bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenium Attenuates TBHP-Induced Apoptosis of Nucleus Pulposus Cells by Suppressing Mitochondrial Fission through Activating Nuclear Factor Erythroid 2-Related Factor 2
Authors: Wang Peng , Zhang Shuo , Liu Weijian , Chen Songfeng , Lv Xiao , Hu Binwu , Shao Zengwu
Published: April 2022

Intervertebral disc (IVD) degeneration (IDD), the leading cause of low back pain (LBP), remains intractable due to a lack of effective therapeutic strategies. Several lines of studies have documented that nucleus pulposus cell (NPC) death induced by excessive oxidative stress is a crucial contributor to IDD. However, the concrete role and regulation mechanisms have not been fully clarified. Selenium (Se), a vital prosthetic group of antioxidant enzymes, is indispensable for maintaining redox homeostasis and promoting cell survival. However, no light was shed on the role of Se on IDD progression, especially regulation on mitochondrial dynamics and homeostasis. To fill this research gap, the current study focuses on the effects of Se, including sodium selenite (SS) and selenomethionine (Se-Met), on IDD progression and the underlying mechanisms. In vitro, we found that both SS and Se-Met alleviated tert-butyl hydroperoxide- (TBHP-) induced oxidative stress, protected mitochondrial function, and inhibited apoptosis of NPCs. Further experiments indicated that Se suppressed TBHP-induced mitochondrial fission and rescued the imbalance of mitochondrial dynamics. Promoting mitochondrial fission by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) partially counteracted the cytoprotective effects of Se. Moreover, blocking nuclear factor erythroid 2-related factor 2 (Nrf2) with ML385 proved that the effect of Se on regulating mitochondrial dynamics was attributed to the activation of the Nrf2 pathway. In the puncture-induced rat IDD model, a supplement of Se-Met ameliorated degenerative manifestations. Taken together, our results demonstrated that Se suppressed TBHP-induced oxidative stress and mitochondrial fission by activating the Nrf2 pathway, thereby inhibiting the apoptosis of NPCs and ameliorating IDD. Regulation of mitochondrial dynamics by Se may have a potential application value in attenuating the pathological process of IDD.
Rapid Extraction of Clothing Sample Profile Based on the Improved Canny Algorithm
Authors: Liu Na , Ma Yanyan , Shao Linyi , Wang Hao
Published: April 2022

In order to reduce the difficulty of clothing diversity on the edge extraction link, this study proposes an improved Canny algorithm that segments the pattern, styles, and contours of the clothing image after creating a sample library of a women’s image. Extract, improve the accuracy of the edge, and reduce the noise formed by texture and clothing. The results show that in the simulation experiment, the contour extraction of multiple categories of clothing is carried out, and compared with the differential operator algorithm and Canny algorithm, the experimental results show that the improved algorithm can more accurately segment the edge of clothing, extract the style contour, and express the characteristics of clothing.
Identification of EMT-Related lncRNAs as Potential Prognostic Biomarkers and Therapeutic Targets for Pancreatic Adenocarcinoma
Authors: Deng Yanyao , Hu Hai , Xiao Le , Cai Ting , Gao Wenzhe , Zhu Hongwei , Wang Shuai , Liu Jixing
Published: April 2022

Epithelial-mesenchymal transition (EMT) can promote carcinoma progression by multiple mechanisms; many studies demonstrated the invasiveness of pancreatic adenocarcinoma (PAAD) associated with the EMT, but how it acts through an lncRNA-dependent manner is unknown. Here, we investigated 146 samples from The Cancer Genome Atlas (TCGA) and 92 samples from the International Cancer Genome Consortium (ICGC). By gene set variation analysis (GSVA) and weighted correlation network analysis (WGCNA), we explored the EMT-related long noncoding RNAs (EMTlnc). Then, we performed univariate Cox regression analysis to screen their prognostic value for PAAD. The least absolute contraction and selection operator (LASSO) Cox regression was used to establish EMT-related lncRNA prognostic signal (EMT-LPS). In addition, we established a competitive endogenous ceRNA network. Then, we identified 33 prognostic EMTlnc as prognostic lncRNAs and established an EMT-LPS which showed strong prognostic ability in stratification analysis. By corresponding risk scores, patients were divided into low-risk and high-risk subgroups. Principal component analysis (PCA) showed that these subgroups had individual EMT status. Enrichment analysis showed that in the high-risk subgroup, biological processes, pathways, and hallmarks related to malignant tumors are more common. What is more, we constructed a nomogram that had powerful ability to predict the overall survival rate (OS) of PAAD patients in two datasets. So, EMT-LPS are a principal element in PAAD’s carcinoma progression and may help us in choosing the way of prognosis assessment and provide some clues to design the new drugs for PAAD.
Optimization and Evaluation of an Intelligent Short-Term Blood Glucose Prediction Model Based on Noninvasive Monitoring and Deep Learning Techniques
Authors: Zhang Yongjun , Gao Guangheng
Published: April 2022

Continuous noninvasive blood glucose monitoring and estimation management by using photoplethysmography (PPG) technology always have a series of problems, such as substantial time variability, inaccuracy, and complex nonlinearity. This paper proposes a blood glucose (BG) prediction model for more precise prediction based on BG series decomposition by complete aggregation empirical mode decomposition based on adaptive white noise (CEEMDAN) and the gated recurrent unit (GRU) that is optimized by improved bacterial foraging optimization (IBFO). Hierarchical clustering technology recombines the decomposed BG series according to their sample entropy and the correlations with the original BG trends. Dynamic BG trends are regressed separately for each recombined BG series by the GRU model to realize the more precise estimations, which are optimized by IBFO for its structure and superparameters. Through experiments, the optimized and basic LSTM, RNN, and support vector regression (SVR) are compared to evaluate the performance of the proposed model. The experimental results indicate that the root mean square error (RMSE) and mean absolute percentage error (MAPE) of the 15-min IBFO-GRU prediction is improved on average by about 13.1% and 18.4%, respectively, compared with those of the RNN and LSTM optimized by IBFO. Meanwhile, the proposed model improved the Clarke error grid results by about 2.6% and 5.0% compared with those of the IBFO-LSTM and IBFO-RNN in 30-min prediction and by 4.1% and 6.6% in 15-min ahead forecast, respectively. The evaluation outcomes of our proposed CEEMDAN-IBFO-GRU model have high accuracy and adaptability and can effectively provide early intervention control of the occurrence of hyperglycemic complications.
Tinctoride A, a New Hopan-Type Triterpenoic Peracid from the Thallus of Lichen Parmotrema Tinctorum (Despr. ex Nyl.) Hale
Authors: Hoang Le-Thuy-Thuy-Trang , Tran Thanh-Nha , Vo Thi-Phi-Giao , Phan Hoang-Vinh-Truong , Dong Phan-Si-Nguyen , Mai Dinh-Tri , Nguyen Ngoc-An , Huynh Thi-Minh-Suong , Luu Hong Truong , Le Tien-Dung , Dao Minh-Trung , Nguyen Van-Kieu
Published: April 2022

A new hopan-type triterpenoic peracid, tinctoride A (1), together with three known compounds, zeorin (2), 6β,22-dihydroxyhopane (3), and ergosterol peroxide (4), was isolated from Parmotrema tinctorum (Despr. ex Nyl.) Hale. Their chemical structures were identified by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy and compared with those reported in the literature. The enzyme inhibitory potential of compounds 1–3 against α-glucosidase was investigated, exhibiting nil to weak inhibitory activity.
Can the First Fasting Plasma Glucose Test in Pregnancy Predict Subsequent Gestational Complications?
Authors: Burlina Silvia , Dalfrà Maria Grazia , Belloni Pietro , Ottanelli Serena , Mecacci Federico , Mello Giorgio , Lapolla Annunziata
Published: April 2022

Objective. To determine the best cut-off level of pregnant women’s first fasting plasma glucose (FFPG) test results for the prediction of subsequent onset of gestational diabetes mellitus (GDM) and to examine the association between FFPG and maternal and neonatal outcomes in a large Caucasian population. Methods. 1437 medical records of women with singleton pregnancies followed up between 2015 and 2018 were retrospectively analyzed. Data on FFPG tested in the first trimester and 75 g oral glucose tolerance test (OGTT) findings performed according to IADPSG criteria and Italian guidelines were collected and evaluated. The women’s clinical and metabolic characteristics (age, prepregnancy body mass index (BMI), previous pregnancies complicated by GDM, timing of delivery, and gestational hypertension) were also recorded. The fetal variables considered were being large for gestational age (LGA) or small for gestational age (SGA), macrosomia, and hypoglycemia. Results. Among the 1437 pregnant women studied, 684 had a normal glucose tolerance (NGT) and 753 developed GDM. In a univariate analysis FFPG ≥92 mg/dl predicts the risk of GDM with an OR = 2.36 (95% CI 1.930–3.186;

p
<
0.001

). In multivariate analysis, after adjusting for principal risk factors of GDM (BMI, previous GDM, age >35 years, family history of diabetes) FFPG ≥92 mg/dl was associated with the risk of GDM (OR = 1.92; 95% CI 1.488–2.492;

p
<
0.001

). In univariate analysis, FFPG ≥92 mg/dl predict the risk of insulin therapy in GDM women with a OR = 1.88 (95% CI 1.230–2.066;

p
<
0.001

). As regards LGA, in a multivariate analysis, after adjusting for BMI, FFPG ≥92 mg/dl was associated with the risk of LGA only in NGT women (OR = 2.34; 95% CI 1.173–4.574;

p
=
0.014

), but not in GDM women. FFPG was not associated with other maternal or neonatal outcomes. Conclusions. FFPG ≥92 mg/dl is related to GDM diagnosis and to the need of insulin therapy if GDM is diagnosed. An early diagnosis and a prompt start of insulin therapy are essential to prevent maternal and fetal complications.
Quantum Dot Phase Transition Simulation with Hybrid Quantum Annealing via Metropolis-Adjusted Stochastic Gradient Langevin Dynamics
Authors: Kodai Shiba , Sugiyama Ryo , Yamaguchi Koichi , Sogabe Tomah
Published: April 2022

We report a hybrid quantum-classical simulation approach for simulating the optical phase transition observed experimentally in the ultrahigh-density type-II InAs quantum dot array. A hybrid simulation scheme, which contains stochastic gradient Langevin dynamics (a well-known Bayesian machine learning algorithm for big data) along with adiabatic quantum annealing, is developed to reproduce the experimentally observed phase transition. By implementing the simulation scheme into a quantum circuit, we successfully verified the phase transition observed in the experiment. Our work demonstrates for the first time the feasibility of hybridizing quantum computation with classical Langevin dynamics for the analysis of carrier dynamics and quantum phase transition of the quantum dot.
Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models
Authors: Quiros-Gonzalez Isabel , Tomaszewski Michal R. , Golinska Monika A. , Brown Emma , Ansel-Bollepalli Laura , Hacker Lina , Couturier Dominique-Laurent , Sainz Rosa M. , Bohndiek Sarah E.
Published: April 2022

Angiogenesis is an established prognostic factor in advanced breast cancer, yet response to antiangiogenic therapies in this disease remains highly variable. Noninvasive imaging biomarkers could help identify patients that will benefit from antiangiogenic therapy and provide an ideal tool for longitudinal monitoring, enabling dosing regimens to be altered with real-time feedback. Photoacoustic tomography (PAT) is an emerging imaging modality that provides a direct readout of tumor hemoglobin concentration and oxygenation. We hypothesized that PAT could be used in the longitudinal setting to provide an early indication of response or resistance to antiangiogenic therapy. To test this hypothesis, PAT was performed over time in estrogen receptor–positive and estrogen receptor–negative breast cancer xenograft mouse models undergoing treatment with the antiangiogenic bevacizumab as a single agent. The cohort of treated tumors, which were mostly resistant to the treatment, contained a subset that demonstrated a clear survival benefit. At endpoint, the PAT data from the responding subset showed significantly lower oxygenation and higher hemoglobin content compared with both resistant and control tumors. Longitudinal analysis revealed that tumor oxygenation diverged significantly in the responding subset, identifying early treatment response and the evolution of different vascular phenotypes between the subsets. Responding tumors were characterized by a more angiogenic phenotype when analyzed with IHC, displaying higher vessel density, yet poorer vascular maturity and elevated hypoxia. Taken together, our findings indicate that PAT shows promise in providing an early indication of response or resistance to antiangiogenic therapy.

Significance:

Photoacoustic assessment of tumor oxygenation is a noninvasive early indicator of response to bevacizumab therapy, clearly distinguishing between control, responding, and resistant tumors within just a few weeks of treatment.
Targeting CD73 with AB680 (Quemliclustat), a Novel and Potent Small-Molecule CD73 Inhibitor, Restores Immune Functionality and Facilitates Antitumor Immunity
Authors: Piovesan Dana , Tan Joanne B.L. , Becker Annette , Banuelos Jesus , Narasappa Nell , DiRenzo Daniel , Zhang Kristen , Chen Ada , Ginn Elaine , Udyavar Akshata R. , Yin Fangfang , Paprcka Susan L. , Purandare Bhamini , Park Timothy W. , Kimura Nikki , Kalisiak Jaroslaw , Young Stephen W. , Powers Jay P. , Schindler Uli , Sivick Kelsey E. , Walters Matthew J.
Published: April 2022

T cells play a critical role in the control of cancer. The development of immune checkpoint blockers (ICB) aimed at enhancing antitumor T-cell responses has revolutionized cancer treatment. However, durable clinical benefit is observed in only a subset of patients, prompting research efforts to focus on strategies that target multiple inhibitory signals within the tumor microenvironment (TME) to limit tumor evasion and improve patient outcomes. Adenosine has emerged as a potent immune suppressant within the TME, and CD73 is the major enzyme responsible for its extracellular production. CD73 can be co-opted within the TME to impair T-cell–mediated antitumor immunity and promote tumor growth. To target this pathway and block the formation of adenosine, we designed a novel, selective, and potent class of small-molecule inhibitors of CD73, including AB680 (quemliclustat), which is currently being tested in patients with cancer. AB680 effectively restored T-cell proliferation, cytokine secretion, and cytotoxicity that were dampened by the formation of immunosuppressive adenosine by CD73. Furthermore, in an allogeneic mixed lymphocyte reaction where CD73-derived adenosine had a dominant suppressive effect in the presence of PD-1 blockade, AB680 restored T-cell activation and function. Finally, in a preclinical mouse model of melanoma, AB680 inhibited CD73 in the TME and increased the antitumor activity of PD-1 blockade. Collectively, these data provide a rationale for the inhibition of CD73 with AB680 in combination with ICB, such as anti–PD-1, to improve cancer patient outcomes.
A New Class of Selective ATM Inhibitors as Combination Partners of DNA Double-Strand Break Inducing Cancer Therapies
Authors: Zimmermann Astrid , Zenke Frank T. , Chiu Li-Ya , Dahmen Heike , Pehl Ulrich , Fuchss Thomas , Grombacher Thomas , Blume Beatrix , Vassilev Lyubomir T. , Blaukat Andree
Published: April 2022

Radiotherapy and chemical DNA-damaging agents are among the most widely used classes of cancer therapeutics today. Double-strand breaks (DSB) induced by many of these treatments are lethal to cancer cells if left unrepaired. Ataxia telangiectasia-mutated (ATM) kinase plays a key role in the DNA damage response by driving DSB repair and cell-cycle checkpoints to protect cancer cells. Inhibitors of ATM catalytic activity have been shown to suppress DSB DNA repair, block checkpoint controls and enhance the therapeutic effect of radiotherapy and other DSB-inducing modalities. Here, we describe the pharmacological activities of two highly potent and selective ATM inhibitors from a new chemical class, M3541 and M4076. In biochemical assays, they inhibited ATM kinase activity with a sub-nanomolar potency and showed remarkable selectivity against other protein kinases. In cancer cells, the ATM inhibitors suppressed DSB repair, clonogenic cancer cell growth, and potentiated antitumor activity of ionizing radiation in cancer cell lines. Oral administration of M3541 and M4076 to immunodeficient mice bearing human tumor xenografts with a clinically relevant radiotherapy regimen strongly enhanced the antitumor activity, leading to complete tumor regressions. The efficacy correlated with the inhibition of ATM activity and modulation of its downstream targets in the xenograft tissues. In vitro and in vivo experiments demonstrated strong combination potential with PARP and topoisomerase I inhibitors. M4076 is currently under clinical investigation.
Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts
Authors: Ellegast Jana M. , Alexe Gabriela , Hamze Amanda , Lin Shan , Uckelmann Hannah J. , Rauch Philipp J. , Pimkin Maxim , Ross Linda S. , Dharia Neekesh V. , Robichaud Amanda L. , Conway Amy Saur , Khalid Delan , Perry Jennifer A. , Wunderlich Mark , Benajiba Lina , Pikman Yana , Nabet Behnam , Gray Nathanael S. , Orkin Stuart H. , Stegmaier Kimberly
Published: April 2022

Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator IRF2BP2 as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene-expression studies demonstrated that IRF2BP2 represses IL1β/TNFα signaling via NFκB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival.

Significance:

This study exploits inflammatory programs inherent to AML blasts to identify genetic vulnerabilities in this disease. In doing so, we determined that AML cells are dependent on the transcriptional repressive activity of IRF2BP2 for their survival, revealing cell-intrinsic inflammation as a mechanism priming leukemic blasts for regulated cell death.

See related commentary by Puissant and Medyouf, p. 1617.

This article is highlighted in the In This Issue feature, p. 1599
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution
Authors: Nirmal Ajit J. , Maliga Zoltan , Vallius Tuulia , Quattrochi Brian , Chen Alyce A. , Jacobson Connor A. , Pelletier Roxanne J. , Yapp Clarence , Arias-Camison Raquel , Chen Yu-An , Lian Christine G. , Murphy George F. , Santagata Sandro , Sorger Peter K.
Published: April 2022

Cutaneous melanoma is a highly immunogenic malignancy that is surgically curable at early stages but life-threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially resolved microregion transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis involving precursor states, melanoma in situ, and invasive tumor. Hallmarks of immunosuppression are already detectable in precursor regions. When tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor–stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1, and by PD1–PDL1-mediated cell contacts involving macrophages, dendritic cells, and T cells. A few millimeters away, cytotoxic T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can coexist within a few millimeters of each other in a single specimen.

Significance:

The reorganization of the tumor ecosystem in primary melanoma is an excellent setting in which to study immunoediting and immune evasion. Guided by classic histopathology, spatial profiling of proteins and mRNA reveals recurrent morphologic and molecular features of tumor evolution that involve localized paracrine cytokine signaling and direct cell–cell contact.

This article is highlighted in the In This Issue feature, p. 1397
Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Authors: Wang Mengzhao , Yang James Chih-Hsin , Mitchell Paul L. , Fang Jian , Camidge D. Ross , Nian Weiqi , Chiu Chao-Hua , Zhou Jianying , Zhao Yanqiu , Su Wu-Chou , Yang Tsung-Ying , Zhu Viola W. , Millward Michael , Fan Yun , Huang Wen-Tsung , Cheng Ying , Jiang Liyan , Brungs Daniel , Bazhenova Lyudmila , Lee Chee Khoon , Gao Bo , Xu Yan , Hsu Wei-Hsun , Zheng Li , Jänne Pasi A.
Published: April 2022

Epidermal growth factor receptor exon 20 insertion mutations (EGFRexon20ins) are detected in approximately 2% of patients with non–small cell lung cancer (NSCLC). Due to a lack of effective therapy, the prognosis of these patients is typically poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible, and selective EGFR tyrosine kinase inhibitor, showing activity against EGFRexon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase I clinical studies, sunvozertinib was tolerated up to 400 mg once daily. The most common drug-related adverse events included diarrhea and skin rash. Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFRexon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response has not been reached.

Significance:

We report the discovery and early clinical development of sunvozertinib, a potential treatment option for the unmet medical need of EGFRexon20ins NSCLC.

This article is highlighted in the In This Issue feature, p. 1599
Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C
Authors: Weiss Andreas , Lorthiois Edwige , Barys Louise , Beyer Kim S. , Bomio-Confaglia Claudio , Burks Heather , Chen Xueying , Cui Xiaoming , de Kanter Ruben , Dharmarajan Lekshmi , Fedele Carmine , Gerspacher Marc , Guthy Daniel Alexander , Head Victoria , Jaeger Ashley , Núñez Eloísa Jiménez , Kearns Jeffrey D. , Leblanc Catherine , Maira Sauveur-Michel , Murphy Jason , Oakman Helen , Ostermann Nils , Ottl Johannes , Rigollier Pascal , Roman Danielle , Schnell Christian , Sedrani Richard , Shimizu Toshio , Stringer Rowan , Vaupel Andrea , Voshol Hans , Wessels Peter , Widmer Toni , Wilcken Rainer , Xu Kun , Zecri Frederic , Farago Anna F. , Cotesta Simona , Brachmann Saskia M.
Published: April 2022

Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket. JDQ443 potently inhibits KRASG12C-driven cellular signaling and demonstrates selective antiproliferative activity in KRASG12C-mutated cell lines, including those with G12C/H95 double mutations. In vivo, JDQ443 induces AUC exposure-driven antitumor efficacy in KRASG12C-mutated cell-derived (CDX) and patient-derived (PDX) tumor xenografts. In PDX models, single-agent JDQ443 activity is enhanced by combination with inhibitors of SHP2, MEK, or CDK4/6. Notably, the benefit of JDQ443 plus the SHP2 inhibitor TNO155 is maintained at reduced doses of either agent in CDX models, consistent with mechanistic synergy. JDQ443 is in clinical development as monotherapy and in combination with TNO155, with both strategies showing antitumor activity in patients with KRASG12C-mutated tumors.

Significance:

JDQ443 is a structurally novel covalent KRASG12C inhibitor with a unique binding mode that demonstrates potent and selective antitumor activity in cell lines and in vivo models. In preclinical models and patients with KRASG12C-mutated malignancies, JDQ443 shows potent antitumor activity as monotherapy and in combination with the SHP2 inhibitor TNO155.

See related video: https://vimeo.com/720726054

This article is highlighted in the In This Issue feature, p. 1397
Disharmony in Gut Microbiota – Should This Be a Priority for Public Health Nutrition?
Authors: Avery Amanda
Published: April 2022

The gut microbiota is responsible for recovering energy from food, providing hosts with vitamins, and providing a barrier function against exogenous pathogens. In addition, it is involved in maintaining the integrity of the intestinal epithelial barrier, crucial for the functional maturation of the gut immune system. The Western diet (WD) – an unhealthy diet with high consumption of fats – can be broadly characterized by overeating, frequent snacking, and a prolonged postprandial state. The term WD is commonly known and intuitively understood. However, the strict digital expression of nutrient ratios is not precisely defined. Based on the US data for 1908–1989, the calory intake available from fats increased from 32% to 45%. Besides the metabolic aspects (hyperinsulinemia, insulin resistance, dyslipidemia, sympathetic nervous system and renin-angiotensin system overstimulation, and oxidative stress), the consequences of excessive fat consumption (high-fat diet-HFD) comprise dysbiosis, gut barrier dysfunction, increased intestinal permeability, and leakage of toxic bacterial metabolites into the circulation. These can strongly contribute to the development of low-grade systemic inflammation. This narrative review highlights the most important recent advances linking HFD-driven dysbiosis and HFD-related inflammation, presents the pathomechanisms for these phenomena, and examines the possible causative relationship between pro-inflammatory status and gut microbiota changes.
Cell-in-cell phenomenon in urinary sediment
Authors: Martínez-Figueroa Carlos , Cortés-Sarabia Karen , Tesser Poloni José Antonio , Molina-Avilez Enrique Alejandro , Palaoro Luis A. , Vences-Velázquez Amalia
Published: April 2022

The internalization of apoptotic cells by non-phagocytic cells has been observed in different tissues and could be an important mechanism for the elimination of dying cells. Here, we describe a probable event of phagocytosis of apoptotic cells mediated by urothelial cells in urinary sediment. A 90-years-old male patient was admitted unconscious to the hospital, visible signs included: pale skin and dry mucous membranes, presumptively diagnosed as dehydration. Blood test revealed anaemia (haemoglobin 130 g/L) and hyperglycaemia (glucose 7.8 mmol/L), urinalysis showed a picture of urinary tract infection (leukocyturia and bacteriuria). The microscopic analysis of urinary sediment revealed the presence of urothelial cells and leukocytes internalized in urothelial cells. Anti-CD68 (membrane marker of macrophages) was tested by immunocytochemistry and a negative result was observed. Based on the findings phagocytosis of apoptotic cells mediated by urothelial cells was identified. This phenomenon can be observed in urinary sediment and should not be confused with a neoplastic process since it is a physiological event of cell elimination.
From Sister-Wife to Brother-Neighbor: Rosenzweig Reads the Song of Songs
Authors: Cooper Andrea Dara
Published: April 2022

This paper investigates a sibling metaphor central to Rosenzweig’s reading of the Song of Songs in The Star of Redemption, in which the lovers yearn to be united in societal fraternity. His interpretation is marked by fraternal tropes and the subsequent effacement of gender. Rosenzweig transposes the erotic energy in the Song from a celebration of difference to a longing for sameness, a move that has exegetical, philosophical, and theological implications. Ultimately, the erotic sphere of revelation is surpassed by neighborly “brotherliness” in communal redemption.
1. The Theoretical Framework
Authors: Nebel Mathias
Published: April 2022

Mathias Nebel develops in this chapter the theoretical foundation of a common good approach to development. Building on Foucault, Arendt, Bourdieu, Giddens, Oström, Taylor, and Riordan, he proposes to understand the common good from the perspective of the interactions structuring our communal life. The chapter takes up many of the Antique and Medieval insights of the notion but then reframes the concept from the perspective of a philosophy of action. This is actually the main shift in his approach to the concept. He argues that the common good is essentially linked to the way our social interactions are generated and thrive. A common good perspective on society is therefore neither totalitarian nor conservative. On the contrary, it is creative, capable of novelty and inclusiveness; it embraces not only plurality, justice and law, but also the purpose of the good life in politics.

In the interest of pedagogical clarity, the chapter structures its theoretical insights around a vocabulary of the common good, that will then be coherently used by all other articles in this book. He distinguishes between the many specific and limited common goods existing in a society and coins the expression nexus of common goods to explain the dynamic system of specific common goods in a given society. Both are differentiated from the universal common good, which is in itself a goal and a task, and whose content is our common humanity.
Do All Isolated Traumatic Subarachnoid Hemorrhages Need to Be Transferred to a Level 1 Trauma Center?
Authors: Forney Eric D. , Montgomery Anne , Williams Marshal , Patel Mital D. , Ashley Dennis W.
Published: April 2022

Background

The management of isolated traumatic subarachnoid hemorrhage (itSAH) in non-trauma centers usually results in transfer to a Level 1 trauma center with neurosurgical capabilities. Due to lack of trauma center resources, we sought to evaluate if patients with itSAH need transfer to a Level I trauma center.

Methods

A retrospective review of the trauma registry was conducted from Jan 2015-Dec 2020. Patients with itSAH on initial computed tomographic imaging and a Glasgow Coma Scale score >13 were included. Patients with any other intracranial pathology, skull fractures, multi-system trauma or age less than 15 were excluded.

Results

120 patients were identified with itSAH. Mean age was 63 years, and 44% were male. Mean injury severity score was 4.7 with 48% on anticoagulation/antiplatelet therapy. Radiology Reports were reviewed and only 2 scans (1.7%) showed an increase in itSAH, 98.3% reports revealed no change, improvement, or resolution. No patients deteriorated and no patients underwent neurosurgical intervention. Once admitted, 27 (23%) were treated for acute medical conditions and 39 (33%) required subspecialty medical consultations. There was no difference in increased itSAH on repeat imaging between patients on anticoagulation/antiplatelet therapy and those without. The population taking anticoagulant/antiplatelet therapy was older, more likely to have suffered a fall, have more comorbid conditions, was more likely to be treated for a non-traumatic medical condition and have a subspecialty medical consultation.

Discussion

Patients with itSAH do not require transfer to a Level 1 trauma center for acute neurosurgical intervention.
Systemic Immune-Inflammation Index as a Predictor of Microvascular Dysfunction in Patients With Cardiac Syndrome X
Authors: Yaşar Erdoğan , Bayramoğlu Adil
Published: April 2022

The systemic immune inflammation index (SII; platelet count x neutrophil-lymphocyte ratio), a new marker, predicts adverse clinical outcomes in many conditions, including acute and chronic coronary syndromes, pulmonary embolism, cancers, and contrast nephropathy. The aim of this study was to determine the relationship between SII and microvascular dysfunction in patients with Cardiac Syndrome X (CSX); 105 patients with CSX and 105 patients with normal coronary arteries were included. Microvascular dysfunction was determined angiographically using myocardial blush grade (MBG) and total myocardial blush score (TMBS). We observed that the SII levels were higher in the CSX (+) group (687 [355–2211] vs 418 [198–1614], P<.001). The SII levels were also found to be significant independent predictors for CSX in multiple regression analysis ( P=.001). SII levels >440 had 83.8% sensitivity and 55.2% specificity (area under the curve [AUC]: .923, 95% CI: .895–.999, P<.001) for predicting CSX. There is a significant correlation between SII levels and CSX.
A Nomogram Model for Predicting the Postoperative Recurrence of Localized Laryngeal Amyloidosis
Authors: Mao Meiling , Liang Na , Ren Ran , Zhao Yihua , Ma Donglin , Liu Honggang
Published: April 2022

Objective:

To analyze the factors related to postoperative recurrence in patients with localized laryngeal amyloidosis (LocLA) and to construct a nomogram prediction model (NPM).

Methods:

We collected the data for LocLA patients diagnosed from March 2000 to May 2019 and clinical characteristics data were extracted. Factors related to recurrence were analyzed using multivariate logistic regression. The NPM was constructed for predicting the recurrence risk of LocLA. The receiver operating characteristic (ROC) curve evaluated the distinguishing ability using the area under curve (AUC). The calibration curve was created to evaluate the consistency of the NPM.

Results:

A total of 226 confirmed LocLA cases were included. One hundred seventy-five cases (77.4%) had localized single nodule, and 51 cases had more than one lesions. Sixty-three (27.9%) cases had no multinucleated giant cell (MGC) around amyloid, and 163 (72.1%) cases had MGC around amyloid. Multivariate logistic regression analysis showed that more than one lesions (odds ratio [OR] = 3.206 and 95% confidence interval [CI]: 1.492-6.888; P value: .003), subglottic involvement (OR = 2.926 and 95% CI: 1.300-6.585; P = .010), and no multinucleated giant cell (MGC) around amyloid (OR = 2.503 and 95% CI: 1.173-5.342; P = .018) had a statistically significant effect on postoperative LocLA recurrence ( P < .05). The AUC of the ROC curve was 0.753 (95% CI: 0.667-0.832). The bias-corrected curve approached the ideal curve, with an average absolute error of 0.037.

Conclusions:

More than one lesions, subglottic involvement, and no MGC around amyloid are risk factors for postoperative recurrence of LocLA. The NPM constructed has good applicability.
COMMENTARY – SHOULD WASHINGTON HAVE PRESSED KYIV INTO A COMPROMISE WITH MOSCOW?
Authors: Umland Andreas
Published: April 2022

This article was submitted in late 2021, and became dated after Russia's demonstrative preparation as well as start of an open, large‐scale invasion of Ukraine early 2022. We nevertheless publish this commentary here in order to document the debate about the events leading to the escalation. No adaptations to the original 2021 article were made after the outbreak of high‐intensity war on 24 February 2022. Avoiding a larger military escalation in the Russian–Ukrainian conflict is an important aim. Yet, historical experience suggests that concessions by Ukraine or its Western partners toward Russian revanchist aspirations in the Donbas may not help achieve it. On the contrary, Western softness, and Ukrainian weakness vis‐à‐vis the Kremlin will lead to further confrontation.
Enhancing Employee Voice and Inclusion Through Inclusive Leadership in Public Sector Organizations
Authors: Alang Tho , Stanton Pauline , Rose Mark
Published: April 2022

This article explores the impact of inclusive leadership behaviors on Indigenous voice and the perception of workplace inclusion by Indigenous employees in Vietnam public agencies. Drawing from qualitative research with managers and Indigenous employees in three public organizations, we found that, first, inclusive leadership behaviors promoted workplace diversity by supporting Indigenous presence through recruitment; training and development opportunities; and promotion into decision making roles. Second, inclusive leadership facilitated Indigenous belongingness by accepting Indigenous employees as important group members, and sympathizing with their challenges. Third, in the context of a Confucian and collectivist-influenced country, inclusive leadership played a crucial role in valuing Indigenous uniqueness by encouraging their voice over their work; valuing their contributions; and respecting their differences. Theoretical and practical implications are discussed.
U.S. Veterans and Civilians Describe Military News Coverage as Mediocre, Think Stories Affect Others More Than Themselves
Authors: Parrott Scott , Albright David L. , Eckhart Nicholas , Laha-Walsh Kirsten
Published: April 2022

The news media often portray military veterans in stereotypical ways, providing audiences narrow representations in which veterans are traumatized heroes. What happens when a veteran sees these storylines and assumes they affect how the public thinks about veterans? This question informs this study, which used a two-prong approach (online, telephone) to survey 1,047 American adults about news media and veterans. Respondents, including veterans and civilians, were asked to recall news stories about veterans, assess the quality of news coverage of veterans, and offer opinions concerning whether news coverage affects themselves and other people. When respondents could recall a news story about veterans, they described stereotypical stories related to victimization/harm, heroism, charity/social support, mental illness, and violence. Respondents, both civilian and veteran, described news coverage as mediocre and felt the news affects other people more than themselves.
Trade union influence on innovation in the British private sector: Direct and indirect paths
Authors: Wang Wen , Heyes Jason , Seifert Roger
Published: April 2022

This article examines relationships between trade unions and firms’ innovation activity. Drawing on nationally representative data covering 1,384 firms in the UK, the article employs probit analysis to estimate the effect of trade union representation at the workplace on different types of innovation. The findings show significant and positive correlations between trade union representation and the introduction of new processes and new methods of marketing. The study also found a positive and moderately significant indirect effect on innovation arising from union influence on training provision and employee involvement practices. In addition, when unions are associated with shaping long-term oriented staffing practices, the positive indirect effects are strengthened.
Organic geochemistry and controlling factors of alkaline source rocks within sequence stratigraphic framework in the Fengcheng Formation, Mahu sag, Junggar Basin, NW China
Authors: Chen Gangqiang , Wang Dongyong , Yang Fan , Tang Yuantao , Zou Xianli , Ma Wanyun , Li Minhang
Published: April 2022

The Fengcheng Formation (P1 f) source rock, which was deposited in an alkaline water body, is one of the most significant source rocks in the Mahu sag, Junggar Basin. However, its evolution and mechanism of organic matter accumulation are still not understood. Using seismic, core, and log data, P1 f is divided into 3 third-order sequences, i.e., SQ1, SQ2, and SQ3, from bottom to top. Pyrolysis data of core samples shows that SQ1 and SQ3 mainly are characterized by poor to fair source rocks, with Type III to Type II2 kerogen, while SQ2 mainly are characterized by fair to good to excellent source rocks, with Type II2 to Type I kerogen. The biomarker parameters of 40 source rock samples from different sequences suggest that the reducibility of sedimentary water is characterized by SQ2 > SQ1 > SQ3. The organic matter contribution in different sequences is obviously different. SQ1 organic matter contain more bacteria and algae than that of SQ2 and SQ3, and terrigenous higher plants may have contributed to SQ3 organic matter. Lake level changes and water salinity dominate organic matter origin, accumulation, and preservation. During SQ1 deposition, the lake level was the highest, the salinity of sedimentary water was moderate, and the organic matter contained more conventional algae sources. During SQ2 deposition, the lake level was the lowest and the salinity was the highest, and the organic matter contained special algae characterized by C29 regular steroids. The lake level of SQ3 was higher than that of SQ2, the salinity was the lowest, and terrigenous higher plants may have contributed to organic matter during this period.
A multi-centre prospective random control study of superimposed high-frequency jet ventilation and conventional jet ventilation for interventional bronchoscopy
Authors: Wang Ting , Pei Yinghua , Qiu Xiaojian , Wang Juan , Wang Yuling , Zhang Jie
Published: April 2022

Introduction: Superimposed high-frequency jet ventilation (SHFJV) is a new type of jet ventilation that simultaneously uses high- and low-frequency types of jet ventilation. We compared SHFJV with the conventional high-frequency jet ventilation (CHFJV) in interventional bronchoscopy in terms of safety and effectiveness. Methods: A multi-centre prospective random single-blind clinical trial was conducted by three interventional bronchoscopy centres. Patients who underwent diagnostic or therapeutic bronchoscopy under general anaesthesia were admitted and divided into two groups: SHFJV group (trial group) and CHFJV group (control group). PaO2 and PaCO2 were recorded before anaesthesia and during and after the procedure. SpO2 and etCO2 were recorded every 10 min throughout the procedure. Patients were observed until 24 h post-bronchoscopy. Results: Sixty patients were included in the study. Twenty-nine were in the trial group, and 31 were in the control group. Both groups had no significant differences in demographic data. In the control group, the PaO2 measured in the operation was higher than that in the trial group (p = 0.023). The values of etCO2 in the control group were more dispersed than those of the trial group. When the procedure time was over 90 minutes, the etCO2 in the control group significantly increased (p = 0.01), while the etCO2 in trial group remained stable (p = 0.594). There were more patients with PaCO2 ≥ 50 mmHg during the procedure in the control group than in the trial group (p = 0.042). Conclusion: SHFJV is effective and safe in interventional bronchoscopy. It may provide more effective and stabilised ventilation than CHFJV in cases with long procedure times.
Pelvic CT in addition to MRI to differentiate between rectal and sigmoid cancer on imaging using the sigmoid take-off as a landmark
Authors: Bogveradze Nino , Maas Monique , el Khababi Najim , Schurink Niels W , Lahaye Max J , Bakers Frans CH , Tanis Pieter J , Kusters Miranda , Beets Geerard L , Beets-Tan Regina GH , Lambregts Doenja MJ
Published: April 2022

Background

The sigmoid take-off (STO) is a recently established landmark to discern rectal from sigmoid cancer on imaging. STO-assessment can be challenging on magnetic resonance imaging (MRI) due to varying axial planes.

Purpose

To establish the benefit of using computed tomography (CT; with consistent axial planes), in addition to MRI, to anatomically classify rectal versus sigmoid cancer using the STO.

Material and Methods

A senior and junior radiologist retrospectively classified 40 patients with rectal/rectosigmoid cancers using the STO, first on MRI-only (sagittal and oblique-axial views) and then using a combination of MRI and axial CT. Tumors were classified as rectal/rectosigmoid/sigmoid (according to published STO definitions) and then dichotomized into rectal versus sigmoid. Diagnostic confidence was documented using a 5-point scale.

Results

Adding CT resulted in a change in anatomical tumor classification in 4/40 cases (10%) for the junior reader and in 6/40 cases (15%) for the senior reader. Diagnostic confidence increased significantly after adding CT for the junior reader (mean score 3.85 vs. 4.27; P < 0.001); confidence of the senior reader was not affected (4.28 vs. 4.25; P = 0.80). Inter-observer agreement was similarly good for MRI only (κ=0.77) and MRI + CT (κ=0.76). Readers reached consensus on the classification of rectal versus sigmoid cancer in 78%–85% of cases.

Conclusion

Availability of a consistent axial imaging plane – in the case of this study provided by CT – in addition to a standard MRI protocol with sagittal and oblique-axial imaging views can be helpful to more confidently localize tumors using the STO as a landmark, especially for more junior readers.
Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix
Authors: Zhang Yunqiang , Ding Jingxin , Zhang Xuyin , Hua Keqin
Published: April 2022

Objective

To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix (SCNEC) and to further explore their roles and mechanisms in tumor progression.

Methods

Differentially expressed genes in SCNEC compared with squamous cell carcinoma (SCC) and adenocarcinoma (AC) were screened by microarray and immunohistochemical analyses. The biological functions of the identified genes were examined in a SCNEC cell line using RNA interference and over-expression plasmid-transfection technologies. Co-expression network analysis and immunoprecipitation technology were used to explore the potential mechanisms.

Results

Compared with SCC and AC, UCHL1 (encoding ubiquitin C-terminal hydrolase L1) was identified as a specific differentially expressed gene in SCNEC, which was positively related to lymph node metastasis (LNM). Migration and invasion of SCNEC tumor cells were induced by UCHL1 over-expression and suppressed by UCHL1 down-regulation, as shown by scratch and transwell invasion assays. Co-expression network analysis suggested that Prospero homeobox protein 1 (PROX1) might interact with UCHL1, and in vivo immunoprecipitation and western blots verified that levels of ubiquitinated PROX1 were significantly decreased following UCHL1 overexpression.

Conclusion

UCHL1 is a potential biomarker of LNM in SCNEC. UCHL1 might promote SCNEC cell migration and invasion by reducing PROX1 ubiquitination.