bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene regulatory landscape of cerebral cortex folding
Authors: Singh Aditi , Del-Valle-Anton Lucia , de Juan Romero Camino , Zhang Ziyi , Ortuño Eduardo Fernández , Mahesh Arun , Espinós Alexandre , Soler Rafael , Cárdenas Adrián , Fernández Virginia , Lusby Ryan , Tiwari Vijay K. , Borrell Víctor
Published: June 2024

Folding of the cerebral cortex is a key aspect of mammalian brain development and evolution, and defects are linked to severe neurological disorders. Primary folding occurs in highly stereotyped patterns that are predefined in the cortical germinal zones by a transcriptomic protomap. The gene regulatory landscape governing the emergence of this folding protomap remains unknown. We characterized the spatiotemporal dynamics of gene expression and active epigenetic landscape (H3K27ac) across prospective folds and fissures in ferret. Our results show that the transcriptomic protomap begins to emerge at early embryonic stages, and it involves cell-fate signaling pathways. The H3K27ac landscape reveals developmental cell-fate restriction and engages known developmental regulators, including the transcription factor
Cux2
. Manipulating
Cux2
expression in cortical progenitors changed their proliferation and the folding pattern in ferret, caused by selective transcriptional changes as revealed by single-cell RNA sequencing analyses. Our findings highlight the key relevance of epigenetic mechanisms in defining the patterns of cerebral cortex folding.
Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation
Authors: Guglielmi Valeria , Lam Davina , D’Angelo Maximiliano A.
Published: June 2024

Nucleoporins, the components of nuclear pore complexes (NPCs), can play cell type– and tissue-specific functions. Yet, the physiological roles and mechanisms of action for most NPC components have not yet been established. We report that Nup358, a nucleoporin linked to several myeloid disorders, is required for the developmental progression of early myeloid progenitors. We found that Nup358 ablation in mice results in the loss of myeloid-committed progenitors and mature myeloid cells and the accumulation of myeloid-primed multipotent progenitors (MPPs) in bone marrow. Accumulated MPPs in Nup358 knockout mice are greatly restricted to megakaryocyte/erythrocyte-biased MPP2, which fail to progress into committed myeloid progenitors. Mechanistically, we found that Nup358 is required for histone deacetylase 3 (HDAC3) nuclear import and function in MPP2 cells and established that this nucleoporin regulates HDAC3 nuclear translocation in a SUMOylation-independent manner. Our study identifies a critical function for Nup358 in myeloid-primed MPP2 differentiation and uncovers an unexpected role for NPCs in the early steps of myelopoiesis.
Arylazopyrazole-modulated stable dual-mode phototransistors
Authors: Li Huchao , Shangguan Zhichun , Li Tao , Zhang Zhao-Yang , Ji Deyang , Hu Wenping
Published: June 2024

High-performance organic devices with dynamic and stable modulation are essential for building devices adaptable to the environment. However, the existing reported devices incorporating light-activated units exhibit either limited device stability or subpar optoelectronic properties. Here, we synthesize a new optically tunable polymer dielectric functionalized with photochromic arylazopyrazole units with a cis-isomer half-life of as long as 90 days. On this basis, stable dual-mode organic transistors that can be reversibly modulated are successfully fabricated. The trans-state devices exhibit high carrier mobility reaching 7.4 square centimeters per volt per second and excellent optical figures of merit, whereas the cis-state devices demonstrate stable but starkly different optoelectronic performance. Furthermore, optical image sensors are prepared with regulatable nonvolatile memories from 36 hours (cis state) to 108 hours (trans state). The achievement of dynamic light modulation shows remarkable prospects for the intelligent application of organic optoelectronic devices.
Overcoming analytical and preanalytical challenges associated with extragenital home collected STI specimens
Authors: Hockman B. E. , Qi M. , Rotblatt H. , Borenstein L. , Flynn R. A. , Muldrow R. A. , Rajagopalan S. , Greene D. N.
Published: June 2024

Home sample collection for sexually transmitted infection (STI) screening options can improve access to sexual healthcare across communities. For
Chlamydia trachomatis
(CT) and
Neisseria gonorrhoeae
(NG), genital infections have classically been the focus for remote collection options. However, infections may go undiagnosed if sampling is limited to urogenital sites because some individuals only participate in oral and/or anal intercourse. Here we evaluated samples for CT/NG detection after several pre-analytical collection challenges. A paired provider to self-collection validation was performed on rectal [
n
= 162; 22 + for CT and 9 + for NG by provider-collected (PC)] and throat (
N
= 158; 2 + for CT and 11 + for NG by provider-collected) swabs. The positive percent agreement for CT and NG ranged from 90.9% to 100%. The discrepancies were more often positive on self-collected (SC) (
n
= 9 SC+/PC−;
n
= 1 PC+/SC−;
n
= 1 PC+/SC Equiv.;
n
= 2 PC−/SC Equiv.). An empirical limit of detection (LoD) lower than the manufacturer’s claim (0.031 vs 2.5 IFU/mL for CT and 0.063 vs 124.8 CFU/ml for NG, respectively) was used to challenge additional variables. Common hand contaminants, including soap, hand sanitizer, lotion, and sunscreen were added to known positive (3× empirical LoD) or negative samples and did not influence detection. Samples at 2× and 10× the empirical LoD were challenged with extreme temperature cycling and extended room temperature storage. Detection was not affected by these conditions. These results indicate that remote self-collection is an appropriate method of sample acquisition for detecting extragenital CT/NG infections. Additionally, they provide a foundation towards meeting the regulatory standards for commercial testing of home collected extragenital samples.

IMPORTANCE

There is a clinical need for expanded extragenital bacterial sexually transmitted infection (STI) testing options, but the current regulatory landscape limits the wide-spread promotion and adoption of such services. Improved access, particularly for the LGBTQ+ community, can be achieved by validating testing for specimens that are self-collected at a remote location and arrive at the laboratory via a postal carrier or other intermediary route. Here we provide valuable data showing that self-collected samples for anal and oropharyngeal STI testing are equally or increasingly sensitive compared with those collected by a provider. We systematically consider the effects of storage time, exposure to temperature extremes, and the addition of common toiletries on results.
Supplemental Material: Generation of Archean TTGs via sluggish subduction
Authors: Foley Bradford J.
Published: June 2024

 Extended description of the methods and benchmark comparisons to two-dimensional dynamic subduction models are provided. Further robustness tests of the main results to assumptions in the model setup are also shown.  
A note on the representations of SO(1,d + 1)
Authors: Sun Zimo
Published: June 2024

[Formula: see text] is the isometry group of [Formula: see text]-dimensional de Sitter spacetime ([Formula: see text]) and the conformal group of [Formula: see text]. This note gives a pedagogical introduction to the representation theory of [Formula: see text], from the perspective of de Sitter quantum field theory and using tools from conformal field theory. Topics include (1) the construction and classification of all unitary irreducible representations (UIRs) of [Formula: see text] and [Formula: see text], (2) the construction and classification of all UIRs of [Formula: see text] that describe integer-spin fields in [Formula: see text], (3) a physical framework for understanding these UIRs, (4) the definition and derivation of Harish-Chandra group characters of [Formula: see text] and (5) a comparison between UIRs of [Formula: see text] and [Formula: see text].
On K-contact metric manifolds satisfying an almost gradient Ricci–Bourguignon soliton
Authors: Dey Santu , Suh Young Jin
Published: June 2024

The main purpose of the paper is to study an almost gradient Ricci–Bourguignon soliton (RB soliton) within the framework of [Formula: see text]-contact manifolds and [Formula: see text]-contact manifolds. First, we prove that if complete [Formula: see text]-contact manifold endows a gradient RB soliton, then the manifold is compact Sasakian and isometric to unit sphere [Formula: see text]. Next, we show that if a complete contact metric satisfies an almost RB soliton with a non-zero potential vector field is collinear with the Reeb vector field [Formula: see text] and the Reeb vector field [Formula: see text] acting as an eigenvector of the Ricci operator, then it is compact Einstein Sasakian and the potential vector field is a constant multiple of the Reeb vector field [Formula: see text]. Lastly, we prove that if the metric of a non-Sasakian [Formula: see text]-contact manifold is an almost gradient RB soliton, then it is flat in dimension 3 and in higher dimensions it is locally isometric to [Formula: see text].
An entropy bound due to symmetries
Authors: Longo Roberto , Morinelli Vincenzo
Published: June 2024

Let [Formula: see text] be a local net of real Hilbert subspaces of a complex Hilbert space [Formula: see text] on the family [Formula: see text] of double cones of the spacetime [Formula: see text] ([Formula: see text] odd), covariant with respect to a positive energy, unitary representation [Formula: see text] of the Poincaré group [Formula: see text], with the Bisognano–Wichmann property for the wedge modular group. We set an upper bound on the local entropy [Formula: see text] of a vector [Formula: see text] in a given region [Formula: see text] that depends only on [Formula: see text] and the PCT anti-unitary canonically associated with [Formula: see text]. A similar result holds for local, Möbius covariant nets of standard subspaces on the circle. We compute the entropy increase with respect to the dual net and illustrate this bound for the nets associated with the [Formula: see text]-current derivatives.
Local smooth convergence of 𝔽-limit flows
Authors: Chan Pak-Yeung , Ma Zilu , Zhang Yongjia
Published: June 2024

The metric flow is introduced and extensively studied by Bamler [Compactness theory of the space of super Ricci flows, preprint (2020), arXiv:2008.09298; Structure theory of non-collapsed limits of Ricci flows, preprint (2020), arXiv:2009.03243], especially as an [Formula: see text]-limit of a sequence of smooth Ricci flows with uniformly bounded Nash entropy, in which case each regular point on the limit is a point of smooth convergence. In this note, we shall consider the [Formula: see text]-convergence of a sequence of [Formula: see text]-limit flows, and, like Bamler, show that each regular point on the limit is also a point of smooth convergence. The main result will be applied in another work of the authors [P.-Y. Chan, Z. Ma and Y. Zhang, Dimension reduction for positively curved steady solitons, preprint (2023), arXiv:2310.14020].
New optical wave solutions of M-fractional nonlinear Schrödinger’s complex hyperbolic model by an efficient method
Authors: Zafar Asim , Raheel M. , Ali Khalid K. , Bekir Ahmet
Published: June 2024

In this paper, we succeed to obtain the new optical wave solutions to the truncated M-fractional (2+1)-dimensional nonlinear Schrödinger’s complex hyperbolic model by utilizing the Sardar sub-equation method. The obtained solutions are in the form of trigonometric, hyperbolic and mixed form. These solutions have many applications in nonlinear optics, fiber optics, and other areas of physics and engineering where the propagation of nonlinear waves is important. Achieved solutions are verified with the use of Mathematica software. Some of the achieved solutions are also described graphically by two-dimensional, three-dimensional and contour plots. The gained solutions are helpful for the further development of concerned model. Finally, this technique is simple, fruitful and reliable to handle the nonlinear PDEs.
On geodesics in spherical Rindler space
Authors: Culetu Hristu
Published: June 2024

The geodesics in various spherical Rindler frames are investigated. A display of some kinematical quantities of the spacetime is given. The constant acceleration from the metric acts as the surface gravity of the horizon [Formula: see text]. The radial geodesics are computed both for the Balasubramanian et al. form of the spherical Rindler space and for the non-diagonal metric of Huang and Sun.
Quantization of length in spaces with position-dependent noncommutativity
Authors: Aryampilly Jishnu , Balasundaram Muthukumar , Rashid Aamir
Published: June 2024

In this paper, we present a novel approach to quantizing the length in noncommutative spaces with positional-dependent noncommutativity. The method involves constructing ladder operators that change the length not only along a plane but also along the third direction due to a noncommutative parameter that is a combination of canonical/Weyl–Moyal-type and Lie algebraic-type. The primary quantization of length in canonical-type noncommutative space takes place only on a plane, while in the present case, it happens in all three directions. We establish an operator algebra that allows for the raising or lowering of eigenvalues of the operator corresponding to the square of the length. We also attempt to determine how the obtained ladder operators act on different states and work out the eigenvalues of the square of the length operator in terms of eigenvalues corresponding to the ladder operators. We conclude by discussing the results obtained.
Unraveling the Nexus Between Financial Openness and Environmental Quality: Green Finance as the Catalyst in CEE Countries
Authors: Dilanchiev Azer , Somthawinpongsai Chanyanan , Urinov Bobur , Eyvazov Elchin
Published: June 2024

The use of fossil fuels, which is still seen as the cheapest energy source today, has increased carbon emissions and contributed to the formation of greenhouse gases, and this gas has reached levels that threaten world health. While studies on this problem often question the relationship between production volume, energy use, and carbon emissions, few studies question the effects of the financial assets, which are the providers of investments made for production purposes, on environmental degradation. This study used the fixed effect model and system GMM technique to analyse the moderating effect of green finance in connection to financial openness and environmental quality from 2015 to 2020 in the CEE countries. Findings show, among other things that (1) CO2 in CEE countries is still growing; (2) financial openness is a positive and significant indicator of CO2 emission; and (3) that green finance usage reduces the positive impact of financial openness on CO2 emissions. The study suggests that financial openness, renewable energy (RE) investment, and green technology innovation (GTI)– consistently drive CO2 emissions in CEE countries. The study suggests that policies promoting green finance, particularly RE investment and GTI, can help mitigate environmental degradation and reduce CO2 emissions.
Interpersonal Communication Interconnection in Media Convergence Metaverse
Authors: Wang Xin , Lv Jianhui , Shankar Achyut , Maple Carsten , Li Keqin , Li Qing
Published: June 2024

The metaverse aims to provide immersive virtual worlds connecting with the physical world. To enable real-time interpersonal communications between users across the globe, the metaverse places high demands on network performance, including low latency, high bandwidth, and fast network speeds. This paper proposes a novel Media Convergence Metaverse Network (MCMN) framework to address these challenges. Specifically, the META controller serves as MCMN's logically centralized control plane, responsible for holistic orchestration across edge sites and end-to-end path computation between metaverse users. We develop a model-free deep reinforcement learning-based metaverse traffic optimization algorithm that learns to route flows while satisfying the Quality of Service (QoS) boundaries. The network slicing engine leverages artificial intelligence and machine learning to create isolated, customized virtual networks tailored for metaverse traffic dynamics on demand. It employs unsupervised and reinforcement learning techniques using network telemetry from the META controller to understand application traffic patterns and train cognitive slicer agents to make quality of service -aware decisions accordingly. Optimized delivery of diverse concurrent media types necessitates routing intelligence to meet distinct requirements while mitigating clashes over a shared infrastructure. Media-aware routing enhances traditional shortest-path approaches by combining topological metrics with workflow sensitivities. We realize an edge-assisted rendering fabric to offload complex processing from bandwidth-constrained endpoints while retaining visual realism. Extensive simulations demonstrate MCMN's superior performance compared to conventional networking paradigms. MCMN shows great promise to enable seamless interconnectivity and ultra-high fidelity communications to unlock the true potential of the metaverse.
A Compact Vulnerability Knowledge Graph for Risk Assessment
Authors: Yin Jiao , Hong Wei , Wang Hua , Cao Jinli , Miao Yuan , Zhang Yanchun
Published: June 2024

Software vulnerabilities, also known as flaws, bugs or weaknesses, are common in modern information systems, putting critical data of organizations and individuals at cyber risk. Due to the scarcity of resources, initial risk assessment is becoming a necessary step to prioritize vulnerabilities and make better decisions on remediation, mitigation, and patching. Datasets containing historical vulnerability information are crucial digital assets to enable AI-based risk assessments. However, existing datasets focus on collecting information on individual vulnerabilities while simply storing them in relational databases, disregarding their structural connections. This article constructs a compact vulnerability knowledge graph, VulKG, containing over 276 K nodes and 1 M relationships to represent the connections between vulnerabilities, exploits, affected products, vendors, referred domain names, and more. We provide a detailed analysis of VulKG modeling and construction, demonstrating VulKG-based query and reasoning, and providing a use case of applying VulKG to a vulnerability risk assessment task, i.e., co-exploitation behavior discovery. Experimental results demonstrate the value of graph connections in vulnerability risk assessment tasks. VulKG offers exciting opportunities for more novel and significant research in areas related to vulnerability risk assessment. The data and codes of this article are available at
https://github.com/happyResearcher/VulKG.git
.
Ocular working memory signals are flexible to behavioral priority and subjective imagery strength
Authors: Dong Yueying , Kiyonaga Anastasia
Published: June 2024

The pupillary light response was long considered a brainstem reflex, outside of cognitive influence. However, newer findings indicate pupil dilation (and eye movements) can reflect content in working memory (WM). These findings may reshape understanding of ocular and WM mechanisms, but it is unclear whether the signals are artifactual or functional to WM. Here, we ask whether peripheral and oculomotor WM signals are sensitive to the task-relevance or 'attentional state' of memoranda. During eye-tracking, human participants saw both dark and bright WM stimuli, then were retroactively cued to the most likely to be tested item. Critically, we manipulated the attentional priority among items by varying the cue reliability across blocks. We confirmed previous findings that remembering darker items is associated with larger pupils, and that gaze is biased toward cued item locations. Moreover, we discovered that pupil and eye movement responses were influenced differently by WM item relevance. Feature-specific pupillary effects emerged only for highly prioritized WM items but were eliminated when cues were less reliable, and pupil effects also increased with self-reported visual imagery strength. Conversely, gaze position veered toward the cued item location, regardless of cue reliability. However, biased microsaccades occurred at a higher frequency when cues were reliable, though only during a limited post-cue time window. Therefore, peripheral sensorimotor processing is sensitive to the task-relevance or functional state of internal WM content, but pupillary and eye movement WM signals show distinct profiles. These results highlight potential roles for early visual processing in maintaining multiple WM content dimensions.
An Analysis of PIK3CA Hotspot Mutations and Response to Neoadjuvant Therapy in Patients with Breast Cancer from Four Prospective Clinical Trials
Authors: Jank Paul , Karn Thomas , van Mackelenbergh Marion , Lindner Judith , Treue Denise , Huober Jens , Engels Knut , Solbach Christine , Diebold Kurt , Marmé Frederik , Müller Volkmar , Schneeweiss Andreas , Sinn Hans-Peter , Fehm Tanja , Schem Christian , Stickeler Elmar , Fasching Peter , Budczies Jan , Felder Bärbel , Nekljudova Valentina , Holtschmidt Johannes , Untch Michael , Denkert Carsten , Loibl Sibylle
Published: June 2024

Purpose:

The PI3K signaling pathway is frequently dysregulated in breast cancer, and mutations in PIK3CA are relevant for therapy resistance in HER2-positive (HER2pos) breast cancer. Mutations in exons 9 or 20 may have different impacts on response to neoadjuvant chemotherapy-based treatment regimens.

Experimental Design:

We investigated PIK3CA mutations in 1,691 patients with early breast cancer who were randomized into four neoadjuvant multicenter trials: GeparQuattro (NCT00288002), GeparQuinto (NCT00567554), GeparSixto (NCT01426880), and GeparSepto (NCT01583426). The role of different PIK3CA exons and hotspots for pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT) and patient survival were evaluated for distinct molecular subgroups and anti-HER2 treatment procedures.

Results:

A total of 302 patients (17.9%) of the full cohort of 1,691 patients had a tumor with a PIK3CA mutation, with a different prevalence in molecular subgroups: luminal/HER2-negative (HER2neg) 95 of 404 (23.5%), HER2pos 170 of 819 (20.8%), and triple-negative breast cancer 37 of 468 patients (7.9%). We identified the mutations in PIK3CA exon 20 to be linked with worse response to anti-HER2 treatment (OR = 0.507; 95% confidence interval, 0.320–0.802; P = 0.004), especially in hormone receptor–positive HER2-positive breast cancer (OR = 0.445; 95% confidence interval, 0.237–0.837; P = 0.012). In contrast, exon 9 hotspot mutations p.E452K and p.E545K revealed no noteworthy differences in response therapy. Luminal/HER2neg patients show a trend to have worse treatment response when PIK3CA was mutated. Interestingly, patients with residual disease following neoadjuvant treatment had better survival rates when PIK3CA was mutated.

Conclusions:

The PIK3CA hotspot mutation p.H1047R is associated with worse pCR rates following NACT in HER2pos breast cancer, whereas hotspot mutations in exon 9 seem to have less impact.
Supplementary Table S5 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Significantly Altered Proteins Following Treatment with the Combination of Eribulin and Copanlisib including All 8 PDX Models
Supplementary Table S4 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Significantly Altered Levels of Proteins Following Treatment with Eribulin
Supplementary Table S1 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Clinical Characteristics of Patient Derived Xenografts
Supplementary Figure S1 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Tumor growth response of TNBC PDX models to eribulin monotherapy
FIGURE 5 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Expression of protein markers significantly altered by treatment with eribulin in combination with copanlisib in three eribulin-resistant models (WHIM3, WHIM4, and WHIM6). Expression of indicated RPPA protein markers are shown. Aurora_pT288_pT232_pT198, and Histone H3_pS10, were significantly upregulated, with FDR-adjusted P value <0.1, at the completion of 3–4 weeks of treatment with the combination of eribulin and copanlisib versus vehicle. Caspase 7 cleaved was upregulated following combination therapy, although did not reach statistical significance.
FIGURE 4 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Apoptotic induction following treatment with eribulin and copanlisib, either alone or in combination by IHC. Representative IHC pictures (A) and quantifications of IHC scores (B) of cleaved PARP on WHIM29 and WHIM34 PDX tumors harvested on day 3 following treatment with either vehicle (day 1), eribulin (day 1), copanlisib (days 1 and 2), or the combination, and FDG PET 4 hours after treatment on day 2.
FIGURE 3 from Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models
Authors: Guo Zhanfang , Luo Jingqin , Mashl R. Jay , Hoog Jeremy , Maiti Piyush , Fettig Nikki , Davies Sherri R. , Aft Rebecca , Held Jason M. , Govindan Ramaswamy , Ding Li , Li Shunqiang , von Morze Cornelius , Wulf Gerburg M. , Shoghi Kooresh I. , Ma Cynthia X.
Published: June 2024

Expression of protein markers significantly altered by treatment with eribulin in combination with copanlisib in all PDX models. A, Expression of RPPA protein markers significantly altered, with FDR-adjusted P value <0.1, comparing treatment with the combination of eribulin and copanlisib versus vehicle are shown for individual tumors from each PDX model at the completion of 3–4 weeks of treatment with either vehicle, eribulin, copanlisib, or eribulin plus copanlisib. Note that WHIM34 and WHIM29 tumors treated with eribulin or eribulin in combination with copanlisib were missing in the analysis due to insufficient quantity of tumors at the completion of treatment. B, Heat map of estimated coefficient for FDR significantly altered markers (P < 0.1) comparing copanlisib plus eribulin versus vehicle.
MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults
Authors: Pappas Colleen , Bauer Christopher E. , Zachariou Valentinos , Maillard Pauline , Caprihan Arvind , Shao Xingfeng , Wang Danny J.J. , Gold Brian T.
Published: June 2024

Vascular risk factors contribute to cognitive aging, with one such risk factor being dysfunction of the blood brain barrier (BBB). Studies using non-invasive magnetic resonance imaging (MRI) techniques, such as diffusion prepared arterial spin labeling (DP-ASL), can estimate BBB function by measuring water exchange rate (kw). DP-ASL kw has been associated with cognition, but the directionality and strength of the relationship is still under investigation. An additional variable that measures water in extracellular space and impacts cognition, MRI free water (FW), may help explain prior findings. A total of 94 older adults without dementia (Mean age = 74.17 years, 59.6% female) underwent MRI (DP-ASL, diffusion weighted imaging (DWI)) and cognitive assessment. Mean kw was computed across the whole brain (WB), and mean white matter FW was computed across all white matter. The relationship between kw and three cognitive domains (executive function, processing speed, memory) was tested using multiple linear regression. FW was tested as a mediator of the kw-cognitive relationship using the PROCESS macro. A positive association was found between WB kw and executive function [F(4,85) = 7.81, p < .001, R2= 0.269; β = .245, p = .014]. Further, this effect was qualified by subsequent results showing that FW was a mediator of the WB kw-executive function relationship (indirect effect results: standardized effect = .060, bootstrap confidence interval = .0006 to .1411). Results suggest that lower water exchange rate (kw) may contribute to greater total white matter (WM) FW which, in turn, may disrupt executive function. Taken together, proper fluid clearance at the BBB contributes to higher-order cognitive abilities.
Comparative study on ionic dissolution and structural changes of montmorillonite, kaolinite and muscovite during interfacial reactions with oxalic acid solution
Authors: Zeng Li , Peng Tongjiang , Sun Hongjuan , Zhang Xiyue , Zhao Dingran
Published: June 2024

Organic acids are commonly found in soils and sediments, playing an important role in the alteration and weathering of minerals and influencing a series of geochemical processes such as soil fertility, metal cycling and pollutant migration. In order to better comprehend the reaction mechanisms of different layered silicate minerals with organic acids, three minerals with various structure types, namely montmorillonite, kaolinite and muscovite, were investigated in this work. In particular, the effects of interfacial reactions with oxalic acid on the crystal structure, chemical composition, morphology and specific surface area of minerals were compared. The composition and structure of montmorillonite, kaolinite and muscovite during the interfacial reaction with oxalic acid were characterised using powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) methods. It was shown that Si4+ and Al3+ were dissolved gradually during the interfacial reactions and that the changes in the properties of minerals depended on structural characteristics. After 300 days of the interfacial reactions with oxalic acid, the dissolution percentages of Si4+ and Al3+ in montmorillonite, kaolinite and muscovite were 12.7%, 8.4%, 3.8% and 62.1%, 30.7%, 6.1%, respectively. Moreover, the lamellar morphology of montmorillonite was destroyed upon the interfacial reaction with oxalic acid, and irregular particles with sizes of ~100–500 nm were formed on the surface. The diameter of kaolinite flake particles decreased from 400–1500 nm to 50–400 nm, and the surface of rod-shaped particles was ruptured. The small particles disappeared from the muscovite surface, and the initially sharp edges became blunted. The specific surface area and the total pore volume of montmorillonite and kaolinite increased after the interfacial reaction with oxalic acid, whereas the opposite results were obtained for muscovite. The differential dissolution of the minerals during their interfacial reaction with oxalic acid was mainly related to the differences between cation occupancies, structural types, chemical bond strengths and specific surface areas.
bsgenova: an accurate, robust, and fast genotype caller for bisulfite-sequencing data
Authors: Feng Yance , Gao Fei
Published: June 2024

Background

Bisulfite sequencing (BS-Seq) is a fundamental technique for characterizing DNA methylation profiles. Genotype calling from bisulfite-converted BS-Seq data allows allele-specific methylation analysis and the concurrent exploration of genetic and epigenetic profiles. Despite various methods have been proposed, single nucleotide polymorphisms (SNPs) calling from BS-Seq data, particularly for SNPs on chromosome X and in the presence of contaminative data, poses ongoing challenges.

Results

We introduce bsgenova, a novel SNP caller tailored for bisulfite sequencing data, employing a Bayesian multinomial model. The performance of bsgenova is assessed by comparing SNPs called from real-world BS-Seq data with those from corresponding whole-genome sequencing (WGS) data across three human cell lines. bsgenova is both sensitive and precise, especially for chromosome X, compared with three existing methods. Moreover, in the presence of low-quality reads, bsgenova outperforms other methods notably. In addition, bsgenova is meticulously implemented, leveraging matrix imputation and multi-process parallelization. Compared to existing methods, bsgenova stands out for its speed and efficiency in memory and disk usage. Furthermore, bsgenova integrates bsextractor, a methylation extractor, enhancing its flexibility and expanding its utility.

Conclusions

We introduce bsgenova for SNP calling from bisulfite-sequencing data. The source code is available at https://github.com/hippo-yf/bsgenova under license GPL-3.0.
Identification and analysis of short-term and long-term salt-associated lncRNAs in the leaf of Avicennia marina
Authors: Wang Lingling , Fu Yixuan , Yuan Zixin , Wang Jingyi , Guan Yali
Published: June 2024

As a highly salt-resistant mangrove, Avicennia marina can thrive in the hypersaline water. The leaves of Avicennia marina play a crucial role in salinity stress adaptability by secreting salt. Although the functions of long non-coding RNAs (lncRNAs) in leaves remain unknown, they have emerged as regulators in leaf development, aging and salt response. In this study, we employed transcriptomic data of both short-term and long-term salt treated leaves to identify salt-associated lncRNAs of leaf tissue. As a result, 687 short-term and 797 long-term salt-associated lncRNAs were identified. Notably, both short-term and long-term salt-associated lncRNAs exhibited slightly longer lengths and larger exons, but smaller introns compared with salt-non-associated lncRNAs. Furthermore, salt-associated lncRNAs also displayed higher tissue-specificity than salt-non-associated lncRNAs. Most of the salt-associated lncRNAs were common to short- and long-term salt treatments. And about one fifth of the downregulated salt-associated lncRNAs identified both in two terms were leaf tissue-specific lncRNAs. Besides, these leaf-specific lncRNAs were found to be involved in the oxidation–reduction and photosynthesis processes, as well as several metabolic processes, suggesting the noticeable functions of salt-associated lncRNAs in regulating salt responses of Avicennia marina leaves.
Germination responses of Lens Culiunaris L. seeds to osmotic potentials at cardinal temperatures using hydrothermal time model
Authors: Ullah Ibrar , Ullah Sami , Amin Fazal , Al-Hawadi Jehad S. , Okla Mohammad K. , Alaraidh Ibrahim A. , AbdElgawad Hamada , Liu Ke , Harrison Matthew Tom , Saud Shah , Hassan Shah , Nawaz Taufiq , Zhu Mo , Liu Haitao , Fahad Shah
Published: June 2024

Background

Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil was to assess the hydrothermal time model’s capacity to explain the dynamics of Lens culinaris L. var. Markaz-09 seed germination, as well as to ascertain the germination responses at various sub-optimal temperatures (T) and water potentials (Ψ). In order to study lentil seed germination (SG) behavior at variable water potentials (Ψs) and temperatures (Ts). A lab experiment employing the hydrothermal time model was created. Seeds were germinated at six distinct temperatures: 15 0С, 20 0С, 25 0С, 30 0С, 35 0С, and 40 0С, with five Ψs of 0, -0.3, -0.6, -0.9, and − 1.2 MPa in a PEG-6000 (Polyethylene glycol 6000) solution.

Results

The results indicated that the agronomic parameters like Germination index (GI), Germination energy (GE), Timson germination index (TGI), were maximum in 25 0C at (-0.9 MPa) and lowest at 40 0C in 0 MPa. On other hand, mean germination time (MGT) value was highest at 15 0C in -1.2 MPa and minimum at 40 0C in (-0.6 MPa) while Mean germination rate (MGR) was maximum at 40 0C in (0 MPa) and minimum at 15 0C in (-0.6 MPa).

Conclusions

The HTT model eventually defined the germination response of Lens culinaris L. var. Markaz-09 (Lentil) for all Ts and Ψs, allowing it to be employed as a predictive tool in Lens culinaris L. var. Markaz-09 (Lentil) seed germination simulation models.
High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022
Authors: Tang Jie , Wang Yong , Lu Weiqin , Gao Zhihong , Xu Mingfeng , Wu Lin , Jin Jianhua
Published: June 2024

Background

China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy.

Methods

From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China).

Results

Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively.

Conclusion

Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.
Evaluation of awareness and performance towards COVID-related disinfectant use: a comparative study between Jordan and United Arab Emirates
Authors: Ghach Wissam , Takshe Aseel A. , Rababa Mohammad , Al-Rawashdeh Sami , Alwan Nisreen
Published: June 2024

Background

The World Health Organization recommended the use of chemical-based disinfectants as an effective prevention of the COVID-19 pandemic. However, calls for poisoning were reported in several medical centers. The widespread use of chemical-based disinfectants as a preventive measure during the COVID-19 pandemic has underscored potential gaps in community awareness and performance, posing health risks. This study evaluates and compares levels of awareness and performance regarding the safe use of disinfectants in Jordan and UAE.

Methods

The study was conducted between October 2022 and June 2023 via an online questionnaire. Data of respondents from Jordan (n = 828) and UAE (n = 619) were analyzed using SPSS. ANOVA, Mann-Whitney, and Kruskal-Wallis tests evaluated significant differences in awareness and performance levels across different demographic groups in Jordan/UAE and between them. Spearman’s correlation test examined the correlation between awareness and performance among respondents. Multinomial logistic regression analysis explored associations between various variables and awareness/performance levels within each population.

Results

Findings reveal weak awareness (72.4% and 9.03% in UAE and Jordan, respectively) and moderate performance level (98.8% in UAE and Jordan), with a weak correlation (UAE, rho = 0.093; Jordan, rho = 0.164) observed between the two countries (P < 0.05). Multinomial logistic regression analysis indicates gender-related associations with awareness levels and education-related associations with performance levels.

Conclusions

The study emphasizes the urgent need for awareness campaigns and workshops to promote safer disinfectant practices to develop effective interventions aligning with sustainable development goals.
Evaluation of the extracranial “multifocal arcuate sign,” a novel MRI finding for the diagnosis of giant cell arteritis, on STIR and contrast-enhanced T1-weighted images
Authors: Hiraka Toshitada , Sugai Yasuhiro , Konno Yoshihiro , Toyoguchi Yuuki , Obata Yoshie , Ohara Shin , Shibata Akiko , Takeda Yusuke , Nishitsuka Koichi , Ichikawa Kazunobu , Watanabe Masafumi , Sonoda Yukihiko , Kanoto Masafumi
Published: June 2024

Background

While early diagnosis of giant cell arteritis (GCA) based on clinical criteria and contrast-enhanced MRI findings can lead to early treatment and prevention of blindness and cerebrovascular accidents, previously reported diagnostic methods which utilize contrast-enhanced whole head images are cumbersome. Diagnostic delay is common as patients may not be aware of initial symptoms and their significance. To improve current diagnostic capabilities, new MRI-based diagnostic criteria need to be established. This study aimed to evaluate the “multifocal arcuate sign” on short tau inversion recovery (STIR) and contrast-enhanced T1-weighted (CE-T1W) images as a novel extracranial finding for the diagnosis of GCA.

Methods

A total of 17 consecutive patients (including five with GCA) who underwent CE-T1W and whole-brain axial STIR imaging simultaneously between June 2010 and April 2020 were enrolled. We retrospectively reviewed their MR images. The “multifocal arcuate sign” was defined as “multiple distant arcuate areas with high signal intensity in extracranial soft tissues such as subcutaneous fat, muscles, and tendons.” Extracranial abnormal high-signal-intensity areas were classified as “None,” when no lesions were detected; “Monofocal,” when lesions were detected only in one place; and “Multifocal,” when lesions were detected in multiple places. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of “Multifocal” areas were calculated using cross tabulation. Fisher’s exact test was used to compare “Multifocal” areas in five patients with GCA and those with other diseases. In addition, mean Cohen’s kappa and Fleiss’ kappa statistics were used to compare inter-reader agreement.

Results

The sensitivity, specificity, PPV, and NPV of the “multifocal arcuate sign” in patients with GCA were 60%, 92–100%, 75–100%, and 85–86%, respectively. Significantly more patients with GCA had “Multifocal” areas compared to those with other diseases (Fisher’s exact test, p = 0.008–0.027). Mean Cohen’s kappa and Fleiss’ kappa for inter-reader agreement with respect to the five GCA patients were 0.52 and 0.49, respectively, for both STIR and CE-T1W sequences.

Conclusions

The new radiologic finding of “multifocal arcuate sign” on STIR and CE-T1W images may be used as a radiologic criterion for the diagnosis of GCA, which can make plain MRI a promising diagnostic modality.
Treatment outcomes of patients with primary tracheal tumors - analysis of a large retrospective series
Authors: Piórek Aleksandra , Płużański Adam , Knetki-Wróblewska Magdalena , Winiarczyk Kinga , Tabor Sylwia , Teterycz Paweł , Kowalski Dariusz M. , Krzakowski Maciej
Published: June 2024

Objective

Primary tracheal tumors are very rare and their management is not definitely established. Due to its rarity, providing patient care in terms of optimal management poses a considerable challenge. The purpose of this study was to investigate treatment outcomes in patients with these rare tumors.

Methods

We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, over sixteen years. The study assessed patient demographics, tumor characteristics and treatment. Different treatment options were compared in terms of overall survival, disease-free survival, and progression-free survival.

Results

A total of 89 patients were included in the study. In the group presented, 45 patients underwent primary radical treatment and 44 were qualified for palliative treatment. Surgical resection was performed in 13 patients out of radically treated patients. The 5 year OS rates in the group of patients who underwent radical treatment and in the group of patients who underwent palliative treatment were 45.9% and 2.3%, respectively. In the group of patients who underwent radical surgical treatment, the 5 year OS was 76.9% compared to 35.8% in the group of patients who underwent nonsurgical treatment.

Conclusion

A multidisciplinary team should decide treatment options, including in-depth consideration of surgical treatment options.