bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between postoperative hypoalbuminemia and postoperative pulmonary imaging abnormalities patients undergoing craniotomy for brain tumors: a retrospective cohort study
Authors: Zhao Da-wei , Zhao Feng-chun , Zhang Xu-yang , Wei Kai-yan , Jiang Yi-bin , Liu Dan , Zhang Shui-xian , Feng Hua , Hu Rong
Published: January 2022

Hypoalbuminemia is associated with poor outcome in patients undergoing surgery intervention. The main aim for this study was to investigate the incidence and the risk factors of postoperative hypoalbuminemia and assessed the impact of postoperative hypoalbuminemia on complications in patients undergoing brain tumor surgery. This retrospective study included 372 consecutive patients who underwent brain tumors surgery from January 2017 to December 2019. The patients were divided into hypoalbuminemia (< 35 g/L) and non-hypoalbuminemia group (≥ 35 g/L) based on postoperative albumin levels. Logistic regression analyses were used to determine risk factors. Of the total 372 patients, 333 (89.5%) developed hypoalbuminemia after surgery. Hypoalbuminemia was associated with operation time (OR 1.011, P < 0.001), preoperative albumin (OR 0.864, P = 0.015) and peroperative globulin (OR 1.192, P = 0.004). Postoperative pulmonary imaging abnormalities had a higher incidence in patients with than without hypoalbuminemia (41.1% vs 23.1%, P = 0.029). The independent predictors of postoperative pulmonary imaging abnormalities were age (OR 1.053, P < 0.001), operation time (OR 1.003, P = 0.013) and lower postoperative albumin (OR 0.946, P = 0.018). Pulmonary imaging abnormalities [OR 19.862 (95% CI 2.546–154.936, P = 0.004)] was a novel independent predictors of postoperative pneumonia. Postoperative hypoalbuminemia has a higher incidence with the increase of operation time, and may be associated with postoperative complications in patients undergoing brain tumor surgery.
Relative fat mass, a new index of adiposity, is strongly associated with incident heart failure: data from PREVEND
Authors: Suthahar Navin , Meems Laura M. G. , Withaar Coenraad , Gorter Thomas M. , Kieneker Lyanne M. , Gansevoort Ron T. , Bakker Stephan J. L. , van Veldhuisen Dirk J. , de Boer Rudolf A.
Published: January 2022

Body-mass index (BMI), waist circumference, and waist-hip ratio are commonly used anthropometric indices of adiposity. However, over the past 10 years, several new anthropometric indices were developed, that more accurately correlated with body fat distribution and total fat mass. They include relative fat mass (RFM), body-roundness index (BRI), weight-adjusted-waist index and body-shape index (BSI). In the current study, we included 8295 adults from the PREVEND (Prevention of Renal and Vascular End-Stage Disease) observational cohort (the Netherlands), and sought to examine associations of novel as well as established adiposity indices with incident heart failure (HF). The mean age of study population was 50 ± 13 years, and approximately 50% (n = 4134) were women. Over a 11 year period, 363 HF events occurred, resulting in an overall incidence rate of 3.88 per 1000 person-years. We found that all indices of adiposity (except BSI) were significantly associated with incident HF in the total population (P < 0.001); these associations were not modified by sex (P interaction > 0.1). Amongst adiposity indices, the strongest association was observed with RFM [hazard ratio (HR) 1.67 per 1 SD increase; 95% confidence interval (CI) 1.37–2.04]. This trend persisted across multiple age groups and BMI categories, and across HF subtypes [HR: 1.76, 95% CI 1.26–2.45 for HF with preserved ejection fraction; HR 1.61, 95% CI 1.25–2.06 for HF with reduced ejection fraction]. We also found that all adiposity indices (except BSI) improved the fit of a clinical HF model; improvements were, however, most evident after adding RFM and BRI (reduction in Akaike information criteria: 24.4 and 26.5 respectively). In conclusion, we report that amongst multiple anthropometric indicators of adiposity, RFM displayed the strongest association with HF risk in Dutch community dwellers. Future studies should examine the value of including RFM in HF risk prediction models.
A randomized trial to determine the minimum effective lidocaine volume for median nerve block using hydrodissection
Authors: Dufour Eric , Jaziri Souhail , Novillo Marie Alice , Aubert Lila , Chambon Anne , Kutz Rainer , Vallée Alexandre , Fischler Marc
Published: January 2022

Ultrasound-guided hydrodissection with 5% dextrose in water (DW5) creates a peri-nervous compartment, separating the nerve from the neighboring anatomical structures. The aim of this randomized study was to determine the minimum volume of lidocaine 2% with epinephrine 1:200,000 required when using this technique to achieve an effective median nerve block at the elbow in 95% of patients (MEAV95). Fifty-two patients scheduled for elective hand surgery received an ultrasound-guided circumferential perineural injection of 4 ml DW5 and an injection of local anesthetic (LA) following a biased coin up-and-down sequential allocation method. A successful block was defined as a light touch completely suppressed on the two distal phalanges of the index finger within a 30-min evaluation period. The MEAV95 of lidocaine 2% with epinephrine was 4 ml [IQR 3.5–4.0]. Successful median nerve block was obtained in 38 cases (82.6%) with median onset time of 20.0 [10.0–21.2] minutes (95% CI 15–20). The analgesia duration was 248 [208–286] minutes (95% CI 222–276). Using an ultrasound-guided hydrodissection technique with DW5, the MEAV95 to block the median nerve at the elbow with 2% lidocaine with epinephrine was 4 ml [IQR 3.5–4.0]. This volume is close to that usually recommended in clinical practice.

Trial registration clinicaltrials.gov. NCT02438657, Date of registration: May 8, 2015.
Validation of a combined ultrasound and bioluminescence imaging system with magnetic resonance imaging in orthotopic pancreatic murine tumors
Authors: Rojas Juan D. , Joiner Jordan B. , Velasco Brian , Bautista Kathlyne Jayne B. , Aji Adam M. , Moore Christopher J. , Beaumont Nathan J. , Pylayeva-Gupta Yuliya , Dayton Paul A. , Gessner Ryan C. , Czernuszewicz Tomasz J.
Published: January 2022

Preclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics. Recent reports have highlighted the need for utilizing orthotopic implantation to represent clinical disease more accurately, however the deep tissue location of these tumors makes longitudinal assessment challenging without the use of imaging techniques. The purpose of this study was to evaluate the performance of a new multi-modality high-throughput in vivo imaging system that combines bioluminescence imaging (BLI) with robotic, hands-free ultrasound (US) for evaluating orthotopic mouse models. Long utilized in cancer research as independent modalities, we hypothesized that the combination of BLI and US would offer complementary advantages of detection sensitivity and quantification accuracy, while mitigating individual technological weaknesses. Bioluminescent pancreatic tumor cells were injected into the pancreas tail of C57BL/6 mice and imaged weekly with the combination system and magnetic resonance imaging (MRI) to serve as a gold standard. BLI photon flux was quantified to assess tumor activity and distribution, and US and MRI datasets were manually segmented for gross tumor volume. Robotic US and MRI demonstrated a strong agreement (R2 = 0.94) for tumor volume measurement. BLI showed a weak overall agreement with MRI (R2 = 0.21), however, it offered the greatest sensitivity to detecting the presence of tumors. We conclude that combining BLI with robotic US offers an efficient screening tool for orthotopic tumor models.
Ablation of VLA4 in multiple myeloma cells redirects tumor spread and prolongs survival
Authors: Hathi Deep , Chanswangphuwana Chantiya , Cho Nicholas , Fontana Francesca , Maji Dolonchampa , Ritchey Julie , O’Neal Julie , Ghai Anchal , Duncan Kathleen , Akers Walter J. , Fiala Mark , Vij Ravi , DiPersio John F. , Rettig Michael , Shokeen Monica
Published: January 2022

Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone microenvironment. Delineating specific molecules and pathways for their role in cancer supportive interactions in the BM is vital for developing new therapies. Very Late Antigen 4 (VLA4, integrin α4β1) is a key player in cell–cell adhesion and signaling between MM and BM cells. We evaluated a VLA4 selective near infrared fluorescent probe, LLP2A-Cy5, for in vitro and in vivo optical imaging of VLA4. Furthermore, two VLA4-null murine 5TGM1 MM cell (KO) clones were generated by CRISPR/Cas9 knockout of the Itga4 (α4) subunit, which induced significant alterations in the transcriptome. In contrast to the VLA4+ 5TGM1 parental cells, C57Bl/KaLwRij immunocompetent syngeneic mice inoculated with the VLA4-null clones showed prolonged survival, reduced medullary disease, and increased extramedullary disease burden. The KO tumor foci showed significantly reduced uptake of LLP2A-Cy5, confirming in vivo specificity of this imaging agent. This work provides new insights into the pathogenic role of VLA4 in MM, and evaluates an optical tool to measure its expression in preclinical models.
Use and safety of prophylactic endoscopy from a single center serving urban and rural children with portal hypertension
Authors: Slowik Voytek , Bernardez Anissa , Wasserkrug Heather , Fischer Ryan T. , Daniel James F. , Grammatikopoulos Tassos
Published: January 2022

Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p < 0.001) with no difference in immediate complications (1% vs 2%, p = 0.173) or 2-week complications (1% vs 2%, p = 0.097). No deaths were related to variceal bleeding or endoscopy. Kaplan–Meier Survival Curve suggests improved transplant and shunt free survival in the primary prophylaxis group (log-rank p < 0.001). Primary and secondary endoscopic prophylaxis should be considered safe for the prevention of variceal hemorrhage in pediatric portal hypertension. There are differences in outcomes in primary and secondary prophylaxis, but unclear if this is due to patient characteristics versus treatment strategy. Further study is needed to compare safety and efficacy to watchful waiting.
Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device
Authors: Sarnelli Anna , Negrini Matteo , Mezzenga Emilio , Feliciani Giacomo , D’Arienzo Marco , Amato Antonino , Paganelli Giovanni
Published: January 2022

The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y β-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and β), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.
The impact of bariatric surgery on serum tryptophan–kynurenine pathway metabolites
Authors: Yeung Kai Tai Derek , Penney Nicholas , Whiley Luke , Ashrafian Hutan , Lewis Matthew R. , Purkayastha Sanjay , Darzi Ara , Holmes Elaine
Published: January 2022

This study aims to explore the immediate effects of bariatric surgery on serum tryptophan–kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).
A generalized strain approach to anisotropic elasticity
Authors: Shariff M. H. B. M.
Published: January 2022

This work proposes a generalized Lagrangian strain function $$f_\alpha$$

f
α

(that depends on modified stretches) and a volumetric strain function $$g_\alpha$$

g
α

(that depends on the determinant of the deformation tensor) to characterize isotropic/anisotropic strain energy functions. With the aid of a spectral approach, the single-variable strain functions enable the development of strain energy functions that are consistent with their infinitesimal counterparts, including the development of a strain energy function for the general anisotropic material that contains the general 4th order classical stiffness tensor. The generality of the single-variable strain functions sets a platform for future development of adequate specific forms of the isotropic/anisotropic strain energy function; future modellers only require to construct specific forms of the functions $$f_\alpha$$

f
α

and $$g_\alpha$$

g
α

to model their strain energy functions. The spectral invariants used in the constitutive equation have a clear physical interpretation, which is attractive, in aiding experiment design and the construction of specific forms of the strain energy. Some previous strain energy functions that appeared in the literature can be considered as special cases of the proposed generalized strain energy function. The resulting constitutive equations can be easily converted, to allow the mechanical influence of compressed fibres to be excluded or partial excluded and to model fibre dispersion in collagenous soft tissues. Implementation of the constitutive equations in Finite Element software is discussed. The suggested crude specific strain function forms are able to fit the theory well with experimental data and managed to predict several sets of experimental data.
Human IgE does not bind to human FcRn
Authors: Brinkhaus Maximilian , van der Kooi Elvera J. , Bentlage Arthur E. H. , Ooijevaar-de Heer Pleuni , Derksen Ninotska I. L. , Rispens Theo , Vidarsson Gestur
Published: January 2022

The neonatal Fc receptor (FcRn) is known to mediate placental transfer of IgG from mother to unborn. IgE is widely known for triggering immune responses to environmental antigens. Recent evidence suggests FcRn-mediated transplacental passage of IgE during pregnancy. However, direct interaction of FcRn and IgE was not investigated. Here, we compared binding of human IgE and IgG variants to recombinant soluble human FcRn with β2-microglobulin (sFcRn) in surface plasmon resonance (SPR) at pH 7.4 and pH 6.0. No interaction was found between human IgE and human sFcRn. These results imply that FcRn can only transport IgE indirectly, and thereby possibly transfer allergenic sensitivity from mother to fetus.
OpenWeedLocator (OWL): an open-source, low-cost device for fallow weed detection
Authors: Coleman Guy , Salter William , Walsh Michael
Published: January 2022

The use of a fallow phase is an important tool for maximizing crop yield potential in moisture limited agricultural environments, with a focus on removing weeds to optimize fallow efficiency. Repeated whole field herbicide treatments to control low-density weed populations is expensive and wasteful. Site-specific herbicide applications to low-density fallow weed populations is currently facilitated by proprietary, sensor-based spray booms. The use of image analysis for fallow weed detection is an opportunity to develop a system with potential for in-crop weed recognition. Here we present OpenWeedLocator (OWL), an open-source, low-cost and image-based device for fallow weed detection that improves accessibility to this technology for the weed control community. A comprehensive GitHub repository was developed, promoting community engagement with site-specific weed control methods. Validation of OWL as a low-cost tool was achieved using four, existing colour-based algorithms over seven fallow fields in New South Wales, Australia. The four algorithms were similarly effective in detecting weeds with average precision of 79% and recall of 52%. In individual transects up to 92% precision and 74% recall indicate the performance potential of OWL in fallow fields. OWL represents an opportunity to redefine the approach to weed detection by enabling community-driven technology development in agriculture.
Multistable autonomous motion of fruit on a smooth hotplate
Authors: Bandyopadhyay Promode R.
Published: January 2022

Origin of scale coupling may be clarified by the understanding of multistability, or shifts between stable points via unstable equilibrium points due to a stimulus. When placed on a glasstop hotplate, cobs of corn underwent multistable autonomous oscillation, with unsteady viscous lubrication below and transitional plumes above, where the buoyancy to inertia force ratio is close to ≥ 1.0. Subsequently, viscous wall-frictional multistability occurred in six more types of smooth fruit with nominal symmetry. Autonomous motion observed are: cobs roll, pitch and yaw; but green chillies, blueberries, tropical berries, red grapes, oblong grapes and grape tomatoes roll and yaw. The cross products of the orthogonal angular momentum produce the observed motion. The prevalence of roll and yaw motion are the most common. Lubricant film thickness h$$\propto$$
∝
U/(TF), for cob mass F, tangential velocity U and temperature T. In heavier cobs, the film thins, breaking frequently, changing stability. Lighter cobs have high h, favoring positive feedback and more spinning: more T rises, more viscosity of water drops, increasing U and h more, until cooling onsets. Infrequent popping of the tender corn kernel has the same mean sound pressure level as in hard popcorn. The plume vortex jets lock-in to the autonomous rolling cob oscillation. Away from any solid surface, the hot-cold side boundary produces plumes slanted at ± 45°. Surface fencing (13–26 μm high) appears to control motion drift.
Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus
Authors: Obata Youhei , Kubota-Sakashita Mie , Kasahara Takaoki , Mizuno Masafumi , Nemoto Takahiro , Kato Tadafumi
Published: January 2022

Monoamine oxidase (MAO) is a key enzyme responsible for the degradation of neurotransmitters and trace amines. MAO has two subtypes (MAO-A and MAO-B) that are encoded by different genes. In the brain, MAO-B is highly expressed in the paraventricular thalamic nucleus (PVT); however, its substrate in PVT remains unclear. To identify the MAO-B substrate in PVT, we generated Maob knockout (KO) mice and measured five candidate substrates (i.e., noradrenaline, dopamine, 3-methoxytyramine, serotonin, and phenethylamine [PEA]) by liquid chromatography tandem mass spectrometry. We showed that only PEA levels were markedly elevated in the PVT of Maob KO mice. To exclude the influence of peripheral MAO-B deficiency, we developed brain-specific Maob KO mice, finding that PEA in the PVT was increased in brain-specific Maob KO mice, whereas the extent of PEA increase was less than that in global Maob KO mice. Given that plasma PEA levels were elevated in global KO mice, but not in brain–specific KO mice, and that PEA passes across the blood–brain barrier, the substantial accumulation of PEA in the PVT of Maob KO mice was likely due to the increase in plasma PEA. These data suggest that PEA is a substrate of MAO-B in the PVT as well as other tissues.
Light sheet based volume flow cytometry (VFC) for rapid volume reconstruction and parameter estimation on the go
Authors: Kumar Prashant , Joshi Prakash , Basumatary Jigmi , Mondal Partha Pratim
Published: January 2022

Optical imaging is paramount for disease diagnosis and to access its progression over time. The proposed optical flow imaging (VFC/iLIFE) is a powerful technique that adds new capabilities (3D volume visualization, organelle-level resolution, and multi-organelle screening) to the existing system. Unlike state-of-the-art point-illumination-based biomedical imaging techniques, the sheet-based VFC technique is capable of single-shot sectional visualization, high throughput interrogation, real-time parameter estimation, and instant volume reconstruction with organelle-level resolution of live specimens. The specimen flow system was realized on a multichannel (Y-type) microfluidic chip that enables visualization of organelle distribution in several cells in-parallel at a relatively high flow-rate (2000 nl/min). The calibration of VFC system requires the study of point emitters (fluorescent beads) at physiologically relevant flow-rates (500–2000 nl/min) for determining flow-induced optical aberration in the system point spread function (PSF). Subsequently, the recorded raw images and volumes were computationally deconvolved with flow-variant PSF to reconstruct the cell volume. High throughput investigation of the mitochondrial network in HeLa cancer cell was carried out at sub-cellular resolution in real-time and critical parameters (mitochondria count and size distribution, morphology, entropy, and cell strain statistics) were determined on-the-go. These parameters determine the physiological state of cells, and the changes over-time, revealing the metastatic progression of diseases. Overall, the developed VFC system enables real-time monitoring of sub-cellular organelle organization at a high-throughput with high-content capacity.
Hall effect in gated single-wall carbon nanotube films
Authors: Yomogida Yohei , Horiuchi Kanako , Okada Ryotaro , Kawai Hideki , Ichinose Yota , Nishidome Hiroyuki , Ueji Kan , Komatsu Natsumi , Gao Weilu , Kono Junichiro , Yanagi Kazuhiro
Published: January 2022

The presence of hopping carriers and grain boundaries can sometimes lead to anomalous carrier types and density overestimation in Hall-effect measurements. Previous Hall-effect studies on carbon nanotube films reported unreasonably large carrier densities without independent assessments of the carrier types and densities. Here, we have systematically investigated the validity of Hall-effect results for a series of metallic, semiconducting, and metal–semiconductor-mixed single-wall carbon nanotube films. With carrier densities controlled through applied gate voltages, we were able to observe the Hall effect both in the n- and p-type regions, detecting opposite signs in the Hall coefficient. By comparing the obtained carrier types and densities against values derived from simultaneous field-effect-transistor measurements, we found that, while the Hall carrier types were always correct, the Hall carrier densities were overestimated by up to four orders of magnitude. This significant overestimation indicates that thin films of one-dimensional SWCNTs are quite different from conventional hopping transport systems.
Incidence and clearance of anal high-risk Human Papillomavirus infection and their risk factors in men who have sex with men living with HIV
Authors: Donà Maria Gabriella , Giuliani Massimo , Rollo Francesca , Vescio Maria Fenicia , Benevolo Maria , Giglio Amalia , Giuliani Eugenia , Morrone Aldo , Latini Alessandra
Published: January 2022

HIV-infected men who have sex with men (MSM) display the highest prevalence of anal infection by high-risk Human Papillomaviruses (hrHPVs) and incidence of anal carcinoma. Anal specimens were genotyped by the Linear Array. Incidence and clearance of anal infection by hrHPVs, hrHPVs other than HPV16, low-risk HPVs, and four individual types (6,11,16,18) were estimated using a two-state Markov model. Determinants for incidence and clearance were assessed by logistic regression. Overall, 204 individuals were included (median age 42 years, IQR = 34–49). For hrHPVs, incidence and clearance rates were 36.1 × 1000 person-months (p-m) (95% CI 23.3–56.5) and 15.6 × 1000 p-m (95% CI 10.7–23.3), respectively. HPV16 showed a higher incidence than HPV18 (10.2 vs. 7.2 × 1000 p-m). Its clearance was more than twofold lower than that of HPV18 (30.1 vs. 78.2 × 1000 p-m). MSM receiving cART displayed a 68% to 88% decrease in risk of acquiring hrHPVs, hrHPVs other than HPV16, HPV16, and HPV18 (adjusted Hazard Ratio [aHR] 0.13, 95% CI 0.02–0.67; aHR 0.22, 95% CI 0.06–0.78; aHR 0.32, 95% CI 0.12–0.90; aHR 0.12, 95% CI 0.04–0.31, respectively) than patients not treated. A nadir CD4 + count < 200 cells/mm3 significantly reduced the clearance of hrHPVs other than HPV16 (aHR 0.39, 95% CI 0.17–0.90). cART use reduces the risk of acquiring anal infection by hrHPVs.
Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection
Authors: Sheikh Abdalla , Jackson Jennie , Shim Hanjoo Brian , Yau Clement , Seo Jung Hee , Abraham Ninan
Published: January 2022

Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366–374 and PA224–233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224–233-specific than NP366–374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.
Network models of prostate cancer immune microenvironments identify ROMO1 as heterogeneity and prognostic marker
Authors: Wang Lei , Liu Xudong , Liu Zhe , Wang Yafan , Fan Mengdi , Yin Jinyue , Zhang Yu , Ma Ying , Luo Jia , Li Rui , Zhao Xue , Zhang Peiju , Zhao Lijun , Fan Jinke , Chen Yuxuan , Lu Wei , Song Xinqiang
Published: January 2022

Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level. First, the data were retrieved from TCGA dataset, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them. Here, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 to predict PCa prognosis. Cox regression analysis of ROMO1 was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1. In conclusion, we putative ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa, which provides new insights into the diagnosis and treatment of PCa.
Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
Authors: Albericio Guillermo , Aguilar Susana , Torán Jose Luis , Yañez Rosa , López Juan Antonio , Vázquez Jesús , Mora Carmen , Bernad Antonio
Published: January 2022

Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.
Multiple bacterial partners in symbiosis with the nudibranch mollusk Rostanga alisae
Authors: Zhukova Natalia V. , Eliseikina Marina G. , Balakirev Evgeniy S. , Ayala Francisco J.
Published: January 2022

The discovery of symbiotic associations extends our understanding of the biological diversity in the aquatic environment and their impact on the host’s ecology. Of particular interest are nudibranchs that unprotected by a shell and feed mainly on sponges. The symbiotic association of the nudibranch Rostanga alisae with bacteria was supported by ample evidence, including an analysis of cloned bacterial 16S rRNA genes and a fluorescent in situ hybridization analysis, and microscopic observations. A total of 74 clones belonging to the phyla α-, β-, γ-Proteobacteria, Actinobacteria, and Cyanobacteria were identified. FISH confirmed that bacteriocytes were packed with Bradyrhizobium, Maritalea, Labrenzia, Bulkholderia, Achromobacter, and Stenotrophomonas mainly in the foot and notum epidermis, and also an abundance of Synechococcus cyanobacteria in the intestinal epithelium. An ultrastructural analysis showed several bacterial morphotypes of bacteria in epidermal cells, intestine epithelium, and in mucus layer covering the mollusk body. The high proportion of typical bacterial fatty acids in R. alisae indicated that symbiotic bacteria make a substantial contribution to its nutrition. Thus, the nudibranch harbors a high diversity of specific endo- and extracellular bacteria, which previously unknown as symbionts of marine invertebrates that provide the mollusk with essential nutrients. They can provide chemical defense against predators.
Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis
Authors: Wu Yi , Liu Xinqiao , Li Guiwei
Published: January 2022

Huangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein–protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log2FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis.
Whole-genome-scale identification of novel non-protein-coding RNAs controlling cell proliferation and survival through a functional forward genetics strategy
Authors: Tonge D. P. , Darling D. , Farzaneh F. , Williams G. T.
Published: January 2022

Identification of cell fate-controlling lncRNAs is essential to our understanding of molecular cell biology. Here we present a human genome-scale forward-genetics approach for the identification of lncRNAs based on gene function. This approach can identify genes that play a causal role, and immediately distinguish them from those that are differentially expressed but do not affect cell function. Our genome-scale library plus next-generation-sequencing and bioinformatic approach, radically upscales the breadth and rate of functional ncRNA discovery. Human gDNA was digested to produce a lentiviral expression library containing inserts in both sense and anti-sense orientation. The library was used to transduce human Jurkat T-leukaemic cells. Cell populations were selected using continuous culture ± anti-FAS IgM, and sequencing used to identify sequences controlling cell proliferation. This strategy resulted in the identification of thousands of new sequences based solely on their function including many ncRNAs previously identified as being able to modulate cell survival or to act as key cancer regulators such as AC084816.1*, AC097103.2, AC087473.1, CASC15*, DLEU1*, ENTPD1-AS1*, HULC*, MIRLET7BHG*, PCAT-1, SChLAP1, and TP53TG1. Independent validation confirmed 4 out of 5 sequences that were identified by this strategy, conferred a striking resistance to anti-FAS IgM-induced apoptosis.
Ultra-fast data sanitization of SRAM by back-biasing to resist a cold boot attack
Authors: Han Seong-Joo , Han Joon-Kyu , Yun Gyeong-Jun , Lee Mun-Woo , Yu Ji-Man , Choi Yang-Kyu
Published: January 2022

Although SRAM is a well-established type of volatile memory, data remanence has been observed at low temperature even for a power-off state, and thus it is vulnerable to a physical cold boot attack. To address this, an ultra-fast data sanitization method within 5 ns is demonstrated with physics-based simulations for avoidance of the cold boot attack to SRAM. Back-bias, which can control device parameters of CMOS, such as threshold voltage and leakage current, was utilized for the ultra-fast data sanitization. It is applicable to temporary erasing with data recoverability against a low-level attack as well as permanent erasing with data irrecoverability against a high-level attack.
Prediction scenarios of past, present, and future environmental suitability for the Mediterranean species Arbutus unedo L.
Authors: Almeida Alice Maria , Martins Maria João , Campagnolo Manuel Lameiras , Fernandez Paulo , Albuquerque Teresa , Gerassis Saki , Gonçalves José Carlos , Ribeiro Maria Margarida
Published: January 2022

Climate change is a challenge for forests in the coming decades, with a major impact on species adaptation and distribution. The Mediterranean Basin is one of the most vulnerable hotspots for biodiversity conservation under climate change in the world. This research aimed at studying a Mediterranean species well adapted to the region: the Arbutus unedo L. (strawberry tree). The MaxEnt, a presence-only species-distribution software, was used to model A. unedo’s environmental suitability. The current species potential distribution was accessed based on actual occurrences and selected environmental variables and subsequently projected for the Last Glacial Maximum (LGM), the Mid-Holocene (MH), and the years 2050 and 2070, considering the two Representative Concentration Pathways: RCP4.5 and RCP8.5. Results from the LGM projection suggest the presence of refugia in the core of the Mediterranean Basin, in particular the Iberian Peninsula (IP). The projections for the MH indicate increasing climatic suitability for the species and an eastward expansion, relatively to LGM. The predicted future environmental changes will most likely act as a catalyst for suitable habitat loss and a range shift towards the North is likely to occur.
Mortality associated with nonrestorative short sleep or nonrestorative long time-in-bed in middle-aged and older adults
Authors: Yoshiike Takuya , Utsumi Tomohiro , Matsui Kentaro , Nagao Kentaro , Saitoh Kaori , Otsuki Rei , Aritake-Okada Sayaka , Suzuki Masahiro , Kuriyama Kenichi
Published: January 2022

Associations of sleep duration with human health could differ depending on whether sleep is restorative. Using data from 5804 participants of the Sleep Heart Health Study, we examined the longitudinal association of sleep restfulness combined with polysomnography-measured total sleep time (TST) or time in bed (TIB), representing different sleeping behaviors, with all-cause mortality. Among middle-aged adults, compared with restful intermediate TST quartile, the lowest TST quartile with feeling unrested was associated with higher mortality (hazard ratio [HR], 1.54; 95% confidence interval [CI] 1.01–2.33); the highest TST quartile with feeling rested was associated with lower mortality (HR, 0.55; 95% CI 0.32–0.97). Among older adults, the highest TIB quartile with feeling unrested was associated with higher mortality, compared with restful intermediate TIB quartile (HR, 1.57; 95% CI 1.23–2.01). Results suggest a role of restorative sleep in differentiating the effects of sleep duration on health outcomes in midlife and beyond.
Regulation of gene expression by the APP family in the adult cerebral cortex
Authors: Cha Hye Ji , Shen Jie , Kang Jongkyun
Published: January 2022

Amyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. APP has two homologs, amyloid precursor-like protein 1 and 2 (APLP1 and APLP2), and they have functional redundancy. APP intracellular c-terminal domain (AICD), produced by sequential α- or β- and γ-secretase cleavages, is thought to control gene expression, similarly as the ICD of Notch. To investigate the role of APP family in transcriptional regulation, we examined gene expression changes in the cerebral cortex of APP/APLP1/APLP2 conditional triple knockout (cTKO) mice, in which APP family members are selectively inactivated in excitatory neurons of the postnatal forebrain. Of the 12 previously reported AICD target genes, only Nep and Npas4 mRNA levels were significantly reduced in the cerebral cortex of cTKO mice, compared to littermate controls. We further examined global transcriptional changes by RNA-seq and identified 189 and 274 differentially expressed genes in the neocortex and hippocampus, respectively, of cTKO mice relative to controls. Gene Ontology analysis indicated that these genes are involved in a variety of cellular functions, including extracellular organization, learning and memory, and ion channels. Thus, inactivation of APP family alters transcriptional profiles of the cerebral cortex and affects wide-ranging molecular pathways.
Effects of neighboring transitions on the mechanisms of electromagnetically induced absorption and transparency in an open degenerate multilevel system
Authors: Jadoon Zeeshan Ali Safdar , Noh Heung-Ryoul , Kim Jin-Tae
Published: January 2022

In this study, optical Bloch equations with and without neighboring hyperfine states near the degenerate two-level system (DTLS) in the challenging case of $$^{85}$$

85

Rb D2 transition, which involves the Doppler broadening effect, are solved. The calculated spectra agree well with the experimental results obtained based on the coupling-probe scheme with orthogonal linear polarizations of the coupling and probe fields. The mechanisms of electromagnetically induced absorption (electromagnetically induced transparency) for the open $$F_g=3 \rightarrow F_e=2$$

F
g

=
3
→

F
e

=
2

and 3 transitions (open $$F_g=2 \rightarrow F_e=2$$

F
g

=
2
→

F
e

=
2

and 3 transitions) are determined to be the effect of the strong closed $$F_g=3 \rightarrow F_e=4$$

F
g

=
3
→

F
e

=
4

transition line (strong closed $$F_g=2 \rightarrow F_e=1$$

F
g

=
2
→

F
e

=
1

transition line); this finding is based on a comparison between the calculated absorption profiles of the DTLS without neighboring states and those of all levels with neighboring states, depending on the coupling and probe power ratios. Furthermore, based on the aforementioned comparison, the crucial factors that enhance or reduce the coherence effects and lead to the transformation between electromagnetically induced absorption and electromagnetically induced transparency, are (1) the power ratios between the coupling and probe beams, (2) the openness of the excited state, and (3) effects of the neighboring states due to Doppler broadening in a real atomic system.
MiR-29b may suppresses peritoneal metastases through inhibition of the mesothelial–mesenchymal transition (MMT) of human peritoneal mesothelial cells
Authors: Kimura Yuki , Ohzawa Hideyuki , Miyato Hideyo , Kaneko Yuki , Saito Akira , Takahashi Kazuya , Tojo Mineyuki , Yamaguchi Hironori , Kurashina Kentaro , Saito Shin , Hosoya Yoshinori , Lefor Alan Kawarai , Sata Naohiro , Kitayama Joji
Published: January 2022

Peritoneal dissemination is a major metastatic pathway for gastrointestinal and ovarian malignancies. The miR-29b family is downregulated in peritoneal fluids in patients with peritoneal metastases (PM). We examined the effect of miR-29b on mesothelial cells (MC) which play critical a role in the development of PM through mesothelial-mesenchymal transition (MMT). Human peritoneal mesothelial cells (HPMCs) were isolated from surgically resected omental tissue and MMT induced by stimulation with 10 ng/ml TGF-β1. MiR-29b mimics and negative control miR were transfected by lipofection using RNAiMAX and the effects on the MMT evaluated in vitro. HPMC produced substantial amounts of miR-29b which was markedly inhibited by TGF-β1. TGF-β1 stimulation of HPMC induced morphological changes with decreased expression of E-cadherin and calretinin, and increased expression of vimentin and fibronectin. TGF-β1 also enhanced proliferation and migration of HPMC as well as adhesion of tumor cells in a fibronectin dependent manner. However, all events were strongly abrogated by simultaneous transfection of miR-29b. MiR-29b inhibits TGF-β1 induced MMT and replacement of miR-29b in the peritoneal cavity might be effective to prevent development of PM partly through the effects on MC.
High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD)
Authors: Beppu Shohei , Kinoshita Makoto , Wilamowski Jan , Suenaga Tadahiro , Yasumizu Yoshiaki , Ogawa Kotaro , Ishikura Teruyuki , Tada Satoru , Koda Toru , Murata Hisashi , Shiraishi Naoyuki , Sugiyama Yasuko , Kihara Keigo , Sugimoto Tomoyuki , Arase Hisashi , Standley Daron M. , Okuno Tatsusada , Mochizuki Hideki
Published: January 2022

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease characterized by the presence of pathogenic autoantibodies, anti-aquaporin 4 (AQP4) antibodies. Recently, HLA-DQA1*05:03 was shown to be significantly associated with NMOSD in a Japanese patient cohort. However, the specific mechanism by which HLA-DQA1*05:03 is associated with the development of NMOSD has yet to be elucidated. In the current study, we revealed that HLA-DQA1*05:03 exhibited significantly higher cell surface expression levels compared to other various DQA1 alleles, and that its expression strongly depended on the amino acid sequence of the α1 domain, with a preference for leucine at position 75. Moreover, in silico analysis indicated that the HLA-DQ encoded by HLA-DQA1*05:03 preferentially presents immunodominant AQP4 peptides, and that the peptide major histocompatibility complexes (pMHCs) are more energetically stable in the presence of HLA-DQA1*05:03 than other HLA-DQA1 alleles. In silico 3D structural models were also applied to investigate the validity of the energetic stability of pMHCs. Taken together, our findings indicate that HLA-DQA1*05:03 possesses a distinct property to play a pathogenic role in the development of NMOSD.