bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and prognostic significance of malnutrition in patients with secondary mitral regurgitation undergoing transcatheter edge‐to‐edge repair
Authors: Pezzola Elisa , Tomasoni Daniela , Caneiro‐Queija Berenice , Raposeiras‐Roubin Sergio , Freixa Xavier , Arzamendi Dabit , Benito‐González Tomas , Montefusco Antonio , Pascual Isaac , Nombela‐Franco Luis , Rodes‐Cabau Josep , Shuvy Mony , Portolés‐Hernández Antonio , Godino Cosmo , Haberman Dan , Metra Marco , Estévez‐Loureiro Rodrigo , Adamo Marianna
Published: May 2024

Background

Malnutrition is associated with poor prognosis in several cardiovascular diseases; however, its role in patients with secondary mitral regurgitation (SMR) is poorly known.

Aims

To evaluate the impact of nutritional status, assessed using different scores, on clinical outcomes in patients with SMR undergoing transcatheter edge‐to‐edge repair (TEER) in a real‐world setting.

Methods

A total of 658 patients with SMR and complete nutritional data were identified from the MIVNUT registry. Nutritional status has been assessed using controlling nutritional status index (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) scores. Outcomes of interest were all‐cause mortality and all‐cause mortality or heart failure (HF) hospitalization.

Results

Any malnutrition grade was observed in 79.4%, 16.7%, and 47.9% of patients by using CONUT, PNI, and GNRI, respectively, while moderate to severe malnutrition was noted in 24.7%, 16.7%, and 25.6% of patients, respectively. At a median follow‐up of 2.2 years, 212 patients (32.2%) died. Moderate‐severe malnutrition was associated with a higher rate of all‐cause mortality (HR: 2.46 [95% CI: 1.69−3.58], HR: 2.18 [95% CI: 1.46−3.26], HR: 1.97 [95% CI: 1.41−2.74] for CONUT, PNI, and GNRI scores, respectively). The combined secondary endpoint of all‐cause mortality and HF rehospitalization occurred in 306 patients (46.5%). Patients with moderate‐severe malnutrition had a higher risk of the composite endpoint (HR: 1.56 [95% CI: 1.20−2.28], HR: 1.55 [95% CI: 1.01−2.19], HR: 1.36 [95% CI: 1.02−1.80] for CONUT, PNI, and GNRI scores, respectively). After adjustment for multiple confounders, moderate‐severe malnutrition remained independently associated with clinical outcomes.

Conclusions

Moderate‐severe malnutrition was common in patients with SMR undergoing TEER. It was independently associated with poor prognosis regardless of the different scores used.
Single and Binary Adsorption of Benzene, Phenol, and p‐Nitrophenol: Effect of Physical Interactions
Authors: Boutillara Yasmine , Tazibet Sana , Fernandez Velasco Leticia , Smati Yakoub , Boudjemaa Moussa , Betache Zohra
Published: May 2024

This work aims at emphasizing the impact of different physical interactions such as intermolecular ones between co‐adsorbed molecules on the adsorption mechanisms in the liquid phase. Thus, the adsorption of a low concentration (5 ppm) of benzene, phenol, and p‐nitrophenol from aqueous medium in single and binary mixture solutions is studied. Two activated carbons were prepared from two different activating agents and used in this regard. The adsorbed amounts are determined by high‐performance liquid chromatography. The results showed the great importance of the aforementioned interactions in the adsorption of phenol, particularly the interactions with the co‐adsorbed compounds. Indeed, phenol was remarkably better retained in binary mixture solutions than in a single one.
Asymmetric Carbene Transfer: Enhancing Chemical Diversity for Drug Discovery
Authors: Shi Taoda , Hu Wenhao
Published: May 2024

The quest to explore chemical space is vital for identifying novel disease targets, impacting both the effectiveness and safety profile of therapeutic agents. The tangible chemical space, currently estimated at a conservative 108 synthesized compounds, pales in comparison to the theoretically conceivable diversity of 1060 molecules. To bridge this vast gap, organic chemists are spearheading innovative methodologies that promise to broaden this limited chemical diversity. A beacon of this progressive wave is Asymmetric Carbene Transfer (ACT), a burgeoning strategy that significantly boosts molecular diversity with efficient bond‐formation and precise chiral control. This review focuses on the capabilities of ACT in creating pharmaceutically significant molecules, encompassing an array of natural products and bioactive compounds. Through the lens of ACT, we discern its substantial influence on drug discovery, paving the way for novel therapeutic avenues by expanding the boundaries of molecular diversity. This review will shed light on prospective methodological developments of ACT and articulate their conceivable contributions to the medicinal chemistry arena.
Coinage Metal Complexes of a Sterically Encumbered Anionic Pyridylborate
Authors: Vanga Mukundam , Muñoz‐Castro Alvaro , Dias H. V. Rasika
Published: May 2024

Sterically loaded, anionic pyridine has been synthesized and utilized successfully in the stabilization of a isoleptic series of coinage metal complexes. The treatment of [4‐(Ph3B)‐2,6‐Trip2Py]K (Trip=2,4,6‐iPr3C6H2) with CuBr(PPh3), AgCl(PPh3) or AuCl(PPh3) (Py=pyridine) afforded the corresponding [4‐(Ph3B)‐2,6‐Trip2Py]M(PPh3) (M=Au, Ag, Cu) complexes, via salt metathesis, as isolable, crystalline solids. Notably, these reactions avoid the facile single electron transfer chemistry reported with the less bulky ligand systems. The X‐ray structures revealed that they are two‐coordinate metal adducts. The M−N and M−P bond distances are longest in the silver and shortest in the copper adduct among the three group 11 family members. Computational analysis revealed an interesting stability dependence on steric bulk of the anionic pyridine (i. e., pyridyl borate) ligand. A comparison of structures and bonding of [4‐(Ph3B)‐2,6‐Trip2Py]Au(PPh3) to pyridine and m‐terphenyl complexes, {[2,6‐Trip2Py]Au(PPh3)}[SbF6] and [2,6‐Trip2Ph]Au(PPh3) are also provided. The Au(I) isocyanide complex, [4‐(Ph3B)‐2,6‐Trip2Py]Au(CNBut) has been stabilized using the same anionic pyridylborate illustrating that it can support other gold‐ligand moieties as well.
Iron‐Catalyzed, Light‐Driven Decarboxylative Alkoxyamination
Authors: Innocent Milan , Tanguy Clément , Gavelle Sigrid , Aubineau Thomas , Guérinot Amandine
Published: May 2024

An iron‐catalyzed visible‐light driven decarboxylative alkoxyamination is disclosed. In the presence of FeBr2 and TEMPO, a large array of carboxylic acids including marketed drugs and biobased molecules is turned into the corresponding alkoxyamine derivatives. The versatility of the latter offers an entry towards molecular diversity generation from abundant starting materials and catalyst. Overall, this method proposes a unified and general approach for LMCT‐based iron‐catalyzed decarboxylative functionalization.
Ligand Basicity and Chelate Effects on Sulfur Insertion vs. Sulfur Reduction by Zinc Thiolate Complexes
Authors: Seo W. T. Michael , Tsang Victor A. , Ballesteros Moises , Tsui Emily Y.
Published: May 2024

4‐ and 5‐coordinate zinc thiolate complexes supported either by bis(carboxamide)pyridine frameworks or by substituted tris(pyrazolyl)borate ligands react with elemental sulfur (S8) following two distinct pathways. Some zinc thiolate moieties insert sulfur atoms to form zinc polysulfanide complexes, while others reduce sulfur and oxidize the thiolate. Here, we compare the effects of ligand electronics, strain, and sterics for selecting the respective reaction pathway. These results show that chelating and electron‐deficient thiolate ligands better stabilize persistent zinc‐bound polysulfanide species.
Screening of Astec® CHIRALDEX™ G‐PN and LIPODEX™ D gas chromatography columns for enantioseparation of amphetamine derivatives
Authors: Hubner Eva‐Maria , Schützinger Sophie , Molnárová Katarína , Schmid Martin G.
Published: May 2024

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class.

Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G‐PN column containing 2,6‐di‐O‐pentyl‐3‐propionyl‐γ‐cyclodextrin and a Lipodex™ D column containing heptakis‐(2,6‐di‐O‐pentyl‐O‐acetyl)‐β‐cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS‐QP2010 SE system.

Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA‐derivatives.

A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G‐PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.
Stable Electron Spin Pan on Aromatic Oxalic Acid Radical
Authors: Huang Jiaxing , Liao Chenghui , Guan Longtian , Meng Qiao , Gu Sichen , He Zhicai , Li Yuan
Published: May 2024

Comprehensive Summary

The stability of organic radicals in ambient condition is important for their practical application. During the development of organic radical chemistry, the electron‐withdrawing and steric hindrance groups are usually introduced to improve the stability of radicals via reducing the reactivity of radicals with oxygen in air. Herein, the electron‐withdrawing carbonyl groups are introduced to construct a planar aromatic oxalic acid radical (IDF‐O8) with two‐dimensional electron spin pan structure. Interestingly, IDF‐O8 exhibited a low optical bandgap of 0.91 eV in film, however, the multiple quinone resonance structures between electron‐withdrawing ketone and phenol radicals contribute to the high stability of open‐shell radical IDF‐O8 without protection of large steric hindrance groups. Under the irradiation of 808 nm (1.2 W·cm–2), IDF‐O8 reaches 147 °C in powder state. This work provides an efficient synthesis route for the open‐shell electron spin pan system, which is different from the famous fullerene, carbon nanotube and graphene. The electron spin pan can be extended to spin tube or spin sphere system based on the design strategy of aromatic inorganic acid radicals in future.
A one‐dimensional computational model for blood flow in an elastic blood vessel with a rigid catheter
Authors: Pradhan Aseem Milind , Mut Fernando , Cebral Juan Raul
Published: May 2024

Strokes are one of the leading causes of death in the United States. Stroke treatment involves removal or dissolution of the obstruction (usually a clot) in the blocked artery by catheter insertion. A computer simulation to systematically plan such patient‐specific treatments needs a network of about 105 blood vessels including collaterals. The existing computational fluid dynamic (CFD) solvers are not employed for stroke treatment planning as they are incapable of providing solutions for such big arterial trees in a reasonable amount of time. This work presents a novel one‐dimensional mathematical formulation for blood flow modeling in an elastic blood vessel with a centrally placed rigid catheter. The governing equations are first‐order hyperbolic partial differential equations, and the hypergeometric function needs to be computed to obtain the characteristic system of these hyperbolic equations. We employed the Discontinuous Galerkin method to solve the hyperbolic system and validated the implementation by comparing it against a well‐established 3D CFD solver using idealized vessels and a realistic truncated arterial network. The results showed clinically insignificant differences in steady flow cases, with overall variations between 1D and 3D models remaining below 10%. Additionally, the solver accurately captured wave reflection phenomena at domain discontinuities in unsteady cases. A primary advantage of this model over 3D solvers is its ease in obtaining a discretized geometry of complex vasculatures with multiple arterial branches. Thus, the 1D computational model offers good accuracy and applicability in simulating complex vasculatures, demonstrating promising potential for investigating patient‐specific endovascular interventions in strokes.
Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium–Glucose Cotransporter 2 Inhibitors vs. Non‐Users
Authors: Lee Hsin‐Fu , Chan Yi‐Hsin , Hsu Tzyy‐Jer , Chuang Chi , Li Pei‐Ru , Yeh Yung‐Hsin , Su Hung‐Chi , Hsiao Fu‐Chih , See Lai‐Chu
Published: May 2024

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium–glucose cotransporter‐2 inhibitors (SGLT2i) vs. non‐use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow‐up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24–0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39–0.89; P = 0.0126), and all‐cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50–0.95; P = 0.0225) compared with the non‐SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.
Self‐Modification of Defective TiO2 under Controlled H2/Ar Gas Environment and Dynamics of Photoinduced Surface Oxygen Vacancies
Authors: Tjardts Tim , Elis Marie , Shondo Josiah , Voß Lennart , Schürmann Ulrich , Faupel Franz , Kienle Lorenz , Veziroglu Salih , Aktas Oral Cenk
Published: May 2024

In recent years, defective TiO2 has caught considerable research attention because of its potential to overcome the limits of low visible light absorption and fast charge recombination present in pristine TiO2 photocatalysts. Among the different synthesis conditions for defective TiO2, ambient pressure hydrogenation with the addition of Ar as inert gas for safety purposes has been established as an easy method to realize the process. Whether the Ar gas might still influence the resulting photocatalytic properties and defective surface layer remains an open question. Here, we reveal that the gas flow ratio between H2 and Ar has a crucial impact on the defective structure as well as the photocatalyic activity of TiO2. In particular, transmission electron microscopy (TEM) in combination with electron energy loss spectroscopy (EELS) revealed a larger width of the defective surface layer when using a H2/Ar (50 %–50 %) gas mixture over pure H2. A possible reason could be the increase in dynamic viscosity of the gas mixture when Ar is added. Additionally, photoinduced enhanced Raman spectroscopy (PIERS) is implemented as a complementary approach to investigate the dynamics of the defective structures under ambient conditions which cannot be effortlessly realized by vacuum techniques like TEM.
How dispersal rates depend on the prey capture strategy: A case study of Georgia's spiders
Authors: Tarkhnishvili David , Seropian Armen , Erhardt Christoph , Kachlishvili Nino , Krammer Hans‐Joachim , Hein Nils
Published: May 2024

Large‐scale barcoding projects help to aggregate information on genetic variability of multiple species throughout their ranges. Comparing DNA sequences of both non‐conspecific and conspecific individuals from distant parts of their ranges helps to compare level of genetic isolation‐by‐distance patterns in different species and adaptive types. We compared mitochondrial CO1 gene sequences of 223 spiders from Georgia (Caucasus), representing 124 species and eight families, with 3097 homological sequences from spiders mostly from Europe, but also from other parts of the World. In most families, a significant isolation‐by distance pattern was observed on family level. On species level, a significant isolation‐by‐distance was observed in 40 species, although this low proportion is most likely related to a lack of data. Simultaneously, remarkable differences in spatial structure were shown for different species. Although the majority of the studied species have a broad western Palearctic range, web‐building spiders from families Araneidae, Theridiidae, and Linyphiidae are less isolated spatially than flower spiders (Thomisidae), jumping spiders (Salticidae), wolf spiders (Lycosidae), sac spiders (Clubionidae), and ground spiders (Gnaphosidae). This pattern is related with more common ballooning in web building than in actively hunting spiders, which commonly remain isolated since preglacial time. Ground spiders build the most isolated populations in the Caucasus.
Relative predation intensity of an intertidal gastropod on artificial coastal defense structures
Authors: Yeo Hannah H. J. , Yeo Jing Ying , Todd Peter A.
Published: May 2024

Despite seawalls becoming ubiquitous coastal features, and having some physical similarities to natural rocky shores, it remains unclear how these urban habitats influence predator–prey interactions. Predators can affect intertidal mobile prey densities through two pathways: (1) successful predation directly influences prey mortality rates, and (2) direct and indirect effects of predation can scare and induce motile prey to seek safer areas. In this study, we investigated whether intertidal predators affect the density of the marine gastropod, Nerita undata, at four seawall sites in Singapore. Using a tethering method that we developed, we monitored the mortality and other evidence of predation (shell state) of tethered N. undata. Field experiments revealed high (22.5%–82.5%) predation potential of N. undata across the four sites, with significantly higher predation risk at lower shore heights and for snails with mixed shell coloration. Observations and analysis of the shell state after 3 days showed that predation on seawalls was primarily by crushing predators such as fish. Other predators of N. undata include predatory snails, with various feeding methods that left behind different predator signatures. Our results add substantially to the limited knowledge on predator–prey interactions on seawalls, particularly for Nerita undata, and suggest that seawall systems are more dynamic than previously thought. This further highlights the role of these artificial structures as important habitats and feeding grounds in urban coastal ecosystems.
Camouflaged liability: How the distinction between civilians and soldiers influences moral judgement of permissible harm in war
Authors: Marulanda‐Hernández Juan Carlos , Wiegmann Alex , Waldmann Michael R.
Published: May 2024

Previous research has shown that people judge sacrificing a few people to save a larger number to be morally permissible when the intervention targets the threat but not when it targets the victims. We investigated whether this distinction according to the locus of intervention influences people's evaluations of wartime scenarios and whether such evaluations vary according to different types of victims (e.g., civilians vs. soldiers). We observed a significant effect of locus of intervention in situations in which a smaller number of civilians were sacrificed to save a larger number of civilians (Study 1; N = 142). However, the effect of locus of intervention was less pronounced in scenarios in which soldiers were sacrificed to save civilians (Studies 2 and 3; N = 173 and N = 841). A fourth experiment (N = 477) explored why participants treated soldiers and civilians differently. Participants believed that it is more permissible to sacrifice soldiers because they consent to being harmed.
Terrestriality across the primate order: A review and analysis of ground use in primates
Authors: Estrada Gene R. , Marshall Andrew J.
Published: May 2024

Terrestriality is relatively rare in the predominantly arboreal primate order. How frequently, and when, terrestriality appears in primate evolution, and the factors that influence this behavior, are not well understood. To investigate this, we compiled data describing terrestriality in 515 extant nonhuman primate taxa. We describe the geographic and phylogenetic distribution of terrestriality, including an ancestral state reconstruction estimating the frequency and timing of evolutionary transitions to terrestriality. We review hypotheses concerning the evolution of primate terrestriality and test these using data we collected pertaining to characteristics including body mass and diet, and ecological factors including forest structure, food availability, weather, and predation pressure. Using Bayesian analyses, we find body mass and normalized difference vegetation index are the most reliable predictors of terrestriality. When considering subsets of taxa, we find ecological factors such as forest height and rainfall, and not body mass, are the most reliable predictors of terrestriality for platyrrhines and lemurs.
Osteoblastoma of the thumb with a novel PRSS44::ALK fusion and literature review of osteoblastoma of hands and feet bones
Authors: Brandea Andrew I. , Afkhami Michelle , Klein Michael J. , Bell Diana
Published: May 2024

Osteoblastomas (OBs) are benign neoplasms constituting approximately 1% of primary bone tumors with a predilection for the spine and sacrum. We describe an OB of the proximal phalanx of the left thumb in a 38‐year‐old female. MRI of left hand demonstrated a 29‐mm mildly expansile enhancing lesion involving the entire proximal phalanx of the first digit. Histology displayed a bone‐forming tumor consisting of trabeculae of remodeled woven bone framed by plump osteoblasts in a vascularized background. Next‐generation sequencing analysis identified a PRSS44::ALK fusion gene.
PM2.5 toxicity in blood impairs cardiac redox balance and promotes mitochondrial dysfunction in rat heart that further aggravates ischemia reperfusion injury by modulating PI3K/AKT/mTOR/NF‐kB signaling axis
Authors: Sivakumar Bhavana , Kurian Gino A.
Published: May 2024

According to the pathophysiological mechanisms linking particulate matter (PM2.5) exposure and cardiovascular diseases, PM2.5 may directly translocate into the blood stream and remote target organs and thereby induce cardiovascular effects. The toxicity of PM2.5 is known to induce oxidative stress in pulmonary tissue, but its impact on the redox state in heart (distant organ) is unknown and how it modulates the cardiac response to ischemia reperfusion (IR) remains unclear. In the present study, we evaluated the toxic effect of PM2.5 on cardiac physiology in the presence and absence of IR after introducing PM2.5 into the blood. Female Wistar rats were injected with diesel particulate matter (DPM) via i.p & i.v routes at a concentration of 10 µg/ml. The toxic impact of PM2.5 not only adversely affects the cardiac ultra‐structure (leading to nuclear infiltration, edema, irregularities in heart muscle and nuclear infiltration), but also altered the cellular redox balance, elevated inflammation and promoted the upregulation of proapoptotic mediator genes at the basal level of myocardium. The results showed alterations in cardiac ultrastructure, elevated oxidative stress and significant redox imbalance, increased inflammation and proapoptotic mediators at the basal level of myocardium. Moreover, the cardioprotective pro survival signaling axis was declined along with an increased NF‐kB activation at the basal level. IR inflicted further injury with deterioration of cardiac hemodynamic indices (Heart rate [HR], Left ventricular developed pressure [LVDP], Left ventricular end‐diastolic pressure [LVEDP] and rate pressure product [RPP]) along with prominent inactivation of signaling pathways. Furthermore, the levels of GSH/GSSG, NADH/NAD, NADPH/NADP were significantly low along with increased lipid peroxidation in mitochondria of PM2.5 treated IR rat hearts. This observation was supported by downregulation of glutaredoxin and peroxiredoxin genes in the myocardium. Similarly the presence of oxidative stress inducing metals was found at a higher concentration in cardiac mitochondria. Thus, the toxic impact of PM2.5 in heart augment the IR associated pathological changes by altering the physiological response, initiating cellular metabolic alterations in mitochondria and modifying the signaling molecules.
Bone bruise distribution predicts anterior cruciate ligament tear location in non‐contact injuries
Authors: Ubl Steffen T. , Vieider Romed P. , Seilern und Aspang Jesse , Gaebler Christian , Platzgummer Hannes
Published: May 2024

Purpose

It is unclear whether different injury mechanisms lead to divergent anterior cruciate ligament (ACL) tear locations. This study aims to analyse the relationship between bone bruise (BB) distribution or depth and ACL tear location.

Methods

A retrospective analysis of 446 consecutive patients with acute non‐contact ACL injury was performed. Only patients with complete ACL tears verified during subsequent arthroscopy were included. Magnetic resonance imaging (MRI) was used to classify BB location, BB depth, ACL tear location and concomitant injuries (medial/lateral meniscus and medial/lateral collateral ligament). Demographic characteristics included age, gender, body mass index (BMI), type of sport and time between injury and MRI. Multiple linear regression analysis was used to identify independent predictors of ACL tear location.

Results

One hundred and fifty‐eight skeletally mature patients met the inclusion criteria. The presence of BB in the lateral tibial plateau was associated with a more distal ACL tear location (β = −0.27, p < 0.001). Less BB depth in the lateral femoral condyle showed a tendency towards more proximal ACL tears (β = −0.14; p = 0.054). Older age predicted a more proximal ACL tear location (β = 0.31, p < 0.001). No significant relationship was found between ACL tear location and gender, BMI, type of sport, concomitant injuries and time between injury and MRI.

Conclusion

ACL tear location after an acute non‐contact injury is associated with distinct patterns of BB distribution, particularly involving the lateral compartment, indicating that different injury mechanisms may lead to different ACL tear locations.

Level of Evidence

Level III.
Extracellular vesicles as human therapeutics: A scoping review of the literature
Authors: Fusco Clorinda , De Rosa Giusy , Spatocco Ilaria , Vitiello Elisabetta , Procaccini Claudio , Frigè Chiara , Pellegrini Valeria , La Grotta Rosalba , Furlan Roberto , Matarese Giuseppe , Prattichizzo Francesco , de Candia Paola
Published: May 2024

Extracellular vesicles (EVs) are released by all cells and contribute to cell‐to‐cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans.

The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well‐designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options.
Ubiquity of oriented rays
Authors: Gut Florian , Krill Thilo , Reich Florian
Published: May 2024

A digraph is called ubiquitous if every digraph that contains vertex‐disjoint copies of for every also contains infinitely many vertex‐disjoint copies of . We characterise which digraphs with rays as underlying undirected graphs are ubiquitous.
Density of 3‐critical signed graphs
Authors: Beaudou Laurent , Haxell Penny , Nurse Kathryn , Sen Sagnik , Wang Zhouningxin
Published: May 2024

We say that a signed graph is ‐critical if it is not ‐colorable but every one of its proper subgraphs is ‐colorable. Using the definition of colorability due to Naserasr, Wang, and Zhu that extends the notion of circular colorability, we prove that every 3‐critical signed graph on vertices has at least edges, and that this bound is asymptotically tight. It follows that every signed planar or projective‐planar graph of girth at least 6 is (circular) 3‐colorable, and for the projective‐planar case, this girth condition is best possible. To prove our main result, we reformulate it in terms of the existence of a homomorphism to the signed graph , which is the positive triangle augmented with a negative loop on each vertex.
Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study
Authors: Hao Yu‐Wei , Ning Xue‐Yi , Wang He , Bai Xu , Zhao Jian , Xu Wei , Zhang Xiao‐Jing , Yang Da‐Wei , Jiang Jia‐Hui , Ding Xiao‐Hui , Cui Meng‐Qiu , Liu Bai‐Chuan , Guo Hui‐Ping , Ye Hui‐Yi , Wang Hai‐Yi
Published: May 2024

Background

Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension.

Purpose

To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs.

Study Type

Retrospective.

Population

797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses.

Field Strength/Sequences

3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion‐weighted imaging, a dual‐echo chemical shift (in‐ and opposed‐phase) T1 weighted imaging, multiphase dynamic contrast‐enhanced imaging.

Assessment

Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions.

Statistical Tests

Random‐effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05.

Results

The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993).

Conclusion

The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool.

Evidence Level

4.

Technical Efficacy

Stage 2.
Time‐to‐Event Endpoints in Imaging Biomarker Studies
Authors: Chen Ruizhe , Wang Hao
Published: May 2024

Time‐to‐event endpoints are widely used as measures of patients' well‐being and indicators of prognosis. In imaging‐based biomarker studies, there are increasingly more studies that focus on examining imaging biomarkers' prognostic or predictive utilities on those endpoints, whether in a trial or an observational study setting. In this educational review article, we briefly introduce some basic concepts of time‐to‐event endpoints and point out potential pitfalls in the context of imaging biomarker research in hope of improving radiologists' understanding of related subjects. Besides, we have included some review and discussions on the benefits of using time‐to‐event endpoints and considerations on selecting overall survival or progression‐free survival for primary analysis.

Level of Evidence

5

Technical Efficacy

Stage 3
Assessing herpes zoster vaccine efficacy in patients with diabetes: A community‐based cohort study
Authors: Kornelius Edy , Lo Shih‐Chang , Huang Chien‐Ning , Wang Chi‐Chih , Wang Yu‐Hsun , Yang Yi‐Sun
Published: May 2024

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real‐world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non‐HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non‐HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non‐HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83–1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93–1.34) for Shingrix versus non‐HZ vaccine, 1.02 (95% CI: 0.86–1.20) for Zostavax versus non‐HZ vaccine, and 1.06 (95% CI: 0.87–1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow‐up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.
Antarctica's hidden mycoviral treasures in fungi isolated from mosses: A first genomic approach
Authors: Nobre Steffany V. A. , de Andrade Guilherme A. K. , Metz Geferson F. , Lucini Fabíola , de Albuquerque Margéli P. , Victória Filipe de C.
Published: May 2024

This study investigates the presence of mycoviruses in Antarctic fungi and elucidates their evolutionary relationships. To achieve this, we aligned mycoviral gene sequences with genomes of previously sequenced Antarctic endophytic fungi, made available by our research group and accessible via Joint Genome Institute. Our findings reveal that the most prevalent genetic regions in all endophytic fungi are homologous to Partitiviruses, Baculoviridae, and Phycodnaviridae. These regions display evidence of positive selection pressure, suggesting genetic diversity and the accumulation of nonsynonymous mutations. This phenomenon implies a crucial role for these regions in the adaptation and survival of these fungi in the challenging Antarctic ecosystems. The presence of mycoviruses in Antarctic endophytic fungi may indicate shared survival strategies between the virus and its host, shedding light on their evolutionary dynamics. This study underscores the significance of exploring mycoviruses within endophytic fungi and their contributions to genetic diversity. Future research avenues could delve into the functional implications of these conserved mycoviral genetic regions in Antarctic endophytic fungi, providing a comprehensive understanding of this intriguing association and genomic retention of viral region in fungi.
The mitigative role of novel aflatoxin‐degrading enzymes in diverse broiler performance indicators and gut microbiota following the consumption of diets contaminated with aflatoxins
Authors: Jia Ru , Tian Senmiao , Yang Zhaofeng , Lu Simeng , Wang Lan , Zhang Guohua
Published: May 2024

BACKGROUND

This study aims to explore both the toxic effects of aflatoxins (AFs) and the protective effects of degrading enzymes (DE) on broilers exposed to AFs.

RESULTS

The findings reveal that a diet contaminated with 69.15 μg kg−1 of aflatoxin B1 had significant adverse effects on broilers. Specifically, it led to a reduction in average daily gain, dressed yield percentage, half‐eviscerated yield with giblet yield percentage, eviscerated yield percentage, as well as serum superoxide dismutase (SOD), glutathione peroxidase activity and liver SOD activity (P < 0.05). Conversely, the diet increased the feed conversion ratio, liver index, serum glutamic oxaloacetic transaminase levels and malondialdehyde levels in both serum and liver (P < 0.05). Additionally, AFs disrupted the intestinal microflora significantly (P < 0.05), altering the relative abundance of Enterococcus, Lactobacillus and Escherichia in broiler jejunum. The addition of DE to AF‐contaminated feed mitigated these negative effects and reduced the residues of aflatoxin B1, aflatoxin B2 and aflatoxin M1 in the liver and duodenum (P < 0.05). We also observed that broilers fed the diet pelleted at 80 °C exhibited improved dressing percentage and water holding capacity compared to those on the 75 °C diet.

CONCLUSION

In summary, DE serves as an effective feed additive for mitigating AF contamination in poultry production. © 2024 Society of Chemical Industry.
Externally validated treatment algorithm acceptably predicts nonoperative treatment success in patients with anterior cruciate ligament rupture
Authors: de Vos Floris H. , Meuffels Duncan E. , Baart Sara J. , van Es Eline M. , Reijman Max
Published: May 2024

Purpose

This study aims to develop and externally validate a treatment algorithm to predict nonoperative treatment success or failure in patients with anterior cruciate ligament (ACL) rupture.

Methods

Data were used from two completed studies of adult patients with ACL ruptures: the Conservative versus Operative Methods for Patients with ACL Rupture Evaluation study (development cohort) and the KNee osteoArthritis anterior cruciate Ligament Lesion study (validation cohort). The primary outcome variable is nonoperative treatment success or failure. Potential predictor variables were collected, entered into the univariable logistic regression model and then incorporated into the multivariable logistic regression model for constructing the treatment algorithm. Finally, predictive performance and goodness‐of‐fit were assessed and externally validated by discrimination and calibration measures.

Results

In the univariable logistic regression model, a stable knee measured with the pivot shift test and a posttrauma International Knee Documentation Committee (IKDC) score <50 were predictive of needing an ACL reconstruction. Age >30 years and a body mass index > 30 kg/m2 were predictive for not needing an ACL reconstruction. Age, pretrauma Tegner score, the outcome of the pivot shift test and the posttrauma IKDC score are entered into the treatment algorithm. The predictability of needing an ACL reconstruction after nonoperative treatment (discrimination) is acceptable in both the development and the validation cohort: area under the curve = resp. 0.69 (95% confidence interval [CI]: 0.58–0.81) and 0.68 (95% CI: 0.58–0.78).

Conclusion

This study shows that the treatment algorithm can acceptably predict whether an ACL injury patient will have a(n) (un)successful nonoperative treatment (discrimination). Calibration of the treatment algorithm suggests a systematical underestimation of the need for ACL reconstruction. Given the limitations regarding the sample size of this study, larger data sets must be constructed to improve the treatment algorithm further.

Level of Evidence

Level II.
Varus knee osteoarthritis with ankle osteoarthritis demonstrates greater hindfoot inversion and larger ankle inversion loading during gait following total knee arthroplasty compared to varus knee osteoarthritis alone
Authors: Kikuchi Naoya , Kanamori Akihiro , Kadone Hideki , Okuno Kosuke , Hyodo Kojiro , Yamazaki Masashi
Published: May 2024

Purpose

Although patients with varus knee osteoarthritis (KOA) and concurrent ankle osteoarthritis (AOA) may experience increased ankle joint pain after total knee arthroplasty (TKA), the underlying mechanism remains unclear. This study aimed to investigate the effects of concurrent AOA on ankle and hindfoot alignment, frontal plane ankle and hindfoot biomechanics during gait following TKA and the clinical outcomes.

Methods

Twenty‐four patients with varus KOA who underwent TKA were included in this retrospective cohort study. Patients were categorized into two groups: with and without AOA. Radiographic evaluations of lower‐limb, ankle and hindfoot alignment, and knee and ankle clinical outcomes were conducted preoperatively and 6 months postoperatively. In addition, gait analyses were performed to investigate knee, ankle and hindfoot kinematics and kinetics. Each data was compared between patients with and without AOA.

Results

Concomitant AOA was found in eight ankles. The AOA group exhibited greater postoperative hindfoot varus and increased postoperative ankle pain than the non‐AOA group. Gait analysis showed no significant differences in knee varus alignment or tibial tilt after TKA between the groups. However, the AOA group demonstrated significantly greater hindfoot inversion and larger ankle inversion loading.

Conclusion

One third of patients who underwent TKA had concurrent AOA associated with hindfoot varus. Despite achieving proper coronal knee alignment postoperatively, these patients experienced greater hindfoot and ankle joint inversion load during gait. Surgeons should consider the inability to evert the hindfoot and the possibility of increased ankle joint pain when planning and performing TKA.

Level of Evidence

Level III.
Excimer laser coronary angioplasty combined with drug‐coated balloon in the treatment of in‐stent restenosis
Authors: He Pan , Chen Haiwei , Yang Junjie , Gao Lei , Guo Jun , Chen Yundai , Wang Qi
Published: May 2024

Objectives

The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug‐coated balloons (DCBs) in the treatment of in‐stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA.

Methods

We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow‐up 1 year after the procedure. The primary endpoint was the 1‐year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention).

Results

A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well‐balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57–1.69],p < 0.001), The reduction in 1‐year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11–0.99]; log‐rankp = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001).

Conclusions

The combination of ELCA and DCB is a safe and effective treatment strategy for in‐stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long‐term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.
Current progress in chimeric antigen receptor T‐cell therapy for malignant tumors
Authors: Zheng Yashang , Huang Jiaqian , Xu Yuhong , Luo Hui‐Yan
Published: May 2024

In the realm of malignant tumor treatment, particularly regarding hematologic malignancies, chimeric antigen receptor T‐cell (CAR‐T) immunotherapy has witnessed remarkable advancements in recent years. This approach involves genetically modifying and engineering a patient's T‐cells ex vivo to express a specific CAR, known as CAR‐T cells. When these modified cells are reintroduced into the patient, they can specifically recognize target antigens and exhibit highly efficient cytotoxicity against cells expressing these antigens, making them suitable for the treatment of malignant tumors. CD19, which is expressed on the surface of B lymphocytes at different stages of differentiation, has been identified as a suitable target for the treatment of most B‐cell lymphomas. CAR‐T cells targeting CD19 have demonstrated excellent specificity, cytotoxicity, and persistence in both in vitro and clinical trials, showing tremendous potential for application. However, identifying appropriate targets for CAR‐T therapy in solid tumors remains a challenge, leading to limited advancements in this area. This review discusses the mechanisms, applications, limitations, and prospects of CAR‐T therapy in hematologic malignancies and solid tumors, aiming to provide directions for future research in this field.