuclei competent for both unisexuality and bisexuality have persisted in invaded habitats for at least 17 but potentially as long as 30 years. The diverse reproductive strategies of invasive death caps are likely facilitating its rapid spread, suggesting a profound similarity between plant, animal and fungal invasions.
De novo design of knotted tandem repeat proteins
Authors: Doyle Lindsey A. , Takushi Brittany , Kibler Ryan D. , Milles Lukas F. , Orozco Carolina T. , Jones Jonathan D. , Jackson Sophie E. , Stoddard Barry L. , Bradley Philip
Published: October 2023

De novo protein design methods can create proteins with folds not yet seen in nature. These methods largely focus on optimizing the compatibility between the designed sequence and the intended conformation, without explicit consideration of protein folding pathways. Deeply knotted proteins, whose topologies may introduce substantial barriers to folding, thus represent an interesting test case for protein design. Here we report our attempts to design proteins with trefoil (31) and pentafoil (51) knotted topologies. We extended previously described algorithms for tandem repeat protein design in order to construct deeply knotted backbones and matching designed repeat sequences (N = 3 repeats for the trefoil and N = 5 for the pentafoil). We confirmed the intended conformation for the trefoil design by X ray crystallography, and we report here on this protein’s structure, stability, and folding behaviour. The pentafoil design misfolded into an asymmetric structure (despite a 5-fold symmetric sequence); two of the four repeat-repeat units matched the designed backbone while the other two diverged to form local contacts, leading to a trefoil rather than pentafoil knotted topology. Our results also provide insights into the folding of knotted proteins.
Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial
Authors: Pouyiourou Maria , Kraft Bianca N. , Wohlfromm Timothy , Stahl Michael , Kubuschok Boris , Löffler Harald , Hacker Ulrich T. , Hübner Gerdt , Weiss Lena , Bitzer Michael , Ernst Thomas , Schütt Philipp , Hielscher Thomas , Delorme Stefan , Kirchner Martina , Kazdal Daniel , Ball Markus , Kluck Klaus , Stenzinger Albrecht , Bochtler Tilmann , Krämer Alwin
Published: October 2023

Cancer of unknown primary has a dismal prognosis, especially following failure of platinum-based chemotherapy. 10-20% of patients have a high tumor mutational burden (TMB), which predicts response to immunotherapy in many cancer types. In this prospective, non-randomized, open-label, multicenter Phase II trial (EudraCT 2018-004562-33; NCT04131621), patients relapsed or refractory after platinum-based chemotherapy received nivolumab and ipilimumab following TMBhigh vs. TMBlow stratification. Progression-free survival (PFS) represented the primary endpoint; overall survival (OS), response rates, duration of clinical benefit and safety were the secondary endpoints. The trial was prematurely terminated in March 2021 before reaching the preplanned sample size (n = 194). Among 31 evaluable patients, 16% had a high TMB ( > 12 mutations/Mb). Overall response rate was 16% (95% CI 6-34%), with 7.7% (95% CI 1-25%) vs. 60% (95% CI 15-95%) in TMBlow and TMBhigh, respectively. Although the primary endpoint was not met, high TMB was associated with better median PFS (18.3 vs. 2.4 months) and OS (18.3 vs. 3.6 months). Severe immune-related adverse events were reported in 29% of cases. Assessing on-treatment dynamics of circulating tumor DNA using combined targeted hotspot mutation and shallow whole genome sequencing as part of a predefined exploratory analysis identified patients benefiting from immunotherapy irrespective of initial radiologic response.
Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring
Authors: Oelkrug Rebecca , Harder Lisbeth , Pedaran Mehdi , Hoffmann Anne , Kolms Beke , Inderhees Julica , Gachkar Sogol , Resch Julia , Johann Kornelia , Jöhren Olaf , Krause Kerstin , Mittag Jens
Published: October 2023

It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3’,5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor β (TRβ) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TRβ activation to the fetal programming of a thermoregulatory phenotype in the offspring.
Uncertainty-inspired open set learning for retinal anomaly identification
Authors: Wang Meng , Lin Tian , Wang Lianyu , Lin Aidi , Zou Ke , Xu Xinxing , Zhou Yi , Peng Yuanyuan , Meng Qingquan , Qian Yiming , Deng Guoyao , Wu Zhiqun , Chen Junhong , Lin Jianhong , Zhang Mingzhi , Zhu Weifang , Zhang Changqing , Zhang Daoqiang , Goh Rick Siow Mong , Liu Yong , Pang Chi Pui , Chen Xinjian , Chen Haoyu , Fu Huazhu
Published: October 2023

Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.
Twistedly hydrophobic basis with suitable aromatic metrics in covalent organic networks govern micropollutant decontamination
Authors: Qin Chencheng , Yang Yi , Wu Xiaodong , Chen Long , Liu Zhaoli , Tang Lin , Lyu Lai , Huang Danlian , Wang Dongbo , Zhang Chang , Yuan Xingzhong , Liu Wen , Wang Hou
Published: October 2023

The pre-designable structure and unique architectures of covalent organic frameworks (COFs) render them attractive as active and porous medium for water crisis. However, the effect of functional basis with different metrics on the regulation of interfacial behavior in advanced oxidation decontamination remains a significant challenge. In this study, we pre-design and fabricate different molecular interfaces by creating ordered π skeletons, incorporating different pore sizes, and engineering hydrophilic or hydrophobic channels. These synergically break through the adsorption energy barrier and promote inner-surface renewal, achieving a high removal rate for typical antibiotic contaminants (like levofloxacin) by BTT-DATP-COF, compared with BTT-DADP-COF and BTT-DAB-COF. The experimental and theoretical calculations reveal that such functional basis engineering enable the hole-driven levofloxacin oxidation at the interface of BTT fragments to occur, accompanying with electron-mediated oxygen reduction on terphenyl motif to active radicals, endowing it facilitate the balanced extraction of holes and electrons.
Synergistic performance of a new bimetallic complex supported on magnetic nanoparticles for Sonogashira and C–N coupling reactions
Authors: Nasseri Fatemeh , Nasseri Mohammad Ali , Kassaee Mohamad Zaman , Yavari Issa
Published: October 2023

This paper describes the synthesis of a novel Cu–Ni bimetallic system comprising of magnetic nanoparticles, as the core, and 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole (4-ABPT), as a conjugated bridge, between nickel and copper species. With low Cu and Ni loading (0.06 mol% Ni, 0.08 mol% Cu), the resulting Fe3O4@SiO2@4-ABPT/Cu–Ni showed to be a highly efficient catalyst for the Sonogashira and C–N cross-coupling reactions. The developed catalyst was well characterized by FT-IR, XRD, EDX-mapping, FE-SEM, TEM, ICP, VSM, TGA/DTG/DTA, LSV, and XPS techniques. Fe3O4@SiO2@4-ABPT/Cu–Ni nanocatalyst was compatible with a wide range of amines and aryl halides in the Sonogashira and C–N cross-coupling reactions and offered desired coupling products in high to excellent yields under palladium- and solvent-free conditions. Based on the XPS results, the 4-ABPT ligand can adjust electron transfer between Ni and Cu in Fe3O4@SiO2@4-ABPT/Cu–Ni, promoting the formation and stabilization of Cu+ and Ni3+ species. Electronic interactions and the synergistic effect between these metals increased the selectivity and activity of Fe3O4@SiO2@4-ABPT/Cu–Ni catalyst in the Sonogashira and C–N cross-coupling reactions compared with its monometallic counterparts. Additionally, the magnetic properties of Fe3O4@SiO2@4-ABPT/Cu–Ni facilitated its separation from the reaction mixture, promoting its reuse for several times with no significant loss in its catalytic activity or performance.
Knee synovial fluid flow and heat transfer, a power law model
Authors: Hasnain Shahid , Abbas Imran , Al-Atawi Nawal Odah , Saqib Muhammad , Afzaal Muhammad F. , Mashat Daoud S.
Published: October 2023

For the purpose of understanding, the governing system of partial differential equations for synovial fluid flow velocity and temperature distribution in the knee joint has been successfully solved for the first time. Therefore, such an article is shedding light on the convective diffusion of the viscous flow along the articular surfaces of the joints through the introduction of power-law fluids with different features of permeability, and stagnation point flow along a magnetic field. Henceforth, the frictional energy causes the knee joint’s temperature to increase. By way of filtration, heated synovial fluid reaches the articular cartilage and provides heat to the bone and cartilage. The lubricant in the joint cavity is properly mixed with this cooled fluid. A rectangular region flow and diffusion model is used to define the issue, thermal diffusion and flow inside the intra-articular gap, as well as flow and thermal diffusion within the porous matrix covering the approaching bones at the joint. Using the similarity solution approach, the linked mixed boundary value problem is addressed. The fluid has been shown to resist moving into or out of the cartilage in certain sick and/or aging synovial joints, causing the temperature to increase. By changing the values of the parameters from their usual levels, it is observed that the temperature did increase in aged and sick joints which impact cartilage and/or synovial fluid degradation.
Evaluation of antimicrobial usage in companion animals at a Veterinary Teaching Hospital in Nigeria
Authors: Adebowale O. O. , Jimoh A. B. , Adebayo O. O. , Alamu A. A. , Adeleye A. I. , Fasanmi O. G. , Olasoju M. , Olagunju P. O. , Fasina F. O.
Published: October 2023

This study investigated various qualitative and quantitative indices of antimicrobial use (AMU) in companion animals (CAs) at a Veterinary Teaching Hospital (VTH-A) and its annex (VTH- B) from 2019 to 2021. For 694 documented animals, antimicrobial administrations (AADs) were 5, 278 times, of which 98.8% (5217) and 1.2% (61) were in dogs and cats respectively. At the VTH- A, oxytetracycline (1185 times, 22.5%) was mostly administered in dogs and metronidazole (26 times, 0.5%) in cats. Similarly, at VTH- B, oxytetracycline was administered 895 times (17.0%) in dogs while amoxicillin was given 7 times (0.1%) in cats. The prescription diversity (PD) was estimated at 0.73 and 0.82 in VTH-A and VTH-B respectively. The quantity of antimicrobials (AMs) used was 10.1 kg (A, 6.2 kg and B, 3.9 kg). Oxytetracycline administrations and quantity of metronidazole (P < 0.0001) were higher than other Active Ingredients (AIs). Furthermore, 16.5% of AIs were classified as Critically Important Antibiotics (CIA) with the highest priority, while enrofloxacin, ciprofloxacin, and azithromycin fell under the World Health Organisation (WHO) Watch group. The In-Depth Interview (IDI) indicated that the high frequency of oxytetracycline administrations was linked with being the first choice for blood parasite treatment by the clinicians at the hospital. The quantity of metronidazole used was perceived to be higher due to the clinicians' preference for the treatment of acute gastroenteritis, its wider dose range, and the frequency of administration (bi-daily). The study provides baseline data on AMU indices in CAs, for the development of antimicrobial stewardship (AMS) and communication training, and policy modifications to enhance antimicrobial therapy optimization in tertiary veterinary hospital care in Nigeria.
Evolutionary and ecological correlates of thiaminase in fishes
Authors: Rowland Freya E. , Richter Catherine A. , Tillitt Donald E. , Walters David M.
Published: October 2023

Thiamine (vitamin B1) is required by all living organisms in multiple metabolic pathways. It is scarce in natural systems, and deficiency can lead to reproductive failure, neurological issues, and death. One major cause of thiamine deficiency is an overreliance on diet items containing the enzyme thiaminase. Thiaminase activity has been noted in many prey fishes and linked to cohort failure in salmonid predators that eat prey fish with thiaminase activity, yet it is generally unknown whether evolutionary history, fish traits, and/or environmental conditions lead to production of thiaminase. We conducted literature and GenBank BLAST sequence searches to collect thiaminase activity data and sequence homology data in expressed protein sequences for 300 freshwater and marine fishes. We then tested whether presence or absence of thiaminase could be predicted by evolutionary relationships, trophic level, omega-3 fatty acid concentrations, habitat, climate, invasive potential, and body size. There was no evolutionary relationship with thiaminase activity. It first appears in Class Actinoptergyii (bony ray-finned fishes) and is present across the entire Actinoptergyii phylogeny in both primitive and derived fish orders. Instead, ecological factors explained the most variation in thiaminase: fishes were more likely to express thiaminase if they fed closer to the base of the food web, were high in polyunsaturated fatty acids, lived in freshwater, and were from tropical climates. These data provide a foundation for understanding sources of thiaminase leading to thiamine deficiency in fisheries and other organisms, including humans that eat uncooked fish.
A machine learning approach to predict the glaucoma filtration surgery outcome
Authors: Agnifili Luca , Figus Michele , Porreca Annamaria , Brescia Lorenza , Sacchi Matteo , Covello Giuseppe , Posarelli Chiara , Di Nicola Marta , Mastropasqua Rodolfo , Nucci Paolo , Mastropasqua Leonardo
Published: October 2023

This study aimed at predicting the filtration surgery (FS) outcome using a machine learning (ML) approach. 102 glaucomatous patients undergoing FS were enrolled and underwent ocular surface clinical tests (OSCTs), determination of surgical site-related biometric parameters (SSPs) and conjunctival vascularization. Break-up-time, Schirmer test I, corneal fluorescein staining, Meibomian gland expressibility; conjunctival hyperemia, upper bulbar conjunctiva area of exposure, limbus to superior eyelid distance; and conjunctival epithelial and stromal (CET, CST) thickness and reflectivity (ECR, SCR) at AS-OCT were considered. Successful FS required a 30% baseline intraocular pressure reduction, with values ≤ 18 mmHg with or without medications. The classification tree (CT) was the ML algorithm used to analyze data. At the twelfth month, FS was successful in 60.8% of cases, whereas failed in 39.2%. At the variable importance ranking, CST and SCR were the predictors with the greater relative importance to the CART tree construction, followed by age. CET and ECR showed less relative importance, whereas OSCTs and SSPs were not important features. Within the CT, CST turned out the most important variable for discriminating success from failure, followed by SCR and age, with cut-off values of 75 µm, 169 on gray scale, and 62 years, respectively. The ROC curve for the classifier showed an AUC of 0.784 (0.692–0.860). In this ML approach, CT analysis found that conjunctival stroma thickness and reflectivity, along with age, can predict the FS outcome with good accuracy. A pre-operative thick and hyper-reflective stroma, and a younger age increase the risk of FS failure.
Radiomics–clinical nomogram based on pretreatment 18F-FDG PET-CT radiomics features for individualized prediction of local failure in nasopharyngeal carcinoma
Authors: Ding Jianming , Li Zirong , Lin Yuhao , Huang Chaoxiong , Chen Jiawei , Hong Jiabiao , Fei Zhaodong , Zhou Qichao , Chen Chuanben
Published: October 2023

To explore the prognostic significance of PET/CT-based radiomics signatures and clinical features for local recurrence-free survival (LRFS) in nasopharyngeal carcinoma (NPC). We retrospectively reviewed 726 patients who underwent pretreatment PET/CT at our center. Least absolute shrinkage and selection operator (LASSO) regression and the Cox proportional hazards model were applied to construct Rad-score, which represented the radiomics features of PET-CT images. Univariate and multivariate analyses were used to establish a nomogram model. The concordance index (C-index) and calibration curve were used to evaluate the predictive accuracy and discriminative ability. Receiver operating characteristic analysis was performed to stratify the local recurrence risk of patients. The nomogram was validated by evaluating its discrimination ability and calibration in the validation cohort. A total of eight features were selected to construct Rad-score. A radiomics–clinical nomogram was built after the selection of univariate and multivariable Cox regression analyses, including the Rad-score and maximum standardized uptake value (SUVmax). The C-index was 0.71 (0.67–0.74) in the training cohort and 0.70 (0.64–0.76) in the validation cohort. The nomogram also performed far better than the 8th T-staging system with an area under the receiver operating characteristic curve (AUC) of 0.75 vs. 0.60 for 2 years and 0.71 vs. 0.60 for 3 years. The calibration curves show that the nomogram indicated accurate predictions. Decision curve analysis (DCA) revealed significantly better net benefits with this nomogram model. The log-rank test results revealed a distinct difference in prognosis between the two risk groups. The PET/CT-based radiomics nomogram showed good performance in predicting LRFS and showed potential to identify patients at high-risk of developing NPC.
Examining indicators of complex network vulnerability across diverse attack scenarios
Authors: Al Musawi Ahmad F. , Roy Satyaki , Ghosh Preetam
Published: October 2023

Complex networks capture the structure, dynamics, and relationships among entities in real-world networked systems, encompassing domains like communications, society, chemistry, biology, ecology, politics, etc. Analysis of complex networks lends insight into the critical nodes, key pathways, and potential points of failure that may impact the connectivity and operational integrity of the underlying system. In this work, we investigate the topological properties or indicators, such as shortest path length, modularity, efficiency, graph density, diameter, assortativity, and clustering coefficient, that determine the vulnerability to (or robustness against) diverse attack scenarios. Specifically, we examine how node- and link-based network growth or depletion based on specific attack criteria affect their robustness gauged in terms of the largest connected component (LCC) size and diameter. We employ partial least squares discriminant analysis to quantify the individual contribution of the indicators on LCC preservation while accounting for the collinearity stemming from the possible correlation between indicators. Our analysis of 14 complex network datasets and 5 attack models invariably reveals high modularity and disassortativity to be prime indicators of vulnerability, corroborating prior works that report disassortative modular networks to be particularly susceptible to targeted attacks. We conclude with a discussion as well as an illustrative example of the application of this work in fending off strategic attacks on critical infrastructures through models that adaptively and distributively achieve network robustness.
Continuous therapy response references for BCR::ABL1 monitoring in pediatric chronic myeloid leukemia
Authors: Volz Christian , Zerjatke Thomas , Gottschalk Andrea , Semper Sabine , Suttorp Meinolf , Glauche Ingmar , Krumbholz Manuela , Metzler Markus
Published: October 2023

Response to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) is monitored by quantification of BCR::ABL1 transcript levels. Milestones for assessing optimal treatment response have been defined in adult CML patients and are applied to children and adolescents although it is questionable whether transferability to pediatric patients is appropriate regarding genetic and clinical differences. Therefore, we analyzed the molecular response kinetics to TKI therapy in 129 pediatric CML patients and investigated whether response assessment based on continuous references can support an early individual therapy adjustment. We applied a moving quantiles approach to establish a high-resolution response target curve and contrasted the median responses in all patients with the median of the ideal target curve obtained from a subgroup of optimal responders. The high-resolution response target curve of the optimal responder group presents a valuable tool for continuous therapy monitoring of individual pediatric CML patients in addition to the fixed milestones. By further comparing BCR::ABL1 transcript levels with BCR::ABL1 fusion gene copy numbers, it is also possible to model the differential dynamics of BCR::ABL1 expression and cell number under therapy. The developed methodology can be transferred to other biomarkers for continuous therapy monitoring.
Spatial correspondence in relative space regulates serial dependence
Authors: Lim Jaeseob , Lee Sang-Hun
Published: October 2023

Our perception is often attracted to what we have seen before, a phenomenon called ‘serial dependence.’ Serial dependence can help maintain a stable perception of the world, given the statistical regularity in the environment. If serial dependence serves this presumed utility, it should be pronounced when consecutive elements share the same identity when multiple elements spatially shift across successive views. However, such preferential serial dependence between identity-matching elements in dynamic situations has never been empirically tested. Here, we hypothesized that serial dependence between consecutive elements is modulated more effectively by the spatial correspondence in relative space than by that in absolute space because spatial correspondence in relative coordinates can warrant identity matching invariantly to changes in absolute coordinates. To test this hypothesis, we developed a task where two targets change positions in unison between successive views. We found that serial dependence was substantially modulated by the correspondence in relative coordinates, but not by that in absolute coordinates. Moreover, such selective modulation by the correspondence in relative space was also observed even for the serial dependence defined by previous non-target elements. Our findings are consistent with the view that serial dependence subserves object-based perceptual stabilization over time in dynamic situations.
Effects of iguratimod on inflammatory factors and apoptosis of submandibular gland epithelial cells in NOD mice
Authors: Wang Shuying , Yu Jiake , Yang Jie , Ge Yan , Tian Jing
Published: October 2023

Non-obese diabetic (NOD) mice were taken as primary Sjögren’s syndrome (pSS) model mice to examine the therapeutic impact of iguratimod (IGU) on inflammatory factors levels and apoptosis of submandibular epithelial cells, and provide experimental basis for the treatment of pSS by iguratimod. Twenty-four NOD murine models were divided into the model, high-dose (IGU 30 mg/kg) and low-dose (IGU 10 mg/kg) groups, eight mice per group. The normal control group comprised eight C57B/L mice. From 8 weeks of age, the NOD mice were administered IGU by intragastric gavage administration every day for 8 weeks; their water consumption, saliva secretion, submandibular gland, and spleen indices were measured. The levels of serum inflammatory factor (IL-1β, TNF-α, IL-6, and IL-17) were evaluated, and Bax, caspase-3, and Bcl-2 levels were detected. The histological alterations in the submandibular glands were discovered. IGU can reduce the water intake of NOD mice (p < 0.01), increase the saliva secretion and the submandibular gland index (p < 0.01); reduce the spleen index and the serum inflammatory factors (p < 0.01); improve the pathological tissue damage and cell apoptosis of the submandibular gland (p < 0.05). IGU can reduce the expression levels of inflammatory mediators in the serum and the extent of lymphocyte infiltration and apoptosis in submandibular gland epithelial cells. It can also regulate apoptosis-related protein expression, thereby improving the secretory function of exocrine glands.