bluuebunny/crossref_metadata_2025 huggingface dataset:
p53 as Exemplar Next-generation Immunohistochemical Marker: A Molecularly Informed, Pattern-based Approach, Methodological Considerations, and Pan-cancer Diagnostic Applications
Authors: Bellizzi Andrew M.
Published: July 2023

This review is based on a webinar I presented for the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) in February 2022. It is intended that all ISIMM webinars will ultimately be published in AIMM as review articles. This work is also dedicated to Clive Taylor, who has deeply impacted my career. It presents a molecularly informed, pattern-based approach to p53 immunohistochemistry interpretation, methodological considerations (ie, antibody selection, optimization, validation, controls, and external quality assessment), and pan-cancer diagnostic applications, including those drawn from gastrointestinal, genitourinary, gynecological, neuroendocrine, hematopathology, and neuropathology. It intends to prove the thesis statement that p53 is an exemplar next-generation immunohistochemical marker “born” ahead of its time.
A Familial Alzheimer’s Disease Associated Mutation in Presenilin-1 Mediates Amyloid-Beta Independent Cell Specific Neurodegeneration
Authors: Parvand Mahraz , Liang Joseph JH , Bozorgmehr Tahereh , Born Dawson , Cortes Alvaro Luna , Rankin Catharine H.
Published: July 2023

Mutations in the presenilin (PS) genes are a predominant cause of familial Alzheimer’s disease (fAD). An ortholog ofPSin the genetic model organismCaenorhabditis elegans (C. elegans)issel-12. Mutations in the presenilin genes are commonly thought to lead to fAD by upregulating the expression of amyloid beta (Aβ), however this hypothesis has been challenged by recent evidence. AsC. eleganslack amyloid beta (Aβ), the goal of this work was to examine Aβ-independent effects of mutations insel-12andPS1/PS2on behaviour and sensory neuron morphology across the lifespan in aC. elegansmodel. Olfactory chemotaxis experiments were conducted onsel-12(ok2078) loss-of-function mutant worms. Adultsel-12mutant worms showed significantly lower levels of chemotaxis to odorants compared to wild-type worms throughout their lifespan, and this deficit increased with age. The chemotaxis phenotype insel-12mutant worms is rescued by transgenic over-expression of human wild-typePS1, but not the classic fAD-associated variantPS1C410Y, when expression was driven by either the endogenoussel-12promoter (Psel-12), a pan-neuronal promoter (Primb-1), or by a promoter whose primary expression was in the sensory neurons responsible for the chemotaxis behavior (Psra-6,Podr-10). The behavioural phenotype was also rescued by over-expressing an atypical fAD-linked mutation inPS1(PS1ΔS169) that has been reported to leave the Notch pathway intact. An examination of the morphology of polymodal nociceptive (ASH) neurons responsible for the chemotaxis behavior also showed increased neurodegeneration over time insel-12mutant worms that could be rescued by the same transgenes that rescued the behaviour, demonstrating a parallel with the observed behavioral deficits. Thus, we report an Aβ-independent neurodegeneration inC. elegansthat was rescued by cell specific over-expression of wild-type human presenilin.
Correcting systematic errors in diffraction data with modern scaling algorithms
Authors: Aldama Luis A. , Dalton Kevin M. , Hekstra Doeke R.
Published: July 2023

X-ray diffraction enables the routine determination of the atomic structure of materials. Key to its success are data-processing algorithms that allow experimenters to determine the electron density of a sample from its diffraction pattern. Scaling, the estimation and correction of systematic errors in diffraction intensities, is an essential step in this process. These errors arise from sample heterogeneity, radiation damage, instrument limitations and other aspects of the experiment. New X-ray sources and sample-delivery methods, along with new experiments focused on changes in structure as a function of perturbations, have led to new demands on scaling algorithms. Classically, scaling algorithms use least-squares optimization to fit a model of common error sources to the observed diffraction intensities to force these intensities onto the same empirical scale. Recently, an alternative approach has been demonstrated which uses a Bayesian optimization method, variational inference, to simultaneously infer merged data along with corrections, or scale factors, for the systematic errors. Owing to its flexibility, this approach proves to be advantageous in certain scenarios. This perspective briefly reviews the history of scaling algorithms and contrasts them with variational inference. Finally, appropriate use cases are identified for the first such algorithm, Careless, guidance is offered on its use and some speculations are made about future variational scaling methods.
Pregnancy‐related mortality up to 1 year postpartum in sub‐Saharan Africa: an analysis of verbal autopsy data from six countries
Authors: Gazeley Ursula , Reniers Georges , Romero‐Prieto Julio E. , Calvert Clara , Jasseh Momodou , Herbst Kobus , Khagayi Sammy , Obor David , Kwaro Daniel , Dube Albert , Dheresa Merga , Kabudula Chodziwadziwa W. , Kahn Kathleen , Urassa Mark , Nyaguara Amek , Temmerman Marleen , Magee Laura A. , von Dadelszen Peter , Filippi Veronique
Published: July 2023

Objective

To compare the causes of death for women who died during pregnancy and within the first 42 days postpartum with those of women who died between >42 days and within 1 year postpartum.

Design

Open population cohort (Health and Demographic Surveillance Systems).

Setting

Ten Health and Demographic Surveillance Systems (HDSS) in The Gambia, Kenya, Malawi, Tanzania, Ethiopia and South Africa.

Population

2114 deaths which occurred within 1 year of the end of pregnancy where a verbal autopsy interview was conducted from 2000 to 2019.

Methods

InterVA5 and InSilicoVA verbal autopsy algorithms were used to attribute the most likely underlying cause of death, which were grouped according to adapted International Classification of Diseases‐Maternal Mortality categories. Multinomial regression was used to compare differences in causes of deaths within 42 days versus 43–365 days postpartum adjusting for HDSS and time period (2000–2009 and 2010–2019).

Main outcome measures

Cause of death and the verbal autopsy Circumstances of Mortality Categories (COMCATs).

Results

Of 2114 deaths, 1212 deaths occurred within 42 days postpartum and 902 between 43 and 365 days postpartum. Compared with deaths within 42 days, deaths from HIV and TB, other infectious diseases, and non‐communicable diseases constituted a significantly larger proportion of late pregnancy‐related deaths beyond 42 days postpartum, and health system failures were important in the circumstances of those deaths. The contribution of HIV and TB to deaths beyond 42 days postpartum was greatest in Southern Africa. The causes of pregnancy‐related mortality within and beyond 42 days postpartum did not change significantly between 2000–2009 and 2010–2019.

Conclusions

Cause of death data from the extended postpartum period are critical to inform prevention. The dominance of HIV and TB, other infectious and non‐communicable diseases to (late) pregnancy‐related mortality highlights the need for better integration of non‐obstetric care with ante‐, intra‐ and postpartum care in high‐burden settings.
Metformin in Gestational Diabetes The Offspring Follow Up (MiGTOFU): Associations between maternal characteristics and size and adiposity of boys and girls at nine years
Authors: Rowan Janet Alison , Rush Elaine Carolyn , Plank Lindsay Dudley
Published: July 2023

Data from 98 women recruited in the Metformin in Gestational Diabetes trial and dual‐energy X‐ray absorptiometry studies of their children at nine years were analysed to investigate associations between maternal measures during pregnancy and their children's size and adiposity. Mothers of boys (n = 56) and girls (n = 42) had been randomised to metformin or insulin treatment at 30.1 ± 2.8 and 29.3 ± 4.1 weeks gestation, respectively. In boys, fat‐free mass indexed to height squared was associated with maternal weight, body mass index, maternal glycaemia and metformin treatment. In boys and girls, fat mass indexed to height squared was associated with maternal glycaemia measures before gestational diabetes treatment.
Ultraflexible endovascular probes for brain recording through micrometer-scale vasculature
Authors: Zhang Anqi , Mandeville Emiri T. , Xu Lijun , Stary Creed M. , Lo Eng H. , Lieber Charles M.
Published: July 2023

Implantable neuroelectronic interfaces have enabled advances in both fundamental research and treatment of neurological diseases but traditional intracranial depth electrodes require invasive surgery to place and can disrupt neural networks during implantation. We developed an ultrasmall and flexible endovascular neural probe that can be implanted into sub-100-micrometer–scale blood vessels in the brains of rodents without damaging the brain or vasculature. In vivo electrophysiology recording of local field potentials and single-unit spikes have been selectively achieved in the cortex and olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.
Unusual manifestation of pulmonaryVerruconis gallopavainfection with synchronous reactive pericardial effusion in a non-transplanted patient
Authors: Jirawat Napat , Leelayuwatanakul Nophol
Published: July 2023

Verruconis gallopavais an emerging causative agent in solid organ transplant patients, increasing in prevalence both in non-transplanted patients and also in immunocompetent ones, albeit rarely. In this case report, we describe an unusualV. gallopavainfection in a patient with steroid-dependent autoimmune haemolytic anaemia. The chest CT scan revealed a mass-like consolidation in the superior segment of the right lower lobe, and bronchoscopic examination confirmedV. gallopavafrom bronchoalveolar lavage. The histopathology showed non-necrotising granulomatous inflammation concurrent with septate-pigmented hyphae, which is compatible with dematiaceous fungi. After 3 weeks of posaconazole treatment, the patient developed a new pericardial effusion. Further investigations, including culture, cytology and histopathology, yielded negative results, leading to suspicion of reactive pericardial effusion associated withV. gallopavapulmonary infection. The patient received antifungal therapy for 9 months, after which a follow-up chest CT scan showed complete resolution of consolidation and pericardial effusion.
AGATA: mechanics and infrastructures
Authors: Smith R. , Menegazzo R. , Aufranc C. , Bez N. , Burrows I. , Cahoreau M. , Debras G. , Gibelin L. , Goasduff A. , Grant A. , Joannem T. , Karkour N. , Karolak M. , Kieffer J. , Lotodé A. , Million B. , Morrall P. S. , Ramina L. , Rampazzo M. , Roger A. , Simpson J. , Solenne N. , Stézowski O. , Tzvetkov S. , Zago L. , Zielińska M.
Published: July 2023

The successful operation of AGATA requires a complex mechanical support structure for the safe and reliable operation of the detectors. Three mechanical structures were designed for the scientific campaigns at LNL, GSI and GANIL, each accommodating an increasing number of detectors. The present phase of the project, to increase the number of detectors from 60 to 180 (the $$4\pi $$

4
π

spectrometer), required a new concept in mechanical support. The detectors also require a suite of associated instrumentation, infrastructures and good system
design for their optimum performance. This includes the automatic liquid nitrogen filling system, high and low voltage power supplies, and a series of signal cables and distribution systems. A well-designed electromagnetic compatibility across all the sub-systems is essential. An additional requirement is an easily accessible database that records the status of the wide range of components utilised on the project. This article describes all aspects of the mechanics and infrastructures.
Systematic Trojan Detection in Crypto-Systems Using the Model Checker
Authors: Hosseintalaee Hamed , Jahanian Ali , Alizadeh Bijan
Published: July 2023

Formal methods have been introduced as the efficient approach for Trojan detection using the model checking approach. However, systematic property generation for detecting a wide range of Trojans is the main challenge in these methods. In other words, the efficient property generation to pinpoint projected Trojan precisely in targeted hardware has been a bottleneck in this approach. This paper evaluated the feasibility of the systematic property generation methodology for Trojan detection in Cryptosystems by analyzing the vulnerable points of an implemented design respecting Trojans’ covered class. The vulnerability analysis reduces the search space of formal methods and considerably improves the scalability of these methods. We have shown in this research that these properties can be generated systematically and prove that the generated properties can be used in conventional model-checking tools to find hard-to-detect Trojans efficiently. Experimental results show that the proposed method reduces Trojan detection time considerably. Also, the memory required to evaluate circuits is possible for several hundreds of clock cycles.
Ins Finder: A Practical CPU Undocumented Instruction Detection Framework
Authors: Dong Renhai , Cui Baojiang , Sun Yi , Yang Jun
Published: July 2023

As the basic and core component of electronic systems, CPU security is extremely important to network security. Even an unremarkable faulty instruction on the CPU may lead to serious security problems, such as the operating system crashes or privilege increase since it is often considered as a trusted black box. Therefore, CPU instruction detection is particularly crucial to CPU security. However, most existing methods of CPU instruction detection, based on the inconsistency of microarchitecture and instruction set design, suffer from slow speed and low accuracy. Our work is motivated to propose a practical framework for searching CPU undocumented instruction with fast speed and high accuracy. In this paper, we put forward a general framework InsFinder to detect undocumented instruction on CISC and RISC CPU by an efficient and accurate fuzzing method. It makes use of the instruction format to make advanced predictions, which greatly reduces the search space. Moreover, by introducing classification, de-redundancy, and verification, InsFinder greatly improves the detection accuracy. Experiments show that compared with the existing methods, InsFinder is more effective which costs at least 50% less processing time in detecting undocumented instructions on x86-64, ARM64, and RISC-V, and more accurate which divided the detection results into 4 categories. After filtering, the detection results were reduced from millions to less than 10,000.
A Machine Learning-Based Approach for Crop Price Prediction
Authors: Gururaj H. L. , Janhavi V. , Lakshmi H. , Soundarya B. C. , Paramesha K. , Ramesh B. , Rajendra A. B.
Published: July 2023

Agriculture is associated with the production of essential food crops for decades and is the one which is playing an important role in the economy of a country as well as in life of an individual. Due to various uncertain variations in the climatic conditions such as rain and other affecting factors, crop prices vary in an unusual pattern. This variation of prices without the knowledge of the farmer may lead to losses in the economy of the individual who is involved in agriculture. In this paper, we have discussed a well-designed system which accurately predicts the crop prices of future months. We have used a Supervised Machine Learning algorithm that is Decision Tree Regression technique for the design of the prediction model as the data is of continuous form. The parameters, which are considered in the dataset, include crop name, month, year, rainfall and wholesale price index (WPI). We have considered the data of 22 crops in total with 4 parameters. We have developed a user-friendly user interface consisting of 22 crop profiles with the predicted prices. Our results show that the regression model achieved an accuracy of 97.32% which will help the farmer on decision of future crop selection for the growth and also hyperinflation can be avoided.
Dynamic Parameter Optimization of High-Speed Pantograph Based on Swarm Intelligence and Machine Learning
Authors: Zhou Rui , Xu Xianghong
Published: July 2023

Good pantograph–catenary interaction quality is a fundamental premise for ensuring stable and reliable current collection of high-speed trains, and the optimization of dynamic parameters of high-speed pantographs provides an effective approach to improve the current collection quality of the pantograph–catenary system. In this paper, with the objective of minimizing the standard deviation of the pantograph–catenary contact force, the multi-parameter joint optimization for pantograph at different filtering frequencies and running speeds was carried out by using swarm intelligence optimization algorithm and artificial neural network method. First, the selection operator in genetic algorithm (GA) was introduced into crow search algorithm (CSA), and the selective CSA was proposed, which can effectively improve the solution accuracy and convergence rate of multi-parameter optimization. Second, a radial basis function (RBF) neural network was used to construct a surrogate model of the standard deviation of contact force with respect to the running speed and pantograph dynamic parameters, and a method for optimizing the upper limit of mapping interval of the decision variables by the selective crow search algorithm (SCSA) was proposed, which effectively improves the generalization ability of the surrogate model. Finally, by combining the surrogate model and SCSA, optimization iterations for a total of 630 combined conditions such as cut-off frequency, running speed and pantograph dynamic parameters were conducted, and an optimization method for high-speed pantograph dynamic parameters with universal applicability was proposed.
High Performance of Gas Sensor Based on Novel Cu-Based Binary Composite Phase-Modified ZnO
Authors: Zhang Manjun , Wang Jianchao , Li Li , Tang Nian , Li Xiaodian , Sun Dongwei , Si Renjun , Zhang Shunping
Published: July 2023

Novel Cu-based binary composite phases were synthesized with an octadecylamine (ODA) synthetic system. HR-TEM was used to characterize the binary composite phase indicating that the Cu-based binary composite phase was a mixed phase of two oxides. ZnO gas sensing films decorated with Cu-based binary composite phase were parallel fabricated. The gas sensing performance to nitric oxides (NO, N2O, NO[Formula: see text] was studied. Cu–Mo–O binary composite phase-modified ZnO was screened out with high sensitivity and selectivity to NO. The gas sensing response to 0.5 ppm NO was 128.1. The detection limit of Cu–Mo–O binary composite phase-modified ZnO to NO was less than 10 ppb. Cu–Mo–O binary composite phase-modified ZnO also shows good selectivity to NO even using NO2as interference gas. It is of great importance for the detection of NO.
V2C-based lithium batteries: The influence of magnetic phase and Hubbard interaction
Authors: González Jhon W. , Vizcaya Sanber , Morell Eric Suárez
Published: July 2023

MXenes are a family of two-dimensional materials that could be attractive for use as electrodes in lithium batteries due to their high specific capacity. For this purpose, it is necessary to evaluate magnitudes such as the lithium adsorption energy and the magnitude of the open-circuit voltage for different lithium concentrations. In this paper, we show through first-principles calculations that in a V2C monolayer, we must consider the high correlation between the electrons belonging to vanadium to obtain correct results of these quantities. We include this correlation employing the Hubbard coupling parameter obtained by a linear response method. We found that the system is antiferromagnetic and that the quantities studied depend on the magnetic phase considered. Indirectly, experimental results could validate the theoretical value of the Hubbard parameter.
Enhanced power graphs of certain non-abelian groups
Authors: Parveen  , Dalal Sandeep , Kumar Jitender
Published: July 2023

The enhanced power graph of a group [Formula: see text] is a simple undirected graph with vertex set [Formula: see text] and two vertices are adjacent if they belong to the same cyclic subgroup. In this paper, we obtain the Laplacian spectrum of the enhanced power graph of certain non-abelian groups, viz. semidihedral, dihedral and generalized quaternion. Also, we obtained the metric dimension and the resolving polynomial of the enhanced power graphs of these groups. At the final part of this paper, we study the distant properties and the detour distant properties, namely: closure, interior, distance degree sequence, eccentric subgraph of the enhanced power graph of semidihedral group, dihedral group and generalized quaternion group, respectively.
Theoretical investigation of the performance of nonlinear optical properties in Push–pull chromophores derivatives of acrylo–azobenzene
Authors: Boutaleb Miloud , Doumi Bendouma , Bensaid Djillali , Guemra Kaddour , Sayede Adlane
Published: July 2023

Due to their strong molecular hyperpolarizability, organic push–pull materials are gaining interest for nonlinear optical applications. We were able to characterize the intramolecular charge transfer and the distribution of the electron cloud within the molecular unit by exciting these materials under the influence of an electric field. The series products of conjugated monomers derived from acrylo–azobenzene containing in the para position the attracting groups (–H, –NO2, –COOC2H5, –SO3H and –COOH) exhibit good nonlinear optical activity. We computed the nonlinear optical characteristics of these compounds as well as exploiting the theoretical calculations of DFT and AM1 to determine their hyperpolarizabilities. Besides, we investigated the increase in hyperpolarizability in the push–pull model of organic compounds under the effect of the strength of attracting groups, the existence of the conjugated [Formula: see text]-electron and the azo bridge.
Physicochemical hazard assessment of ash and dome rock from the 2021 eruption of La Soufrière, St Vincent, for the assessment of respiratory health impacts and water contamination
Authors: Horwell C. J. , Damby D. E. , Stewart C. , Joseph E. P. , Barclay J. , Davies B. V. , Mangler M. F. , Marvin L. G. , Najorka J. , Peek S. , Tunstall N.
Published: July 2023

La Soufrière, St Vincent, began an extrusive eruption on 27 December 2020. The lava dome was destroyed, along with much of the pre-existing 1979 dome, in explosive eruptions from 9 to 22 April 2021. Lava domes generate crystalline silica – inhalation of which can cause silicosis in occupational settings – which can become hazardous when dome material is incorporated into volcanic ash.

La Soufrière ash (17 samples) was analysed, according to IVHHN protocols, to rapidly quantify crystalline silica and test for other health-relevant properties. The basaltic andesitic ash contained <5 wt% crystalline silica, which agrees with previous analyses of ash of similar compositions and mirrors the low quantities measured in dome samples (2 area %). It contained substantial inhalable material (7–21 vol% <10 µm). Few fibre-like particles were observed, reducing concern about particle shape. Leaching assays found low concentrations of potentially toxic elements, which indicates low potential to impact health, contaminate drinking-water sources or harm grazing animals through ingestion. Collectively, these data indicate that the primary health concern from this eruption was the potential for fine-grained ash to increase ambient particulate matter, an environmental risk factor for respiratory and cardiovascular morbidity and mortality. Precautionary measures were advised to minimize exposure.
Twin Identification over Viewpoint Change: A Deep Convolutional Neural Network Surpasses Humans
Authors: Parde Connor J. , Strehle Virginia E. , Banerjee Vivekjyoti , Hu Ying , Cavazos Jacqueline G. , Castillo Carlos D. , O’Toole Alice J.
Published: July 2023

Deep convolutional neural networks (DCNNs) have achieved human-level accuracy in face identification (Phillips et al., 2018), though it is unclear how accurately they discriminate highly-similar faces. Here, humans and a DCNN performed a challenging face-identity matching task that included identical twins. Participants (
N
= 87) viewed pairs of face images of three types: same-identity, general imposters (different identities from similar demographic groups), and twin imposters (identical twin siblings). The task was to determine whether the pairs showed the same person or different people. Identity comparisons were tested in three viewpoint-disparity conditions: frontal to frontal, frontal to 45° profile, and frontal to 90° profile. Accuracy for discriminating matched-identity pairs from twin-imposter pairs and general-imposter pairs was assessed in each viewpoint-disparity condition. Humans were more accurate for general-imposter pairs than twin-imposter pairs, and accuracy declined with increased viewpoint disparity between the images in a pair. A DCNN trained for face identification (Ranjan et al., 2018) was tested on the same image pairs presented to humans. Machine performance mirrored the pattern of human accuracy, but with performance at or above all humans in all but one condition. Human and machine similarity scores were compared across all image-pair types. This item-level analysis showed that human and machine similarity ratings correlated significantly in six of nine image-pair types [range
r
= 0.38 to
r
= 0.63], suggesting general accord between the perception of face similarity by humans and the DCNN. These findings also contribute to our understanding of DCNN performance for discriminating high-resemblance faces, demonstrate that the DCNN performs at a level at or above humans, and suggest a degree of parity between the features used by humans and the DCNN.
Ionic Liquid Boosted Conductivity of Biopolymer Gel Electrolyte
Authors: Tavares Fabiele C. , Cholant Camila M. , Kohlrausch Emerson C. , R. Bolzan Gustavo , Gonçalves Paulo F. B. , Gil Eduarda S. , Khan Sherdil , Dupont Jairton , Avellaneda César O. , Leite Santos Marcos J.
Published: July 2023

Herein, we have developed a new biopolymer gel electrolyte based on xanthan, a material widely used in the food and pharmaceutical industry. The incorporation of the ionic liquids 1-butyl-2,3-dimethylimidazolium iodide (BMMI.I) and 1-ethyl-2,3-dimethylimidazolium iodide (EMMI.I) has significantly enhanced ionic conductivity by 136% and 181%, respectively. These ionic liquids possess a substantial permanent dipole moment, which can induce the alignment of other dipoles around them, through conformational changes. The interplay between the ionic liquid and the segmental motion of the polymer was investigated through temperature-dependent conductivity measurements using the Vogel-Tamman-Fulcher equation. Analysis of the complex dielectric (ε′and ε″) constants revealed the polarization effect of ionic species at the electrode/electrolyte interface. Additionally, the analysis of the complex electric modulus (M′and M″) and the loss tangent (tang δ) show that the incorporation of EMMI.I resulted in an electrolyte with the shortest relaxation time, indicating greater segmental motion of the polymeric chain, ultimately leading to higher ionic conductivity. DSSCs assembled with biopolymer gel electrolytes containing ionic liquids demonstrated an improvement in the short-circuit current, which is related to the high ionic conductivity.
Effectiveness of Persian Golnar on Excessive Menstrual Bleeding in Women with Abnormal Uterine Bleeding, Compared to Tranexamic Acid: A Triple‐Blind, Randomized Equivalence Trial
Authors: Es-haghee Ashteany Somayeh , Vahid Dastjerdi Marzieh , Tabarrai Malihe , Nejatbakhsh Fatemeh , Sadati Lamardi Seyede Nargess , Rahmani Azam , Azizkhani Mohammad , Tavoli Zahra
Published: July 2023

Introduction. Abnormal uterine bleeding (AUB) is a major healthcare problem in females of reproductive age and impacts women’s health and quality of life (QoL). This study aimed to test the equivalence of Persian Golnar (PG) and tranexamic acid (TA) for the treatment of excessive menstrual bleeding. Method. A triple‐blind randomized equivalence trial with parallel design and block randomization technique was performed. A total of 80 patients with AUB were randomly allocated to receive either PG or TA for three consecutive menstrual cycles. Blood loss was measured by the Pictorial Blood Loss Assessment Chart (PBAC). Hematological evaluations were done before the intervention and after treatment. QoL and premenstrual dysphoric disorder (PMDD) as secondary outcomes were assessed using the menorrhagia questionnaire (MQ) and Premenstrual Symptoms Screening Tool (PSST). Statistical analysis was performed using an independent t‐test, paired t‐test, χ2 test, Mann–Whitney test, and Wilcoxon signed‐rank test. Results. Seventy‐six women completed the 12‐week follow‐up. Both PG and TA groups experienced a significant reduction in blood loss. Furthermore, the serum level of hemoglobin in the PG group enhanced significantly (P < 0.001). QoL and PMDD scores were significantly improved in both groups (P< 0.001). Conclusion. The findings of the current trial supposed that the Golnar product is as effective as tranexamic acid in controlling bleeding and enhancing the quality of life and premenstrual symptoms.
Polycyclic Aromatic Hydrocarbons in Soil and Vegetation of Niger Delta, Nigeria: Ecological Risk Assessment
Authors: Okoye Esther Amaka , Ezejiofor Anthonet N. , Nwaogazie Ify L. , Frazzoli Chiara , Orisakwe Orish E.
Published: July 2023

The Niger Delta, Nigeria, is noted for crude oil exploration. Whereas there seems to be a handful of data on soil polycyclic aromatic hydrocarbon (PAH) levels in this area, there is a paucity of studies that have evaluated soil and vegetation PAHs simultaneously. The present study has addressed this information gap. Fresh Panicum maximum (Jacq) (guinea grass), Pennisetum purpureum Schumach (elephant grass), Zea mays (L.) (maize), and soil samples were collected in triplicate from Choba, Khana, Trans-Amadi, Eleme, Uyo, and Yenagoa. PAHs determination was carried out using GC-MS. The percentage composition of the molecular weight distribution of PAHs, the molecular ratio of selected PAHs for identification of possible sources, and the isomeric ratio and total index of soil were evaluated. Pennisetum purpureum Schumach (elephant grass) from Uyo has the highest (10.0 mg·kg−1) PAH while Panicum maximum (Jacq) (guinea grass) has the highest PAH (32.5 mg·kg−1 from Khana. Zea mays (L.) (maize) from Uyo (46.04%), Pennisetum purpureum Schumach (elephant grass) from Trans-Amadi (47.7%), guinea grass from Eleme (49.2%), and elephant grass from Choba (39.9%) contained the highest percentage of high molecular weight (HMW) PAHs. Soil samples from Yenagoa (53.5%) and Khana (55.3%) showed the highest percentage of HMW PAHs. The total index ranged 0.27–12.4 in Uyo, 0.29–8.69 in Choba, 0.02–10.1 in Khana, 0.01–5.53 in Yenagoa, 0.21–9.52 in Eleme, and 0.13–8.96 in Trans-Amadi. The presence of HMW PAHs and molecular diagnostic ratios suggest PAH pollution from pyrogenic and petrogenic sources. Some soils in the Niger Delta show RQ(NCs) values higher than 800 and require remediation to forestall ecohealth consequences.
miR-145 Alleviates Smooth Muscle Cell Phenotype Transition via ADAM17-Mediated ACE2 Shedding
Authors: Wen Juan , Tang Baiyi , Guo Lan , Chen Wei , Tang Xiaohong
Published: July 2023

It has been shown that miR-145 is involved in the differentiation of vascular smooth muscle cells (VSMCs) and may regulate vascular remodeling. However, the molecular mechanisms behind these pathological processes in hypertension are not fully elucidated. The present study was to examine whether miR-145 modulates phenotypic transformation of VSMCs under normal state and synthetic state and to explore the possible role of ADAM17-mediated ACE2 shedding and ACE2-Ang-(1–7)-Mas receptor axis. Wistar rats were fed with high-sucrose/high-fat diet for 30 weeks to establish a metabolic hypertension animal model. VSMCs were cultured and treated with Ang II with or without miR-145 mimics or miR-145 inhibitor. Results showed the expression of contractile markers α-SMA and SM22α, miR-145, ACE2, and Mas receptor reduced in the thoracic aorta of metabolic hypertensive rats (MHRs), while that of synthetic marker OPN increased as compared to the control group. In in vitro study, miR-145 inhibitor inhibited the expression of α-SMA, SM22α, ACE2, Mas receptor, and the Ang-(1–7) excretion and induced the expression of synthetic markers OPN, EREG, and MMP2. However, miR-145 mimic produced opposite effects on the VSMCs. In addition, in the synthetic VSMC induced by Ang II, miR-145 inhibitor partially reversed the induced expression of OPN, EREG, and MMP2 by Ang II, while further decreasing the expression of α-SMA and SM22α and ACE2-Ang-(1–7)-Mas receptor. Cotreatment with ADAM17 siRNA partially reversed the inducible effect of miR-145 inhibitor on the EREG and MMP2, induced Ang-(1–7) excretion, and upregulated ACE2 and Mas receptor expression. In conclusion, miR-145 alleviates phenotype transition from contractile to synthetic type via ADAM17-mediated ACE2 shedding in VSMCs and retains the activation of ACE2-Ang-(1–7)-Mas axis, which may benefit the vascular structural remodeling in the metabolic hypertension.
Prognostic Markers in Pediatric Acute Liver Failure
Authors: Nogueira Andreia Filipa , Teixeira Catarina , Fernandes Carla , Moinho Rita , Gonçalves Isabel , Pinto Carla Regina , Carvalho Leonor
Published: July 2023

Introduction: Acute liver failure (ALF), although rare in children, is a complex progressive pathology, with multisystem involvement and high mortality. Isolated variables or those included in prognostic scores have been studied, to optimize organ allocation. However, its validation is challenging. This study aimed to assess the accuracy of several biomarkers and scores as predictors of prognosis in pediatric ALF (PALF). Methods: An observational study with retrospective data collection, including all cases of ALF, was defined according to the criteria of the Pediatric Acute Liver Failure Study Group, admitted to a pediatric intensive care unit (PICU) for 28 years. Two groups were defined: spontaneous recovery (SR) and non-SR (NSR) – submitted to liver transplantation (LT) or death at PICU discharge. Results: Fifty-nine patients were included, with a median age of 24 months, and 54% were female. The most frequent etiologies were metabolic (25.4%) and infectious (18.6%); 32.2% were undetermined. SR occurred in 21 patients (35.6%). In NSR group (N = 38, 64.4%), 25 required LT (42.4%) and 19 died (32.2%), 6 (15.7%) of whom after LT. The accuracy to predict NSR was acceptable for lactate at admission (AUC 0.72; 95% CI: 0.57–0.86; p = 0.006), ammonia peak (AUC 0.72; 95% CI: 0.58–0.86; p = 0.006), and INR peak (AUC 0.70; 95% CI: 0.56–0.85; p = 0.01). The cut-off value for lactate at admission was 1.95 mmol/L (sensitivity 78.4% and specificity 61.9%), ammonia peak was 64 μmol/L (sensitivity 100% and specificity 38.1%), and INR peak was 4.8 (sensitivity 61.1% and specificity 76.2%). Lactate on admission was shown to be an independent predictor of NSR on logistic regression model. Two prognostic scores had acceptable discrimination for NSR, LIU (AUC 0.73; 95% CI: 0.59–0.87; p = 0.004) and PRISM (AUC 0.71; 95% CI: 0.56–0.86; p = 0.03). In our study, the PALF delta score (PALF-ds) had lower discrimination capacity (AUC 0.63; 95% CI: 0.47–0.78; p = 0.11). Conclusions: The lactate at admission, an easily obtained parameter, had a similar capacity than the more complex scores, LIU and PRISM, to predict NSR. The prognostic value in our population of the promising dynamic score, PALF-ds, was lower than expected.
Meningococcal ACWY conjugate vaccine immunogenicity in adolescents with primary or secondary immune deficiencies, a prospective observational cohort study
Authors: Ohm Milou , van Straalen Joeri W , de Joode-Smink Gerrie , van Montfrans Joris , Bartels Marije , van Wildenbeest Joanne G , Lindemans Caroline A , Wennink Roos AW , de Boer Joke H , Sanders Elisabeth AM , Verduyn-Lunel Frans M , Berbers Guy AM , Wulffraat Nico M , Jansen Marc H.A.
Published: July 2023

Background

Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure.

Findings

We enrolled 69 individuals aged 14–18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3–6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15–0.47] and 0.22 [95% CI: 0.10–0.49], respectively). No serious adverse events were reported by study participants.

Conclusions

The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.
Evaluation of clinical outcomes, complication rate, feasibility, and applicability of transfacet pedicle-sparing approach in thoracic disc herniation: a systematic review and meta-analysis
Authors: Hamid Shafi , Moradi Farid , Bagheri Seyed Reza , Zarpoosh Mahsa , Amirian Parsa , Ghasemi Hooman , Alimohammadi Ehsan
Published: July 2023

Objective

This study aimed to evaluate the clinical outcomes, complication rate, feasibility, and applicability of transfacet pedicle-sparing approach for treating thoracic disc herniation.

Methods

We searched three databases including the Cochrane Library, PubMed, and Embase for eligible studies until Dec 2022. The quality of studies and their risk of bias were assessed using the methodological index for non‐randomized studies. We evaluated the heterogeneity between studies using the I2 statistic and the P-value for the heterogeneity.

Results

A total of 328 patients described in 11 included articles were published from 2009 to 2022. Pain outcomes using the visual analog scale (VAS score) were reported in four studies. The standardized mean difference was reported as 0.749 (CI 95% 0.555–0.943). The obtained result showed the positive effect of the procedure and the improvement of patients' pain after the surgery. Myelopathy outcomes using the Nurick score were reported in five studies. The standardized mean difference was reported as 0.775 (CI 95% 0.479–1.071). The result showed the positive effect of the procedure. Eight studies assessed postoperative complications and neurological deterioration. The pooled overall complication was 12.4% (32/258) and 3.5% (9/258) neurological worsening.

Conclusion

The results of this study demonstrated a positive effect of the transfacet pedicle-sparing approach on the clinical outcomes of patients with thoracic disc herniation surgery. The technique has been shown to be safe and effective for the right patient. The technique is associated with lower rates of complications and a shorter hospital stay compared to other surgical approaches. This information can assist clinicians in making informed decisions when selecting the most appropriate surgical technique for their patients with thoracic disc herniation.
Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer
Authors: Park Yeon Hee , Im Seock-Ah , Park Kyunghee , Wen Ji , Lee Kyung-Hun , Choi Yoon-La , Lee Won-Chul , Min Ahrum , Bonato Vinicius , Park Seri , Ram Sripad , Lee Dae-Won , Kim Ji-Yeon , Lee Su Kyeong , Lee Won-Woo , Lee Jisook , Kim Miso , Kim Hyun Seon , Weinrich Scott L. , Ryu Han Suk , Kim Tae Yong , Dann Stephen , Kim Yu-Jin , Fernandez Diane R. , Koh Jiwon , Wang Shuoguo , Park Song Yi , Deng Shibing , Powell Eric , Ravi Rupesh Kanchi , Bienkowska Jadwiga , Rejto Paul A. , Park Woong-Yang , Kan Zhengyan
Published: July 2023

Background

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2− MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance.

Methods

Tissue was collected from 89 patients with HR+/HER2− MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival.

Results

Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors withTP53mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression inRB1,ESR1, PTEN, andKMT2C.

Conclusions

We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET.

Trial registration

ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.
Long Covid active case finding study protocol: A co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)
Authors: Alwan Nisreen A. , Clutterbuck Donna , Pantelic Marija , Hayer Jasmine , Fisher Lere , Hishmeh Lyth , Heightman Melissa , Allsopp Gail , Wootton Dan , Khan Asad , Hastie Claire , Jackson Monique , Rayner Clare , Brown Darren , Parrett Emily , Jones Geraint , Smith Kerry , Clarke Rowan , Mcfarland Sammie , Gabbay Mark , Banerjee Amitava ,   for the STIMULATE-ICP Consortium
Published: July 2023

Background and aim

Long Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups’ experiences of Long Covid, and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area in London, United Kingdom to test the feasibility of a community-based approach of identifying Long Covid cases that have not been clinically diagnosed and have not been referred to Long Covid specialist services. We will explore the barriers to accessing recognition, care, and support, as well as experiences of stigma and perceived discrimination.

Methods

This protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, a study leaflet will be distributed in the local community to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed. Potential participants will be assessed according to the study’s inclusion criteria and offered the opportunity to participate if they fit them. Awareness of Long Covid and associated symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered a referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic.
Boldness, activity, and aggression: Insights from a large-scale study in Baltic salmon (Salmo salar L)
Authors: Axling Johanna , Vossen Laura E. , Peterson Erik , Winberg Svante
Published: July 2023

Atlantic salmon (Salmo salar) display high levels of agonistic behavior in aquaculture farms, resulting in fin damage and chronic stress. Aggression affects fish growth and performance negatively, and presents a serious welfare problem. Indeed, it would be beneficial to identify, separate or exclude overly aggressive individuals. Research on behavioral syndromes suggests that aggressive behavior may correlate with other behavioral traits, such as boldness and locomotory activity. We aimed to develop a high-throughput method to quantify and predict aggressive behavior of individual parr in hatchery-reared Baltic salmon (Salmo salar L.). We screened approximately 2000 parr in open field (OF) and mirror image stimulation (MIS) tests. We extracted seven variables from video tracking software for each minute of the tests; distance moved and duration moving (activity), the duration in and number of entries to the center of the arena (boldness), the distance moved in and duration spent in the area adjacent to the mirror during the MIS test (aggressiveness) and head direction (lateralization). To investigate the relationship between activity, boldness and aggression we first correlated the first six variables to one another. Second, we assigned individuals to high, medium, low or zero aggression groups based on the MIS test and quantified activity and boldness in each group. Third, we analyzed whether the fish viewed the mirror with the left or right eye. Our results show that medium and low aggressive fish were the most active, while highly aggressive fish showed average activity. Aggressive groups did not differ in boldness. Activity and boldness were positively correlated. Finally, we detected a preference for fish to view the mirror with the left eye. We conclude that aggressiveness cannot be predicted from the results of the OF test alone but that the MIS test can be used for large-scale individual aggression profiling of juvenile salmon.