bluuebunny/crossref_metadata_2025 huggingface dataset:
$$\varLambda (1405)$$ mediated triangle singularity in the $$K^-d\rightarrow p\varSigma ^-$$ reaction
Authors: Feijoo A. , Molina R. , Dai L. R. , Oset Eulogio
Published: November 2022

We study for the first time the $$p\varSigma ^-\rightarrow K^-d$$

p

Σ
-

→

K
-

d

and $$K^-d\rightarrow p\varSigma ^-$$

K
-

d
→
p

Σ
-

reactions close to threshold and show that they are driven by a triangle mechanism, with the $$\varLambda (1405)$$

Λ
(
1405
)

, a proton and a neutron as intermediate states, which develops a triangle singularity close to the $${\bar{K}}d$$

K

¯

d

threshold. We find that a mechanism involving virtual pion exchange and the $$K^-p\rightarrow \pi ^+\varSigma ^-$$

K
-

p
→

π
+

Σ
-

amplitude dominates over another one involving kaon exchange and the $$K^-p\rightarrow K^-p$$

K
-

p
→

K
-

p

amplitude. Moreover, of the two $$\varLambda (1405)$$

Λ
(
1405
)

states, the one with higher mass around 1420 MeV, gives the largest contribution to the process. We show that the cross section, well within measurable range, is very sensitive to different models that, while reproducing $${\bar{K}}N$$

K

¯

N

observables above threshold, provide different extrapolations of the $${\bar{K}}N$$

K

¯

N

amplitudes below threshold. The observables of this reaction will provide new constraints on the theoretical models, leading to more reliable extrapolations of the $${\bar{K}}N$$

K

¯

N

amplitudes below threshold and to more accurate predictions of the $$\varLambda (1405)$$

Λ
(
1405
)

state of lower mass.
Higgs-boson visible and invisible constraints on hidden sectors
Authors: Biekötter Thomas , Pierre Mathias
Published: November 2022

We investigate the impact of interactions between hidden sectors and the discovered Higgs boson $$h_{125}$$

h
125

, allowing for additional invisible decay channels of $$h_{125}$$

h
125

. We perform $$\chi ^2$$

χ
2

-fits to the measurements of the Higgs-boson cross sections as a function of the invisible branching ratio and different combinations of coupling modifiers, where the latter quantify modifications of the couplings of $$h_{125}$$

h
125

compared to the predictions of the Standard Model. We present generic results in terms of exclusion limits on the coupling modifiers and the invisible branching ratio of $$h_{125}$$

h
125

. Additionally, we apply our results to a variety of concrete model realizations containing a hidden sector: dark matter within Higgs- and singlet-portal scenarios, models featuring (pseudo) Nambu–Goldstone bosons and two Higgs doublet extensions. One of the main conclusions of our work is that in a wide class of models the indirect constraints resulting from the measurements of the cross sections of $$h_{125}$$

h
125

provide substantially stronger constraints on the invisible Higgs-boson branching ratio compared to the direct limits obtained from searches for the invisible decay of $$h_{125}$$

h
125

. However, we demonstrate that the presence of an invisible decay mode of $$h_{125}$$

h
125

can also open up parameter space regions which otherwise would be excluded as a result of the indirect constraints. As a byproduct of our analysis, we show that in light of the new results from the LZ collaboration a fermionic DM candidate within the simplest Higgs-portal scenario is ruled out under standard assumptions.
Proton-induced X-ray emission analysis of the Chinese yam
Authors: Nogami M. , Hitomi K. , Ishii K.
Published: November 2022

The Chinese yam is a major component of the Japanese diet consumed in raw and cooked form. It is important to determine the nutrient contents of yam, which contains high potassium levels; a simple measurement method is required. We performed proton-induced X-ray emission (PIXE) analysis of fully grown and immature yams. Analysis of the yam trunk, skin, and hair roots revealed that the skin potassium concentration was 10-fold higher than that of the trunk; consumption of the skin is thus recommended. Longitudinal measurements of mineral concentrations in a growing yam revealed that the concentrations increased in the growth direction.
Faking Patience with Tacit Collusion
Authors: Parilina Elena , Tampieri Alessandro
Published: November 2022

This paper analyzes coordination in tacit collusion when firms’ discount factor is private information. We consider an infinitely repeated duopoly where two states of the world randomly occur, with different incentives for collusion. Depending on its own discount factor, a firm chooses cooperative behavior in both states (patient), in none of the states (impatient) or in one state (mildly patient). The presence of different states affects the strategic role of beliefs. A mildly patient firm has an incentive in “faking patience” to get the deviation profit. Interestingly, this effect prevents or delays collusion when the belief in patience is strong.
Financial Sector Development and Energy Consumption in Sub-Saharan Africa: Does Institutional Governance Matter? Dynamic Panel Data Analysis
Authors: Ndubuisi Paul , Okere Kingsley Ikechukwu , Iheanacho Eugene
Published: November 2022

The failure of energy economists and planners to comprehend the dynamics and paradigm shift in the finance and institutional quality domain that drive energy use is blamed for the ongoing energy consumption concerns. Consequently, this study revisits and contributes to repositories by examining the relationship between finance-renewable energy consumption and institution-renewable energy consumption. The research question raised is: Do governance indicators moderate the impact of finance on renewable energy consumption? With panel dataset of 46 countries in sub-Saharan Africa spanning from 2010 to 2020 and using political stability, voice and accountability, government effectiveness, and regulatory quality indicators of governance, the research output is as follows: (i) Financial development exerts a significant positive impact on renewable energy consumption and intensity, but the level of impact is weak (i.e., at a 10% level significant). (ii) The governance indicators significantly drag renewable energy consumption and intensity. (iii) The negative interaction between financial development and governance indicators is sufficient to worsen the weak relationship between finance and renewable energy in sub-Saharan Africa. (iv) Governance threshold eroded the weak positive effect of financial development on renewable energy consumption and intensity, leading to negative synergy effect in some cases, and (v) The net effect from the moderating impact of governance indicators on finance is significantly different across model specification. The study demonstrates the undeveloped nature of finance and institutional framework in sub-Saharan Africa, considering the weak association between the key variables.
Does Globalization, Tourism, Foreign Direct Investment, and Natural Resources Influencing Ecological Footprint?
Authors: YAQOOB Tanzeela , BABI Maria , KHALID Rimsha
Published: November 2022

The environmental problem has become a worldwide issue that must be frequently examined. Thus, this study investigates the relation of tourism, natural resources, globalization, and foreign direct investment on the ecological footprint of the USA, the UK, Pakistan, China, and India by using annual data from 1995 to 2020. The study applied Zivot and Andrews (1992) test to demonstrate the stationarity properties of the series, and an autoregressive distributed lag (ARDL) approach was employed to estimate the long-run and short-run dynamics. The long-run findings disclose that tourism has a significantly positive effect on China and Pakistan, but a significantly negative impact on India. The outcomes further suggest that foreign direct investment increases environmental degradation in India and China in both long and short periods, but contributes to improving the UK’s ecosystem. Besides, globalization in China tends to save its environment. Natural resources in the long run also harm the ecosystems of Pakistan, China, and the USA. The error correction term is negatively significant for all countries. The reliability of the model is investigated through diagnostic tests. The selected model is stable as the critical value of CUSUM and CUSUMSQ lie within the 5% significance level.
Elemental inheritance evaluation for geochemical elements in soil of the Daliangshan area, China
Authors: Zhang Zhen-Jie , Liu Hong , Ouyang Yuan
Published: November 2022

The inheritance and migration characters of different elements in the soil profile can serve agriculture, environmental protection, mineral exploration and other related research fields. These characters are mainly determined by the various geochemical behaviours of different elements. However, the elemental behaviours for the same element might vary wildly due to various local physical, chemical and biological environments, because the transformation of rock to soil includes rock-weathering and pedogenic processes. Here, we propose a framework for evaluating the elemental inheritance and migration characters from the underlying rocks or C horizons during local rock-weathering and pedogenic processes. In this framework, random forest regression was used to evaluate the importance of controlling factors, i.e. parent material or rock, climate, vegetation and topography, for individual elements during both processes. Further hierarchical clustering analysis was used to group elements into three inheritance categories according to their controlling factors. The framework was then applied in the Daliangshan area. Finally, we give some suggestions on the assessment of mineral resources, environment and agriculture according to the elemental inheritance categories in the Daliangshan area. This methodological approach can be applied to other localalities.

Thematic collection:
This article is part of the Applications of Innovations in Geochemical Data Analysis collection available at:
https://www.lyellcollection.org/topic/collections/applications-of-innovations-in-geochemical-data-analysis

Supplementary material:
The original data and average feature importance for 5000 simulations are available at
https://doi.org/10.6084/m9.figshare.c.6274315
Taphonomy of bivalve skeletal remains as a means of detecting changes in oxygen depletion and recognizing ancient upwelling environments
Authors: Edelman-Furstenberg Yael
Published: November 2022

Bivalve shells from shelf and slope environments of the Benguela upwelling system were examined for their state of preservation for the first time, and were used to test whether their preservation is a proxy for spatially variable seafloor taphonomic conditions that lead to different degrees of time averaging. Distinctive shell damage-profiles show increasing shell damage further from the centre of the upwelling cells affected by anoxic conditions (opal and organic-rich) and towards the carbonate- and phosphate-rich facies (with slower sedimentation rates at the margins of the cells. Discrete taphofacies range from a very low damage profile (opal and organic-rich, facies 1) to very high damage (phosphate, facies 3), with elevated numbers of rounded, fragmented and bored shells as well as very little associated sedimentary matrix. This gradient in taphofacies is associated with a gradient from census assemblages with low damage to (within-habitat time-averaged) assemblages in carbonate and (environmentally-condensed) phosphate facies of moderate and higher species richness that are associated with increasing time averaging. This pattern follows the upwelling facies gradient of high opal and organic matter in areas of most intense upwelling cells and outward to aerated but food-abundant carbonate-rich seafloors and spatially coexisting phosphorite-rich concentrations. Thus, the taphonomic gradient ranges from stressful, oxygen-depleted seafloor environment under upwelling regimes that limit metazoan predators and borers (and thus minimize destruction), to well-oxygenated seafloors with increased predators and micro-boring animals that all foster post-mortem shell destruction. The rarity of encrusters is a conspicuous feature of these facies across the whole gradient that may reflect temporary recurrence of oxygen-depleting conditions even at the carbonatic and phosphatic facies. The state of preservation of these shells can serve as a modern analogue for identifying similar settings in the geological record but also for Anthropocene settings affected by eutrophication and expanding oxygen minimum zones. Molluscan taphofacies with unusually low levels of skeletal damage from borers and encrusters can thus represent sensitive proxies of conditions affected by Anthropocene deoxygenation and eutrophication.
Understanding Human Object Vision: A Picture Is Worth a Thousand Representations
Authors: Bracci Stefania , Op de Beeck Hans P.
Published: November 2022

Objects are the core meaningful elements in our visual environment. Classic theories of object vision focus upon object recognition and are elegant and simple. Some of their proposals still stand, yet the simplicity is gone. Recent evolutions in behavioral paradigms, neuroscientific methods, and computational modeling have allowed vision scientists to uncover the complexity of the multidimensional representational space that underlies object vision. We review these findings and propose that the key to understanding this complexity is to relate object vision to the full repertoire of behavioral goals that underlie human behavior, running far beyond object recognition. There might be no such thing as core object recognition, and if it exists, then its importance is more limited than traditionally thought.
Molecular Beam Epitaxy of AlGaN Epilayers on Si for Vertical Deep Ultraviolet Light-Emitting Diodes
Authors: Zhang Qihua , Parimoo Heemal , Martel Eli , Zhao Songrui
Published: November 2022

Silicon (Si) has been an appealing substrate for vertical aluminum gallium nitride (AlGaN) deep ultraviolet (UV) light-emitting diodes (LEDs), toward which, the first step is to demonstrate AlGaN deep UV LEDs on Si. Nonetheless, the epitaxy of AlGaN epilayers on Si remains a challenge. Herein, we demonstrate the molecular beam epitaxy of AlGaN epilayers on Si using a nanowire-based template over a wide Al content range from 35%–70%. Smooth AlGaN surface down to a rms roughness of 0.4 nm is obtained using this approach. Vertical AlGaN deep UV LEDs emitting down to 247 nm are also demonstrated.
Design and Investigation of a Novel Gate-All-Around Vertical Tunnel FET with Improved DC and Analog/RF Parameters
Authors: Karthik Kadava R. N. , Pandey Chandan Kumar
Published: November 2022

In this paper, a novel structure of gate-all-around vertical TFET (GAA-VTFET) is proposed and investigated for the first time with the help of 3D TCAD simulator. It is found that GAA-VTFET offers much improvement in various DC parameters like ION, IOFF, subthreshold swing (SSAVG), and turn-on voltage (VT) as compared with the conventional GAA-TFET. As the tunneling direction of charge carriers is in parallel to the gate electric field, channel thickness in GAA-VTFET is rigorously reduced without compromising with the tunneling area and thus, improving the tunneling rate at source/channel interface during ON-state. Further, subthreshold leakage of the charge carriers is significantly reduced due to deployment of a dielectric layer beneath channel/drain interface extending up to source region. The impact of variation in geometric dimensions is also analysed to obtain the optimum performance of the proposed device. The current-switching ratio (ION/IOFF) is observed to be in order of ∼1013 while SSAVG of 56 mV decade−1 is achieved in the proposed device. Moreover, analog/RF parameters are also analysed in this work and it is noticed that an improved cut-off frequency of 593 GHz can be achieved due to reduced parasitic capacitances along with improved transconductance in GAA-VTFET. Next, the proper benchmarking reveals that GAA-VTFET offers better ION/IOFF, VT, and SSAVG as compared with the similar devices. Finally, based on the transient analysis of inverter circuit, the proposed GAA-VTFET is found to be more suitable for digital applications as it offers less rise-time along with full-voltage swing.
Study on the Mechanism of miR-146a in Gingival Mesenchymal Stem Cells
Authors: Wang Fang , Jing Zheng , Wei Ting , Jiang Hui , Li Xiaojun
Published: November 2022

This study aimed to investigate the molecular mechanisms of microRNA-146a (miR-146a) on gingival mesenchymal stem cells (MSCs). Gingival MSCs were isolated from the gingiva tissues of patients with periodontal disease to reveal the function of miR-146a in regulating osteoblast differentiation. miR-146a inhibits osteoblast differentiation by inhibiting phosphorylated cyclic-AMP response binding (CREB) protein translocation into the nucleus and ultimately attenuating runt-related transcription factor 2 (Runx2) expression. Furthermore, silencing miR-146a promotes the proliferation of gingival MSCs. Of note, targeted inhibition of miR-146a also inhibited LPS-induced inflammatory response and promoted the proliferation of gingival MSCs via CREB/Runx2 axis. MiR-146a is a key negative regulator of gingival MSCs proliferation and osteogenic differentiation, and targeting to reduce the miR-146a expression is essential for bone formation signaling. Therefore, we propose that miR-146a is a useful therapeutic target for the development of bone anabolic strategies.
A Covert-Aware Anonymous Communication Network for Social Communication
Authors: Cheng Xinda , Hu Ning , Zhao Yue , Wu Kaijun , Zou Jincai , Chen Yixing
Published: November 2022

To effectively protect the communication content and communication behavior of social networks, anonymous communication technologies are widely used. However, the anonymous communication networks represented by Tor and I2P lack the covertness of the control plane design, which leads to important user behavioral characteristics in the process of accessing anonymous communication networks. Therefore, network monitors can analyze users' communication behavior by tracking these characteristics. In this paper, the concept of covert measurement is proposed. On this basis, a software-defined anonymous communication network architecture is presented, which also considers the covertness of the anonymous communication network control plane and the data plane. According to the theoretical analysis and experimental results, the anonymous communication network architecture proposed in this paper has better anonymity and usability than traditional anonymous communication networks, such as Tor.
Applications of Metallic Nanoparticles in the Skin Cancer Treatment
Authors: Marzi Mahrokh , Osanloo Mahmoud , Vakil Mohammad Kazem , Mansoori Yaser , Ghasemian Abdolmajid , Dehghan Azizallah , Zarenezhad Elham
Published: November 2022

Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water‐soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high‐efficient, nontoxic, low‐cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off‐target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled‐release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019‐2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.
Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury
Authors: Xu Meng-Meng , Kang Jia-Ying , Ji Shuang , Wei Yuan-Yuan , Wei Si-Liang , Ye Jing-Jing , Wang Yue-Guo , Shen Ji-Long , Wu Hui-Mei , Fei Guang-He
Published: November 2022

Influenza virus infection is one of the strongest pathogenic factors for the development of acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS). However, the underlying cellular and molecular mechanisms have not been clarified. In this study, we aim to investigate whether melatonin modulates macrophage polarization, oxidative stress, and pyroptosis via activating Apolipoprotein E/low-density lipoprotein receptor (ApoE/LDLR) pathway in influenza A-induced ALI. Here, wild-type (WT) and ApoE-/- mice were instilled intratracheally with influenza A (H3N2) and injected intraperitoneally with melatonin for 7 consecutive days. In vitro, WT and ApoE-/- murine bone marrow-derived macrophages (BMDMs) were pretreated with melatonin before H3N2 stimulation. The results showed that melatonin administration significantly attenuated H3N2-induced pulmonary damage, leukocyte infiltration, and edema; decreased the expression of proinflammatory M1 markers; enhanced anti-inflammatory M2 markers; and switched the polarization of alveolar macrophages (AMs) from M1 to M2 phenotype. Additionally, melatonin inhibited reactive oxygen species- (ROS-) mediated pyroptosis shown by downregulation of malonaldehyde (MDA) and ROS levels as well as inhibition of the NLRP3/GSDMD pathway and lactate dehydrogenase (LDH) release. Strikingly, the ApoE/LDLR pathway was activated when melatonin was applied in H3N2-infected macrophages and mice. ApoE knockout mostly abrogated the protective impacts of melatonin on H3N2-induced ALI and its regulatory ability on macrophage polarization, oxidative stress, and pyroptosis. Furthermore, recombinant ApoE3 (re-ApoE3) inhibited H3N2-induced M1 polarization of BMDMs with upregulation of MT1 and MT2 expression, but re-ApoE2 and re-ApoE4 failed to do this. Melatonin combined with re-ApoE3 played more beneficial protective effects on modulating macrophage polarization, oxidative stress, and pyroptosis in H3N2-infected ApoE-/- BMDMs. Our study indicated that melatonin attenuated influenza A- (H3N2-) induced ALI by inhibiting the M1 polarization of pulmonary macrophages and ROS-mediated pyroptosis via activating the ApoE/LDLR pathway. This study suggested that melatonin-ApoE/LDLR axis may serve as a novel therapeutic strategy for influenza virus-induced ALI.
Analytical Validation of TaqMan™ Assays on the OpenArray™ Platform Using Applied Biosystems QuantStudio™ 12K Flex for the Rapid Identification of Nail Microbiota
Authors: Khan Irfan A. , Ali Ishrat I. , Khan Saeed , Ahmed Sagheer
Published: November 2022

Several microorganisms are known to play a role in nail infections. For the successful treatment of nail microbiota, especially fungi, there is a need for precise and robust diagnostic methods. This test utilizes real-time PCR amplification to detect the presence of a microorganism in a nail sample by amplifying the genomic DNA of the organism. Here, we described a TaqMan™-OpenArray™ nail microbiota assay that is efficient and easy-to-use for the characterization of key nail microbial targets through real-time PCR. The analytical accuracy and specificity of the nail panel were 100% and 99.90% across all assays and controls tested, respectively, and it was significantly more sensitive than culture. TaqMan™-OpenArray™ testing is fast and robust to contamination. In this paper, the main questions discussed were the replacement of culture by a broad-spectrum fungal TaqMan™-OpenArray™ testing and the implementation of TaqMan™-OpenArray™ testing into routine clinical laboratory settings.
Acute Hemorrhagic Leukoencephalitis (AHLE): A Comprehensive Review on Causes, Symptoms, Link with COVID‐19, Diagnosis, and Treatment
Authors: Alromaihi Mona
Published: November 2022

Acute hemorrhagic leukoencephalitis (AHLE), also called Hurst disease, is a rare demyelinating disease of the central nervous system (CNS) marked by rapid progression and acute inflammation of the white matter. Due to the correlation in their suspected postinfectious autoimmune pathogenesis, it is regarded as the most severe form of acute disseminated encephalomyelitis (ADEM). Because this clinical scenario has a high mortality rate, aggressive and immediate treatment is required. Although the exact cause of AHLE is unknown, it usually occurs after a bacterial or viral infection, or, less frequently, after a measles or rabies vaccination. AHLE has been reported in patients with coronavirus disease 2019 (COVID‐19) as a rare but serious neurological complication. However, due to the lack of evidence‐based diagnostic criteria, diagnosis is difficult. The small number of cases described in the literature, which most likely reflects underreporting and/or low incidence, necessitates greater public awareness. Increased clinical suspicion and early imaging identification of this entity may allow clinicians to pursue more aggressive treatment options, potentially reducing fatal outcomes. This study focuses on symptoms and causes of AHLE, difference between AHLE and ADME, diagnosis and treatment of AHLE, and its link with COVID‐19.
Correlation between Lpa, APO-A, APO-B, and Stenosis of Middle Cerebral Artery in Patients with Cerebral Ischemic Stroke
Authors: Chen Xinxu , Lu Xuefei , Li Wei , Zhang Hongyan , Wang Tan
Published: November 2022

Ischemic stroke (CIS) is characterized by a high incidence, disability, and mortality. Numerous studies have demonstrated that intracranial arterial stenosis is an important pathological basis of CIS, and its main cause is atherosclerosis. Dyslipidemia is an important risk factor for atherosclerosis. Lysophosphatidic acid (Lpa), apolipoprotein -A(APO-A), and apolipoprotein -B(APO-B) proved to be significantly correlated with the severity of coronary artery disease. This study retrospectively collected the case data of 186 patients with CIS treated from May 2020 to May 2022 and explored the correlation between Lpa, APO-A, APO-B, and middle cerebral artery (MCA) stenosis in CIS patients.
A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas
Authors: Qian Xi-Feng , Zhang Jia-Hao , Mai Yue-Xue , Yin Xin , Zheng Yu-Bin , Yu Zi-Yuan , Zhu Guo-Dong , Guo Xu-Guang
Published: November 2022

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan–Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration–approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.
Effects of Du Meridian Moxibustion Combined with Mild Moxibustion on Female Pelvic Floor Myofascial Pain Syndrome: A Retrospective Cohort Study
Authors: Wei Yehong , Chen Xufeng , Wang Tianyu , Dong Xianna , Zhu Zheng
Published: November 2022

Objective. This study aimed to investigate the efficacy and safety of moxibustion in the treatment of pelvic floor myofascial pain syndrome. Methods. A total of 80 women with pelvic floor myofascial pain syndrome (cold coagulation and blood stasis type) were included in this retrospective study and divided into a moxibustion group and a drug treatment group. Patients who received Celebrex oral analgesia, health education, and lifestyle improvement were included in the drug treatment group. The patients that received Du meridian moxibustion combined with mild moxibustion, health education, and lifestyle improvement were included in the moxibustion group. The comparison of pelvic pain, the TCM clinical symptom score, and the curative effect was made between the two groups before treatment and after 1–3 weeks of treatment, respectively. Results. An intragroup comparison showed a stepwise decrease in the VAS score and the TCM clinical symptom score of the two groups during the treatment. An intergroup comparison revealed that the VAS score of the moxibustion group was lower than that of the drug treatment group, while TCM clinical symptoms and clinical efficacy significantly improved in the moxibustion group compared to those in the drug treatment group (

P
<
0.05

). Conclusion. Du meridian moxibustion combined with mild moxibustion alleviates pelvic floor myofascial pain syndrome, thus helping improve women’s quality of life and providing patients with a more effective and safer treatment plan.
Asynchronous Intermittent Regulation of Human Arm Movement with Markovian Jumping Parameters
Authors: Ma Chao , Wu Wei
Published: November 2022

In this paper, the regulation stability problem of the human arm continuous movement is investigated based on Markovian jumping parameters. In particular, the intermittent control mechanism is adopted in the arm movement regulation procedure to model the human intermittent motor control strategy. Furthermore, by taking into account the Markovian jumping parameters with different modes, the asynchronous regulation issue is proposed to model mode mismatch between the motor control and arm movement. On the basis of model transformation, sufficient stability conditions are established during the arm movements, and the desired regulation gain can be obtained by the convex optimization method. In the end, an illustrative example is presented to show the applicability and effectiveness of our developed model and optimized regulation approach.
Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia
Authors: Lalosevic Miodrag , Kotur-Stevuljevic Jelena , Vekic Jelena , Rizzo Manfredi , Kosanovic Tijana , Blagojevic Iva Perovic , Zeljkovic Aleksandra , Jeremic Danilo , Mihajlovic Marija , Petkovic Aleksa , Hajdarpasic Lejla , Djordjevic Marjana , Dobrilovic Violeta , Erceg Sanja , Vujcic Sanja , Marjanovic Jelena , Jovanovic Jovana Milijic , Saponjski Jovica , Bogavac-Stanojevic Natasa
Published: November 2022

Background. Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods. The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results. Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions. Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.
Deletion of a Putative GPI-Anchored Protein-Encoding Gene Aog185 Impedes the Growth and Nematode-Trapping Efficiency of Arthrobotrys oligospora by Disrupting Transmembrane Transport Homeostasis
Authors: Peng Hui , Lu Hengqian , Dong Xinyuan , Liang Xiao , Sheng Kangliang , Wang Jingmin , Kong Xiaowei , Zha Xiangdong , Wang Yongzhong
Published: November 2022

Nematode-trapping fungus (NTF) is a crucial predator of nematodes, which can capture nematodes by developing specific trapping devices. However, there is limited understanding of the role and mechanism of cell surface proteins attached to the surface of mycelia or trapping cells. Here, the effects of a putative GPI-anchored protein-encoding gene Aog185 on the growth and nematode-trapping efficiency of A. oligospora were investigated. Compared to the wild-type (WT) strain, the ΔAog185 mutant grew more slowly, exhibited a 20% decrease in conidiation, delayed conidial germination, generated fewer traps, attenuated nematode trapping efficiency, and was more sensitive to chemical stressors. Transcriptomic analysis indicated that a large number of transmembrane transport-related genes were differentially expressed between the WT and ΔAog185 mutant strains. Aog185 deletion could damage the intrinsic components of the membrane and cytoskeleton. Specifically, knockout of Aog185 disrupted transmembrane transport homeostasis during the phagocytosis, cell autophagy, and oxidative phosphorylation processes, which were associated with the fusion of cells and organelle membranes, transport of ions and substrates, and energy metabolism. Hence, the putative GPI-anchored protein-encoding gene Aog185 may contribute to the lifestyle switch of NTF and nematode capture, and the effect of Aog185 gene on cell transmembrane transport is considered key to this process. Our findings provide new insights into the mechanism of Aog185 gene during the process of nematode trapping by NTF.
Statin Use Is Associated with Better Prognosis of Patients with Prostate Cancer after Definite Therapies: A Systematic Review and Meta-Analysis of Cohort Studies
Authors: An Ye , Sun Jian-Xuan , Xu Meng-Yao , Liu Chen-Qian , Xu Jin-Zhou , Zhong Xing-Yu , Hu Jia , Xia Qi-Dong , Hu Heng-Long , Wang Shao-Gang
Published: November 2022

Objective. Although the prognostic effect of statins on patients with prostate cancer (PCa) has been frequently evaluated, a consistent result is still lacking. We aimed to evaluate the association between statin use and mortality among patients with PCa after definite therapies. Methods. A systematic search of PubMed and other databases for cohort studies about the effect of statins on patients with PCa was performed until April 2022. Meta-analysis was performed using R software version 4.1.2. Results. 24 cohort studies involving 369, 206 participants were finally included. We found statin use significantly reduced the risk of prostate cancer-specific mortality (PCSM) with a pooled hazard ratio (pHR) = 0.76 (95% CI: 0.69–0.84, 18 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.77–0.85) and patients who accepted androgen deprivation therapy (ADT): pHR = 0.69 (95% CI: 0.59–0.81). Statin use was also associated with a 24% reduction in the risk of all-cause mortality (ACM): pHR = 0.76 (95% CI: 0.68–0.85, 17 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.78–0.85) and patients treated with ADT: pHR = 0.72 (95% CI: 0.63–0.82) or radiotherapy (RT): pHR = 0.68 (95% CI: 0.50–0.93). Conclusion. In conclusion, the use of statins could promote the prognosis of patients with PCa, especially for postdiagnostic users. For patients who received either ADT or radical prostatectomy (RP), statin use could decrease the PCSM. As for those who received either ADT or RT, statin use could decrease the ACM.
Truncal Dynamics May Trump: Serial ctDNA to Predict Early Therapeutic Response
Authors: Eluri Madhulika , Kopetz Scott , Parseghian Christine M.
Published: November 2022

Promising utility of using serial ctDNA in metastatic colorectal cancer to both refine patient selection, reduce toxicity due to chemotherapy, and to evaluate emerging resistance mechanisms may lead the way to novel therapeutic strategies. However, important questions remain in validating its use as a predictive biomarker of treatment response.

See related article by Vidal et al., p. 379
Abstract A024: Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma
Authors: Arbelaez Carlos M. Mejia , Shan Xining , Robert Tseng , Robert Marie E. , Ma Xiaomei , Escobar-Hoyos Luisa F.
Published: November 2022

Approximately, 70% of pancreatic ductal adenocarcinomas (PDACs) have mutations in the TP53 gene; however, it is still unknown if gain- or loss- of function mutations in TP53 provide differential prognostic value to guide therapy. To fill this gap, we assessed the potential effect of wild-type, missense (gain-of-function) and truncating (loss-of-function) TP53 mutations in patient survival, in two independent clinical cohorts (The Cancer Genome Atlas cohort=141, and the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets cohort=376 PDACs). We employed multivariable Cox proportional hazards regression models adjusting for patient demographic (age at diagnosis, sex, race/ethnicity) and tumor characteristics (presence of distant metastasis at diagnosis). Additionally, we conducted stratified analyses by the status of “druggable” (DNA repair gene mutations) and other driver mutations (SMAD4 and CDKN2A genes). We found that PDACs with missense TP53 mutations were associated with a worse patient survival compared to tumors with wild-typeTP53 (HR = 1.47, 95% CI: 1.00-2.17; p=0.051). Similarly, patients with truncating mutations in TP53 had a trend to worse OS (HR=1.11, 95% CI, 0.70-1.76; p=0.654) compared to patients with wild-type TP53, however, these associations were not significant. Furthermore, we found that mutations in DNA repair genes, SMAD4 and CDKN2A genes did not show any prognostic value. Our findings suggest that molecular characterization of specific TP53 mutations may help to determine differences in patient prognosis and potentially guide future clinical management of patients.

Citation Format: Carlos M. Mejia Arbelaez, Xining Shan, Tseng Robert, Marie E. Robert, Xiaomei Ma, Luisa F. Escobar-Hoyos. Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A024.
Abstract A027: Validation of an early-stage pancreatic cancer classification model using 5-Hydroxymethylation profiles in plasma-derived cell-free DNA
Authors: Bergamaschi Anna , Haan David , Collins Micah , Guler Gulfem , Peters Melissa , Gigliotti Lauren , Chowdhury Shimul , Volkmuth Wayne , Levy Samuel
Published: November 2022

Background: Pancreatic cancer outcomes are poor, mostly due to the detection of cancer at late stages. Early-detection enables prompt initiation of treatment and has been reported to significantly improve outcomes. We have developed a novel sequencing-based epigenomics technology for cancer early-detection that enriches 5-hydroxymethylcytosine (5hmC) loci in cell-free DNA (cfDNA), and via machine learning algorithms, enables the detection of pancreatic cancer. Method: Whole-blood was obtained from a training cohort of 660 individuals (consisting of 132 pancreatic cancers (PaCa) and 528 non-cancers) and a validation cohort of 593 individuals (consisting of 86 PaCa and 507 non-cancers). cfDNA was isolated from plasma and 5hmC and whole-genome libraries were sequenced. Logistic regression algorithms were employed using 5hmC feature sets combined with physical characteristics to optimally partition cancers from non-cancers. Results: We trained and cross-validated a binomial logistic-regression model on PaCa and non-cancer samples. Cross validation of the training model yielded an overall sensitivity of 65.9%, early-stage (stage I-II) sensitivity of 57.1% and a specificity of 98%. The model was further validated on an independent set and yielded an overall sensitivity of 64%, early-stage sensitivity of 64.7% and a specificity of 98%. Conclusion: Our results demonstrate that plasma-derived cfDNA 5hmC profiles enable the detection of PaCa in early-stage disease providing a valuable tool especially for those individuals at high risk. A larger clinical study (NODMED: NCT05188586) is underway to validate the test in a high-risk population that would most benefit from early-detection.

Citation Format: Anna Bergamaschi, David Haan, Micah Collins, Gulfem Guler, Melissa Peters, Lauren Gigliotti, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy. Validation of an early-stage pancreatic cancer classification model using 5-Hydroxymethylation profiles in plasma-derived cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A027.
Abstract A041: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer
Authors: Halder Kuntal , Jameson Gayle , Borazanci Erkut , Vrana Amber , Cridebring Derek , Von Hoff Daniel , Han Haiyong
Published: November 2022

Pancreatic cancer is a highly lethal disease that is often diagnosed at a late stage, when it has metastasized to other organs. Several therapeutic options have been shown to be effective at significantly shrinking the tumor and improving survival. Unfortunately, very few of these treatments lead to the total disappearance of tumor and therefore require changes to the treatment strategy. One of the challenges is rapidly identifying if a treatment works or when it stops working so patients can be switched to another regimen. Currently, the best blood-based marker for tracking disease burden in patients with pancreatic cancer is CA19-9. Unfortunately, 15-20% of pancreatic cancer patients do not have elevated levels of this marker with a disproportionate number of non-CA19-9 elevated cases being African American and Hispanic patients. In addition, changes in this marker do not always correlate with disease burden since there are other factors that can change CA19-9 levels. In this study, we have identified two blood extracellular vesicle (EV) based protein markers THBS2 (Thrombospondin 2) and ALPPL2 (Alkaline phosphatase, placental-like 2) that aid in monitoring pancreatic cancer disease burden in both CA19-9 secretors and non-secretors. We found that the number of THBS2+ or ALPPL2+ EVs was significantly higher in serum samples from patients with pancreatic cancer than those from healthy controls. The level of THBS2+ or ALPPL2+ EVs in patients with pancreatic cancer correlated with a patient's response to treatment. In patients who have elevated CA19-9, the level of THBS2+ or ALPPL2+ EVs correlates with the changes in CA19-9 upon treatment. In CA19-9 negative patients, the level of THBS2+ EVs or ALPPL2+ EVs correlates with the tumor size changes (RECIST response) upon treatment. Hence, EVs containing THBS2 or ALPPL2 can potentially serve as additional and more informative biomarkers for monitoring disease burden in patients with pancreatic cancer regardless of their CA19-9 status. This work was supported by the Flinn Foundation and the HonorHealth Research Institute).

Citation Format: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Amber Vrana, Derek Cridebring, Daniel Von Hoff, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A041.
Abstract A074: Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models
Authors: Fulton Alexander J. P. , Saeb-Parsy Kourosh , Basu Bristi
Published: November 2022

Pancreatic cancer (PDAC) remains one of the most lethal malignancies due to its late diagnosis and poor response to treatment. Preclinical models reflecting the uniquely complex structure of PDAC cells and the surrounding tumor microenvironment (TME) are required to ensure translational results. PDAC organoids, ex vivo 3D models of primary tumor cells, form an exciting preclinical model that reflects the complexity of PDAC. Tumor organoids co-cultured with stromal and immune cells have been previously explored in vitro but have thus far remained limited in any in vivo capacity. We therefore aimed to establish and characterize in vitro co-cultured PDAC organoids using primary human PDAC tumor samples plus autologous peripheral or splenic lymphocytes. Subsequent preliminary in vivo models have been established by engrafting co-cultured PDAC organoids and PDAC cancer associated fibroblasts into immunocompromised mice. The pilot data assessed retention, growth kinetics and metastatic potential and will subsequently form the foundation for comparable experiments using autologous humanized mouse models. This humanized mouse model, consisting of autologous human malignant, stromal and immune compartments, will add to the existing repertoire of preclinical models by more closely representing the entire tumor volume. In vitro and in vivo data compared to other preclinical models. Additional preliminary therapeutic response data may provide translational value and warrant further evaluation.

Citation Format: Alexander J. P. Fulton, Kourosh Saeb-Parsy, Bristi Basu. Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A074.