bluuebunny/crossref_metadata_2025 huggingface dataset:
Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection
Authors: Farjo Mireille , Koelle Katia , Martin Michael A. , Gibson Laura L. , Walden Kimberly K. O. , Rendon Gloria , Fields Christopher J. , Alnaji Fadi G. , Gallagher Nicholas , Luo Chun Huai , Mostafa Heba H. , Manabe Yukari C. , Pekosz Andrew , Smith Rebecca L. , McManus David D. , Brooke Christopher B.
Published: January 2024

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.

IMPORTANCE

We detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.
Histopathology and quantification of green fluorescent protein-tagged
Fusarium oxysporum
f. sp.
luffae
isolate in resistant and susceptible
Luffa
germplasm
Authors: Namisy Ahmed , Chen Shu-Yun , Huang Jin-Hsing , Unartngam Jintana , Thanarut Chinnapan , Chung Wen-Hsin
Published: January 2024

Fusarium oxysporum
f. sp.
luffae
(Folu) is a severe plant pathogen that causes vascular wilt and root rot in
Luffa
plants worldwide. A green fluorescent protein (GFP)-tagged isolate of Folu (Fomh16-GFP) was utilized to investigate the infection progress and colonization of Fomh16-GFP in resistant (LA140) and susceptible (LA100)
Luffa
genotypes. Seven days post-inoculation (dpi), it was observed that Fomh16-GFP had successfully invaded and colonized the vascular bundle of all LA100 parts, including the roots, hypocotyl, and stem. Pathogen colonization continued to increase over time, leading to the complete wilting of plants by 14–17 dpi. In LA140, the Fomh16-GFP isolate colonized the roots and hypocotyl vascular system at 7 dpi. Nevertheless, this colonization was restricted in the hypocotyl and decreased significantly, and no fungal growth was detected in the vascular system at 21 dpi. Thus, the resistant genotype might trigger a robust defense mechanism. In addition, while the pathogen was present in LA140, the inoculated plants did not exhibit any symptoms until 28 dpi. Quantitative PCR was utilized to measure the Fomh16-GFP biomass in various parts of LA100 and LA140 at different time points. The findings indicated a positive correlation between the quantity of Fomh16-GFP DNA and disease development in LA100. Alternatively, a high amount of Fomh16-GFP DNA was identified in the roots of LA140. Nonetheless, no significant correlations were found between DNA amount and disease progression in LA140. Aqueous extracts from LA140 significantly reduced Fomh16-GFP spore germination, while no significant reduction was detected using LA100 extracts.

IMPORTANCE

Fusarium wilt of
Luffa
, caused by
Fusarium oxysporum
f. sp.
luffae
(Folu), causes great losses in
Luffa
plants worldwide. This study used a green fluorescent protein (GFP)-tagged isolate of Folu (Fomh16-GFP) to investigate the infection progress and colonization dynamics of Fomh16-GFP in the resistant and susceptible
Luffa
genotypes, which could be important in understanding the resistance mechanism of Folu in
Luffa
plants. In addition, our work highlights the correlations between DNA amount and disease progression in resistant plants using real-time PCR. We observed a positive correlation between the quantity of Fomh16-GFP DNA and disease progression in LA100, while no significant correlation was found in LA140. These results could be valuable to further investigate the resistance mechanism of
Luffa
genotypes against Folu. Gaining a better understanding of the interaction between Folu and
Luffa
plants is crucial for effectively managing Fusarium wilt and enhancing resistance in
Luffa
rootstock and its varieties.
LA-ICP-MS zircon U–Pb ages, geochemistry, and genesis of Paleozoic granites from Biezhentao Mountain, Western Tianshan, Xinjiang
Authors: Li Xiang , Xia Fang , Gao Ling-Ling , Chen Chuan , Du Xiao-Fei , Li Shun-Da
Published: January 2024

The geologic history of the Western Tianshan region is important for understanding the evolution of the Central Asian Orogenic Belt and accretionary orogenesis. Paleozoic and Mesozoic igneous rocks are present along the northern margin of the Yili Block; however, studies of Paleozoic subduction and collisional events have been relatively limited. Published geochronologies of Middle Devonian magmatic rocks in this region are also lacking. Therefore, this study analyzed the zircon U–Pb ages and major and trace elemental compositions of three granite types collected from Biezhentao Mountain (Wenquan County, Western Tianshan). The medium-grained diorite (384.1 ± 3.6 Ma) and diorite–porphyrite (382 ± 3.2 Ma) are silica-rich, weakly peraluminous, alkali-rich, enriched in large-ion lithophile elements, depleted in high field strength elements, and belong to the calc–alkaline series, with A-type granite characteristics. The monzogranite (423.3 ± 9.4 Ma) exhibits A-type granite characteristics and belongs to the peraluminous calc–alkaline series. The findings suggest that the granitoids recorded two stages of tectonomagmatism during the Middle Devonian–Late Silurian. The Middle Devonian medium-grained diorite and diorite–porphyrite formed in a back-arc extensional setting, whereas the Late Silurian monzogranite formed in an active continental margin setting during the subduction of the North Tianshan Ocean. These results provide insights into the tectonic and magmatic processes that occurred during the evolution of the Western Tianshan region and the formation and evolution of the Central Asian Orogenic Belt.
Electroweak loop contributions to the direct detection of wino dark matter
Authors: Ellis John , Nagata Natsumi , Olive Keith A. , Zheng Jiaming
Published: January 2024

Electroweak loop corrections to the matrix elements for the spin-independent scattering of cold dark matter particles on nuclei are generally small, typically below the uncertainty in the local density of cold dark matter. However, as shown in this paper, there are instances in which the electroweak loop corrections are relatively large, and change significantly the spin-independent dark matter scattering rate. An important example occurs when the dark matter particle is a wino, e.g., in anomaly-mediated supersymmetry breaking (AMSB) and pure gravity mediation (PGM) models. We find that the one-loop electroweak corrections to the spin-independent wino LSP scattering cross section generally interfere constructively with the tree-level contribution for AMSB models with negative Higgsino mixing, $$\mu < 0$$

μ
<
0

, and in PGM-like models for both signs of $$\mu $$
μ
, lifting the cross section out of the neutrino fog and into a range that is potentially detectable in the next generation of direct searches for cold dark matter scattering.
Design and Implementation of Novel Hybrid and Multiscale- Assisted CNN and ResNet Using Heuristic Advancement of Adaptive Deep Segmentation for Iris Recognition
Authors: Babu Gorla , Khayum Pinjari Abdul
Published: January 2024

Due to its significant applications in security, the iris recognition process has been considered as the most active research area over the last few decades. In general, the iris recognition framework has been crucially utilized for various security applications because it includes a set of features as well as does not alter its character according to the time. In recent times, emerging deep learning techniques have attained huge success, particularly in the field of the iris recognition framework model. Moreover, in considering the field of iris recognition, there is no possibility for the remarkable capability of the deep learning model as well as to attain superior performance. To handle the issues in the conventional model of iris recognition, a novel heuristic-aided deep learning framework has been implemented for recognizing the iris system. Initially, the required source iris images are gathered from the data sources. It is then followed by the pre-processing stage, where the pre-processed image is obtained. Consequently, the image segmentation process is carried out by Adaptive Deeplabv3+layers, in which the parameters are optimized using the Modified Weighted Flow Direction Algorithm (MWFDA). Finally, the iris recognition is accomplished by hybrid Hybridization of Multiscale Dilated-Assisted Learning (MDAL) that will be composed of both a Convolutional Neural Network (CNN) and a Residual Network (ResNet). To achieve optimal recognition results, the parameters in CNN and ResNet are tuned optimally by using MWFDA. The experimental results are estimated with the help of distinct measures. Contrary to conventional methods, the empirical results prove that the recommended model achieves the desired value to enhance the recognition performance.
Late Paleozoic magmatism and foreland deformation associated with opening and closing of marginal basins in the North Patagonian Andes
Authors: Rapela C. W. , García M. , Hervé F. , Pankhurst R. J. , Calderón M. , Fanning C. M. , Verdecchia S. O.
Published: January 2024

Remnants of coeval Devonian oceanic and continental foreland rocks are preserved in the basement of the North Patagonian Andes. Our previous studies of the igneous rocks here have shown that the primitive oceanic and continental igneous rocks are coeval and belong to a marginal basin that opened and closed over 50 Myr. A structural study and four new U–Pb SHRIMP ages and zircon Hf–O determinations allowed the identification of three metamorphic episodes, the first one of which, M
1
(D
1
-S
1
), is coeval with Andean-type granite intrusion in the foreland (405–380 Ma). This activity was simultaneous with the development of an oceanic ridge and a marginal basin, at the outer edge of which a primitive granitic oceanic arc formed (380–385 Ma; zircon

δ

18
O 3.6–5.2‰). The extinction of this ridge initiated under-thrusting of the oceanic crust below the continent and an important mid- to high-grade metamorphic event, M
2
(D
2
-S
2
) at 375–360 Ma, its peak dated by metamorphic zircon rims in migmatite at 365 ± 3 Ma. Basin closure occurred after the intrusion of S-type granites (357 ± 2 Ma; zircon

δ

18
O 7.4–10.4‰) in the foreland and the accretion of gabbros, cumulate gabbros and trondhjemites at the proto-Pacific margin. Compression prevailed for 20 Myr in the foreland, causing a mylonitic medium-grade M
3
(D
3
-S
3
) event.

Supplementary material:
Datasets are available at
https://doi.org/10.6084/m9.figshare.c.6989873
Simultaneous well spacing and completion optimization using an automated machine learning approach. A case study of the Marcellus Shale reservoir, northeastern United States
Authors: Fathi Ebrahim , Takbiri-Borujeni Ali , Belyadi Fatemeh , Adenan Mohammad Faiq
Published: January 2024

Optimizing unconventional field development requires simultaneous optimization of well spacing and completion design. However, the conventional practice of using cross plots and sensitivity analysis via Monte Carlo simulations for independent optimization of well spacing and completion design has proved inadequate for unconventional reservoirs. This is due to the inability of cross plots to capture non-linear cross-correlations between parameters affecting hydrocarbon production, and the computational expense and difficulty of Monte Carlo simulations. Recently, automated machine learning (AutoML) workflows have been used to tackle complex problems. However, applying AutoML workflows to engineering problems presents unique challenges, as achieving high accuracy in forecasting the physics of the problem is crucial. To address this issue, a new physics-informed AutoML workflow based on the TPOT open-source tool developed that guarantees the physical plausibility of the optimum model while minimizing human bias and uncertainty. The workflow has been implemented in a Marcellus Shale reservoir with over 1500 wells to determine the optimal well spacing and completion design parameters for both the field and each well. The results show that using a shorter stage length and a higher sand-to-water ratio is preferable for this field, as it can increase cumulative gas production by up to 8%. Additionally, it is observed that fifty-percentile cumulative gas predictions are in close agreement with actual field productions.

Thematic collection:
This article is part of the Digitally enabled geoscience workflows: unlocking the power of our data collection available at:
https://www.lyellcollection.org/topic/collections/digitally-enabled-geoscience-workflows
From Dissonance to Dialogue: A Token-Based Approach to Bridge the Gap Between Manufacturers and Customers
Authors: Pytel Norman , Ziegler Christian , Winkelmann Axel
Published: January 2024

This article presents a novel token-based recall communication system, which integrates Enterprise Resource Planning (ERP) systems and blockchain technology to enhance recall communication and cooperation between manufacturers and customers. We employed a design science research methodology to develop a set of design principles and features that support the interoperable system. Our findings demonstrate that we can significantly improve recall coordination, traceability, and co-value creation between involved parties. By focusing on the integration potential of traditional technologies like ERP systems with blockchain and token techniques, we reveal innovative synergies for both social and technical subsystems. The study explores the implications of the proposed system for both theory and practice, offering insights into the advantages and challenges of such integration. The evaluation conducted with industry experts demonstrates high reusability of the design principles.
Communication—High-Capacity Hard Carbons Enabled by a Sodium Carborane Solid Electrolyte for Sodium-Ion Batteries
Authors: Niitani Keita , Ushiroda Shin , Kuwata Hiroko , Hozumi Masato , Matsunaga Tomoya , Nakanishi Shinji , Miyazaki Kohei , Abe Takeshi
Published: January 2024

High-energy-density sodium-ion batteries, which are promising alternatives to lithium-ion batteries, require high-capacity hard carbons as negative electrodes. Conventional sodium-ion batteries use carbonate liquid electrolytes that decompose at hard-carbon surfaces, which limits the use of high-surface-area hard carbons. Herein, we report that high-surface-area hard carbons synthesized using magnesium oxide templates exhibit high capacities when combined with a sodium carborane solid electrolyte. Unlike carbonate liquid electrolytes, the solid electrolyte is highly stable and enables reversible electrochemical reactions in hard carbons to deliver high capacities of approximately 500 mA h g−1.
Influence of Water Concentration on High-Temperature Reactive Condensation of Chromium Vapors Generated in 800 °C Air
Authors: van Leeuwen T. K. , Dowdy R. , Guerrero A. , Gannon P.
Published: January 2024

Reactive evaporation of chromium (Cr) from stainless steels used in solid oxide electrochemical systems, such as solid oxide fuel cell (SOFC) and solid oxide electrolysis cell (SOEC) systems, is well-documented. However, the condensation and interactions of volatilized Cr species onto and with surrounding interfaces during complex and dynamic system exposures is less understood. Understanding these interactions during operation is critical for improving system performance and safeguarding environmental, health and safety, as some condensed species contain toxic hexavalent Cr (Cr(VI)). The objective of this study is to investigate the condensation pathways of Cr vapors within representative high-temperature system environments. To accomplish this objective, Cr vapors, produced by high-temperature (800 °C) air exposures of trivalent chromium (Cr(III)) oxide (Cr2O3) powder with variable moisture content, were condensed onto various ceramic materials at lower temperatures (<400 °C). The total amount of Cr and ratios of oxidation states were measured using inductively coupled plasma optical emission spectroscopy (ICP-OES) and diphenyl carbazide (DPC) colorimetric/direct UV–vis spectrophotometer analyses. Increased Cr condensation was observed with increased water content, with similar Cr(VI) to total Cr ratios. Results and interpretations are discussed in context of improving understanding of Cr reactive condensation in SOFC/SOEC and related high-temperature materials and systems.
Performance Enhancement of a Membrane Electrochemical Cell for CO2 Capture
Authors: Muroyama Alexander P. , Abu-Arja Dania , Rogerio Barbara Kohlrausch , Masiello Davide , Winzely Maximilian , Gubler Lorenz
Published: January 2024

The utilization of renewable electrons to capture and valorize CO2 will be a critical component in achieving a net zero emission society. The deployment of electrochemically driven technologies will depend on whether they can operate efficiently and economically at scale. We have proposed an anion exchange membrane-based device to regenerate the alkalinity of a carbonate capture solution while simultaneously concentrating CO2 in an H2 stream. To improve the technology readiness, we have reduced overpotentials in the cell and increased the operating current density through design optimization of the cathode compartment. The use of targeted geometries to promote bubble evacuation from the cell, particularly for the cathode spacer, had a significant effect on reducing the cell voltage and enabled higher current density operation than what was previously attainable. Using a pure K2CO3(aq) feed, the cell achieved a specific energy consumption of 290 kJ∙molCO2
−1 at 100 mA∙cm−2, with a faradaic efficiency of 45% (90% CO3
2− transport). The specific energy consumption reached a minimum at moderate current densities (∼50 mA∙cm−2), with a cell voltage of ∼1 V. This work shows that reasonable specific energy consumption at industrially relevant current densities can be enabled through cell design, material selection, and effective management of bubbles.
Channel Attention-Based Approach with Autoencoder Network for Human Action Recognition in Low-Resolution Frames
Authors: Dastbaravardeh Elaheh , Askarpour Somayeh , Saberi Anari Maryam , Rezaee Khosro
Published: January 2024

Action recognition (AR) has many applications, including surveillance, health/disabilities care, man-machine interactions, video-content-based monitoring, and activity recognition. Because human action videos contain a large number of frames, implemented models must minimize computation by reducing the number, size, and resolution of frames. We propose an improved method for detecting human actions in low-size and low-resolution videos by employing convolutional neural networks (CNNs) with channel attention mechanisms (CAMs) and autoencoders (AEs). By enhancing blocks with more representative features, convolutional layers extract discriminating features from various networks. Additionally, we use random sampling of frames before main processing to improve accuracy while employing less data. The goal is to increase performance while overcoming challenges such as overfitting, computational complexity, and uncertainty by utilizing CNN-CAM and AE. Identifying patterns and features associated with selective high-level performance is the next step. To validate the method, low-resolution and low-size video frames were used in the UCF50, UCF101, and HMDB51 datasets. Additionally, the algorithm has relatively minimal computational complexity. Consequently, the proposed method performs satisfactorily compared to other similar methods. It has accuracy estimates of 77.29, 98.87, and 97.16%, respectively, for HMDB51, UCF50, and UCF101 datasets. These results indicate that the method can effectively classify human actions. Furthermore, the proposed method can be used as a processing model for low-resolution and low-size video frames.
The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis
Authors: Sarkar Sujan Kumar , Willson Annie M. L. , Jordan Margaret A.
Published: January 2024

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate‐like immune cells, such as γδ T cells, NKT cells, MAIT cells, and innate‐like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.
A Single-Center 18-Year Series of 73 Cases of Metaplastic Carcinoma of the Breast
Authors: Thériault Kassandra , Ben Moussa Mariem , Perron Marjorie , Desbiens Christine , Poirier Brigitte , Poirier Éric , Leblanc Dominique , Morin Claudya , Lemieux Julie , Hogue Jean-Charles , Boudreau Dominique
Published: January 2024

Aim. To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy. Methods. This retrospective study included patients with MeBC (n = 73) from a tertiary breast cancer center: the “Centre des Maladies du Sein of the CHU de Québec–Université Laval.” The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results. The median follow-up was 57.2 months. The mean tumor size was 39.5 ± 32.1 (range, 1–200) mm. Most were in grade 3 (75.3%), without evidence of clinical nodal involvement (75.3%), and triple-negative (79.5%). Chemotherapy was given to 49 (67.1%) patients. Thirty-seven patients (50.7%) underwent a mastectomy, and 22/37 (59.5%) received radiotherapy. Adjuvant chemotherapy was given to 36 patients (49.3%), and nine (12.3%) patients were treated with neoadjuvant chemotherapy. The 5-year OS and DFS rates were 60.2% and 66.8%. Among the nine patients who received neoadjuvant chemotherapy, three (33.3%) achieved a partial response, three (33.3%) had stable disease, and three (33.3%) had disease progression. The use of chemotherapy, especially in the adjuvant setting, had a significant positive effect on 5-year OS (P=0.003) and 5-year DFS (P=0.004). Nodal involvement was associated with worse OS (P=0.049) but similar DFS (P=0.157). Lumpectomy was associated with better 5-year OS (P<0.0001) and DFS (P=0.0002) compared with mastectomy. Conclusion. MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Adjuvant chemotherapy was associated with improved OS and DFS. Patients should be carefully selected for neoadjuvant chemotherapy.
Pharmacological and Psychological Treatment Have Common and Specific Effects on Brain Activity in Obsessive-Compulsive Disorder
Authors: van der Straten Anouk , Bruin Willem , van de Mortel Laurens , ten Doesschate Freek , Merkx Maarten J. M. , de Koning Pelle , Vulink Nienke , Figee Martijn , van den Heuvel Odile A. , Denys Damiaan , van Wingen Guido
Published: January 2024

Initial treatment for obsessive-compulsive disorder (OCD) consists of pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) and/or psychological treatment with cognitive behavioral therapy (CBT). The assumption is that both treatments have different neural working mechanisms, but empirical evidence is lacking. We investigated whether these treatments induce similar or different functional neural changes in OCD. We conducted a longitudinal nonrandomized controlled trial in which thirty-four OCD patients were treated with sixteen weeks of CBT or SSRIs. Functional magnetic resonance imaging was performed before and after treatment during emotional processing (emotional face matching and symptom provocation tasks) and response inhibition (stop signal task). Twenty matched healthy controls were scanned twice with a similar time interval. Both CBT and SSRIs were successful in reducing OCD symptoms. Compared to healthy controls, treatment led to a reduction of insula activity in OCD patients during symptom provocation. The comparison between treatment groups revealed widespread divergent brain changes in the cerebellum, posterior insula, caudate nucleus, hippocampus, and occipital and prefrontal cortex during all tasks, explained by relative increases of activity following CBT compared to relative decreases of activity following SSRIs. Pharmacological and psychological treatment primarily lead to opposite changes in brain function, with a common reduction of insula activity during symptom provocation. These findings provide insight into common and specific neural mechanisms underlying treatment response, suggesting that CBT and SSRIs support recovery from OCD along partly distinct pathways. This trial is registered with NTR6575.
The Quality of Life of Pseudomyxoma Peritonei Patients: A Scoping Review
Authors: Taher Rayan , Gray Debra , Ramage John
Published: January 2024

Background. Pseudomyxoma peritonei (PMP) is a form of peritoneal malignancy. It originates from a perforated appendiceal epithelial tumour. Patients with PMP experience various stressful and traumatic events including diagnosis with a rare disease, treatment with extensive and complex surgery, and long hospital stays. Currently, there is a scarcity of studies that primarily aim to assess the quality of life of patients with PMP, and there is no reviews or comprehensive understanding of the quality of life (QoL) issues faced by these patients. Even fewer studies have consulted with patients themselves. Objective. To review the current literature on the QoL of patients with PMP and answer two main questions: What methods are being used to assess the QoL patients with PMP and what are the main findings?. Methods. For the scoping review, five scientific databases were searched (CINAHL, EMBASE, Pubmed, PsycInfo, and Medline). Publications that were published between 2002 and 2022 and in English were included in this review. Studies were screened by two independent reviewers against the review’s eligibility criteria. Data related to the QoL of patients with PMP in the included studies were extracted to answer two main questions (what were the methods used to assess QoL in this population, and what were the findings?). The extracted data was presented in table form and qualitatively analyzed using content analysis. Findings. Fourteen studies were included in this review. Only five studies out of fourteen assessed the QoL of patients with PMP as a main outcome, and all these studies assessed QoL in relation to surgery. Studies that assessed QoL used different validated measures. There was a consensus among studies that patients’ QoL improved by 12 months posttreatment. The most commonly cited symptom of PMP in this review is abdominal pain. Conclusion. The evidence on the QoL of patients with PMP is limited. Studies that assess the quality of life of these patients independent of surgery are needed. There is no consensus on the measure used to assess QoL in this population.
Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies
Authors: Pathak Anchal , Pal Ajay Kumar , Roy Subhadeep , Nandave Mukesh , Jain Keerti
Published: January 2024

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. “Angiogenic switch” indicates a time‐restricted event where the imbalance between pro‐ and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.
Utilizing Human Genetics to Develop Chemoprevention for Cancer—Too Good an Opportunity to be Missed
Authors: Peters Ulrike , Tomlinson Ian
Published: January 2024

Large-scale genetic studies are reliably identifying many risk factors for disease in the general population. Several of these genetic risk factors encode potential drug targets, and genetics has already helped to introduce targeted agents for some diseases, an example being lipid-lowering drugs to reduce the incidence of cardiovascular disease. Multiple drugs have been developed to treat cancers based on somatic mutations and genomics, but in stark contrast, there seems to be a reluctance to use germline genetic data to develop drugs to prevent malignancy, despite the large numbers of people who could benefit, the potential for lowering cancer rates, and the widespread current use of non-pharmaceutical measures to reduce cancer risk factors such as tobacco, alcohol, and infectious diseases. We argue that concerted efforts for cancer prevention based on genetics, including genes influenced by common polymorphisms that modulate cancer risk, are urgently needed. There are enormous, yet underutilized, opportunities to develop novel targeted agents for chemoprevention of cancer based on human germline genetics. Such efforts are likely to require the support of a dedicated funding program by national and international agencies.

See related commentary by Winham and Sherman, p. 13
Leveraging GWAS: Path to Prevention?
Authors: Winham Stacey J. , Sherman Mark E.
Published: January 2024

Developing novel cancer prevention medication strategies is important for reducing mortality. Identification of common genetic variants associated with cancer risk suggests the potential to leverage these discoveries to define causal targets for cancer interception. Although each risk variant confers small increases in risk, researchers propose that blocking those that produce causal carcinogenic effects might have large impacts on cancer prevention. While a promising concept, we describe potential hurdles that may need to be scaled to reach this goal, including: (i) understanding the complexity of risk; (ii) achieving statistical power in studies with binary outcomes (cancer development: yes or no); (iii) characterization of cancer precursors; (iv) heterogeneity of cancer subtypes and the populations in which these diseases occur; (v) impact of static genetic markers across complex events of the life course; (vi) defining gene–gene and gene–environment interactions and (vii) demonstrating functional effects of markers in human populations. We assess short-term prospects for this research against the backdrop of these challenges and the potential to prevent cancer through other means.

See related commentary by Peters and Tomlinson, p. 7
Emerging Strategies for the Prevention of Immune Toxicities Associated with T cell–Engaging Cancer Therapies
Authors: Kowalski Andrew , Lykon Jill , Diamond Benjamin , Coffey David G. , Kaddoura Marcella , Maura Francesco , Hoffman James E. , Kazandjian Dickran , Landgren Ola
Published: January 2024

Immune-related toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common side effects of bispecific antibody and chimeric antigen receptor (CAR) T-cell therapies of hematologic malignancies. As anti-inflammatory therapy (the standard of care) is variably effective in mitigating these toxicities after onset, here we discuss emerging evidence for shifting the strategy from mitigation to prevention.
TABLE 2 from A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial
Authors: Tabernero Josep , Yoshino Takayuki , Stintzing Sebastian , de Gramont Aimery , Gibbs Peter , Jonker Derek J. , Nygren Peter , Papadimitriou Christos , Prager Gerald W. , Tell Roger , Lenz Heinz-Josef
Published: January 2024

Primary efficacy endpoint: ORR (by BICR in ITT population)
Supplementary Table 9 from A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial
Authors: Tabernero Josep , Yoshino Takayuki , Stintzing Sebastian , de Gramont Aimery , Gibbs Peter , Jonker Derek J. , Nygren Peter , Papadimitriou Christos , Prager Gerald W. , Tell Roger , Lenz Heinz-Josef
Published: January 2024

Supplementary Table 9. Grading of Adverse Events Reported in Any Category
Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024
Authors: Lin Lin , Dai Fei , Wei Jinjin , Chen Zheng
Published: January 2024

Background: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-Oxo-ETE) is a metabolite of arachidonic acid shown to promote biological activities in different cell types. Summary: 5-Oxo-ETE is synthesized from the 5-lipoxygenase product 5S-HETE (5S-hydroxy-6,8,11,14-eicosatetraenoic acid) in the presence of the nicotinamide adenine dinucleotide phosphate (NADP)+-dependent enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under some conditions that promote oxidation of NADPH to NADP+, such as the respiratory burst in phagocytic cells, eosinophils, and neutrophils, oxidative stress in monocytes and dendritic cells, and cell death, 5-Oxo-ETE synthesis can be dramatically increased. In addition, 5-Oxo-ETE can also be formed in the absence of 5-lipoxygenase in cells through transcellular biosynthesis by inflammatory cell-derived 5S-HETE. This compound performs its biological activities by the highly selective Gi/o-coupled OXE receptor, which is highly expressed on eosinophils, neutrophils, basophils, and monocytes. As such, 5-Oxo-ETE is a potent chemoattractant for these inflammatory cells, especially for eosinophils. Key Messages: Although the pathophysiological role of 5-Oxo-ETE is not clearly understood, 5-Oxo-ETE may be a significant mediator in allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis. And targeting the OXE receptor may be a novel therapy for this kind of inflammatory condition. Nowadays, selective OXE receptor antagonists are currently under investigation and could become potential therapeutic agents in allergy.
Hypoglykämie: Mit und ohne Diabetes besser im Auge behalten
Authors: Egbring Charlotte
Published: January 2024

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases.
Modeling the potential distribution to present and future of the poorly known species Xenohyla eugenioi Caramaschi, 1998 (Anura: Hylidae) with findings about its distribution, natural history, and conservation
Authors: Andrade Hugo , Dias Eduardo José dos Reis , Almeida Rony Peterson Santos , Costa Bruno Bove da , Neves Matheus Oliveira
Published: January 2024

The distribution of anurans is conditioned by historical factors and ecological drivers. Thus, Species Distribution Models are important tools to provide information on the potential distribution of the species and determine where they will be requirements in future. Here our aim was modeling the current and future distribution and discussing about conservation of Xenohyla eugenioi. We searched for occurrence records through literature and scientific collections data. This species has approximately 650 km in straight line between the extreme localities, occurring mainly in bromeliads near to water bodies. he Ensemble method indicates the most probable areas of occurrence were over ecotonal range between Caatinga and Atlantic Forest and our projections have showed suitable conditions to highlands (up to 1.000 m). While, in the future, is expected erosion of the X. eugenioi populations, due climatic changes, which reinforce the caution to conservation of this poorly known species and necessity of studies about its ecology, natural history and distribution. Moreover, we hope that this work will contribute to the discovery of new records, characterizing the narrower niche space than this species may actually inhabit.
Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels
Authors: Lamb Fred S. , Choi Hyehun , Miller Michael R. , Stark Ryan J.
Published: January 2024

Vascular inflammation underlies the development of hypertension, and the mechanisms by which it increases blood pressure remain the topic of intense investigation. Proinflammatory factors including glucose, salt, vasoconstrictors, cytokines, wall stress, and growth factors enhance contractility and impair relaxation of vascular smooth muscle cells. These pathways share a dependence upon redox signaling, and excessive activation promotes oxidative stress that promotes vascular aging. Vascular smooth muscle cell phenotypic switching and migration into the intima contribute to atherosclerosis, while hypercontractility increases systemic vascular resistance and vasospasm that can trigger ischemia. Here, we review factors that drive the initiation and progression of this vasculopathy in vascular smooth muscle cells. Emphasis is placed on the contribution of reactive oxygen species generated by the Nox1 NADPH oxidase which produces extracellular superoxide (O
2
•−
). The mechanisms of O
2
•−
signaling remain poorly defined, but recent evidence demonstrates physical association of Nox1 with leucine-rich repeat containing 8 family volume-sensitive anion channels. These may provide a pathway for influx of O
2
•−
to the cytoplasm, creating an oxidized cytoplasmic nanodomain where redox-based signals can affect both cytoskeletal structure and vasomotor function. Understanding the mechanistic links between inflammation, O
2
•−
and vascular smooth muscle cell contractility may facilitate targeting of anti-inflammatory therapy in hypertension.
Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants
Authors: Zhai Yujia , Chen Hongyu , Che Bizhong , Liu Yang , Peng Yanbo , Chen Jing , Xu Tan , He Jiang , Zhang Yonghong , Zhong Chongke
Published: January 2024

BACKGROUND:

It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants.

METHODS:

The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms.

RESULTS:

At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all
P
>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71–1.26), 1.08 (0.80–1.44), and 0.91 (0.69–1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (
P
=0.88 for interaction).

CONCLUSIONS:

Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01840072.
Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase
Authors: Kim Diana J. , Singh Nishita , Catanese Luciana , Yu Amy Y.X. , Demchuk Andrew M. , Lloret-Villas Mar I. , Deschaintre Yan , Coutts Shelagh B. , Khosravani Houman , Appireddy Ramana , Moreau Francois , Gubitz Gord , Tkach Aleksander , Dowlatshahi Dar , Medvedev George , Mandzia Jennifer , Pikula Aleksandra , Shankar Jai , Williams Heather , Manosalva Herbert , Siddiqui Muzaffar , Zafar Atif , Imoukhuede Oje , Hunter Gary , Phillips Stephen , Hill Michael D. , Poppe Alexandre Y. , Ademola Ayoola , Shamy Michel , Bala Fouzi , Sajobi Tolulope T. , Swartz Richard H. , Almekhlafi Mohammed A. , Menon Bijoy K. , Field Thalia S.
Published: January 2024

BACKGROUND:

Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase).

METHODS:

AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0–1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes.

RESULTS:

Of 1577 patients treated with intravenous thrombolysis (2019–2022), 755 (47.9%) were women. Women were older (median, 77 [68–86] years in women versus 70 [59–79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70–0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06–1.69]). Adjusted analysis showed no difference in outcomes between sexes.

CONCLUSIONS:

Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03889249.