bluuebunny/crossref_metadata_2025 huggingface dataset:
First-Principles Study of Structural, Electronic, Magnetic and Half-Metallic Properties of Mn2ZrX (X = As, Bi) Full Heusler Alloys
Authors: Khaldi Ahmed , Zemouli Mostefa , Benallou Yassine , Damou Mehdi , Amara Kadda , El Keurti Mohamed
Published: February 2023

In this paper, the structural, electronic, magnetic, and half-metallic properties of full-Heusler alloys Mn2ZrX ([Formula: see text], Bi) in the Hg2CuTi-type structure have been studied by using the first-principles-based density functional theory (DFT) with the full-potential linearized augmented plane-wave (FP-LAPW) method. Mn2ZrX ([Formula: see text], Bi) compounds are found to be half-metallic ferrimagnets. The calculated total magnetic moments of the Mn2ZrX ([Formula: see text], Bi) alloys are estimated at 01[Formula: see text][Formula: see text] according to the Slater–Pauling rule of [Formula: see text] ([Formula: see text]–24) [Formula: see text]. It was discovered that Mn2ZrAs and Mn2ZrBi maintained their half-metallicity for a lattice constant interval of 5.72 to 6.26 Å and 6.33 to 6.62 Å, respectively, and present a maximum degree of spin polarization at the Fermi level. In addition, the predicted formation energy and elastic parameters show that these materials are mechanically stable. All of these results indicate that these new Mn2-based heusler alloys are able to be the candidates for spintronic applications.
AI business models and its impact on business strategic framework
Authors: Mishra Shrutika , Mishra Priyanshu
Published: February 2023

Recently, a lot of research was done on how to evolve the artificial intelligence business model framework. However, one issue was still undeveloped, which was immature to understand. This has been vital for budding and progressive managers, policy decision makers, and academics alike, namely, how businesses transform and develop their AI business models framework to accomplish continuous value formation. Businesses, which achieve to make value over prolonged stages of time effectively, figure, acclimate and recommence their business models with AI technology to fuel such value formation. Sketch on verdicts from a research program on uninterruptedly budding businesses is given. This paper categorizes three perilous competences, namely, an alignment towards investigating with and manipulating innovative business openings, a well-adjusted use of properties, as well as attaining lucidity between management, ethos, and member of staff obligations, together they all decisive key maneuvering schedules. We conclude the paper by signifying the consequences for AI business model framework research and experts and by providing a tool for executives which permits them to reproduce and classify perilous problems relevant for shifting and emerging their business model to sustain value creation. In this paper, we try to explore the keys of Business Model Framework, which will revolutionize business market ecosystem.
Epidermal growth factor receptor inhibition prevents vascular calcifying extracellular vesicle biogenesis
Authors: Bakhshian Nik Amirala , Ng Hooi Hooi , Ashbrook Sophie K. , Sun Patrick , Iacoviello Francesco , Shearing Paul R. , Bertazzo Sergio , Mero Deniel , Khomtchouk Bohdan B. , Hutcheson Joshua D.
Published: February 2023

Here, we investigate the potential of epidermal growth factor receptor (EGFR) inhibition to prevent vascular calcification, a leading indicator of and contributor to cardiovascular morbidity and mortality. EGFR interacts and affects the trafficking of the plasma membrane scaffolding protein caveolin-1. Previous studies reported a key role for caveolin-1 in the development of specialized extracellular vesicles that mediate vascular calcification; however, no role of EGFR has been reported. We demonstrated that EGFR inhibition modulates caveolin-1 trafficking and hinders calcifying extracellular vesicle formation, which prevents vascular calcification. Given that EGFR inhibitors are clinically approved for other indications, this may represent a novel therapeutic strategy for vascular calcification.
Involvement of lysyl oxidase in the pathogenesis of arterial stiffness in chronic kidney disease
Authors: Sharma Ravindra K. , Kamble Shyam H. , Krishnan Suraj , Gomes Joshua , To Brandon , Li Shiyu , Liu I-Chia , Gumz Michelle L. , Mohandas Rajesh
Published: February 2023

Arterial stiffness in CKD is associated with adverse cardiovascular outcomes. However, the mechanisms underlying increased aortic stiffness in CKD are unclear. Herein, we demonstrated that 1) increased aortic stiffness in CKD is independent of hypertension and calcification and 2) LOX-mediated changes in extracellular matrix are at least in part responsible for increased aortic stiffness in CKD. Prevention of excess LOX may have therapeutic potential in alleviating increased aortic stiffness and improving cardiovascular disease in CKD.
Cholinergic nerve contribution to cutaneous active vasodilation during exercise is similar to whole body passive heating
Authors: Francisco Michael A. , Gibson Brandon M. , Simmons Grant H. , Halliwill John R. , Minson Christopher T.
Published: February 2023

Our study establishes the primacy of cholinergic nerves to cutaneous active vasodilation during exercise and confirms this model during passive heating using a crossover study design. In addition, the mode of heating, whether passive or exercise induced, did not change the sensitivity of the cholinergic component of the thermoeffector response to increased internal temperature. Thus, cutaneous active vasodilator nerves are responsible for similar skin blood flow responses regardless of how thermal loading is accomplished.
Human skeletal muscle-specific atrophy with aging: a comprehensive review
Authors: Naruse Masatoshi , Trappe Scott , Trappe Todd A.
Published: February 2023

Age-related skeletal muscle atrophy appears to be a muscle group-specific process, yet only a few specific muscles have been investigated and our understanding in this area is limited. This review provides a comprehensive summary of the available information on age-related skeletal muscle atrophy in a muscle-specific manner, nearly half of which comes from the quadriceps. Decline in muscle-specific size over ∼50 yr of aging was determined from 47 cross-sectional studies of 982 young (∼25 yr) and 1,003 old (∼75 yr) individuals and nine muscle groups: elbow extensors (−20%, −0.39%/yr), elbow flexors (−19%, −0.38%/yr), paraspinals (−24%, −0.47%/yr), psoas (−29%, −0.58%/yr), hip adductors (−13%, −0.27%/yr), hamstrings (−19%, −0.39%/yr), quadriceps (−27%, −0.53%/yr), dorsiflexors (−9%, −0.19%/yr), and triceps surae (−14%, −0.28%/yr). Muscle-specific atrophy rate was also determined for each of the subcomponent muscles in the hamstrings, quadriceps, and triceps surae. Of all the muscles included in this review, there was more than a fivefold difference between the least (−6%, −0.13%/yr, soleus) to the most (−33%, −0.66%/yr, rectus femoris) atrophying muscles. Muscle activity level, muscle fiber type, sex, and timeline of the aging process all appeared to have some influence on muscle-specific atrophy. Given the large range of muscle-specific atrophy and the large number of muscles that have not been investigated, more muscle-specific information could expand our understanding of functional deficits that develop with aging and help guide muscle-specific interventions to improve the quality of life of aging women and men.
Effects of comorbid type II diabetes mellitus and heart failure on rat hindlimb and respiratory muscle blood flow during treadmill exercise
Authors: Butenas Alec L. E. , Copp Steven W. , Hageman K. Sue , Poole David C. , Musch Timothy I.
Published: February 2023

Herein, we demonstrate that rats comorbid with heart failure with reduced ejection fraction (HF-rEF) and type II diabetes mellitus (T2DM) have a higher hindlimb and respiratory muscle blood flow during submaximal treadmill running (20 m·min−1; 10% incline) compared with nondiabetic HF-rEF counterparts. These data may carry important clinical implications for roughly half of all patients with HF-rEF who present with T2DM.
A Clinical-Epidemiological Study on Beta-Blocker Poisonings Based on the Type of Drug Overdose
Authors: Eizadi-Mood Nastaran , Adib Mahtab , Otroshi Arman , Dorooshi Gholamali , Meamar Rokhsareh
Published: February 2023

Background. Beta‐blockers carry a high risk of potentially causing fatal poisoning if overdosed. We aimed to assess the clinical and epidemiological characteristics of patients with beta-blocker poisoning. Methods. Patients were categorized based on the type of drug poisoning into propranolol, other beta-blockers, and the combination of beta-blocker groups, respectively. Demographic data, drug toxicity, and clinical, laboratory, and treatment information of different groups were compared. Results. During the study period, 5086 poisoned patients were hospitalized, of whom 255 (5.1%) had beta-blocker poisoning. Most patients were women (80.8%), married (50.6%), with a history of psychiatric disorders (36.5%), previous suicide attempts (34.6%), and intentional type of exposure (95.3%). The mean ± SD age of the patients was 28.94 ± 11.08 years. Propranolol toxicity was the most common among different beta-blockers (84.4%). There was a significant difference in age, occupation, education level, and history of psychiatric diseases with respect to the type of beta-blocker poisoning (P<0.05). We observed changes in the consciousness level and need for endotracheal intubation only in the third group (combination of beta-blockers). Only 1 (0.4%) patient had a fatal outcome in toxicity with the combination of beta-blockers. Conclusion. Beta-blocker poisoning is not common in our poisoning referral center. Propranolol toxicity was most common among different beta-blockers. Although symptoms are not different among defined beta‐blocker groups, more severe symptoms are observed in the combination of the beta-blocker group. Only one patient had a fatal outcome in the toxicity with the combination of the beta-blocker group. Therefore, poisoning circumstances have to investigate thoroughly to screen coexposure with combined drugs.
IIoT‐Based Intelligent Process Control for Crude Oil Separation: Investigating the Impact of Model‐Based Control and Genetic Algorithms
Authors: Allahloh Ali S. , Sarfraz Mohammad , Ghaleb Atef M. , Mejjaouli Sobhi
Published: February 2023

Integrating the Internet of Things (IIoT) with intelligent process control can improve the performance and efficiency of various industrial processes. However, there is a need for continued research on integrating IIoT‐based control with advanced techniques such as model‐based control and genetic algorithms to fully realize these benefits. This study investigates the impact of such integration on the performance of crude oil separation processes. To this end, we implemented IIoT‐based intelligent process control with model‐based control and genetic algorithms using specific IIoT devices and platforms, such as SCADAPACK 535E and FactoryTalk. The results of our implementation show that this technique can significantly improve the quality of crude oil separation, with an increase from 95% to 99% over two months of production. Overall, our findings suggest that integrating IIoT‐based intelligent process control with advanced techniques such as model‐based control and genetic algorithms can significantly improve the performance of crude oil separation processes and may have similar benefits in other industrial processes. Further research is needed to fully understand these techniques’ potential in different contexts and identify best practices for their implementation.
SEBGLMA: Semantic Embedded Bipartite Graph Network for Predicting lncRNA‐miRNA Associations
Authors: Zhao Zheng-Yang , Lin Jie , Wang Zhen , Guo Jian-Xin , Zhan Xin-Ke , Huang Yu-An , Shi Chuan , Huang Wen-Zhun
Published: February 2023

Identifying the association between long noncoding RNA (lncRNA) and micro‐RNA (miRNA) is of great significance for the treatment of diseases by interfering with the combination of miRNA and messenger RNA (mRNA). Although many efforts and resources have been invested to identify lncRNA‐miRNA associations (LMAs), clinical trials are still expensive and laborious. Nevertheless, the experiments also need to consult a large number of side effects. Therefore, novel computer‐aided models are urgently needed to predict LMAs. This paper proposed a semantic embedded bipartite graph network for predicting lncRNA‐miRNA associations (SEBGLMA), which provided a novel feature extraction method by integrating K‐mer segmentation, word2vec, Gaussian interaction profile (GIP), and graph convolution network (GCN). Concretely, the attribute characteristics of RNA sequences are extracted by K‐mer segmentation and word2vec modules. Afterward, the adjacent matrix is completed by GIP self‐similarity. Then, the attribute characteristics and adjacent matrix are fed into GCN for embedding behavior features. Finally, the features are sent into the rotation forest (RoF) for detecting potential LMAs. The average accuracy, precision, sensitivity, specificity, Matthews correlation coefficient, and F1‐Score are 87.09%, 87.66%, 87.03%, 87.84%, 74.18%, and 86.99% on the benchmark data set. For fairly validating the performance of our model, we conducted various comparisons with different classifiers. Furthermore, the case studies of hsa‐miR‐497‐5P and NONHSAT022145.2 are also established. The results of comparisons and case studies further illustrated that our method is anticipated to become a robust and reliable tool for the identification of LMAs.
Novel Framework for Secure Data Aggregation in Precision Agriculture with Extensive Energy Efficiency
Authors: Nagaraja G. S. , Vanishree K. , Azam Farooque
Published: February 2023

Precision agriculture (PA) is the next generation of a technological revolution in smart farming, where sensing technology is the core technological player. Energy-efficient data transmission in PA via sensing technology is possible only when additional security measures are synchronized. Nevertheless, security considerations often introduce additional overhead. Thus, it is necessary to develop an efficient mechanism to achieve an optimal trade-off between security and resource efficiency. The prime purpose of the proposed study is to introduce a lightweight communication protocol that can ensure an adequate balance between energy efficiency and maximum-security demands to benefit the success of PA. This paper proposes a synchronized framework where unique public-key encryption has been used, unlike any existing approach to facilitate the participation of legitimate on-field sensors in PA. On the other hand, an algorithm for energy efficiency where unique structural management of routing is discussed concerning aggregator nodes. In contrast, the security algorithm discusses a uniquely progressive and noniterative mechanism to perform secure data aggregation with a parallel validation technique. The proposed logic is scripted in MATLAB, considering a suitable PA environment where comparative assessment is carried out on a uniform testbed. The study outcome exhibited the effectiveness of the proposed scheme concerning better energy efficiency and higher resiliency from threats in contrast to existing schemes.
Reconfigurable Intelligent Surface‐Aided AirComp for Large‐Scale IoT Networks
Authors: Chen Yun , Zhang Guoping , Xu Hongbo , Luo Wenxing , Ren Yinshuan , Zhang Jianqiang
Published: February 2023

Traditional wireless data aggregation (WDA) technology based on the principle of separated communication and computation is difficult to achieve large‐scale access under the limited spectrum resources, especially in scenarios with strict constraints on time latency. As an outstanding fast WDA technology, over‐the‐air computation (AirComp) can reduce transmit time while improving spectrum efficiency. Most edge devices in wireless networks are battery‐powered. Therefore, optimizing the transmit power of devices could prolong the life cycle of nodes and save the system power consumption. In this research, we aim to minimize the device transmit power subject to aggregation error constraint. Additionally, to improve the harsh wireless transmission environment, we use reconfigurable intelligent surface (RIS) to assist AirComp. To solve the presented nonconvex problem, we present a two‐step solution method. Specifically, we introduce matrix lifting technology to transform the original problems into semidefinite programming problems (SDP) in the first step and then propose an alternate difference‐of‐convex (DC) framework to solve the SDP subproblems. The numerical results show that RIS‐assisted communication can greatly save system power and reduce aggregation error. And the proposed alternate DC method is superior to the alternate semidefinite relaxation (SDR) method.
Appraisal of the Possible Role of PPARγ Upregulation by CLA of Probiotic Pediococcus pentosaceus GS4 in Colon Cancer Mitigation
Authors: Dubey Vinay , Mishra Alok Kumar , Ghosh Asit Ranjan
Published: February 2023

The prevalence of colon cancer (CC) is increasing at the endemic scale, which is accompanied by subsequent morbidity and mortality. Although there have been noteworthy achievements in the therapeutic strategies in recent years, the treatment of patients with CC remains a formidable task. The current study focused on to study role of biohydrogenation-derived conjugated linoleic acid (CLA) of probiotic Pediococcus pentosaceus GS4 (CLAGS4) against CC, which induced peroxisome proliferator-activated receptor gamma (PPARγ) expression in human CC HCT-116 cells. Pre-treatment with PPARγ antagonist bisphenol A diglycidyl ether has significantly reduced the inhibitory efficacy of enhanced cell viability of HCT-116 cells, suggesting the PPARγ-dependent cell death. The cancer cells treated with CLA/CLAGS4 demonstrated the reduced level of Prostaglandin E2 PGE2 in association with reduced COX-2 and 5-LOX expressions. Moreover, these consequences were found to be associated with PPARγ-dependent. Furthermore, delineation of mitochondrial dependent apoptosis with the help of molecular docking LigPlot analysis showed that CLA can bind with hexokinase-II (hHK-II) (highly expressed in cancer cells) and that this association underlies voltage dependent anionic channel to open, thereby causing mitochondrial membrane depolarization, a condition that initiates intrinsic apoptotic events. Apoptosis was further confirmed by annexin V staining and elevation of caspase 1p10 expression. Taken all together, it is deduced that, mechanistically, the upregulation of PPARγ by CLAGS4 of P. pentosaceus GS4 can alter cancer cell metabolism in association with triggering apoptosis in CC.
Design, Computational Aerodynamic, Aerostructural, and Control Stability Investigations of VTOL-Configured Hybrid Blended Wing Body-Based Unmanned Aerial Vehicle for Intruder Inspections
Authors: Raja Vijayanandh , Murugesan Ramesh , Solaiappan Senthil Kumar , Arputharaj Beena Stanislaus , Rajendran Parvathy , AL-bonsrulah Hussein A. Z. , Thakur Deepak , Razak Abdul , Buradi Abdulrajak , Ketema Abiot
Published: February 2023

Unmanned aerial vehicles (UAVs) are gaining in popularity and sophistication in today’s modern world. UAVs are now available in a wide range of configurations. A UAV’s many applications include aerial photography and videography and target tracking. The upward-pointing propellers of some modern fixed-wing UAVs make it possible for them to take off and land vertically. Surveillance and intruder inspections are two areas where the blended wing body (BWB) configuration shines. This is because its weight is spread uniformly throughout the body, its radar signal is weaker than that of alternative configurations, and there is a relatively small amount of interference with its movement. With common design factors in mind, like vertical takeoff and landing, aerodynamic drag, and fundamental wing stability, the optimal BWB plan form for surveillance is designed. CATIA is used to finish the conceptual design of the BWB-based UAV. A fluid-structure interaction (FSI) study is carried out after the model has been examined in ANSYS Fluent. The UAV’s responsiveness is improved through simulation in the MATLAB environment after a proportional-integral-derivative-type altitude controller was developed. The results demonstrate that providing the UAV with an altitude instruction enhances its performance. Given the flexibility of the suggested BWB UAV’s design, we have decided to limit its maximum forward speed to 75 m/s and its maximum rate of vertical ascension to 50 m/s. Rapid BWB UAVs like the one seen here are quite helpful in dangerous situations.
Neighborhood Socioeconomic Status and Racial and Ethnic Survival Disparities in Oral Cavity and Laryngeal Cancer
Authors: Liu Yupeng , Zhong Lydia , Puram Sidharth V. , Mazul Angela L.
Published: February 2023

Background:

Oral cavity cancer (OCC) and laryngeal cancer are among the most common cancers worldwide. This study investigated survival in non-Hispanic (NH) Black, NH White, Asian, and Hispanic patients with OCC and laryngeal cancer of low, intermediate, and high neighborhood socioeconomic status (nSES).

Methods:

We used data from the SEER 18 Census Tract-level SES and Rurality Database of the National Cancer Institute to create cohorts of OCC and laryngeal cancer patients from 2013 to 2018. Univariate survival analysis was performed with Kaplan–Meier curves and log-rank P values by nSES and then the cross-classification of race, ethnicity, and nSES. We used Cox proportional hazards regression model for multivariable analysis.

Results:

Higher nSES was associated with better OCC survival for NH White, NH Black, and Asian patients, and better laryngeal cancer survival for NH White, NH Black, Hispanic, and Asian patients. In the multivariable analyses of both OCC and laryngeal cancer survival, NH Black patients had worse survival than NH White patients in the high nSES tertile. NH Black patients with OCC were at higher risk of death than NH White patients at all nSES levels. Conversely, Asian patients with laryngeal cancer demonstrated better survival than other races within the high nSES.

Conclusions:

Overall survival differs between racial and ethnic groups of similar nSESs. These health disparities in patients with OCC and laryngeal cancer reflect broader inequities in the cancer control continuum.

Impact:

The cross-classification of race, ethnicity, and nSES revealed disparities in the 5-year overall survival of patients with OCC and laryngeal cancer and highlights the importance of intersectionality in the discussion of health equity.
Rural, Large Town, and Urban Differences in Optimal Subspecialty Follow-up and Survivorship Care Plan Documentation among Childhood Cancer Survivors
Authors: Noyd David H. , Janitz Amanda E. , Baker Ashley A. , Beasley William H. , Etzold Nancy C. , Kendrick David C. , Oeffinger Kevin C.
Published: February 2023

Background:

Children with cancer from rural and nonurban areas face unique challenges. Health equity for this population requires attention to geographic disparities in optimal survivorship-focused care.

Methods:

The Oklahoma Childhood Cancer Survivor Cohort was based on all patients reported to the institutional cancer registry and ≤ 18 years old at diagnosis between January 1, 2005, and September 24, 2014. Suboptimal follow-up was defined as no completed oncology-related clinic visit five to 7 years after their initial diagnosis (survivors were 7–25 years old at end of the follow-up period). The primary predictor of interest was rurality.

Results:

Ninety-four (21%) of the 449 eligible survivors received suboptimal follow-up. There were significant differences (P = 0.01) as 36% of survivors from large towns (n = 28/78) compared with 21% (n = 20/95) and 17% (n = 46/276) of survivors from small town/isolated rural and urban areas received suboptimal follow-up, respectively. Forty-five percent of adolescents at diagnosis were not seen in the clinic compared with 17% of non-adolescents (P < 0.01). An adjusted risk ratio of 2.2 (95% confidence interval, 1.5, 3.2) was observed for suboptimal follow-up among survivors from large towns, compared with survivors from urban areas. Seventy-three percent of survivors (n = 271/369) had a documented survivorship care plan with similar trends by rurality.

Conclusions:

Survivors from large towns and those who were adolescents at the time of diagnosis were more likely to receive suboptimal follow-up care compared with survivors from urban areas and those diagnosed younger than thirteen.

Impact:

Observed geographic disparities in survivorship care will inform interventions to promote equitable care for survivors from nonurban areas.
Targeting the Inducible T-cell Costimulator (ICOS) in Patients with Relapsed/Refractory T-follicular Helper Phenotype Peripheral T-cell and Angioimmunoblastic T-cell Lymphoma
Authors: Chavez Julio C. , Foss Francine M. , William Basem M. , Brammer Jonathan E. , Smith Sonali M. , Prica Anca , Zain Jasmine M. , Tuscano Joseph M. , Shah Harsh , Mehta-Shah Neha , Geethakumari Praveen Ramakrishnan , Wang Ben X. , Zantinge Stephanie , Wang Lisa , Zhang Ling , Boutrin Anmarie , Zhao Weiguang , Cheng Lily , Standifer Nathan , Hewitt Lisa , Enowtambong Enowmpey , Shao Weiping , Sharma Shringi , Carlesso Gianluca , Moscow Jeffrey A. , Siu Lillian L.
Published: February 2023

Purpose:

Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models.

Patients and Methods:

We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791).

Results:

Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01–3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29–86) and the median prior lines of therapies was 3 (1–16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%.

Conclusions:

MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.
IMiDs Augment CD3-Bispecific Antibody–Induced CD8+ T-Cell Cytotoxicity and Expansion by Enhancing IL2 Production
Authors: Li Ji , Slaga Dionysos , Johnston Jennifer , Junttila Teemu T.
Published: February 2023

Although CD3-bispecific antibodies have shown promising activity in the treatment of hematological cancers, insufficient T-cell costimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used in treating multiple myeloma, possess pleiotropic antimyeloma properties and have been described to enhance T-cell responses similar to costimulatory signaling and may therefore have synergistic effects when combined with T-cell bispecifics. In this report, we demonstrate that IMiDs substantially enhance tumor cell killing induced by CD3 bispecifics and increase CD8+ T-cell proliferation and expansion. We further show that the beneficial effects of IMiDs on T-cell function and expansion are mediated by enhanced IL2 production by CD4+ T cells. Our studies provide mechanistic insight into the costimulatory properties of IMiDs and support combination treatments with T-cell agonist therapies in a broad spectrum of indications.
The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes
Authors: Li Junjuan , Gao Jingli , Zhang Xinyuan , Cui Liufu , Hou Jinhong , Gao Bixia , Wu Shouling , Lu Chengzhi
Published: February 2023

Objective: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. Methods: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010–2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. Results: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46–0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20–1.67) for proteinuria, 1.24 (1.01–1.51) for kidney function decline, and 1.56 (1.18–2.06) for proteinuria combined with kidney function decline. Conclusions: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.
High In-Hospital Mortality in SARS-CoV-2-Infected Patients with Active Cancer Disease during Omicron Phase of the Pandemic: Insights from the CORONA Germany Study
Authors: Konermann Francis Maren , Gessler Nele , Wohlmuth Peter , Behr Juergen , Feldhege Johannes , Gloeckner Christian , Gunawardene Melanie A. , Herrlinger Klaus R. , Hoelting Thomas , Pape Ulrich-Frank , Reinmuth Niels , Stang Axel , Sheikhzadeh Sara , Arnold Dirk , Wesseler Claas
Published: February 2023

Introduction: SARS-CoV-2 infected patients with cancer have a worse outcome including a significant higher mortality, compared to non-cancer patients. However, limited data are available regarding in-hospital mortality during the Omicron phase of the pandemic. Therefore, the aim of the study was the comparison of mortality in patients with history of cancer and patients with active cancer disease during the different phases of the COVID-19 pandemic, focusing on the current Omicron variant of concern. Methods: We conducted a multicenter, observational, epidemiological cohort study at 45 hospitals in Germany. Until July 20, 2022, all adult hospitalized SARS-CoV-2 positive patients were included. The primary endpoint was in-hospital mortality regarding cancer status (history of cancer and active cancer disease) and SARS-CoV-2 virus type. Results: From March 11, 2020, to July 20, 2022, a total of 27,490 adult SARS-CoV-2 positive patients were included in the study. 2,578 patients (9.4%) had diagnosis of cancer, of whom 1,065 (41.3%) had history of cancer, whereas 1,513 (58.7%) had active cancer disease. Overall 3,749 out of the total of 27,490 patients (13.6%) died during the hospital stay. Patients with active cancer disease had a significantly higher mortality compared to patients without cancer diagnosis, in both phases of the pandemic (wild-type to Delta: OR 1.940 [1.646–2.285]); Omicron: 2.864 [2.354–3.486]). After adjustment to co-variables, SARS-CoV-2 infected patients with active cancer disease had the highest risk for in-hospital mortality compared to the other groups, in both phases of the pandemic. Conclusion: The CORONA Germany study indicates that hospitalized patients with active cancer disease are at high risk of death during a SARS-CoV-2 infection. Mortality of patients with history of cancer improved to nearly the level of non-cancer patients during Omicron phase.
Notas sobre os Sonhos Yanomami
Authors: Limulja Hanna
Published: February 2023

Este artigo pretende compreender alguns aspectos dos sonhos yanomami, como sua relação com a noite e com o pei utupë – imagem vital que constitui a pessoa yanomami. Neste sentido, apresento o cotidiano de uma casa coletiva e os momentos de uma festa intercomunitária reahu. Entre o dia-a-dia e a festa, passo pelo mito de origem da noite e pelas noções de pessoa e cosmos yanomami, buscando demonstrar como a relação entre a noite e a emergência do sonho e do sentimento de saudade supõe uma outra relação mais profunda entre a noite e a manifestação do pei utupë.Também procuro demonstrar como a festa intercomunitária reahu, ocasião em que se realiza os ritos funerários, se constitui como um simulacro do céu dos pore, destino póstumo yanomami, tomando a forma de um grande sonho.
Phosphoproteomics Reveals the Wolframin-Calcium Axis as an Important Pathogenic Signaling Node in Primary Aldosteronism
Authors: Ma Linqiang , Yang Shumin , Yang Yi , Chen Xiangjun , Yang Jun , He Yifan , Cheng Qingfeng , Li Junlong , Kang Bing , Tang Siying , Zhang Aipin , Shu Xiaoyu , Li Xiaoyu , Shen Hang , Jing Ying , Song Ying , Li Qifu , Hu Jinbo
Published: February 2023

Background:

Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown.

Methods:

We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line.

Results:

The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411,
P
<0.001). Among 97 APA cases for validation, a higher expression level of wolframin was associated with a higher plasma aldosterone concentration postcaptopril challenge test and a higher systolic blood pressure. In vitro, the secretion of aldosterone was enhanced by wolframin overexpression, while aldosterone secretion in response to potassium or angiotensin II was inhibited by the knockdown of wolframin. Further in vivo and in vitro data demonstrated the wolframin-calcium axis as an important regulator of CYP11B2 expression and aldosterone production.

Conclusions:

Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.
Formal Verification of Deep Brain Stimulation Controllers for Parkinson's Disease Treatment
Authors: Nawaz Arooj , Hasan Osman , Jabeen Shaista
Published: February 2023

Deep brain stimulation (DBS) is a widely accepted treatment for the Parkinson's disease (PD). Traditionally, it is done in an open-loop manner, where stimulation is always ON, irrespective of the patient needs. As a consequence, patients can feel some side effects due to the continuous high-frequency stimulation. Closed-loop DBS can address this problem as it allows adjusting stimulation according to the patient need. The selection of open- or closed-loop DBS and an optimal algorithm for closed-loop DBS are some of the main challenges in DBS controller design, and typically the decision is made through sampling based simulations. In this letter, we used model checking, a formal verification technique used to exhaustively explore the complete state space of a system, for analyzing DBS controllers. We analyze the timed automata of the open-loop and closed-loop DBS controllers in response to the basal ganglia (BG) model. Furthermore, we present a formal verification approach for the closed-loop DBS controllers using timed computation tree logic (TCTL) properties, that is, safety, liveness (the property that under certain conditions, some event will eventually occur), and deadlock freeness. We show that the closed-loop DBS significantly outperforms existing open-loop DBS controllers in terms of energy efficiency. Moreover, we formally analyze the closed-loop DBS for energy efficiency and time behavior with two algorithms, the constant update algorithm and the error prediction update algorithm. Our results demonstrate that the closed-loop DBS running the error prediction update algorithm is efficient in terms of time and energy as compared to the constant update algorithm.
Macroscopic Gamma Oscillation With Bursting Neuron Model Under Stochastic Fluctuation
Authors: Yoshikai Yuto , Zheng Tianyi , Kotani Kiyoshi , Jimbo Yasuhiko
Published: February 2023

Gamma oscillations are thought to play a role in information processing in the brain. Bursting neurons, which exhibit periodic clusters of spiking activity, are a type of neuron that are thought to contribute largely to gamma oscillations. However, little is known about how the properties of bursting neurons affect the emergence of gamma oscillation, its waveforms, and its synchronized characteristics, especially when subjected to stochastic fluctuations. In this study, we proposed a bursting neuron model that can analyze the bursting ratio and the phase response function. Then we theoretically analyzed the neuronal population dynamics composed of bursting excitatory neurons, mixed with inhibitory neurons. The bifurcation analysis of the equivalent Fokker-Planck equation exhibits three types of gamma oscillations of unimodal firing, bimodal firing in the inhibitory population, and bimodal firing in the excitatory population under different interaction strengths. The analyses of the macroscopic phase response function by the adjoint method of the Fokker-Planck equation revealed that the inhibitory doublet facilitates synchronization of the high-frequency oscillations. When we keep the strength of interactions constant, decreasing the bursting ratio of the individual neurons increases the relative high-gamma component of the populational phase-coupling functions. This also improves the ability of the neuronal population model to synchronize with faster oscillatory input. The analytical frameworks in this study provide insight into nontrivial dynamics of the population of bursting neurons, which further suggest that bursting neurons have an important role in rhythmic activities.
Weather Types and Their Influence on PM10 and O3 Urban Concentrations in the Cergy-Pontoise Conurbation
Authors: Lagmiri Souad , Dahech Salem
Published: February 2023

Daily atmospheric concentrations of the pollutants PM10 and O3 vary according to weather types. This study aims to identify the weather patterns associated with PM10 and O3 pollution episodes from 2009 to 2020. Episodes characterized by exceedance of World Health Organization standards were identified, and their duration and persistence were studied. The results show that air pollution days are associated with three atmospheric patterns for PM10 and four for O3. The dominant weather pattern corresponds to an anticyclonic situation in central and Eastern Europe with a ridge of high pressure over France at the surface and 500-hPa geopotential height. For PM10, the persistent high-concentration sequences were found to be associated with a thermal inversion constraining the vertical dispersion of pollutants. For O3, the four weather types responsible for ozone pollution all have a higher occurrence in summer. The highest percentage (46% of days) is associated with the presence of a ground-level barometric marsh (an area of the atmosphere between two weather systems where the pressure varies slightly but is slightly low) and a ridge at 500 hPa (weather type T1). Similarly, thermal inversions and thermal winds cause pollution to persist beyond 8 consecutive days.

Significance Statement

Air quality is not only influenced by ground-level emissions, but also by complex meteorological processes that can contribute to pollutant accumulations. The importance of this research is that the prediction of these processes helps to prevent the development of extreme concentrations near the surface. The results of this study provide a better understanding of how characteristic weather patterns in the Cergy-Pontoise conurbation impact PM10 and O3 pollutant levels. These impacts are expressed by the intensity and frequency of pollution episodes.
Stem Cell Therapies for Intracerebral Hemorrhage: Review of Preclinical and Clinical Studies
Authors: Takamiya Soichiro , Kawabori Masahito , Fujimura Miki
Published: February 2023

Despite recent developments in the treatments for ischemic stroke, such as tissue plasminogen activator (t-PA) and thrombectomy, effective therapies for intracerebral hemorrhage (ICH) remain scarce. Stem cell therapies have attracted considerable attention owing to their potential neuro-regenerative ability; preclinical and clinical studies have been conducted to explore strategies for achieving functional recovery following ICH. In this review, we summarize the findings of preclinical studies on stem cell therapies of ICH, with a focus on different animal models, stem cell sources, transplantation methods, and their potential mechanisms of action. We also provide an overview of data from clinical trials to discuss the current status and future perspectives. Understanding the effectiveness and limitations of stem cell therapy and the future prospects could expand the applications of this novel therapeutic approach for ICH.
Bring up the bodies: international order, empire, and re-thinking the Great War (1914–1918) from below
Authors: Sabaratnam Meera
Published: February 2023

What does international order look like when analysed from its margins? Such a question is the obvious consequence of efforts within International Relations (IR) to take empire, colonialism and hierarchy more seriously. This article addresses this question by examining one of IR’s most important touchstones – the Great War – through the experiences of peoples in southeast Africa. It argues that to do this, we should use the methodological approaches of histories ‘from below’ and contrapuntal analysis. When looking at the Great War from the vantage point of southeast Africa (contemporary Mozambique), the key patterns of interaction organising the international look different to those emphasised in traditional accounts of international order and hierarchy. Notable features are the significant continuities and intersections between structures of war and colonialism, the racialisation of death and suffering, the effects of white imperial prestige as a strategic preoccupation and the deep historical roots of anti-colonial resistance. Reading upwards and contrapuntally from these histories, the paper argues for a redescription of international order as reflecting not predominantly a balance of power or a normative framework for the organisation of authority, but a dynamic matrix of structural violence. Reading order from below in this way helps us better capture how the international is implicated in the production and reproduction of everyday life for many people, as well as in more dramatic political transformations such as those generated by experiences of war and resistance to colonialism.
Implantable Shock Absorber Provides Superior Pain Relief and Functional Improvement Compared With High Tibial Osteotomy in Patients with Mild-to-Moderate Medial Knee Osteoarthritis: A 2-Year Report
Authors: Diduch David R. , Crawford Dennis C. , Ranawat Anil S. , Victor Jan , Flanigan David C.
Published: February 2023

Objective

Up to 10 million Americans below the age of 65 years have symptomatic knee osteoarthritis (OA) and may not yet be candidates for arthroplasty. In response, a subcutaneous implantable shock absorber (ISA) that unloads the knee has been developed. The safety and effectiveness of ISA treatment were compared against a surgical unloading control, high tibial osteotomy (HTO).

Design

This was a prospective open-label cohort study with a historical control arm. Subjects underwent ISA placement or HTO. The primary endpoint was a composite variable combining pain, function, specific adverse events, integrity of implant or hardware, and conversion to subsequent surgery. Pain and function outcomes (Western Ontario and McMaster Universities Arthritis Index scores) were assessed through 24 months. Adverse events were tracked.

Results

The primary endpoint demonstrated superiority of the ISA arm versus the HTO arm, with 85.6% of ISA subjects meeting all criteria compared with 65.5% of HTO subjects. In addition, all 5 secondary endpoints showed superiority of ISA over HTO. At 24 months, the proportions of subjects considered responders were 95.8% (ISA) versus 87.9% (HTO) for pain and 91.7% (ISA) versus 81.3% (HTO) for function. The ISA procedure was well tolerated, with 13.4 days to full weightbearing status versus 58.0 days for the HTO arm.

Conclusions

Treatment with an ISA demonstrated noninferiority and superiority versus treatment with HTO in subjects aged 25-65 years who had OA of the medial knee. Treatment with ISA has high clinical benefit and is durable through at least 24 months.