bluuebunny/crossref_metadata_2025 huggingface dataset:
Tipifarnib physiologically‐based pharmacokinetic modeling to assess drug–drug interaction, organ impairment, and biopharmaceutics in healthy subjects and cancer patients
Authors: Okudaira Noriko , Burt Howard , Mitra Amitava
Published: May 2024

A physiologically‐based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and several clinical data in healthy subjects and cancer patients. The final PBPK model was able to recover the clinically observed single and multiple‐dose plasma concentrations of tipifarnib in healthy subjects and cancer patients under several dosing conditions, such as co‐administration with a strong CYP3A4 inhibitor and inducer, an acid‐reducing agent (proton pump inhibitor and H2 receptor antagonist), and with a high‐fat meal. In addition, the model was able to accurately predict the effect of mild or moderate hepatic impairment on tipifarnib exposure. The appropriately verified model was applied to prospectively simulate the liability of tipifarnib as a victim of CYP3A4 enzyme‐based drug–drug interactions (DDIs) with a moderate inhibitor and inducer as well as tipifarnib as a perpetrator of DDIs with sensitive substrates of CYP3A4, CYP2B6, CYP2D6, CYP2C9, and CYP2C19 in healthy subjects and cancer patients. The effect of a high‐fat meal, acid‐reducing agent, and formulation change at the therapeutic dose was simulated. Finally, the model was used to predict the effect of mild, moderate, or severe hepatic, and renal impairment on tipifarnib PK. This multipronged approach of combining the available clinical data with PBPK modeling‐guided dosing recommendations for tipifarnib under several conditions. This example showcases the totality of the data approach to gain a more thorough understanding of clinical pharmacology and biopharmaceutic properties of oncology drugs in development.
Oxygen Stoichiometry Engineering in P‐Type NiOx for High‐Performance NiO/Ga2O3 Heterostructure p–n Diode
Authors: Hong Yuehua , Zheng Xuefeng , Zhang Hao , He Yunlong , Zhu Tian , Liu Kai , Li Ang , Ma Xiaohua , Zhang Weidong , Zhang Jianfu , Hao Yue
Published: May 2024

P‐type NiOx is employed for the fabrication of NiO/Ga2O3 p–n diode. Addressing the challenge of low hole mobility in NiOx, an extensive investigation into the impact of oxygen stoichiometry engineering in NiOx is conducted. The meticulous optimization of the O2/Ar ratio to 30% during the sputtering process results in significant improvements, notably achieving enhanced hole mobility of 1.61 cm2 V−1 s. It leads to a low specific on‐resistance of 2.79 mΩ cm2 and a high rectification ratio of ≈1011, underscoring the efficacy of recombination transport mechanism driven by enhanced hole mobility. Detailed band alignment analysis between NiOx and Ga2O3 reveals a small band offset, with a valence band offset of 2.47 eV and a conduction band offset of 1.70 eV. It suggests a tailored modification of band alignment through the engineering the oxygen stoichiometry in NiOx, facilitating enhanced recombination conduction. The device exhibits a superior breakdown voltage (Vb) of 2780 V and a notable Baliga's figure of merit (BFOM) of 2.77 GW cm−2, surpassing the SiC unipolar figure of merit. The insights gained from this work are expected to inform future designs and optimizations of high‐performance Ga2O3 electronic devices.
How did states in the United States adapt their cancer control plan in response to the COVID‐19 pandemic?
Authors: Semprini Jason
Published: May 2024

The COVID‐19 pandemic upended the delivery of cancer services across the care continuum. By outlining specific strategies for addressing cancer in the state, cancer control plans serve a critical role during a public health emergency. This policy analysis aims to understand how states updated their cancer control plan as a response to COVID‐19. All plans from 50 states and the District of Columbia were reviewed for language related to “COVID.” Among the 51 cancer plans analyzed, 7 plans met the inclusion criteria (Illinois [IL], Iowa [IA], Maine [ME], Nevada [NV], North Carolina [NC], Utah [UT], and Vermont [VT]). These seven plans adapted their cancer control plan in response to the COVID‐19 pandemic across three main themes: (1) improving care across the cancer care continuum, from prevention to screening and treatment; (2) improving cancer care service delivery by expanding telehealth, addressing workforce shortages, and investing in public health systems; and (3) achieving population health equity by addressing social determinants of health. Two states only adapted their plans by prioritizing future monitoring and evaluation activities as related to the COVID‐19 pandemic (ME and VT). The other five states all took different approaches to improve cancer care by adapting their service delivery and addressing social determinants of health. IL prioritized access to cancer screenings through expanding equity informed telehealth models. IA also prioritized equitable screenings as well as clinical trial participation, by addressing workforce shortages. NV focused on prevention, leveraging telehealth and specifically targeted food security and job loss resulting from the pandemic. NC‐directed cancer treatment efforts by addressing workforce shortages. UT integrated telehealth and equity initiatives to combat barriers like food insecurity and social disparities. Continued policy surveillance is needed to ensure that patients receive timely, appropriate cancer care during future public health emergencies. Research evaluating whether these plan adaptations improved outcomes or advanced equity remains warranted.
Mapping emergent coral reefs: a comparison of pixel‐ and object‐based methods
Authors: Stone Amy , Hickey Sharyn , Radford Ben , Wakeford Mary
Published: May 2024

Although emergent coral reefs represent a significant proportion of overall reef habitat, they are often excluded from monitoring projects due to their shallow and exposed setting that makes them challenging to access. Using drones to survey emergent reefs overcomes issues around access to this habitat type; however, methods for deriving robust monitoring metrics, such as coral cover, are not well developed for drone imagery. To address this knowledge gap, we compare the effectiveness of two remote sensing methods in quantifying broad substrate groups, such as coral cover, on a lagoon bommie, namely a pixel‐based (PB) model versus an object‐based (OB) model. For the OB model, two segmentation methods were considered: an optimized mean shift segmentation and the fully automated Segment Anything Model (SAM). Mean shift segmentation was assessed as the preferred method and applied in the final OB model (SAM exhibited poor identification of coral patches on the bommie). While good cross‐validation accuracies were achieved for both models, the PB had generally higher overall accuracy (mean accuracy PB = 75%, OB = 70%) and kappa (mean kappa PB = 0.69, OB = 0.63), making it the preferred method for monitoring coral cover. Both models were limited by the low contrast between Coral features and the bommie substrate in the drone imagery, causing indistinct segment boundaries in the OB model that increased misclassification. For both models, the inclusion of a drone‐derived digital surface model and multiscale derivatives was critical to predicting coral habitat. Our success in creating emergent reef habitat models with high accuracy demonstrates the niche role drones could play in monitoring these habitat types, which are particularly vulnerable to rising sea surface and air temperatures, as well as sea level rise which is predicted to outpace reef vertical accretion rates.
Surface science insight note: Imaging X‐ray photoelectron spectroscopy
Authors: Fernandez Vincent , Fairley Neal , Morgan David , Bargiela Pascal , Baltrusaitis Jonas
Published: May 2024

Quantification of X‐ray photoelectron spectroscopy (XPS) data is often limited by the heterogeneous nature of the material surface. However, it is often the case that heterogeneous material contains areas within the analyzed area that are effectively homogeneous. In this Insight note, concepts, and methods used to analyze both XPS data are presented to extract both spatial and spectral information from heterogeneous surfaces. These concepts and methods are applied to a specific material surface that contains three chemical compounds separated spatially. The analysis entails converting XPS image data to spectral data and is designed to highlight the potential of XPS imaging in revealing compositional information correlation with spatial information. Properties of algorithms used to evaluate XPS images and spectra are described to outline their application to image data. A case study of an imaging XPS data set is presented that demonstrates how poor signal‐to‐noise images, where the signal is recorded for 4 s per image, are still open to analysis yielding useful information. Ultimately, the methods presented here will aid in interpreting complex XPS data obtained from spatially complex materials often obtained during extensive cycling, such as conventional or electrocatalysts.
Highly Efficient and Stable Organic Solar Cells Enabled by a Commercialized Simple Thieno[3,2‐b]thiophene Additive
Authors: Chen Jinwei , Wang Yiwen , Wang Lei , Lin Francis R. , Han Chenyang , Ma Xiao , Zheng Jialu , Li Zhao , Zapien Juan Antonio , Gao Huanhuan , Jen Alex K.‐Y.
Published: May 2024

Delicately manipulating nanomorphology is recognized as a vital and effective approach to enhancing the performance and stability of organic solar cells (OSCs). However, the complete removal of solvent additives with high boiling points is typically necessary to maintain the operational stability of the device. In this study, two commercially available organic intermediates, namely thieno[3,2‐b]thiophene (TT) and 3,6‐dibromothieno[3,2‐b]thiophene (TTB) are introduced, as solid additives in OSCs. The theoretical simulations and experimental results indicate that TT and TTB may exhibit stronger intermolecular interactions with the acceptor Y6 and donor PM6, respectively. This suggests that the solid additives (SAs) can selectively intercalate between Y6 and PM6 molecules, thereby improving the packing order and crystallinity. As a result, the TT‐treated PM6:Y6 system exhibits a favorable morphology, improved charge carrier mobility, and minimal charge recombination loss. These characteristics contribute to an impressive efficiency of 17.75%. Furthermore, the system demonstrates exceptional thermal stability (T80 > 2800 h at 65 °C) and outstanding photostability. The universal applicability of TT treatment is confirmed in OSCs employing D18:L8‐BO, achieving a significantly higher PCE of 18.3%. These findings underscore the importance of using appropriate solid additives to optimize the blend morphology of OSCs, thereby improving photovoltaic performance and thermal stability.
Tell your story: Metrics of success for academic data science collaboration and consulting programs
Authors: Blake Mara Rojeski , Griffith Emily , Pierce Steven J. , Levy Rachel , Parker Micaela , Huebner Marianne
Published: May 2024

Measuring success plays a central role in justifying and advocating for a statistical or data science consulting or collaboration program (SDSP) within an academic institution. We present several specific metrics to report to targeted audiences to tell the story for success of a robust and sustainable program. While gathering such metrics includes challenges, we discuss potential data sources and possible practices for SDSPs to inform their own approaches. Emphasizing essential metrics for reporting, we also share the metric gathering and reporting practices of two programs in greater detail. New or existing SDSPs should evaluate their local environments and tailor their practice to gathering, analysing and reporting success metrics accordingly. This approach provides a strong foundation to use success metrics to tell compelling stories about the SDSP and enhance program sustainability. The area of success metrics provides ample opportunity for future research projects that leverage qualitative methods and consider mechanisms for adapting to the changing landscape of data science.
Fastening in concrete vs. rock mass—Comparative determination of pull‐out loads for artificially created discontinuities in concrete
Authors: Zeman O. , Voit K. , Lamplmair‐Irsigler S.
Published: May 2024

Possible discontinuities in the subsurface have a major impact on the load‐bearing behavior of post‐installed fastenings. For concrete, the behavior of post‐installed anchors and thus their design can be clearly addressed as concrete is assumed as a homogeneous fastening substrate. This is valid except, for example, in the area of building joints and at joints of precast concrete elements, where the formation of structural joints inevitably occurs and which basically correspond to a separation surface. In contrast, rock mass is characterized by the rock type, but is generally also significantly influenced by its discontinuities. These play a decisive role concerning rock mass stability and show a great impact on the load‐bearing capacity of rock, especially for fasteners with a shallow embedment depth. It is to be assumed that the same also applies to separating surfaces in concrete. Furthermore, the question arises as to the non‐destructive preliminary detectability of such weak zones. For carrying out a comparative study under controlled conditions, artificial interfaces of different geometries were generated in concrete in laboratory tests by inserting PTFE layers at different positions of the test member. Pull‐out tests of post‐installed fastening systems were carried out in their vicinity to determine the load transfer as well as the failure mode. It could be shown that discontinuities have a negative effect on pull‐out loads not only in the rock mass, but also in concrete. However, detection of these by means of a rebound hammer was only possible in the rock mass.
Research on Vibration Characteristic Analysis and Fault Diagnosis Method of Oil‐Immersed Transformer Based on Multi‐Physics Coupling
Authors: Yuan Fating , Yan Zhiwei , Zhang Renjie , Yang Yi , Jian Shengkai , Tang Bo
Published: May 2024

The oil‐immersed transformer is a crucial power equipment in power system, which is prone to abnormality or failure under long running. In order to improve the level of operation and maintenance and ensure the safe and reliable operation of the power grid, it is necessary to diagnose the fault of the oil‐immersed transformer in time. Most of the traditional fault vibration methods are off‐line detection, and are easily disturbed by mechanical deterioration. In order to solve the above problems, this paper established a 3D electromagnetic and stress coupling simulation model of oil‐immersed transformer by finite element simulation software. The vibration characteristics of oil‐immersed transformer core winding are obtained, and at the same time, this paper obtained the vibration signals at different positions on transformer core winding and oil tank. According to the vibration signal of the transformer, the best measuring point position of the tank wall is proposed to accurately reflect the vibration characteristics of the transformer. The signal data is preprocessed by CEEMDAN decomposition method, and the signal data is classified by GWO‐BP composite classification algorithm. This paper proposed an online transformer fault diagnosis method based on vibration signal, which achieves the purpose of accurately diagnosing oil‐immersed transformer faults. The test results show that in the case of oil‐immersed transformers the accuracy of the proposed transformer fault diagnosis method is more than 93%, which provides important guiding significance for the safe and stable operation of the transformer. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.
Estimation of Crosswind Disturbances for a Vehicle by LPV‐MHE and its Application to Disturbance Cancellation
Authors: Miyakoshi Minoru , Maeda Ami , Kawano Yu , Yano Yasuhide , Adachi Tomohiko , Wada Nobutaka
Published: May 2024

Crosswinds and transverse slopes of the road surface affect the motion of a ground vehicle as disturbances. The objective of this paper is to develop a method for estimating crosswind disturbances and lateral force disturbances caused by transverse slopes of the road surface under the variation of the vehicle speed. Firstly, a dynamical model of a vehicle is described as a Linear Parameter‐Varying (LPV) system in which the value of the coefficient matrices vary with the vehicle velocity. Then, an algorithm to estimate the disturbance is derived based on Moving Horizon Estimation (MHE) and applied to the derived LPV system. Furthermore, a simple control law which counteracts the effects of the disturbances on the lateral velocity and the yaw rate in steady‐state based on the estimates of the disturbances is presented. The effectiveness of the proposed method is demonstrated by a numerical example. © 2024 The Author(s). IEEJ Transactions on Electrical and Electronic Engineering published by Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.
Genome editing in rice and tomato with a small Un1Cas12f1 nuclease
Authors: Tang Xu , Eid Ayman , Zhang Rui , Cheng Yanhao , Liu Annan , Chen Yurong , Chen Pengxu , Zhang Yong , Qi Yiping
Published: May 2024

The clustered regularly interspaced short palindromic repeats (CRISPR) systems have been demonstrated to be the foremost compelling genetic tools for manipulating prokaryotic and eukaryotic genomes. Despite the robustness and versatility of Cas9 and Cas12a/b nucleases in mammalian cells and plants, their large protein sizes may hinder downstream applications. Therefore, investigating compact CRISPR nucleases will unlock numerous genome editing and delivery challenges that constrain genetic engineering and crop development. In this study, we assessed the archaeal miniature Un1Cas12f1 type‐V CRISPR nuclease for genome editing in rice and tomato protoplasts. By adopting the reengineered guide RNA modifications ge4.1 and comparing polymerase II (Pol II) and polymerase III (Pol III) promoters, we demonstrated uncultured archaeon Cas12f1 (Un1Cas12f1) genome editing efficacy in rice and tomato protoplasts. We characterized the protospacer adjacent motif (PAM) requirements and mutation profiles of Un1Cas12f1 in both plant species. Interestingly, we found that Pol III promoters, not Pol II promoters, led to higher genome editing efficiency when they were used to drive guide RNA expression. Unlike in mammalian cells, the engineered Un1Cas12f1‐RRA variant did not perform better than the wild‐type Un1Cas12f1 nuclease, suggesting continued protein engineering and other innovative approaches are needed to further improve Un1Cas12f1 genome editing in plants.
Effective nutrient removal from aquaculture wastewater utilizing an indoor nutrient film technique hydroponic system
Authors: Rajalakshmi M. , Gunasekaran K.
Published: May 2024

Aquaculture wastewater treatment must remove nutrients to prevent eutrophication of receiving waters and to allow for possible re‐use of the treated water. This study aims to evaluate the shoot and root growth of crops produced in Nutrient Film Technique hydroponic systems and treat aquaculture wastewater using phytoremediation. The average physico‐chemical parameters of the aquaculture wastewater during the study period were pH 6–6.4, temperature 25°C–27°C, EC 0.7–0.8 mS/cm, and total dissolved solids (420–560 ppm). The operating conditions of hydroponic treatment units were hydraulic loading rate of 857.28 m/day, hydraulic retention time of 0.3 h, organic loading rate of 12567.8 Ibs‐BOD5/ft^2/day (BOD5 is 5 – day Biochemical Oxygen Demand) and flow rate of 54 L/h. The study found that the average elimination efficiency of nitrate‐nitrogen in aquaculture wastewater treatment varied from 78.28% by Money plants (Epiprennum aureum), 71% by Crotons (Codiaeum varigatum), 70.25% by Arrowhead plants (Syngonium podophyllum), 67.25% by Purple Heart (Tradescantia pallida), 68.62% by for Spinach (Spinacea oleracia), and 42.85% by Brinjal plants (Solanum melongena). The average removal effectiveness of BOD5 varied from 71.07% by Money plants (Epiprennum aureum), 68.62% by Crotons (Codiaeum varigatum), 78% by Arrowhead plants (Syngonium podophyllum), 72% by Purple Heart (Tradescantia pallida), 68% by Spinach (Spinacea oleracia), and 70% by Brinjal plants (Solanum melongena). Thus, environmentally friendly and economically advantageous method for reducing and removing nitrate‐nitrogen and BOD5 from aquaculture effluent is hydroponic phytoremediation.

The promising potential of using indoor NFT hydroponic systems for nutrient removal particularly nitrate‐nitrogen, from aquaculture wastewater.

Each plant species is assessed for its ability to uptake and reduce nitrate‐nitrogen levels, growth patterns, and overall suitability for wastewater treatment.

The study emphasizes the eco‐friendly and sustainable wastewater management nature of the proposed method.
Is badger culling associated with risk compensation behaviour among cattle farmers?
Authors: Brunton Lucy , Enticott Gareth
Published: May 2024

Background

Risk compensation theory suggests that behaviours are modified in response to interventions that remove risks by substituting them with other risky behaviours to maintain a ‘risk equilibrium’. Alternatively, risk reduction interventions may result in spill‐over behaviours that seek to minimise risks further. This paper assessed evidence for these behavioural risk responses among farmers in response to badger culling that seeks to remove the risk of bovine tuberculosis in cattle.

Methods

Data from the UK's randomised badger culling trial were re‐analysed, comparing farmers’ cattle movement practices in proactive and reactive culling areas and control areas. Analysis compared cattle movements during and after the trial using zero‐inflated negative binomial regression.

Results

The analysis found no strong evidence of risk compensation behaviours among farmers who experienced proactive culling. However, strong evidence for a reduction in cattle movements in reactive culling areas was found. The results indicate high levels of inertia within farming systems in relation to cattle purchasing.

Limitations

Data do not account for the risk of cattle purchases and reflect previous policy regimens. Evidence from recent badger culling interventions should be analysed.

Conclusion

Proactive badger culling was not associated with risk compensation behaviours, while reactive badger culling was associated with decreased risk taking among farmers.
Entanglement entropy in de Sitter: no pure states for conformal matter
Authors: Ageev D. S. , Aref’eva I. Ya. , Belokon A. I. , Pushkarev V. V. , Rusalev T. A.
Published: May 2024

Abstract

In this paper, we consider the entanglement entropy of conformal matter for finite and semi-infinite entangling regions, as well as the formation of entanglement islands in four-dimensional de Sitter spacetime partially reduced to two dimensions. We analyze complementarity and pure state condition of entanglement entropy of pure states as a consistency test of the CFT formulas in this geometrical setup, which has been previously used in the literature to study the information paradox in higher-dimensional de Sitter in the context of the island proposal. We consider two different types of Cauchy surfaces in the extended static patch and flat coordinates, correspondingly. For former, we found that entanglement entropy of a pure state is always bounded from below by a constant and never becomes zero, as required by quantum mechanics. In turn, the difference between the entropies for some region and its complement, which should be zero for a pure state, in direct calculations essentially depends on how the boundaries of these regions evolve with time. Regarding the flat coordinates, it is impossible to regularize spacelike infinity in a way that would be compatible with complementarity and pure state condition, as opposed, for instance, to two-sided Schwarzschild black hole. Finally, we discuss the information paradox in de Sitter and show that the island formula does not resolve it, at least in this setup. Namely, we give examples of a region with a time-limited growth of entanglement entropy, for which there is no island solution, and the region, for which entanglement entropy does not grow, but the island solution exists.
Behind-the-horizon excitations from a single 2d CFT
Authors: Banerjee Souvik , Vos Gideon
Published: May 2024

Abstract

In this work, we consider the atypical non-equilibrium state found in [1708.06328] which holographically represents a behind-the-horizon excitation in a black hole spacetime. The special feature of this state is that it looks like an equilibrium state when probed by a class of low-energy operators. First, we retrieve this property using the uniformization mapping in the limit of a large central charge, in the process we are able to derive rather than presume approximate thermal physics. Furthermore, in the large-c and high-energy limit, we realize these excitations as elements of the commutant algebra of a GNS-representation of the light operator algebra. Instead of analytically continuing a mixed heavy-light Euclidean correlator to a Lorentzian correlator, we identify the Euclidean correlator as a GNS-linear form and interpret the Lorentzian correlator as a vacuum expectation value of representatives of the light operator algebra on the GNS-vacuum.
Gravity-matter sum rules in models with a single extra-dimension
Authors: de Giorgi A. , Vogl S.
Published: May 2024

Abstract

We prove a set of sum rules needed for KK-graviton pair production from matter in orbifolded extra-dimensional models. The sum rules can be found in full generality by considering the properties of solutions to the Sturm-Liouville problem, which describes the wave functions and the masses of the KK-gravitons in four dimensions. They ensure cancellations in the amplitudes of the processes mentioned above which considerably reduce their growth with s in the high-energy limit. This protects extra-dimensional theories from the low-scale unitarity problems that plague other theories with massive spin-2 particles. We argue that such relations are valid for a broader category of models thus generalizing our previous results that were limited to the large μ limit of the Randall-Sundrum model.
Streaming approximation resistance of every ordering CSP
Authors: Singer Noah G. , Sudan Madhu , Velusamy Santhoshini
Published: May 2024

An ordering constraint satisfaction problem (OCSP) is defined by a family$$\mathcal F$$Fof predicates mapping permutations on$$\{1,\ldots,k\}$${1,…,k}to$$\{0,1\}$${0,1}. An instance of ($$\mathcal F$$F) onnvariables consists of a list of constraints, each consisting of a predicate from$$\mathcal F$$Fapplied onkdistinct variables. The goal is to find an ordering of thenvariables that maximizes the number of constraints for which the induced ordering on thekvariables satisfies the predicate. OCSPs capture well-studied problems including ‘maximum acyclic subgraph’ () and “maximum betweenness”. In this work, we consider the task of approximating the maximum number of satisfiable constraints in the (single-pass) streaming setting, when an instance is presented as a stream of constraints. We show that for every$$\mathcal F$$F, ($$\mathcal F$$F) is approximation-resistant to o(n)-space streaming algorithms, i.e., algorithms using o(n) space cannot distinguish streams where almost every constraint is satisfiable from streams where no ordering beats the random ordering by a noticeable amount. This space bound is tight up to polylogarithmic factors. In the case of , our result shows that for every$$\epsilon>0$$ϵ>0, is not$$(1/2+\epsilon)$$(1/2+ϵ)-approximable in o(n) space. The previous best inapproximability result, due to Guruswami & Tao (2019), only ruled out 3/4-approximations in$$o(\sqrt n)$$o(n)space. Our results build on recent works of Chou et al. (2022b, 2024) who provide a tight, linear-space inapproximability theorem for a broad class of “standard” (i.e., non-ordering) constraint satisfaction problems (CSPs) over arbitrary (finite) alphabets. Our results are obtained by building a family of appropriate standard CSPs (one for every alphabet sizeq) from any given OCSP and applying their theorem to this family of CSPs. To convert the resulting hardness results for standard CSPs back to our OCSP, we show that the hard instances from this earlier theorem have the following “partition expansion” property with high probability: For every partition of thenvariables into small blocks, for most of the constraints, all variables are in distinct blocks.
Precision in Practice: The Critical Role of Mesh and Procedure Type Specification in Urogynecological Surgeries and Research
Authors: Rotem Reut , Galvin Daniel , Daykan Yair , Al-shukaili Sumaiya , O’Reilly Barry A. , O’Sullivan Orfhlaith E.
Published: May 2024

Recently, the debate surrounding the use of mesh in urogynecological procedures has intensified, leading to FDA warnings and heightened safety concerns. This clinical opinion emphasizes the vital need to specify mesh types in these procedures, drawing attention to the risk profiles and clinical outcomes associated with various meshes and the procedures that utilize them. A significant issue identified in contemporary literature is the tendency to group diverse mesh types under the same umbrella, disregarding their unique characteristics and applications. We describe the range of mesh types, their application routes, and associated complications, highlighting the risks of this nonspecific approach to patient safety and informed decision making. We critically examine the generalization of mesh terminology in clinical and research dialogues. Concluding with specific recommendations for health care providers and researchers, the paper advocates for a more nuanced understanding and communication in the field, ultimately aiming to improve patient care and safety in urogynecological practice.
Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw
Authors: Kaminogo Kento , Yamaguchi Satoshi , Chen Hui , Yagita Hideo , Toyama Naoto , Urata Yusuke , Hibi Hideharu
Published: May 2024

Medication-related osteonecrosis of the jaw is a serious disease occurring in patients with cancer and osteoporosis, who are undergoing treatment with antiresorptive agents (ARAs) such as bisphosphonate (BP) or denosumab, an antibody targeting receptor activator of NF-κB ligand. Recently, stem cell-based therapy has been shown to be effective in preventing the development of bisphosphonate-related osteonecrosis of the jaw. However, studies on denosumab-related osteonecrosis of the jaw (DRONJ) remain limited. Here, the efficacy of treatment with dental pulp stem cell conditioned media (DPSC-CM) in preventing DRONJ in a murine model was evaluated. Local administration of DPSC-CM into the extraction socket of a mouse with DRONJ decreased the number of empty osteocyte lacunae and the prevalence of ONJ. In tissues surrounding the extraction sockets in the DPSC-CM-treated group, the expression of inflammatory cytokines was attenuated and that of osteogenesis-related molecules was enhanced compared to that in the control group. Further, the expression of Wnt signaling molecules, which had been suppressed, was improved. These findings collectively suggest that DPSC-CM prevents ONJ development in a murine DRONJ model.
Epitope mapping and establishment of a blocking ELISA for mAb targeting the p72 protein of African swine fever virus
Authors: Liao Huan-Cheng , Shi Zheng-Wang , Zhou Gai-Jing , Luo Jun-Cong , Wang Wan-Ying , Feng Lu , Zhang Fan , Shi Xin-Tai , Tian Hong , Zheng Hai-Xue
Published: May 2024

The African swine fever virus (ASFV) has the ability to infect pigs and cause a highly contagious acute fever that can result in a mortality rate as high as 100%. Due to the viral epidemic, the pig industry worldwide has suffered significant financial setbacks. The absence of a proven vaccine for ASFV necessitates the development of a sensitive and reliable serological diagnostic method, enabling laboratories to effectively and expeditiously detect ASFV infection. In this study, four strains of monoclonal antibodies (mAbs) against p72, namely, 5A1, 4C4, 8A9, and 5E10, were generated through recombinant expression of p72, the main capsid protein of ASFV, and immunized mice with it. Epitope localization was performed by truncated overlapping polypeptides. The results indicate that 5A1 and 4C4 recognized the amino acid 20–39 aa, 8A9 and 5E10 are recognized at 263–282 aa, which is consistent with the reported 265–280 aa epitopes. Conserved analysis revealed 20–39 aa is a high conservation of the epitopes in the ASFV genotypes. Moreover, a blocking ELISA assay for detection ASFV antibody based on 4C4 monoclonal antibody was developed and assessed. The receiver-operating characteristic (ROC) was performed to identify the best threshold value using 87 negative and 67 positive samples. The established test exhibited an area under the curve (AUC) of 0.9997, with a 95% confidence interval ranging from 99.87 to 100%. Furthermore, the test achieved a diagnostic sensitivity of 100% (with a 95% confidence interval of 95.72 to 100%) and a specificity of 98.51% (with a 95% confidence interval of 92.02 to 99.92%) when the threshold was set at 41.97%. The inter- and intra-batch coefficient of variation were below 10%, demonstrating the exceptional repeatability of the method. This method can detect the positive standard serum at a dilution as high as 1:512. Subsequently, an exceptional blocking ELISA assay was established with high diagnostic sensitivity and specificity, providing a novel tool for detecting ASFV antibodies.

Key points

• Four strains of ASFV monoclonal antibodies against p72 were prepared and their epitopes were identified.

• Blocking ELISA method was established based on monoclonal antibody 4C4 with an identified conservative epitope.

• The established blocking ELISA method has a good effect on the detection of ASFV antibody.
Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis
Authors: O’Sullivan Niall J. , Temperley Hugo C. , Kyle Eimear T. , Sweeney Kevin J. , O’Neill Maeve , Gilham Charles , O’Sullivan Jacintha , O’Kane Grainne , Mehigan Brian , O’Toole Sharon , Larkin John , Gallagher David , McCormick Paul , Kelly Michael E.
Published: May 2024

Introduction

Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.

Methods

PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS).

Results

Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91–16.03) and 15.15 (95% CI 8.21–27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively.

Conclusion

Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.
Vitamin C deficiency after kidney transplantation: a cohort and cross-sectional study of the TransplantLines biobank
Authors: Yepes-Calderón Manuela , van der Veen Yvonne , Martín del Campo S Fernando , Kremer Daan , Sotomayor Camilo G. , Knobbe Tim J. , Vos Michel J. , Corpeleijn Eva , de Borst Martin H. , Bakker Stephan J. L. ,   TransplantLines Investigators
Published: May 2024

Purpose

Vitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR.

Methods

Plasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients.

Results

Vitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30–41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m2), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84–3.87] and OR 1.84 [95% CI 1.16–2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24–0.61 and OR 0.21, 95% CI 0.09–0.44, respectively).

Conclusion

Vitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR.
Association between the consumption of ultra-processed foods and the incidence of peptic ulcer disease in the SUN project: a Spanish prospective cohort study
Authors: Leone Alessandro , De la Fuente-Arrillaga Carmen , Mas Mariano Valdés , Sayon-Orea Carmen , Menichetti Francesca , Martínez-Gonzalez Miguel Angel , Bes-Rastrollo Maira
Published: May 2024

Purpose

Consumption of ultra-processed foods (UPF) has increased despite potential adverse health effects. Recent studies showed an association between UPF consumption and some gastrointestinal disorders. We evaluated the association between UPF consumption and peptic ulcer disease (PUD) in a large Spanish cohort.

Methods

We conducted a prospective analysis of 18,066 participants in the SUN cohort, followed every two years. UPF was assessed at baseline and 10 years after. Cases of PUD were identified among participants reporting a physician-made diagnosis of PUD during follow-ups. Cases were only partially validated against medical records. Cox regression was used to assess the association between baseline UPF consumption and PUD risk. Based on previous findings and biological plausibility, socio-demographic and lifestyle variables, BMI, energy intake, Helicobacter pylori infection, gastrointestinal disorders, aspirin and analgesic use, and alcohol and coffee consumption were included as confounders.We fitted GEE with repeated dietary measurements at baseline and after 10 years of follow-up. Vanderweele’s proposed E value was calculated to assess the sensitivity of observed associations to uncontrolled confounding.

Results

During a median follow-up of 12.2 years, we recorded 322 new PUD cases (1.56 cases/1000 person-years). Participants in the highest baseline tertile of UPF consumption had an increased PUD risk compared to participants in the lowest tertile (HR = 1.52, 95% CI: 1.15, 2.00, Ptrend=0.002). The E-values for the point estimate supported the observed association. The OR using repeated measurements of UPF intake was 1.39 (95% CI: 1.03, 1.87) when comparing extreme tertiles.

Conclusion

The consumption of UPF is associated with an increased PUD risk.
Influence of nitrate supplementation on motor unit activity during recovery following a sustained ischemic contraction in recreationally active young males
Authors: Esen Ozcan , Bailey Stephen J. , Stashuk Daniel W. , Howatson Glyn , Goodall Stuart
Published: May 2024

Purpose

Dietary nitrate (NO3−) supplementation enhances muscle blood flow and metabolic efficiency in hypoxia, however, its efficacy on neuromuscular function and specifically, the effect on motor unit (MU) activity is less clear. We investigated whether NO3− supplementation affected MU activity following a 3 min sustained ischemic contraction and whether this is influenced by blood flow restriction (BFR) during the recovery period.

Method

In a randomized, double-blinded, cross-over design, 14 males (mean ± SD, 25 ± 6 years) completed two trials following 5 days of supplementation with NO3−-rich (NIT) or NO3−-depleted (PLA) beetroot juice to modify plasma nitrite (NO2−) concentration (482 ± 92 vs. 198 ± 48 nmol·L−1, p < 0.001). Intramuscular electromyography was used to assess MU potential (MUP) size (duration and area) and mean firing rates (MUFR) during a 3 min submaximal (25% MVC) isometric contraction with BFR. These variables were also assessed during a 90 s recovery period with the first half completed with, and the second half completed without, BFR.

Results

The change in MUP area and MUFR, did not differ between conditions (all p > 0.05), but NIT elicited a reduction in MUP recovery time during brief isometric contractions (p < 0.001), and during recoveries with (p = 0.002) and without (p = 0.012) BFR.

Conclusion

These novel observations improve understanding of the effects of NO3− on the recovery of neuromuscular function post-exercise and might have implications for recovery of muscle contractile function.

Trial registration

The study was registered on clinicaltrials.gov with ID of NCT05993715 on August 08, 2023.
The practice of principles: Planck’s vision of a relativistic general dynamics
Authors: Giovanelli Marco
Published: May 2024

Planck’s pioneering contributions to special relativity have received less consideration than one might expect in the historiography and philosophy of physics. Although they are celebrated in isolation, they are mostly not understood as integral to an overarching project. This paper aims (a) to provide a historically accurate overview of Planck’s contributions to the early history of relativity that is reasonably accessible to today’s reader, (b) to demonstrate how these contributions can be presented against the background of Planck’s ‘Helmholtzian’ vision of relativistic general dynamics based on the principle of relativity and principle of least action, and (c) to argue that Planck’s general dynamics serves as an illuminating example of the use of ‘principles’ in physics.
Short term cardiovascular symptoms improvement after deep brain stimulation in patients with Parkinson's disease: a systematic review
Authors: Cucinotta Francescopaolo , Swinnen Bart , Makovac Elena , Hirschbichler Stephanie , Pereira Erlick , Little Simon , Morgante Francesca , Ricciardi Lucia
Published: May 2024

Background

Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly understood. We aimed to assess the effect of DBS on cardiovascular symptoms and objective measures in PD patients.

Methods

We conducted a systematic literature search in PubMed/MEDLINE.

Results

36 out of 472 studies were included, mostly involving DBS of the subthalamic nucleus, and to a lesser extent the globus pallidus pars interna and pedunculopontine nucleus. Seventeen studies evaluated the effect of DBS on patient-reported or clinician-rated cardiovascular symptoms, showing an improvement in the first year after surgery but not with longer-term follow-up. DBS has no clear direct effects on blood pressure during an orthostatic challenge (n = 10 studies). DBS has inconsistent effects on heart rate variability (n = 10 studies).

Conclusion

Current evidence on the impact of DBS on cardiovascular functions in PD is inconclusive. DBS may offer short-term improvement of cardiovascular symptoms in PD, particularly orthostatic hypotension, which may be attributed to dopaminergic medication reduction after surgery. There is insufficient evidence to draw conclusions on the direct effect of DBS on blood pressure and heart rate variability.
Side differences and reproducibility of the Moxy muscle oximeter during cycling in trained men
Authors: Skotzke Philip , Schwindling Sascha , Meyer Tim
Published: May 2024

Purpose

Portable near-infrared spectroscopy devices allow measurements of muscle oxygen saturation (SmO2) in real time and non-invasively. To use NIRS for typical applications including intensity control and load monitoring, the day-to-day variability needs to be known to interpret changes confidently. This study investigates the absolute and relative test–retest reliability of the Moxy Monitor and investigates side differences of SmO2 at the vastus lateralis muscle of both legs in cyclists.

Methods

Twelve trained cyclists and triathletes completed 3 incremental step tests with 5 min step duration starting at 1.0 W/kg with an increase of 0.5 W/kg separated by 2–7 days. SmO2 was averaged over the last minute of each stage. For all power outputs, the intra-class coefficient (ICC), the standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated. Dominant and non-dominant leg SmO2 were compared using a three-factor ANOVA and limits of agreement (LoA).

Results

ANOVA showed no significant systematic differences between trials and side. For both legs and all intensities, the ICC ranged from 0.79 to 0.92, the SEM from 5 to 9% SmO2 and the MDC from 14 to 18% SmO2. The bias and LoA between both legs were −2.0% ± 19.9% SmO2.

Conclusion

Relative reliability of SmO2 was numerically good to excellent according to current standards. However, it depends on the specific analytical goal whether the test–retest reliability is deemed sufficient. Wide LoA indicate side differences in muscle oxygenation during exercise unexplained by leg dominance.