bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkaloid profiling of the new species Corydalis huangshanensis and other 13 medicinal plants in genus Corydalis
Authors: Zhang Haiwen , Chu Shanshan , Jiang Lu , Chan Qingyun , Zhang Zhenyu , Cheng Ming'en
Published: July 2024

Introduction

Corydalis DC., the largest genus of Papaveraceae, comprises numerous species known for their abundant alkaloid content and historical use in clinical medicine. Recently, a new species of genus Corydalis named Corydalis huangshanensis Lu Q. Huang & H. S. Peng was discovered in the Huangshan Mountains of Anhui Province, China.

Objective

To compare the chemical characteristics of C. huangshanensis and other 13 Corydalis species, aiming to elucidate the potential medicinal value of this new species.

Materials and Methods

The chemical constituents of C. huangshanensis and other 13 medicinal plants of genus Corydalis were analyzed using ultra‐high‐performance liquid chromatography Q‐Exactive Plus hybrid quadrupole‐Orbitrap mass spectrometer (Q‐Orbitrap) mass technology. The differences in the alkaloids in the 14 species were distinguished by chemometrics.

Results

The mass spectrometry fragmentation information and relative content of 72 alkaloids were obtained. Orthogonal partial least squares discriminant analysis (OPLS‐DA) and cluster heat mapping analysis showed that these 14 species were divided into two groups. The clustering relationship between C. huangshanensis and C. decumbens (Thunb.) Pers. was similar, exhibiting similar chemical compositions and characteristics. These results indicate the potential pharmacological effects of C. huangshanensis.

Conclusion

This study enhances our understanding of the chemical classification of Corydalis and provides a basis for speculations on the medicinal value of C. huangshanensis.
Conscious vision in blindness: A new perceptual phenomenon implemented on the “wrong” side of the brain
Authors: Bao Yan , Zhou Bin , Yu Xinchi , Mao Lihua , Gutyrchik Evgeny , Paolini Marco , Logothetis Nikos , Pöppel Ernst
Published: July 2024

Patients with lesions in the visual cortex are blind in corresponding regions of the visual field, but they still may process visual information, a phenomenon referred to as residual vision or “blindsight”. Here we report behavioral and fMRI observations with a patient who reports conscious vision across an extended area of blindness for moving, but not for stationary stimuli. This completion effect is shown to be of perceptual and not of conceptual origin, most likely mediated by spared representations of the visual field in the striate cortex. The neural output to extra‐striate areas from regions of the deafferented striate cortex is apparently still intact; this is, for instance, indicated by preserved size constancy of visually completed stimuli. Neural responses as measured with fMRI reveal an activation only for moving stimuli, but importantly on the ipsilateral side of the brain. In a conceptual model this shift of activation to the “wrong” hemisphere is explained on the basis of an imbalance of excitatory and inhibitory interactions within and between the striate cortices due to the brain injury. The observed neuroplasticity indicated by this shift together with the behavioral observations provide important new insights into the functional architecture of the human visual system and provide new insight into the concept of consciousness.
Long‐Term Safety of Teriflunomide in Multiple Sclerosis Patients: Results of Prospective Comparative Studies in Three European Countries
Authors: Magyari Melinda , Koechlin Alice , Duclos Antoine , Kopp Tine Iskov , Allaoui El Maâti , Polazzi Stephanie , Seeldrayers Pierrette , Autier Philippe
Published: July 2024

Background and Objectives

Teriflunomide is a disease‐modifying therapy (DMT) for multiple sclerosis (MS). This post authorisation safety study assessed risks of adverse events of special interest (AESI) associated with teriflunomide use.

Methods

Secondary use of individual data from the Danish MS Registry (DMSR), the French National Health Data System (SNDS), the Belgian national database of health care claims (AIM‐IMA) and the Belgian Treatments in MS Registry (Beltrims). We included patients treated with a DMT at the date of teriflunomide reimbursement or initiating another DMT. Adjusted hazard rates (aHR) and 95% confidence intervals were derived from Cox models with time‐dependent exposure comparing teriflunomide treatment with another DMT.

Results

Of 81 620 patients (72% women) included in the cohort, 22 324 (27%) were treated with teriflunomide. After a median follow‐up of 4 years, teriflunomide use compared to other DMT was not associated with a risk of all‐cause mortality, severe infection, pneumoniae, herpes zoster reactivation, pancreatitis, cardiovascular condition and cancers. For opportunistic infections, aHR for teriflunomide versus other DMT was 2.4 (1.2–4.8) in SNDS, which was not bound to a particular opportunistic agent. The aHR was 2.0 (1.1–3.7) for renal failures in the SNDS, but no association was found in other data sources. A total of 187 SNDS patients had a history of renal failure prior to cohort entry. None of these patients (0%) had a renal failure recurrence when treated with teriflunomide for 19 (13%) recurrences reported for patients on another DMT.

Discussion

We found no evidence that teriflunomide use would be associated with an increased risk of AESI.

Trial Registration EUPAS register: EU PAS 19610.
Kann Kernenergie zur Energiewende beitragen?
Authors: Kleidon Axel , Lesch Harald
Published: July 2024

Im Vergleich zu erneuerbaren Energien sind Kernkraftwerke deutlich teurer in den Stromgestehungskosten. Pro Kilowatt Leistung sind Kernkraftwerke zudem über die letzten Jahrzehnte immer teurer geworden, während die Erneuerbaren immer günstiger wurden. Außerdem wird durch das variable Einspeisen aus Sonne und Wind die verbleibende Netzlast geringer, die noch gedeckt werden muss. Die verbleibenden Lücken in der Stromerzeugung lassen sich gut durch Gaskraftwerke schließen. Diese haben wesentlich geringere Investitionskosten als Kernkraftwerke. Sollten die gegenwärtigen Trends bei der Wasserverfügbarkeit im Zuge des Klimawandels anhalten, dann könnte zudem der Mangel an Kühlwasser den Beitrag von thermischen Kraftwerken an der Stromerzeugung einschränken, vor allem in den trockenen Sommermonaten. Insbesondere die Kernenergie steht also vor zwei Problemen: Sie ist sehr teuer und bietet in künftigen, trockenen Sommern keine Versorgungssicherheit mehr.
Synthesis of isotope‐substituted conjugated ladder polymers
Authors: Leng Mingwan , Cao Zhiqiang , Ma Guorong , Cao Yirui , Hays Megan , Gu Xiaodan , Fang Lei
Published: July 2024

Conjugated ladder polymers (cLPs) represent an intriguing class of macromolecules, characterized by their multi‐stranded structure, with continuous fused π‐conjugated rings forming the backbone. Isotope substitution, such as deuteration and carbon‐13 labeling, offers unique approaches to address the significant challenges associated with elucidating the structure and solution phase dynamics of these polymers. For instance, selective deuteration can highlight parts of the polymer by controlling the scattering length density of specific molecular sections, thereby enhancing the contrast for neutron scattering experiments. In this context, deuteration of side‐chains in cLPs represents a promising approach to uncover the elusive polymer physics properties of their backbone. The synthesis of two distinct types of cLPs with perdeuterated side‐chains are reported here. During the synthesis, 13C isotope labeling was also employed to verify the low levels of defects in the synthesized polymers. Demonstrating these synthetic successes lays the foundation for rigorous characterization of the defects, conformation, and dynamics of cLPs.
A study of tiamulin removal by nanosecond pulsed gas–liquid discharge underwater
Authors: Liu Yang , Liang Jianping , Wang Hongli , Lu Ke , Zhou Zikai , Shen Hongwei , Xu Yihao , Yang Kun , Yang Dezheng
Published: July 2024

In this study, gas–liquid discharge plasma excited by nanosecond pulsed voltage is used to efficiently remove tiamulin (TIA) from water. The discharge produces a large number of reactive species (H2O2, OH radicals, NO3−, etc.) that can attack the TIA molecules. The effects of peak pulse voltage, initial TIA concentration, gas composition, and the addition of ferrous sulfate and persulfate on TIA removal were mainly investigated. The results showed that the oxygen plasma could approach 100% removal within 30 min of treatment time. The addition of the catalyst increased the TIA removal efficiency by approximately 15% during the 10‐min discharge treatment time. The toxicity of 12 intermediates was analyzed and the degradation mechanism of TIA was investigated.
Chondroitin Sulfate‐Modified Hydroxyapatite for Caspase‐1 Activated Induced Pyroptosis through Ca Overload/ER Stress/STING/IRF3 Pathway in Colorectal Cancer
Authors: Chen Qing , Peng Bin , Lin Lifan , Chen Jiawen , Jiang Zhaojun , Luo Yuanwei , Huang Liyong , Li Jin , Peng Yuping , Wu Jiaming , Li Wei , Zhuang Kangmin , Liang Min
Published: July 2024

Immune checkpoint inhibitors, are the fourth most common therapeutic tool after surgery, chemotherapy, and radiotherapy for colorectal cancer (CRC). However, only a small proportion (≈5%) of CRC patients, those with “hot” (immuno‐activated) tumors, benefit from the therapy. Pyroptosis, an innovative form of programmed cell death, is a potentially effective means to mediate a “cold” to “hot” transformation of the tumor microenvironment (TME). Calcium‐releasing hydroxyapatite (HAP) nanoparticles (NPs) trigger calcium overload and pyroptosis in tumor cells. However, current limitations of these nanomedicines, such as poor tumor‐targeting capabilities and insufficient calcium (Ca) ion release, limit their application. In this study, chondroitin sulfate (CS) is used to target tumors via binding to CD44 receptors and kaempferol (KAE) is used as a Ca homeostasis disruptor to construct CS‐HAP@KAE NPs that function as pyroptosis inducers in CRC cells. CS‐HAP@KAE NPs bind to the tumor cell membrane, HAP released Ca in response to the acidic environment of the TME, and kaempferol (KAE) enhances the influx of extracellular Ca, resulting in intracellular Ca overload and pyroptosis. This is associated with excessive endoplasmic reticulum stress triggered activation of the stimulator of interferon genes/interferon regulatory factor 3 pathway, ultimately transforming the TME from “cold” to “hot”.
Toward Scalable Electrochemical Exfoliation of Molybdenum Disulfide Powder through an Accessible Electrode Design
Authors: Wilson Nicholas David , Ozhukil Valappil Manila , Martin Barbara Y. , Siu Teri , Pennings Joel , Mackintosh Mira , Almadhoun Mahmoud N. , Ouyang Jianying , Graddage Neil , Pope Michael A.
Published: July 2024

Cathodic electrochemical intercalation/exfoliation of transition metal dichalcogenides (TMDs) with bulky tetraalkylammonium‐based cations is gaining popularity as it avoids the semiconducting (2H) to metallic (1T) phase transformation in TMDs like molybdenum disulfide (MoS2) and, generally, produces sheets with a larger aspect ratio – important for achieving conformal sheet‐to‐sheet contact in optoelectronic devices. Large single crystals are typically used as the precursor, but these are expensive, often inaccessible, and result in limited quantities of material. In this paper, a 3D‐printable electrochemical cell capable of intercalating gram‐scale quantities of commercially available TMD powders is presented. By incorporating a reference electrode in the cell and physically restraining the powder with a spring‐loaded mechanism, the system can probe the intercalation electrochemistry, for example, determining the onset of intercalation to be near −2.5 V versus the ferrocene redox couple. While the extent of intercalation depends on precursor quantity and reaction time, a high yield of exfoliated product can be obtained exhibiting average aspect ratios as high as 49 ± 44 similar to values obtained by crystal intercalation. The intercalation and exfoliation of a wide variety of pelletized commercial powders including molybdenum diselenide (MoSe2), tungsten diselenide (WSe2), tungsten disulfide (WS2), and graphitic carbon nitride (gCN) are also demonstrated.
A Framework and Taxonomy for Characterizing the Applicability of Software Architecture Recovery Approaches: A Tertiary‐Mapping Study
Authors: Qayum Abdul , Zhang Mengqi , Colreavy Simon , Chochlov Muslim , Buckley Jim , Lin Dayi , Sai Ashish Rajendra
Published: July 2024

Software architecture assists developers in addressing non‐functional requirements and in maintaining, debugging, and upgrading their software systems. Consequently, consistency between the designed architecture and the implemented software system itself is important; without this consistency the non‐functional requirements targeted may not be addressed and architectural documentation may mis‐direct maintenance efforts that target the associated code‐base. But often, when software is initially implemented or subsequently evolved, the designed architecture and software architecture become inconsistent, with the implemented structure degraded due to issues like developer time‐pressures, or ambiguous communication of the designed architecture. In such cases, Software Architecture Recovery (SAR) or consistency approaches can be applied to reconstruct the architecture of the software system and possibly to compare it to/re‐align it with the designed architecture. Many SAR approaches have been proposed in the research. However, choosing an appropriate architecture recovery approach for software systems is still an open issue. Consequently, this research aims to conduct a tertiary‐mapping study based on available secondary studies of architecture recovery approaches, to uncover important characteristics, towards the selection of appropriate SAR approaches. This research has aggregated 13 secondary studies and 10 primary studies beyond 2020 from 5 databases and, in doing so, identified 111 architecture recovery approaches. Based on these approaches, a taxonomy, containing nine main SAR‐selection categories is proposed and a framework (in the form of a supporting tool to help developers select an appropriate SAR approach) has been developed. Finally, this research identifies six potential open research gaps related to the underlying research that could be helpful for guiding research in the future.
Sign‐flip inference for spatial regression with differential regularisation
Authors: Cavazzutti Michele , Arnone Eleonora , Ferraccioli Federico , Galimberti Cristina , Finos Livio , Sangalli Laura M.
Published: July 2024

We address the problem of performing inference on the linear and nonlinear terms of a semiparametric spatial regression model with differential regularisation. For the linear term, we propose a new resampling procedure, based on (partial) sign‐flipping of an appropriate transformation of the residuals of the model. The proposed resampling scheme can mitigate the bias effect induced by the differential regularisation. We prove that the proposed test is asymptotically exact. Moreover, we show, by simulation studies, that it enjoys very good control of Type‐I error also in small sample scenarios, differently from parametric alternatives. Additionally, we show that the proposed test has higher power with respect than recently proposed nonparametric tests on the linear term of semiparametric regression models with differential regularisation. Concerning the nonlinear term, we develop three different inference approaches: a parametric one and two nonparametric alternatives. The nonparametric tests are based on a sign‐flip approach. One of these is proved to be asymptotically exact, while the other is proved to be exact also for finite samples. Simulation studies highlight the good control of Type‐I error of the nonparametric approaches with respect the parametric test, while retaining high power.
Investigating the Impact of Microplastics Type of Polyethylene, Polypropylene, and Polystyrene on Seed Germination and Early Growth of Rice Plants
Authors: Iswahyudi Iswahyudi , Widodo Wahyu , Warkoyo Warkoyo , Sutanto Adi , Garfansa Marchel Putra , Mujiyanti Wahyu Alvina , Sholeh Mohammad Shoimus
Published: July 2024

Microplastics (MPs), which are emerging pollutants in terrestrial ecosystems, could potentially impact plant growth. One of the least explored aspects of crop development is seed germination, a crucial stage in the plant's lifecycle. This study conducted soil cultivation trials to investigate the effects of 1% (w/w) concentrations of polyethylene (PET), polypropylene (PP), and polystyrene (PS) MPs on rice growth over a 15‐day period. Parameters such as fresh weight, shoot height, root length, chlorophyll levels, and MPs identification in the roots were observed. The findings revealed the accumulation of 6–9 MP items in the roots. PET MPs inhibited root elongation (15%–20%), reduced shoot height (15%–30%), and decreased rice fresh weight (12%–37%). MPs PET, PP, and PS contamination reduced the content of chlorophyll a (15%–43%), b (21%–41%), and total (11%–40%) in rice leaves. This study enhances our understanding of the ecotoxicological effects of these three types of MPs on rice. The utilization of this data will further inform our understanding of MPs' behavior in soil vegetation and provide valuable insights into their land‐based impacts.
Pituitary apoplexy is associated with concurrent or subsequent diagnosis of human immunodeficiency virus
Authors: Douglas Jennifer E. , Salmon Mandy K. , Kshirsagar Rijul S. , Eide Jacob G. , White Caitlin , Kharlip Julia , Jackson Christina , Lee John Y. K. , Yoshor Daniel , Kohanski Michael A. , Palmer James N. , Adappa Nithin D.
Published: July 2024

Objective

Pituitary apoplexy (PA) is a rare condition caused by hemorrhage or infarction of the pituitary gland with associated risk of cranial neuropathies, endocrinopathies, and even death. Human immunodeficiency virus (HIV) has been shown to have some association with pituitary apoplexy, however, large‐scale studies have not been performed.

Methods

A retrospective cohort study of subjects greater than 18 years of age was performed using the national TriNetX database. The general population was first compared with those undergoing treatment for PA to compare general demographics and incidence of HIV. The PA cohort was then substratified by HIV status and propensity matched by age and sex to evaluate differences in visual outcomes and endocrine metrics. Using the diagnosis of pituitary apoplexy as an index event, the rate of HIV diagnosis at the time of presentation or in the three months following treatment was calculated. Two‐tailed, unpaired t‐tests were performed.

Results

A total 2066 patients were identified (902 HIV, 1158 controls). Those with HIV showed an increased rate of pituitary apoplexy (odds ratio [OR]: 19.8) versus healthy adults and were more likely to be younger and male. Among patients treated for pituitary apoplexy, patients with HIV were more likely to have increased thyroid stimulating hormone, reduced T4, and increased prolactin compared with healthy controls. There were no significant differences in visual outcomes between HIV positive and control patients. Importantly, 74% of patients did not carry a diagnosis of HIV on presentation but were diagnosed at the time of or in the three months following treatment for pituitary apoplexy.

Conclusions

Diagnosis and treatment of pituitary apoplexy shows a high rate of concurrent or subsequent diagnosis of HIV. Screening for HIV should be considered in patients undergoing treatment for pituitary apoplexy.
Relational bulk reconstruction from modular flow
Authors: Parrikar Onkar , Rajgadia Harshit , Singh Vivek , Sorce Jonathan
Published: July 2024

Abstract

The entanglement wedge reconstruction paradigm in AdS/CFT states that for a bulk qudit within the entanglement wedge of a boundary subregion $$ \overline{A} $$

A
¯

, operators acting on the bulk qudit can be reconstructed as CFT operators on $$ \overline{A} $$

A
¯

. This naturally fits within the framework of quantum error correction, with the CFT states containing the bulk qudit forming a code protected against the erasure of the boundary subregion A. In this paper, we set up and study a framework for relational bulk reconstruction in holography: given two code subspaces both protected against erasure of the boundary region A, the goal is to relate the operator reconstructions between the two spaces. To accomplish this, we assume that the two code subspaces are smoothly connected by a one-parameter family of codes all protected against the erasure of A, and that the maximally-entangled states on these codes are all full-rank. We argue that such code subspaces can naturally be constructed in holography in a “measurement-based” setting. In this setting, we derive a flow equation for the operator reconstruction of a fixed code subspace operator using modular theory which can, in principle, be integrated to relate the reconstructed operators all along the flow. We observe a striking resemblance between our formulas for relational bulk reconstruction and the infinite-time limit of Connes cocycle flow, and take some steps towards making this connection more rigorous. We also provide alternative derivations of our reconstruction formulas in terms of a canonical reconstruction map we call the modular reflection operator.
Charge (in)stability and superradiance of Topological Stars
Authors: Cipriani Andrea , Di Benedetto Carlo , Di Russo Giorgio , Grillo Alfredo , Sudano Giuseppe
Published: July 2024

Abstract

We study linear massive scalar charged perturbations of Topological Stars in the fuzzball and in the black hole (Black String) regimes. The objects that naturally couple to the electric 3-form field strength of these solutions are charged strings, wound around the compact direction. We explore the possibility of instabilities of these solutions, in analogy with the charge instability already highlighted for other non-BPS geometries like JMaRT. This issue is addressed by calculating quasi-normal mode frequencies with a variety of techniques: WKB approximation, direct integration, Leaver method and by exploiting the recently discovered correspondence between black hole/fuzzball perturbation theory and quantum Seiberg-Witten curves. All mode frequencies we find have negative imaginary parts, implying an exponential decay in time. This suggests a linear stability of Topological Stars also in this new scenario. In addition, we study the charge superradiance for the Black String. We compute the amplification factor with the numerical integration method and a quantum Seiberg-Witten motivated definition including instantonic corrections.
Jet classification using high-level features from anatomy of top jets
Authors: Furuichi Amon , Lim Sung Hak , Nojiri Mihoko M.
Published: July 2024

Abstract

Recent advancements in deep learning models have significantly enhanced jet classification performance by analyzing low-level features (LLFs). However, this approach often leads to less interpretable models, emphasizing the need to understand the decision-making process and to identify the high-level features (HLFs) crucial for explaining jet classification. To address this, we consider the top jet tagging problems and introduce an analysis model (AM) that analyzes selected HLFs designed to capture important features of top jets. Our AM mainly consists of the following three modules: a relation network analyzing two-point energy correlations, mathematical morphology and Minkowski functionals for generalizing jet constituent multiplicities, and a recursive neural network analyzing subjet constituent multiplicity to enhance sensitivity to subjet color charges. We demonstrate that our AM achieves performance comparable to the Particle Transformer (ParT) while requiring fewer computational resources in a comparison of top jet tagging using jets simulated at the hadronic calorimeter angular resolution scale. Furthermore, as a more constrained architecture than ParT, the AM exhibits smaller training uncertainties because of the bias-variance tradeoff. We also compare the information content of AM and ParT by decorrelating the features already learned by AM. Lastly, we briefly comment on the results of AM with finer angular resolution inputs.
Minimal complete tri-hypercharge theories of flavour
Authors: Fernández Navarro Mario , King Stephen F. , Vicente Avelino
Published: July 2024

Abstract

The tri-hypercharge proposal introduces a separate gauged weak hypercharge assigned to each fermion family as the origin of flavour. This is arguably one of the simplest setups for building “gauge non-universal theories of flavour” or “flavour deconstructed theories”. In this paper we propose and study two minimal but ultraviolet complete and renormalisable tri-hypercharge models. We show that both models, which differ only by the heavy messengers that complete the effective theory, are able to explain the observed patterns of fermion masses and mixings (including neutrinos) with all fundamental coefficients being of $$ \mathcal{O} $$
O
(1). In fact, both models translate the complicated flavour structure of the Standard Model into three simple physical scales above electroweak symmetry breaking, completely correlated with each other, that carry meaningful phenomenology. In particular, the heavy messenger sector determines the origin and size of fermion mixing, which controls the size and nature of the flavour-violating currents mediated by the two heavy Z′ gauge bosons of the theory. The phenomenological implications of the two minimal models are compared. In both models the lightest Z′ remains discoverable in dilepton searches at the LHC Run 3.
Not all that is β0 is β-function: the DGLAP resummation and the running coupling in NLO JIMWLK
Authors: Kovner Alex , Lublinsky Michael , Skokov Vladimir V. , Zhao Zichen
Published: July 2024

Abstract

We reanalyze the origin of the large transverse logarithms associated with the QCD one loop β function coefficient in the NLO JIMWLK Hamiltonian. We show that some of these terms are not associated with the running of the QCD coupling constant but rather with the DGLAP evolution. The DGLAP-like resummation of these logarithms is mandatory within the JIMWLK Hamiltonian, as long as the color correlation length in the projectile is larger than that in the target. This regime in fact covers the whole range of rapidities at which JIMWLK evolution is supposed to be applicable. We derive the RG equation that resums these logarithms to all orders in αs in the JIMWLK Hamiltonian. This is a nonlinear equation for the eikonal scattering matrix S(x). We solve this equation, and perform the DGLAP resummation in two simple cases: the dilute limit, where both the projectile and the target are far from saturation, and the saturated regime, where the target correlation length also determines its saturation momentum.
Pions from higher-dimensional gluons: general realizations and stringy models
Authors: Dong Jin , Li Xiang , Zhu Fan
Published: July 2024

Abstract

In this paper we revisit the general phenomenon that scattering amplitudes of pions can be obtained from “dimensional reduction” of gluons in higher dimensions in a more general context. We show that such “dimensional reduction” operations universally turn gluons into pions regardless of details of interactions: under such operations any amplitude that is gauge invariant and contains only local simple poles becomes one that satisfies Adler zero in the soft limit. As two such examples, we show that starting from gluon amplitudes in both superstring and bosonic string theories, the operations produce “stringy” completion of pion scattering amplitudes to all orders in α′, with leading order given by non-linear sigma model amplitudes. Via Kawai-Lewellen-Tye relations, they give closed-stringy completion for Born-Infeld theory and the special Galileon theory, which are directly related to gravity amplitudes in closed-string theories. We also discuss how they naturally produce stringy models for mixed amplitudes of pions and colored scalars.
Ultrasound-assisted synthesis of 4-thiazolidinone Schiff bases and their antioxidant, α-glucosidase, α-amylase inhibition, mode of inhibition and computational studies
Authors: Seboletswe Pule , Kumar Gobind , Kubone Lungisani , Olofinsan Kolawole , Idris Almahi , Islam Md. Shahidul , Singh Parvesh
Published: July 2024

Diabetes mellitus (DM) has become a growing concern to global public health, being at the forefront of acute disorders and causes of mortality across the globe. Clinically approved drugs that are currently being used are faced with severe side effects, consequently necessitating the development of new drugs with no/fewer side effects and improved pharmacological potency. Herein, we report a rapid and efficient synthesis of thiazolidinone Schiff bases (2a-2t) from benzylidenehydrazines and thioglycolic acid under neat conditions through ultra-sonication. All the synthesized compounds were obtained in exceptional yields (89–95%) and confirmed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as High-resolution mass spectrometry (HRMS). The synthesized compounds were then evaluated for their antidiabetic activity through α-glucosidase and α-amylase inhibitory potentials and their antioxidant activity through Nitric Oxide (NO), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and Ferric reducing antioxidant power (FRAP) assays. Among them, 2q (IC50 = 96.63 μM) and 2h (IC50 = 125.27 μM) emerged as the most potent derivatives against α-amylase relative to reference drug acarbose (IC50 = 131.63 µM), respectively. Antioxidant evaluation further revealed that the synthesized derivatives were excellent NO scavengers disclosing 2n (IC50 = 44.95 µM) as the most potent derivative. Moreover, in silico ADME calculations predicted these compounds to have excellent drug-like properties. Kinetic studies disclosed the mode of α-amylase inhibition as competitive while molecular docking studies of the most active derivatives performed into the binding active site of human pancreatic α-amylase enzyme deciphered their ligand-protein interactions that explicated their observed experimental potencies.
Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study
Authors: Boström Lennart , Jovic Viktor , Dahlberg Martin , Holtenius Fredrik , Sandblom Gabriel , Järnbert-Pettersson Hans
Published: July 2024

Purpose

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis.

Methods

A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method.

Results

A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%).

Conclusion

Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.
Use of antibiotics in the early COVID-19 pandemic in Poland, the Netherlands and Spain, from erraticism to (more) logic
Authors: Opalska Aleksandra , Gardarsdottir Helga , Kwa Marcel , Wójkowska-Mach Jadwiga , Sabate Monica , Ballarin Maria Elena , de Groot Mark , Leufkens Hubert
Published: July 2024

Introduction

In the Spring of 2020, the world was hit with unparalleled impact by the coronavirus pandemic. Antibiotics were widely used, even without good rationale. The aim of our study was to compare the use of antibiotics in patients with confirmed COVID-19 from three hospitals across Europe (Poland, the Netherlands and Spain) between two subsequent periods in the early days of the pandemic.

Method

We analysed data (antibiotics used and variation in the use of antibiotics, patients, admission and disease-related characteristics) from 300 patients admitted in three hospitals (University Hospital in Cracow, University Medical Center in Utrecht and Vall d’Hebron University Hospital in Barcelona) with confirmed infection of SARS-CoV-2 during Q1 2020 and Q4 2020.

Results

There was ample variation in terms of patient mix and outcomes across the 3 hospitals. The majority of patients (225 out of 300) in all 3 hospitals received at least 1 antibiotic during the hospitalisation period. A minority of patients (68 out of 300) had their bacterial test results positive during their hospitalisation period. Throughout the 2 study periods, third-generation cephalosporins (ceftriaxone in 170 out of 300 patients) emerged as the most commonly used class of antibiotics. There was an apparent shift towards more rational utilisation of antibiotics, in all three hospitals.

Conclusions

Our study shows that during the early stage of COVID-19 pandemic in 2020, antibiotics were frequently used in three European teaching hospitals despite the relatively low incidence of microbiologically confirmed bacterial infections. While in the early days of the COVID-19 pandemic antibiotic prescribing was full of trial and error, we could also confirm a learning curve over time.
Magnetic resonance imaging radiomics-based prediction of severe inflammatory response in locally advanced rectal cancer patients after neoadjuvant radiochemotherapy
Authors: Chen Li , Zhu Wenchao , Zhang Wei , Chen Engeng , Zhou Wei
Published: July 2024

Purpose

To predict severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced rectal cancer (RC) patients using magnetic resonance imaging (MRI) radiomics models.

Methods

This retrospective study included patients who underwent radical surgery for RC cancer after neoadjuvant radiochemotherapy between July 2017 and December 2019 at XXX Hospital. MRI radiomics features were extracted from T2WI images before (pre-nRCT-RF) and after (post-nRCT-RF) neoadjuvant radiochemotherapy, and the variation of radiomics features before and after neoadjuvant radiochemotherapy (delta-RF) were calculated. Eight, eight, and five most relevant features were identified for pre-nRCT-RF, post-nRCT-RF, and delta-RF, respectively.

Results

Eighty-six patients were included and randomized 3:1 to the training and test set (n = 65 and n = 21, respectively). The prediction model based on delta-RF had areas under the curve (AUCs) of 0.80 and 0.85 in the training and test set, respectively. A higher rate of difficult operations was observed in patients with severe inflammation (65.5% vs. 42.9%, P = 0.045).

Conclusion

The prediction model based on MRI delta-RF may be a useful tool for predicting severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced RC patients.
Ethische Dilemmata in der Neurologie bei Sterbeverfügungen
Authors: Novak Helmut F.
Published: July 2024

Seit Inkrafttreten des Sterbeverfügungsgesetzes (StVerfG) in Österreich hat sich im ASCIRS-Register der Österreichischen Palliativgesellschaft (OPG) ein Anteil von 25 % bei neurologischen Erkrankungen abgebildet. Das unterstreicht einerseits deren besondere Bedeutung für die Errichtung einer Sterbeverfügung, begründet aber auch eine besondere Verantwortung der Neurolog:innen, auch wenn sie dadurch an ihre ethischen Grenzen stoßen und in Dilemmata bei Entscheidungen zwischen Neuropalliation und Sterbewilligkeit geraten. Dennoch benötigen gerade Patient:innen mit chronischen neurologischen Erkrankungen eine fachneurologische Begleitung bis zum Lebensende, einschließlich der Beratung für eine krankheitsspezifische Patientenverfügung und der Betreuung der Angehörigen nach einer assistierten Selbsttötung.
Assessing the viability of parking slot utilization as transhipment points for parcel carriers: a case study in Barcelona
Authors: Savall-Mañó Maria , Ribas Imma
Published: July 2024

The measures proposed in the sustainable and smart mobility strategy developed by the European commission are crucial for achieving the environmental objectives for 2030. This strategy includes measures specifically aimed at reducing the impact of e-commerce distribution. One widely adopted strategy for mitigating the impact of e-commerce distribution is the establishment of urban consolidation centres (UCCs). While this infrastructure quickly demonstrates its environmental success in urban areas, achieving long-term economic sustainability proves challenging. In this paper, we introduce a methodology aimed at incentivizing parcel carriers to shift towards an economically feasible and environmentally sustainable distribution mode within urban areas by leveraging their own transhipment space. This methodology includes a mathematical program for determining the quantity and locations of parking slots, taking into account the number of parcels and transportation vehicles used. It also utilizes the Continuous Approximation technique to assess the transportation and environmental costs of the proposed solutions. The proposed methodology is implemented for the city of Barcelona, considering three different sizes of parcel carriers: the carrier handling the largest volume of parcels, the carrier handling the lowest volume of parcels, and an intermediate case. The vehicles considered for delivery from the transhipment points include vans, cargo bikes, and trolleys for distribution on foot. The results indicate that a significant reduction in both transport and environmental costs is achieved when using zero-emissions vehicles for delivery from transhipment points for any of the parcel carriers considered.
US & MR/CT Image Fusion with Markerless Skin Registration: A Proof of Concept
Authors: Paccini Martina , Paschina Giacomo , De Beni Stefano , Stefanov Andrei , Kolev Velizar , Patanè Giuseppe
Published: July 2024

This paper presents an innovative automatic fusion imaging system that combines 3D CT/MR images with real-time ultrasound acquisition. The system eliminates the need for external physical markers and complex training, making image fusion feasible for physicians with different experience levels. The integrated system involves a portable 3D camera for patient-specific surface acquisition, an electromagnetic tracking system, and US components. The fusion algorithm comprises two main parts: skin segmentation and rigid co-registration, both integrated into the US machine. The co-registration aligns the surface extracted from CT/MR images with the 3D surface acquired by the camera, facilitating rapid and effective fusion. Experimental tests in different settings, validate the system’s accuracy, computational efficiency, noise robustness, and operator independence.
Beyond reasonable doubt: reconsidering Neanderthal aesthetic capacity
Authors: Meneganzin Andra , Killin Anton
Published: July 2024

An aesthetic sense—a taste for the creation and/or appreciation of that which strikes one as, e.g., attractive or awesome—is often assumed to be a distinctively H. sapiens phenomenon. However, recent paleoanthropological research is revealing its archaeologically visible, deeper roots. The sensorimotor/perceptual and cognitive capacities underpinning aesthetic activities are a major focus of evolutionary aesthetics. Here we take a diachronic, evolutionary perspective and assess ongoing scepticism regarding whether, and to what extent, aesthetic capacity extends to our evolutionary cousins, the Neanderthals. The goal of this article is twofold. First, it serves as a defence of the attribution of Neanderthal aesthetic capacity by marshalling archaeological data best explained by positing a Neanderthal aesthetic sense. Second, it offers an opportunity to make progress on understanding some epistemically relevant features of the wider debate in evolutionary aesthetics. First, we outline and analyse a range of distinct ‘sceptical arguments’ derived from attitudes and claims found in the literature and broader debate that aim to dial down the case for Neanderthal aesthetic capacity. We show that these arguments not only miss their target, they divert the debate away from more compelling questions. We then consider the case for protoaesthetic capacities and sensitivities in the Acheulean stone tool industry and argue that Neanderthals likely inherited the protoaesthetic package from ancient ancestors that they shared with H. sapiens. Finally, we sketch and defend a research agenda for framing Neanderthal aesthetic niche(s) beyond H. sapiens-derived standards, which we see as a priority for future archaeological, cognitive, and philosophical research. While we resist sceptical arguments and the often-implied inferiority of Neanderthals to humans, we also deny that Neanderthals and ancient humans were indistinguishable. Understanding the differences is an important goal of interpretation, and we apply this line of reasoning to the case of aesthetics.
TiO2/Al-PILC Catalysts Synthesized from a Non-Conventional Aluminum Source of Aluminum and Applied in the Photodegradation of Organic Compounds
Authors: Cardona Yaneth , Gil Antonio
Published: July 2024

This study explores the transformative potential of Pillared InterLayered Clays (PILC) derived from non-conventional aluminum sources as catalytic supports in the synthesis of TiO2/catalysts for the efficient photodegradation of organic pollutants in water. Montmorillonite (Mt) and three alumina-pillared montmorillonite (PILC) synthesized using various aluminum sources, were impregnated with titanium to synthesize TiO2/catalysts. The successful synthesis of these materials was confirmed through several characterization techniques such as X-ray diffraction (XRD), N2 adsorption-desorption at -196 ºC, morphological analysis using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and Energy-Dispersive X-ray Spectrometry (EDX). The photolysis, adsorption, and catalytic behavior of the TiO2/catalysts were studied for the degradation of triclosan (TCS), 2,6-dichlorophenol (2,6-DCP), and bisphenol A (BPA). All synthesized catalysts surpassed the efficacy of commercial anatase, with TiO2/Al-PILC exhibiting superior performance in comparison to TiO2/Mt. Photodegradation was most effective under UV radiation, with TCS demonstrating the highest degradation (approximately 70%). Notably, Al-PILC samples, particularly those synthesized from saline slags, displayed enhanced properties. Among them, TiO2/Al-PILCAE exhibited the highest degradation rates under both UV and visible light, underlining the remarkable potential of saline slags as precursors for Al-PILC synthesis. This study provides valuable insights into the design and development of efficient catalysts for water treatment applications, paving the way for sustainable and effective solutions in the realm of environmental remediation.
Delta radiomics: an updated systematic review
Authors: Nardone Valerio , Reginelli Alfonso , Rubini Dino , Gagliardi Federico , Del Tufo Sara , Belfiore Maria Paola , Boldrini Luca , Desideri Isacco , Cappabianca Salvatore
Published: July 2024

Background

Radiomics can provide quantitative features from medical imaging that can be correlated with various biological features and diverse clinical endpoints. Delta radiomics, on the other hand, consists in the analysis of feature variation at different acquisition time points, usually before and after therapy. The aim of this study was to provide a systematic review of the different delta radiomics approaches.

Methods

Eligible articles were searched in Embase, Pubmed, and ScienceDirect using a search string that included free text and/or Medical Subject Headings (MeSH) with 3 key search terms: 'radiomics,' 'texture,' and 'delta.' Studies were analyzed using QUADAS-2 and the RQS tool.

Results

Forty-eight studies were finally included. The studies were divided into preclinical/methodological (5 studies, 10.4%); rectal cancer (6 studies, 12.5%); lung cancer (12 studies, 25%); sarcoma (5 studies, 10.4%); prostate cancer (3 studies, 6.3%), head and neck cancer (6 studies, 12.5%); gastrointestinal malignancies excluding rectum (7 studies, 14.6%) and other disease sites (4 studies, 8.3%). The median RQS of all studies was 25% (mean 21% ± 12%), with 13 studies (30.2%) achieving a quality score < 10% and 22 studies (51.2%) < 25%.

Conclusions

Delta radiomics shows potential benefit for several clinical endpoints in oncology, such asdifferential diagnosis, prognosis and prediction of treatment response, evaluation of side effects. Nevertheless, the studies included in this systematic review suffer from the bias of overall low methodological rigor, so that the conclusions are currently heterogeneous, not robust and hardly replicable.

Further research with prospective and multicenter studies is needed for the clinical validation of delta radiomics approaches.
Differentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration
Authors: Targett Imogen L. , Crompton Lucy A. , Conway Myra E. , Craig Tim J.
Published: July 2024

There has been much interest in the use of cell culture models of neurones, to avoid the animal welfare and cost issues of using primary and human-induced pluripotent stem cell (hiPSC)-derived neurones respectively. The human neuroblastoma cell line, SH-SY5Y, is extensively used in laboratories as they can be readily expanded, are of low cost and can be differentiated into neuronal-like cells. However, much debate remains as to their phenotype once differentiated, and their ability to recapitulate the physiology of bona fide neurones. Here, we characterise a differentiation protocol using retinoic acid and BDNF, which results in extensive neurite outgrowth/branching within 10 days, and expression of key neuronal and synaptic markers. We propose that these differentiated SH-SY5Y cells may be a useful substitute for primary or hiPSC-derived neurones for cell biology studies, in order to reduce costs and animal usage. We further propose that this characterised differentiation timecourse could be used as an in vitro model for neuronal differentiation, for proof-of principle studies on neurogenesis, e.g. relating to neurodegenerative diseases. Finally, we demonstrate profound changes in Tau phosphorylation during differentiation of these cells, suggesting that they should not be used for neurodegeneration studies in their undifferentiated state.