bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic glycolysis enhances HBx-initiated hepatocellular carcinogenesis via NF-κBp65/HK2 signalling
Authors: Chen Lingjun , Lin Xianyi , Lei Yiming , Xu Xuan , Zhou Qi , Chen Yan , Liu Huiling , Jiang Jie , Yang Yidong , Zheng Fengping , Wu Bin
Published: November 2022

Background

Aerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined.

Methods

A dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx+/+/NF-κBp65f/f and HBx+/+/NF-κBp65Δhepa spontaneous HCC mouse model was used to investigate the effects of NF-κBp65 on HBx-initiated hepatocarcinogenesis. Whether and how NF-κBp65 is involved in aerobic glycolysis induced by HBx in hepatocellular carcinogenesis were analysed in vitro and in vivo.

Results

NF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis.

Conclusion

The data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related HCC.
Investigation of reversible histone acetylation and dynamics in gene expression regulation using 3D liver spheroid model
Authors: Stransky Stephanie , Cutler Ronald , Aguilan Jennifer , Nieves Edward , Sidoli Simone
Published: November 2022

Background

Three-dimensional (3D) cell culture has emerged as an alternative approach to 2D flat culture to model more accurately the phenotype of solid tissue in laboratories. Culturing cells in 3D more precisely recapitulates physiological conditions of tissues, as these cells reduce activities related to proliferation, focusing their energy consumption toward metabolism and homeostasis.

Results

Here, we demonstrate that 3D liver spheroids are a suitable system to model chromatin dynamics and response to epigenetics inhibitors. To delay necrotic tissue formation despite proliferation arrest, we utilize rotating bioreactors that apply active media diffusion and low shearing forces. We demonstrate that the proteome and the metabolome of our model resemble typical liver functions. We prove that spheroids respond to sodium butyrate (NaBut) treatment, an inhibitor of histone deacetylases (HDACi), by upregulating histone acetylation and transcriptional activation. As expected, NaBut treatment impaired specific cellular functions, including the energy metabolism. More importantly, we demonstrate that spheroids reestablish their original proteome and transcriptome, including pre-treatment levels of histone acetylation, metabolism, and protein expression once the standard culture condition is restored after treatment. Given the slow replication rate (> 40 days) of cells in 3D spheroids, our model enables to monitor the recovery of approximately the same cells that underwent treatment, demonstrating that NaBut does not have long-lasting effects on histone acetylation and gene expression. These results suggest that our model system can be used to quantify molecular memory on chromatin.

Conclusion

Together, we established an innovative cell culture system that can be used to model anomalously decondensing chromatin in physiological cell growth and rule out epigenetics inheritance if cells recover the original phenotype after treatment. The transient epigenetics effects demonstrated here highlight the relevance of using a 3D culture model system that could be very useful in studies requiring long-term drug treatment conditions that would not be possible using a 2D cell monolayer system.
Existence of common fixed point in Kannan F-contractive mappings in quasi-partial b-metric space with an application
Authors: Gautam Pragati , Kumar Santosh , Verma Swapnil , Gupta Gauri
Published: November 2022

The purpose of this study is to demonstrate results on fixed point theory in quasi-partial b-metric space recognizing a new type of mapping, which is a blend of F-contraction and Kannan contraction, and to establish the fixed point results in F-expanding type mappings. Additionally, the obtained results are the application of the contractive mappings to functional equations. Furthermore, Mathematica software is used to demonstrate the 3D shapes of the examples discussed here.
Relationship between serum homocysteine, fibrinogen, lipoprotein-a level, and peripheral arterial disease: a dose–response meta-analysis
Authors: Wang Hecheng , Wu Pengpeng , Jiang Deying , Zhang Hao , Zhang Jian , Zong Yu , Han Yanshuo
Published: November 2022

Aim

At present, the relationship between serum homocysteine (Hcy), fibrinogen (FIB), lipoprotein-a (LPa), and PAD is uncertain, and there has been no meta-analysis to establish the dose–response relationship between their exposure levels and PAD.

Methods and results

Relevant literature published in PubMed, Embase, and Web of Science was retrieved. The robust error meta-regression method was used to assess the linear and non-linear dose–response relationship between exposure level and PAD risk. A total of 68 articles, involving 565,209 participants, were included. Combined with continuous variables, the serum Hcy, FIB, and LPa levels of PAD patients were significantly higher than those of healthy individuals. The odds ratios (ORs) of PAD for individuals with high Hcy, FIB, and LPa levels compared with those with low levels were 1.47, 1.14, and 1.76, respectively. The study also showed that circulating Hcy, FIB, and LPa were significantly elevated in patients with PAD compared with controls. The level of Hcy and the risk of PAD presented a U-shaped distribution. The nonlinear dose–response model showed that each 1 μmol/L increase in serum Hcy increased the risk of PAD by 7%. Similarly, for each 10 mg/dL FIB and 10 mg/dL LPa increases, the risk of PAD increased by 3% and 6%, respectively.

Conclusions

This meta-analysis provided evidence that elevated Hcy, PIB, and LPa levels may increase the risk of PAD, and the risk of PAD increases with the increase in serum exposure within a certain range. By controlling Hcy level, the incidence of PAD may be reduced to control the PAD growing epidemic.

Trial registration number: PROSPERO (CRD42021250501),https://www.crd.york.ac.uk/prospero/
Plasma S-Klotho level affects the risk of hyperuricemia in the middle-aged and elderly people
Authors: Xie Haitao , Li Ning , Zhou Guowei , Liu Qian , Wang Haiyan , Han Jie , Shen Le , Yu Peng , Chen Jiandong , Chen Xiaohu
Published: November 2022

Background

Soluble Klotho (S-Klotho) is an anti-aging protein mainly secreted by the kidneys. Hyperuricemia is prevalent among middle-aged and elderly individuals, which affects the development of various chronic diseases. However, there are relatively few studies investigating the association between plasma S-Klotho levels and hyperuricemia in middle-aged and elderly individuals. This study sought to clarify the relationship between S-Klotho and the risk of hyperuricemia in middle-aged and elderly people.

Methods

During 2007–2016, a total of 50,588 people participated in the National Health and Nutrition Examination Survey. Finally, 12,441 middle-aged and elderly people (aged 40–79) completed the soluble Klotho tests and had obtained complete data. S-Klotho was detected by ELISA kit, and the relationship between S-Klotho and hyperuricemia was assessed by multiple logistic regression. Hyperuricemia is defined as serum uric acid levels higher than or equal to 420 mmol/l in men and 360 mmol/l in women.

Results

In the middle-aged and elderly, plasma S-Klotho levels were negatively correlated with hyperuricemia, and there was a saturation effect. The inflection point of S-Klotho was 927.8 pg/ml (logarithmic likelihood ratio test = 0.002). When plasma S-Klotho < 927.8 pg/ml, the prevalence of hyperuricemia in middle-aged and elderly individuals with higher levels of S-Klotho decreased by 25.6% compared with those with low levels of S-Klotho [Q4 vs Q1, OR: 0.744, 95%CI: (0.634, 0.874), P < 0.001]; In different age groups, S-Klotho had a significantly greater effect on hyperuricemia in middle-aged people [age: 40–65 years, Q4 vs Q1, OR (95%CI): 0.69 (0.58, 0.82), P < 0.001; Age > 65 years: Q4 vs Q1, OR (95%CI): 0.72 (0.56, 0.92), P = 0.008)].When the level of S-Klotho was higher, the risk of hyperuricemia in men was lower than that in women [male: Q4 vs Q1, OR (95%CI): 0.67 (0.56, 0.81), P < 0.001; female: Q4 vs Q1 (95%CI):0.72 (0.58, 0.88), P < 0.001].

Conclusions

In middle-aged and elderly individuals, plasma S-Klotho levels were inversely correlated with hyperuricemia, with a saturation effect. Given the limitations of the research results, the underlying mechanism between S-Klotho and hyperuricemia should be further explored.
Tumor microenvironment-associated lactate metabolism regulates the prognosis and precise checkpoint immunotherapy outcomes of patients with lung adenocarcinoma
Authors: Qiu Song , Wang Ying , Rao Hui , Que Qiuyang , Wu Yanyang , Zhu Rui , Feng Xiaofei , Chi Jun , Lai Weiling , Sun Yihang , Xiao Qi , Shi Huaqiu , Xiang Yi
Published: November 2022

Background

Despite the wide clinical application of checkpoint inhibitor immunotherapy in lung adenocarcinoma, its limited benefit to patients remains puzzling to researchers. One of the mechanisms of immunotherapy resistance may be the dysregulation of lactate metabolism in the immunosuppressive tumor microenvironment (TME), which can inhibit dendritic cell maturation and prevent T-cell invasion into tumors. However, the key genes related to lactate metabolism and their influence on the immunotherapeutic effects in lung adenocarcinoma have not yet been investigated in depth.

Methods

In this study, we first surveyed the dysregulated expression of genes related to lactate metabolism in lung adenocarcinoma and then characterized their biological functions. Using machine learning methods, we constructed a lactate-associated gene signature in The Cancer Genome Atlas cohort and validated its effectiveness in predicting the prognosis and immunotherapy outcomes of patients in the Gene Expression Omnibus cohorts.

Results

A 7-gene signature based on the metabolomics related to lactate metabolism was found to be associated with multiple important clinical features of cancer and was an independent prognostic factor.

Conclusions

These results suggest that rather than being simply a metabolic byproduct of glycolysis, lactate in the TME can affect immunotherapy outcomes. Therefore, the mechanism underlying this effect of lactate is worthy of further study.
Structural Behavior of a Laterally Restrained Precast Reinforced Concrete Arch Deck Under Punching Shear Loading
Authors: Yang Dal-Hun , Choi Seung-Jai , Kim Sung-Jae , Kim Jang-Ho Jay
Published: November 2022

In the construction of concrete bridges, the lighter dead load of decks can significantly reduce the number or size of substructure members, such as girders, piers and foundations. Although, the arch decks (ADs) ensure superior load carrying capacity and can have longer span length than flat decks (FDs), relatively minute number of studies was performed on longer span decks manufactured as arch shape to maximize the performance. In the previous study, a precast reinforced concrete (RC) AD with enhanced width of 2.5 m was developed. In this study, the behavior of precast RC AD under punching shear load was studied. Three real-scale AD specimens were tested and analyzed to understand its performance under punching shear loading. Different sizes of the ADs were manufactured to evaluate the punching shear capacity. The punching shear capacity and failure mode were obtained from the test, and the results were then compared to various design provisions. Finite Element Analyses (FEAs) were conducted to validate the experiment results and to verify the arching action of the AD with various thicknesses. The study results clearly verified that the AD had a higher or similar load-carrying capacity than the FD due to the arching action caused by the lateral restraint and arch shape, despite of thinner thickness of AD than FD. An analytical and prediction model for the punching shear behavior of ADs was developed and calibrated. The resulting models are described in a code-friendly formulation.
Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Authors: Westfall Jesse J. , Schwind Wesley N. , Sran Sahibjot , Navarro Jason B. , Leonard Jeffrey , Pindrik Jonathan A. , Pierson Christopher R. , Boué Daniel R. , Koboldt Daniel C. , Ostendorf Adam P. , Wilson Richard K. , Mardis Elaine R. , Miller Katherine E. , Bedrosian Tracy A.
Published: November 2022

Rasmussen encephalitis (RE) is a rare childhood neurological disease characterized by progressive unilateral loss of function, hemispheric atrophy and drug-resistant epilepsy. Affected brain tissue shows signs of infiltrating cytotoxic T-cells, microglial activation, and neuronal death, implicating an inflammatory disease process. Recent studies have identified molecular correlates of inflammation in RE, but cell-type-specific mechanisms remain unclear. We used single-nucleus RNA-sequencing (snRNA-seq) to assess gene expression across multiple cell types in brain tissue resected from two children with RE. We found transcriptionally distinct microglial populations enriched in RE compared to two age-matched individuals with unaffected brain tissue and two individuals with Type I focal cortical dysplasia (FCD). Specifically, microglia in RE tissues demonstrated increased expression of genes associated with cytokine signaling, interferon-mediated pathways, and T-cell activation. We extended these findings using spatial proteomic analysis of tissue from four surgical resections to examine expression profiles of microglia within their pathological context. Microglia that were spatially aggregated into nodules had increased expression of dynamic immune regulatory markers (PD-L1, CD14, CD11c), T-cell activation markers (CD40, CD80) and were physically located near distinct CD4+ and CD8+ lymphocyte populations. These findings help elucidate the complex immune microenvironment of RE.
Early evidence on the mental health of Ukrainian civilian and professional combatants during the Russian invasion
Authors: Pavlova Iuliia , Graf-Vlachy Lorenz , Petrytsa Petro , Wang Senhu , Zhang Stephen X.
Published: November 2022

Background

The ongoing Russian invasion of Ukraine has led many Ukrainians to fight for their country, either in the regular army or as civilian members of voluntary territorial defense forces. There is, however, a dearth of knowledge on the mental health of combatants in this conflict. Prior research on the mental health of combatants is unlikely to translate to the situation at hand because such research is focused on combatants fighting abroad and neglects civilian combatants.

Methods

This study provides the first attempt to investigate the mental health of Ukrainian combatants in the regular army and voluntary territorial defense forces by analyzing the prevalence rates of common mental health issues, as well as their demographic and socioeconomic predictors.

Results

Between March 19 and 31, 2022, the initial period of Russia’s invasion of Ukraine, a sample of 178 Ukrainian combatants (104 in the regular army and 74 civilian combatants) participated in a survey on symptoms of anxiety (GAD-2), depression (PHQ-2), and insomnia (ISI).

Conclusions

A sizable portion of Ukrainian combatants reached cut-off levels for clinical symptoms of anxiety (44·4%), depression (43·3%), and insomnia (12·4%). Importantly, the mental health of Ukrainian combatants varied between professional soldiers and civilian combatants, as well as by gender, marital status, by whether or not they were located in Russian-occupied/active-combat areas, and dependent on whether they were personally involved in combat. This study provides early evidence on the mental health of Ukrainian combatants, pointing to their urgent need for mental health assistance in the ongoing war.
Painlevé analysis for a new (3 +1 )-dimensional KP equation: Multiple-soliton and lump solutions
Authors: Wazwaz Abdul-Majid , Alatawi Naisa S. , Albalawi Wedad , El-Tantawy S. A.
Published: November 2022

The current work proposes a new (3 + 1)-dimensional Kadomtsev-Petviashvili (KP) equation ((3 + 1)-KPE). We verify the integrability of this equation using the Painlevé analysis (PA). The bilinear formula is applied to the extended KPE to explore multiple-soliton solutions. Also, we formally establish a class of lump solutions using distinct values of the parameters.
Antiresorptive Medication Use Is not Associated With Acute Cardiovascular Risk: An Observational Study
Authors: Bliuc Dana , Tran Thach , Chen Weiwen , Alarkawi Dunia , Alajlouni Dima A , Blyth Fiona , March Lyn , Blank Robert D , Center Jacqueline R
Published: November 2022

Context

Bisphosphonates have been reported to be cardioprotective in some, but not all, studies. It is unknown whether denosumab (Dmab) use protects against cardiovascular events (CVEs).

Objective

To determine whether oral bisphosphonate (oBP) or Dmab use is associated with CVEs in persons with incident fracture.

Methods

Participants with an incident minimal trauma fracture from the Sax Institute’s 45 and Up Study, a population-based cohort from NSW, Australia, were followed between 2005/2009 and 2017. Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection [APDC]) by the Centre for Health Record Linkage). Medicare Benefit Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data sets were provided by Services Australia. Data was stored in a secure computing environment (Secure Unified Research Environment). Fractures, CVEs, and comorbidities were identified from the APDC and oBP and Dmab medication from the PBS. oBP and Dmab users were matched to never users (NoRx) by propensity scores. The main outcome measures were association between oBP and Dmab with CVE (acute myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemic attack) and were determined using a stratified Cox's proportional hazards model.

Results

There were 880 pairs of oBP and NoRx (616 women) and 770 pairs of Dmab and NoRx (615 women) followed for ∼4.3 years. CVE risk was similar for oBP and NoRx Hazard Ratios (HR) women, 0.88 [95% CI 0.65-1.18]; men, 1.07 [95% CI 0.72-1.57]). Similar findings were obtained for Dmab (Hazard Ratios (HR) women, 1.08 [95% CI 0.78-1.50]; men, 1.55 [95% CI 0.96-2.48]).

Conclusion

oBP and Dmab use was not associated with CVEs.
A Reduced Pancreatic Polypeptide Response is Associated With New-onset Pancreatogenic Diabetes Versus Type 2 Diabetes
Authors: Hart Phil A , Kudva Yogish C , Yadav Dhiraj , Andersen Dana K , Li Yisheng , Toledo Frederico G S , Wang Fuchenchu , Bellin Melena D , Bradley David , Brand Randall E , Cusi Kenneth , Fisher William , Mather Kieren , Park Walter G , Saeed Zeb , Considine Robert V , Graham Sarah C , Rinaudo Jo Ann , Serrano Jose , Goodarzi Mark O
Published: November 2022

Purpose

Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM).

Methods

Subjects with new-onset DM (<3 years’ duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance while adjusting for age, sex, and body mass index.

Results

The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median, 1.869) and CP-DM (1.813) groups compared with T2DM (3.283; P < 0.01 for both comparisons). The area under the curve of PP concentration was significantly lower in both the PDAC-DM and CP-DM groups than in T2DM regardless of the interval used for calculation and remained significant after adjustments.

Conclusions

Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).
Cotton, Whiteness, and Other Poisons
Authors: Williams Brian , Porter Jayson Maurice
Published: November 2022

This article examines how racial capitalism has shaped the ecological and technological dynamics of cotton production in the United States South. Cotton’s destructive dependence on chemicals and on the extraction of lives and resources was animated and enabled by anti-Blackness, which sanctioned a systematic hostility to life that encoded environmental violence in plantation landscapes from the seed to the root. Agrotechnological notions of scientific progress and development conceived places, plants, and Black people as interchangeable parts. Tracing these trajectories during slavery and after abolition, the article focuses on two dynamics: the use of chemicals to augment soil fertility and manage cotton’s ecologies, and the deployment of chemicals to protect cotton monocultures. In both instances, the manipulations of cotton’s ecologies and biophysical properties helped maintain plantation profitability and dominance in the face of conjoined crises of political-ecological and racial control. Racialized conceptions of chemical-scientific “innovation,” relations of indebtedness, and notions of threat also siphoned capital gains from Black workers and communities. By converting waste products into fertilizers and poisons, planters and industrialists continued to render Black communities, their labor, and their land as fungible but necessary components in the industrialization of racial capitalism.
“These Lusting, Incestuous, Perverse Creatures”
Authors: Jacobs Joela
Published: November 2022

This article traces the emergence of and shifts in ideas about plant sexuality in European literature from the late seventeenth century to the present, with a particular focus on influential British and a few less well-known German texts. Positioned as a specifically phytopoetic history of plants and sexuality, it demonstrates with the help of literature how plants have been shaping human culture—in this context, the sociocultural norms and understandings of sex, gender, and sexuality. Moving from vegetal visions of virtuous, virginal women-plants and their corruption by pollen and “plant prostitutes” to concerns about “crimes against nature” and the persecution of male same-sex desire, this history ultimately arrives at queer reproduction and pleasure as a collective endeavor.
Theorizing the Gay Frog
Authors: Boast Hannah
Published: November 2022

The gay frog has taken on a surprisingly prominent role in contemporary environmental culture. Primarily associated with American shock jock Alex Jones and the so-called alt-right, fears of frogs being turned gay by hormones in water have nevertheless entered the mainstream, while gay frog memes are shared online by users from across the political spectrum. This article offers a genealogy of the gay frog, situating this recent moment in the longer history of “sex panics” over gay animals described by queer ecologists, and in the context of an ongoing backlash against feminism and trans liberation. It argues that the potency of the gay frog as alt-right symbol derives from the capacity of the frog to instantiate racialized and sexualized anxieties about border crossings. By examining the role of humor in gay frog clips and memes, this article shows how liberal mockery of Jones has inadvertently mainstreamed far-right beliefs and served to consolidate alt-right notions of victimhood. In spite of this, it argues that the comic potential of the gay frog holds promise for queer ecologists seeking to think differently about sex and nature.
Toxic Erotics and Bad Ecosex at Windermere Basin
Authors: Neimanis Astrida
Published: November 2022

How do settler colonialism, control of women’s and differently gendered bodies, sex, industry, pollution—but also pleasure, love, care, desire, bodily autonomy, and survival—cleave together and apart in the inland wetland of Windermere Basin park? Starting with this question, this article explores my own attraction to this tiny place in postindustrial and settler colonial Hamilton, Ontario. I am curious about what it can teach us about the complex entanglements of these things, and the toxic desires that are both enabled and foreclosed by the relations that gather here. In the first section, I briefly rehearse the basin’s toxic history and, guided by Audre Lorde’s definition of erotics and Catriona Sandilands formative work on queer ecologies, my own desirous attachments to the life it nonetheless sustains. The next section reveals how, in the context of settler colonialism and climate catastrophe, these erotics are queerly tangled in questions of more-than-human gender, sex, and reproduction, too, in ways that invite a capacious and multivalent understanding of reproductive justice. The final section examines the performance art of white settler ecosexuals Annie Sprinkle and Beth Stephens, but sets this alongside a performance by Vanessa Dion Fletcher at Windermere, in order to insist on a version of ecosexual erotics that, while joyous, remains imbricated in fraught histories, complicity, and an inalienable attention to what Michif scholar Max Liboiron parses as “differences and obligations.” Taking a cue from settler feminist artist and scholar Lindsay Kelley, I refer to this as “bad ecosex.” In its refusal of purity, bad ecosex holds the trouble of contemporary ecological relations together with the pleasurable power of erotics to build a politics of change grounded in feeling deeply.
Tumor Growth Rate in Spinal Giant Cell Tumors of Bone and Association With the Immune Microenvironment and Denosumab Treatment Responsiveness: A Multicenter Study
Authors: Zheng Bo-Wen , Zheng Bo-Yv , Niu Hua-Qing , Yang Yi-Fan , Zhu Guo-Qiang , Li Jing , Zhang Tao-Lan , Zou Ming-Xiang
Published: November 2022

BACKGROUND:

Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB).

OBJECTIVE:

To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB.

METHODS:

A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness.

RESULTS:

High TGR predicted both poor progression-free survival and overall survival (both P < .001). In addition, TGR was associated with postoperative neurological dysfunction (P < .001), Enneking staging (P = .016), denosumab treatment responsiveness (P = .035), and the number of CD3+ (P < .001), PD-1+ (P = .009), PD-L1+ (P < .001), and FoxP3+ tumor-infiltrating lymphocyte (P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB.

CONCLUSION:

These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients.
The ULK complex–LRRK1 axis regulates Parkin-mediated mitophagy via Rab7 Ser-72 phosphorylation
Authors: Fujita Keitaro , Kedashiro Shin , Yagi Takuya , Hisamoto Naoki , Matsumoto Kunihiro , Hanafusa Hiroshi
Published: November 2022

Mitophagy, a type of selective autophagy, specifically targets damaged mitochondria. The ULK complex regulates Parkin-mediated mitophagy, but the mechanism through which the ULK complex initiates mitophagosome formation remains unknown. The Rab7 GTPase (herein referring to Rab7a) is a key initiator of mitophagosome formation, and Ser-72 phosphorylation of Rab7 is important for this process. We have previously identified LRRK1 as a protein kinase responsible for Rab7 Ser-72 phosphorylation. In this study, we investigated the role of LRRK1 in mitophagy. We showed that LRRK1 functions downstream of ULK1 and ULK2 in Parkin-mediated mitophagy. Furthermore, we demonstrated that ectopic targeting of active LRRK1 to mitochondria is sufficient to induce the Ser-72 phosphorylation of Rab7, circumventing the requirement for ATG13, a component of the ULK complex. Thus, the ULK complex recruits LRRK1 to mitochondria by interacting with ATG13 to initiate mitophagosome formation. This study highlights the crucial role of the ULK complex–LRRK1 axis in the regulation of Parkin-mediated mitophagy.
The time course of behavioural phase change in the Central American locust Schistocerca piceifrons
Authors: Foquet Bert , Little Drew W. , Medina-Durán Jorge Humberto , Song Hojun
Published: November 2022

Locusts exhibit an extreme form of phenotypic plasticity and can exist as two alternative phenotypes, known as solitarious and gregarious phases. These phases, which can transform from one to another depending on local population density, show distinctly different behavioural characteristics. The proximate mechanisms of behavioural phase polyphenism have been well studied in the desert locust Schistocerca gregaria and the migratory locust Locusta migratoria, and what is known in these species is often treated as a general feature of locusts. However, this approach might be flawed, given that there are approximately 20 locust species that have independently evolved phase polyphenism. Using the Central American locust Schistocerca piceifrons as a study system, we characterised the time course of behavioural phase change using standard locust behavioural assays, using both a logistic regression-based model and analyses of separate behavioural variables. We found that for nymphs of S. piceifrons, solitarisation was a relatively fast, two-step process, but that gregarisation was a much slower process. Additionally, the density of the gregarisation treatment seemed to have no effect on the rate of phase change. These data are at odds with what we know about the time course of behavioural phase change in S. gregaria, suggesting that the mechanisms of locust phase polyphenism in these two species are different and may not be phylogenetically constrained. Our study represents the most in-depth study of behavioural gregarisation and solitarisation in locusts to date.
Wprowadzenie do Midrasza Bereszit Rabba na przykładzie rabinicznej historii Abrahama i Sary
Authors: Kaczorowski Walter Richard
Published: November 2022

INTRODUCTION TO MIDRASH BERESHIT RABBAH BASED ON THE RABBINICAL INTERPRETATION OF THE STORY OF ABRAHAM AND SARAH The subject of this study is a critical overview of the rabbinical interpretation of the Hebrew Bible in the part regarding the story of Abraham and Sarah with use of the examples from Midrash Bereshit Rabbah (“MBR”), which include a commentary to the Genesis / Sefer Bereshit. The author, following an extensive research and detailed analysis, endeavours to respond the ensuant questions: what methods of interpretation were used in MBR, to what extent may those methods be considered similar to the rabbinical methods of biblical interpretation and how rabbinical interpretation corresponds to further methods of exegesis and interpretation regarding Peshat and Derash. The book also presents a theological role of Abraham in the Midrash, and discusses its theology in the part, which refers to the story of Abraham and Sarah. The study was divided into 5 parts: (1) From Torah to Midrashim; (2) Introduction to MBR and other midrashic literature; (3) Commentary to MBR, including the story of Abraham and Sarah; (4) Methods of rabbinical interpretation on the example of MBR; (5) Theology of MBR to the Book of Bereshit with respect to patriarch Abraham.
Kreowanie negatywnego obrazu instytucji religijnych w polskojęzycznej propagandzie radzieckiej okresu międzywojennego (na podstawie czasopisma „Bezbożnik Wojujący”)
Authors: Ławrynow Daria
Published: November 2022

CREATING A NEGATIVE IMAGE OF RELIGIOUS INSTITUTIONS IN POLISH-LANGUAGE SOVIET PROPAGANDAIN THE INTERWAR PERIOD (BASED ON THE MAGAZINE “BEZBOŻNIK WOJUJĄCY” [“MILITANT ATHEIST”])

The main issue discussed in this article is the negative image of religious institutions present in Polishlanguage propaganda in the interwar period. The research is based on the analysis of Polish-language Soviet magazine “Bezbożnik Wojujący”. It was published in USSR between 1929 and 1935. “Bezbożnik Wojujący” had some language variants (for example Georgian, Latvian, Russian, Ukrainian) and its main goal was anti-religious atheist propaganda among national minority communities. The magazine presented religious institutions as obscurantist, hypocritical, aimed at sabotage, and anti-Soviet. The objects of pejorativization included the Orthodox, Roman and Greek Catholic Churches, but also Protestants, members of locals sects, and certain Church initiatives such as the third order and the rosary circles. In the Soviet propaganda, which was based on Leninism, all religions were alien and hostile for working classes.
Gerd Hentšelʹ: Regionalʹnye osobennosti ispolʹzovaniâ ukrainsko-russkoj smešannoj reči (suržika) i vliânie dialektov: pristavki i predlogi vid / ot
Authors: Палинська Олеся , Хентшель Герд
Published: November 2022

REGIONAL PROPERTIES IN UKRAINIAN-RUSSIAN MIXED SPEECH (SURZHYK) AND THE INFLUENCE OF DIALECTS: PREFIXES AND PREPOSITIONS VID / OT

Ukrainian surzhyk is a form of mixed Ukrainian-Russian code influenced not only by standard dialects of Ukrainian and Russian, but also by Ukrainian dialects. In the analyses of the kind and intensity of the influence of Ukrainian or Russian on surzhyk, particularly problematic are the cases in which a given structural phenomenon occurs in some Ukrainian dialects and in the standard language, while in other dialects it is identical or very similar to the phenomenon occurring in Russian. Examples of such language units include the prefixes and vid / ot prepositions discussed in this article. Based on the corpus material, in this study the authors used quantitative methods to present the possibility to differentiate the basic tendencies that determine the way and scope of dialectal influences and both standard languages (Ukrainian and Russian). The main conclusion from the analyses of this linguistic phenomenon is the observation according to which a variant originating from the standard Ukrainian language is only preserved in those areas of using surzhyk in which only such variant occurs. In the regions in which both variants occur dialectally, or only the variant identical to Russian occurs, the latter is preserved. In general, it means that in Ukrainian-language areas variants of synonymical forms are reduced in the process of dialect-levelling in surzhyk as a mezolect.
Fulminans Purpura due to Morganella morganii
Authors: Guerra Mariana , Marado Daniela
Published: November 2022

Purpura fulminans (PF) is a dermatological manifestation of a life-threatening condition characterized by disseminated intravascular coagulation and endovascular thrombosis. The idiopathic/infectious form is the most common and usually associated with infection by Neisseria meningitidis or Streptococcus pneumoniae. We describe a case of Morganella morganii-induced bacteriaemia complicated with PF in an individual who had undergone a recent urinary tract infection intervention. The patient presented with purpuric skin lesions, fever and hypotension but had no alterations in coagulation parameters or disseminated intravascular coagulation. Aggressive early resuscitation, intravenous antibiotics and wound care were essential to a favourable response.
Sodium–glucose co-transporter-2 inhibitors and the risk of perioperative euglycaemic diabetic ketoacidosis
Authors: Williams Samuel P , Stevens Jia L , Rajendran Yohinee K
Published: November 2022

Sodium–glucose co-transporter-2 inhibitors are increasingly prescribed for patients with type 2 diabetes. Their use has been associated with life-threatening diabetic ketoacidosis. The risk is increased during times of fasting and intercurrent medical illness, which are common in the perioperative period. Diagnosis can be difficult, so perioperative clinicians must be familiar with preventing and recognising such complications.
The effects of shame and stigma on patient care
Authors: Dolezal Luna
Published: November 2022

Stigma in healthcare has been associated with a range of negative outcomes, such as delays in seeking treatment, avoiding clinical encounters and mental distress. This editorial discusses the experience of stigma and argues that understanding shame anxiety and adopting ‘shame-sensitive’ practice is beneficial in healthcare.
Abortion incidence and service availability in the United States, 2020
Authors: Jones Rachel K. , Kirstein Marielle , Philbin Jesse
Published: November 2022

Background

This study provides a baseline assessment of abortion incidence and service delivery prior to Roe v. Wade being overturned.

Methods

We collected information from all facilities known to have provided abortion services in the United States in 2019 and 2020. We examined abortion incidence by state, region and nationally and combined data on number of abortions with population data to estimate abortion rates. We also examined the number of abortion clinics, trends in medication abortion and service disruptions and changes in abortion protocols that occurred during the COVID‐19 pandemic. We compare these findings to those of our prior Abortion Provider Census, which collected information for 2017.

Results

We documented 930,160 abortions in 2020, an 8% increase from 2017. Between 2017 and 2020, abortion incidence increased in all four regions of the country and in a majority of states. The total number of clinics providing abortion care remained stable nationally but increased in the Midwest and the West and declined in the Northeast and South. There were 492,210 medication abortions in 2020, a 45% increase from 2017. A substantial minority of clinics adjusted protocols in response to COVID, most commonly adopting remote pre‐ and post‐abortion counseling.

Discussion

This study did not address factors behind the increase in abortion. However, this report demonstrates that the need for abortion care was growing just prior to the overturning Roe v. Wade, and the impact of this decision will be even more far‐reaching than previously expected.
Spatial multiplexing and optical PAM4 quadruple the date rate in optical fiber systems
Authors: Su Ce , Chowdhury Bilas , Harish Swaroopini , Tu Mingxuan , Murshid Syed
Published: November 2022

This endeavor demonstrates a two-channel spatial division multiplexed
(SDM) system and combines it with an all-optical
four-level pulse amplitude modulation (PAM4) scheme to quadruple the
data rate and presents the experimental setup, system model, as well
as key results. The system initially introduces spatial reuse of
optical frequencies in a single-core multimode optical fiber by
transmitting two SDM channels, where both operate at 1310 nm.
It then complements the two SDM channels with an all-optical PAM4
scheme to enable 2 bits/symbol and 40 Gbps optical
transport while using only 10 Gbps sources. Since all sources
operate at the same wavelength, it effectively achieves PAM16
efficiencies at the given wavelength. The system accomplishes these
results without the use of dedicated PAM4 chipsets.
Real-time orchestration of QoS-aware end-to-end slices across a converged Metro and Access network exploiting burst-mode technology
Authors: Kosmatos E. , Matrakidis C. , Uzunidis D. , Stavdas A. , Horlitz S. , Pfeiffer T. , Lord A. , Riccardi Emilio
Published: November 2022

As we enter the B5G/6G era, the converged Access and Metro segments are facing multi-faceted challenges including the heterogeneity of technologies, an unprecedented density and scale for the interconnection patterns, dynamic traffic profiles, and the inefficiency associated with the overprovisioning of dedicated connectivity resources. Here we present a generic, yet comprehensive, architecture that addresses these challenges. Then, we report the principle of operation of a converged wireline–wireless Access and Metro testbed that exploits such an architecture where the wireline part is exclusively based on nondedicated connectivity resources. The wireline part of the testbed is constructed by means of standardized passive optical network (PON) data planes such as an XGS-PON and a GPON in the Metro and Access network segments, respectively. The converged testbed is controlled by means of an intelligent software-defined-networking-enabled slice manager that allows the creation of new types of quality-of-service (QoS)-aware end-to-end connectivity slices by adjusting in real time the configuration of the wireline technologies to the changing traffic parameters of a WiFi terminal. The end-to-end operation of this testbed is presented, and the specifics of this end-to-end slicing are detailed. The end-to-end QoS-aware slice creation is demonstrated by measuring the response time of the control plane, the corresponding service setup/recovery time, and the round-trip latency performance. A control-plane latency of

<

4.5

s

and a service recovery time of

<

8

s

are measured in all cases. Finally, the benefits of QoS-aware slices in the wireline part are quantified from the ability of the testbed to concurrently share bandwidth when needed, while maintaining an acceptable latency performance.
Reinforcement learning aided geometric shaping and self-canceling coherent detection for a PAM4 FSO communication system
Authors: Liu Yejun , Chen Kun , Song Song , Pan Yuan , Liu Yuchen , Guo Lei
Published: November 2022

This paper focuses on the tolerability of free space optical (FSO) communication with 4-level pulse amplitude modulation (PAM4) against atmospheric turbulence. Aiming at the trade-off between transmission performance and structral complexity, simplified coherent detection and reinforcement learning aided geometric shaping are proposed to enhance the receiver and transmitter of the PAM4 FSO system, respectively. In the proposed coherent detection structure, the intermediate frequency signal becomes immune to the turbulence-induced phase noise and frequency offset by passing through an electrical square-law device. Then, we find through theoretical analysis and demonstrate that the statistical property of the optical intensity varies among different amplitudes of the PAM4 signal when it is affected by atmospheric turbulence, which indicates a chance that geometric shaping can reduce the turbulence effect. In the geometric shaping scheme, a reinforcement learning algorithm is proposed to determine the optimal set of PAM4 amplitudes that fits the channel conditions. The results demonstrate that the proposed coherent detection structure outperforms direct detection in the bit error rate (BER) by up to one order of magnitude. Combined with the proposed geometric shaping scheme, the BER performance can be further improved. In particular, when the turbulence strength is in the weak to strong range, geometric shaping can improve the BER performance by two orders of magnitude.
100 years of Emil Wolf: introduction
Authors: Gbur Greg , Agarwal Girish , Alonso Miguel , Carney P. Scott , Friberg Ari T. , Knight Peter , Rolland Jannick P. , Shirai Tomohiro
Published: November 2022

The groundbreaking research and ideas introduced by Emil Wolf continue
to inspire researchers and motivate ongoing research in the wave
properties of light. This special issue commemorates the legacy of
Emil Wolf with research in physical optics, with specific focus on
those areas where Wolf was active, such as optical coherence theory,
inverse problems, singular optics, imaging, and polarization, and the
intersection of these fields of study. Here we discuss the life of
Emil Wolf and his influence on optical science and the optics
community.
Broadband multimode 3 dB optical power splitter using tapered couplers
Authors: Chen Weiwei , Lin Jian , Li Hongxiang , Wang Pengjun , Dai Shixun , Liu Yuxiao , Yao Runkui , Li Jun , Fu Qiang , Dai Tingge , Yang Jianyi
Published: November 2022

A design of a 1 × 2 multimode 3 dB optical power splitter using tapered couplers is proposed and investigated in this paper. As an example, a 1 × 2 splitter processing five-lowest order transverse-electric-polarized modes is designed and optimized by utilizing finite difference time domain method and particle swarm optimization algorithm. To verify the feasibility of this novel design, the optimized device is fabricated on a silicon-on-insulator platform. The coupling lengths of tapered couplers are respectively 6.5 µm, 6.0 µm, 3.5 µm, 5.0 µm, 5.0 µm, 7.5 µm, 6.0 µm, 5.0 µm, and 8.0 µm. Measurement results reveal that, for the fabricated splitter, the power uniformity varies from 0.041 to 0.88 dB, the crosstalk ranges from -23.96 to -14.12 dB, and the insertion loss changes from 0.089 to 1.50 dB within a bandwidth from 1520 to 1600 nm.