bluuebunny/crossref_metadata_2025 huggingface dataset:
Distúrbios osteomusculares relacionados ao trabalho: uma caracterização da sintomatologia e dos exames diagnósticos
Authors: Santos Iraneide Nascimento dos , Martins Islane Cristina , Santos Amilton da Cruz , Oliveira Adriana Sarmento de , Brasileiro-Santos Maria do Socorro
Published: January 2021

Objetivo: caracterizar as queixas clínicas e os achados de imagem nos distúrbios osteomusculares relacionados ao trabalho (DORT). Método: trata-se de uma pesquisa descritiva, exploratória e transversal, realizada em um Centro de Referência à Saúde do Trabalhador, com uma amostra composta de 60 sujeitos. Foi realizada uma entrevista individual, que utilizou um questionário e um roteiro para análise dos exames. Resultados: a população foi em sua maioria masculina (66,7%), a profissão mais acometida foi o operador de máquina (18,3%), as queixas mais relatadas foram dor (100%) e falta de força (93,3%). Os locais mais citados foram o ombro direito (26,5%) e a coluna lombar (37,5%). Os diagnósticos mais prevalentes foram as tendinopatias nos ombros (39,1%) e os transtornos nos discos vertebrais (28,1%). Os exames mais utilizados para auxiliar no diagnóstico foram a ultrassonografia (38%) e a ressonância (36,5%). As alterações mais encontradas nos tendões, músculos, sinóvias e bursas – inflamações (10,3%) e calcificações (11,2%) - e nos discos vertebrais – protusões discais (13,1%) e presença de osteófitos (10,3%). Considerou-se um nível de significância p< 0,05 e intervalo de confiança (IC) de 95% para os cálculos das frequências. Conclusão: tendo em vista a vulnerabilidade dos trabalhadores aos distúrbios, é importante valorizar as queixas clínicas do paciente e as informações contidas nos exames de imagem, com a finalidade de se ter o diagnóstico clínico precoce e de auxiliar os profissionais de saúde a viabilizarem a terapêutica mais adequada.
Taxa metabólica basal de adolescentes com sobrepeso ou obesidade
Authors: Westphal Greice , Soares Geison Schmidt , Vespasiano Bruno de Souza , Christinelli Heloá Costa Borim , Pereira Igor Alisson Spagnol , Castilho Mario Moreira , Martins Fernando Malentaqui , Nardo Junior Nelson
Published: January 2021

A taxa metabólica basal (TMB) representa o principal componente do gasto energético (GE) em humanos e, por isso, tem grande relevância em programas de tratamento da obesidade. Apesar disso, pouco são os estudos que apresentem dados relacionada a TMB de adolescentes com sobrepeso ou obesidade. Diante disso, o objetivo do presente trabalho é apresentar informações sobre a TMB de adolescentes com idade entre 10 e 18 anos, de ambos os sexos, com IMC entre 25,3 a 52,5 kg/m2. Foram avaliados, mediante o método da calorimetria indireta (CI) 91 adolescentes, sendo 37 meninos e 54 meninas. A prevalência de sobrepeso foi de 23,0%, obesidade 36,3% e obesidade severa (40,6%). A mediana da TMB foi de 2.150,9 e 1.548,4 para meninos e meninas, respectivamente (p<0,05). Apesar disso, não houve diferença significativa na TMB por unidade de massa (TMB/Kg) e nem por unidade de massa magra (TMB/MM). Além disso, foi verificada uma correlação significativa (p<0,000) entre a TMB medida pela CI e a estimada pela bioimpedância elétrica multifrequencial.
Wildfires and Brazilian irrationality on social networks
Authors: Silva HM
Published: January 2021

Recent forest fires in Brazil and Australia have been the subject of irrational discussions on social networks without any legitimate scientific basis. These discussions often overlook or ignore fundamental questions about how limited government reactions, especially from the Brazilian government, to climate change affect these disasters. This article seeks to foster a discussion supported by data about climate change, the consequences of increased frequency of catastrophic weather events, and ways in which aggressiveness and ignorance via the internet and social networks do nothing to address the underlying issues.
Glycotoxines, Carbonyl Stress and Relevance to Diabetes and Its
Complications
Authors: Turk Z
Published: January 2021

A large body of evidence has implicated reactive carbonyl
compounds as glycotoxic mediators of carbonyl stress. This
review is focused on the pathophysiological effects of
α-oxoaldehydes in diabetes and related complications,
summarizing the state-of-the-art on the endogenously produced
carbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, formed
as glycolytic intermediates during metabolic conversion of
glucose, via Maillard reaction by degradation of glycated proteins,
and during lipid peroxidation process. Their role in the advanced
glycation process and detrimental effects on vascular tissue are
discussed.
ECG Body Surface Mapping Changes in Type 1 Diabetic Patients with
and without Autonomic Neuropathy
Authors: Palová S , Szabo K , Charvát J , Slavíček J , Medová E , Mlček M , Kittnar O
Published: January 2021

ECG body surface mapping (BSM) parameters in patients with
diabetes mellitus Type 1 (DM1) are significantly different
comparing to healthy non-diabetic subjects. Hypothesis that
these changes are more pronounced in DM1 patients with
autonomic neuropathy (AN) was tested. The parameters of BSM
were registered by diagnostic system Cardiag 112.2 in 54 DM1
patients including 25 with AN and 30 control subjects. AN was
diagnosed according to Ewing criteria when two or more Ewing
tests were abnormal. In classic 12-lead ECG the heart rate was
increased, QRS and QT shortened (p<0.01) and QTC prolonged in
DM1 patients. The VCG measurement of QRS-STT angles and
spatial QRS-STT angle showed non-significant differences. The
absolute values of maximum and minimum in depolarization and
repolarization isopotential, isointegral, isoarea maps were
significantly different in DM1 patients in comparison with controls
(p<0.01). The changes were more pronounced in DM1 patients
with AN than in DM patients without AN (p<0.05). The QT
duration measured in 82 leads of thorax was significantly
shortened in 68 leads of both groups of DM 1 patients (p<0.01)
when compared with controls. In 34 of them this shortening was
more pronounced in DM1 patients with AN than in DM1 patients
without AN (p<0.05). The results showed that the method of
ECG BSM is capable to confirm the presence of autonomic
neuropathy in diabetic patients.
Spinal Cord Injury Blunted Effects of Endothelin-1 on Ca2+ Transients
and Calcium Current in Isolated Rat Cardiomyocytes
Authors: Guo Y-F , Ren A-J , Chen D-Y , Yuan W , Chen Y , Gou S-H , Jia L-S , Yuan W-J , Liu Y
Published: January 2021

Plasma endothelin-1 (ET-1) levels are elevated in spinal cord
injury (SCI), and ET-1 may be involved in the pathophysiology of
this condition. However, its effects on contractile function of the
heart of SCI rats are still unknown. To define more clearly the
possiblel role of ET-1 following SCI, we investigated the effect of
ET-1 on the contraction, calcium transients and L-type calcium
current (ICa,L) in the cardiomyocytes of control and SCI rats.
Sixteen Sprague-Dawley male rats aged 80-100 days and
weighing 250-350 g were randomized into control and SCI
groups. Fourteen days following compression injury to the spinal
cord, effects of ET-1 on the contraction, calcium transients and
ICa,L were studied in the cardiomyocytes of control and SCI rats
by the technique of simultaneous measurement of intracellular
Ca2+ and contraction and by whole-cell configuration of the
patch-clamp technique. In myocytes from control rats, ET-1
significantly increased contraction, the magnitude of Ca2+
transients and the peak amplitude of ICa,L. However, ET-1 had
little effect on the amplitude of contraction, calcium transients
and ICa,L in myocytes from SCI rats. These results suggest that
the positive inotropic effects of ET-1 on control myocardial
contraction may be altered in pathological states such as SCI.
Surface Modification of Cyclic Olefin Copolymers for Osteochondral
Defect Repair Can Increase Pro-Destructive Potential of Human
Chondrocytes In Vitro
Authors: Polanská M , Hulejová H , Petrtýl M , Bastl Z , Spirovová I , Kruliš Z , Horák Z , Veigl D , Šenolt L
Published: January 2021

Materials on the basis of cycloolefin copolymers (COC) are
suitable for subchondral defect repairs. The objective of this
study was to evaluate the influence of surface modification of
COC and COC/LLDPE blends on the viability and gene expression
of chondrocytes. Human chondrocytes were incubated on the
surface of the studied materials. Half of the materials were
plasmatically modified with a subsequent type II collagen
application. The gene expression of matrix metalloproteinases
(MMP-1,-3,-13), pro-inflammatory cytokines (IL-1, TNF-alpha)
and apoptotic molecules (BAX, Bcl-2) was evaluated using
quantitative Taq-Man PCR after 48 h incubation. Chondrocyte
viability was evaluated by the MTT test after 2, 4 and 8 days of
incubation. The synthesis of MMPs was measured by ELISA assay
in cell culture medium after 48 h of incubation. Chondrocytes
incubated on plasmatically modified in contrast to unmodified
materials demonstrated significantly increased gene expression of
IL-1 (p<0.05), MMP-1 and MMP-3 (p<0.05 for both comparisons)
as well as MMP-13 (p<0.001). Increased gene expression was
confirmed by significantly increased production of active forms of
particular MMPs into the cell culture medium. Unlike surface
unmodified polymers, the modified materials showed timedependent reduction of chondrocyte viability. The gene
expression of TNF-α and apoptotic molecules by chondrocytes
was not significantly changed by different materials. Cycloolefin
copolymers and their blends may represent suitable materials for
tissue engineering, however, their surface modification followed
by collagen type II application may, at least under in vitro
conditions, reduce the viability of chondrocytes and induce their
pro-destructive behavior. The potential benefit or disadvantage
of surface modifications of materials for osteochondral defect
repairs needs to be further elucidated.
Nanomaterial Nitric Oxide Delivery in Traumatic Orthopedic Regenerative Medicine
Authors: Anastasio Albert Thomas , Paniagua Ariana , Diamond Carrie , Ferlauto Harrison R. , Fernandez-Moure Joseph S.
Published: January 2021

Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.
Rapid Fabrication of Cell-Laden Microfibers for Construction of Aligned Biomimetic Tissue
Authors: Lu Bingchuan , Li Mingfeng , Fang Yongcong , Liu Zibo , Zhang Ting , Xiong Zhuo
Published: January 2021

Bottom-up engineering of tissue constructs is being rapidly developed and broadly applied in biomanufacturing. As one type of building block, cell-laden microfibers are promising for reconstruction of oriented structures and functions of linear tissues, such as skeletal muscles, myocardia, and spinal cord tissues. Herein, we propose wet-spinning method with agitating collection, wherein alginate-based material is extruded into an agitated CaCl2 bath with a magnetic rotor acting as the microfiber collector. By applying this method, we achieve rapid fabrication and oriented collection of hydrogel microfibers with diameters ranging from 100 to 400 μm. In addition, we encapsulate myoblasts in the hydrogel to form cell-laden microfibers, which show a high viability (more than 94%) during in vitro culture. Moreover, the method allows to fabricate of cell-laden core–sheath microfibers and hollow microfibers. We also fabricate 3D constructs using various methods of microfiber assembly like weaving and braiding. The assembling results suggest that the proposed method is a promising technology for bottom-up engineering of aligned biomimetic tissue constructs.
Topographic Guidance in Melt-Electrowritten Tubular Scaffolds Enhances Engineered Kidney Tubule Performance
Authors: van Genderen Anne Metje , Jansen Katja , Kristen Marleen , van Duijn Joost , Li Yang , Schuurmans Carl C. L. , Malda Jos , Vermonden Tina , Jansen Jitske , Masereeuw Rosalinde , Castilho Miguel
Published: January 2021

Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (Ø > 2 mm) for mechanical self-support, or smaller (Ø 150–500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported kidney proximal tubules with enhanced properties.

Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (Ø = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality.

Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp).

Discussion and Conclusion: Here, we present smaller diameter engineered kidney tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
PprI: The Key Protein in Response to DNA Damage in Deinococcus
Authors: Lu Huizhi , Hua Yuejin
Published: January 2021

Deoxyribonucleic acid (DNA) damage response (DDR) pathways are essential for maintaining the integrity of the genome when destabilized by various damaging events, such as ionizing radiation, ultraviolet light, chemical or oxidative stress, and DNA replication errors. The PprI–DdrO system is a newly identified pathway responsible for the DNA damage response in Deinococcus, in which PprI (also called IrrE) acts as a crucial component mediating the extreme resistance of these bacteria. This review describes studies about PprI sequence conservation, regulatory function, structural characteristics, biochemical activity, and hypothetical activation mechanisms as well as potential applications.
ZP4 Is Present in Murine Zona Pellucida and Is Not Responsible for the Specific Gamete Interaction
Authors: Izquierdo-Rico Mª José , Moros-Nicolás Carla , Pérez-Crespo Míriam , Laguna-Barraza Ricardo , Gutiérrez-Adán Alfonso , Veyrunes Frédéric , Ballesta José , Laudet Vincent , Chevret Pascale , Avilés Manuel
Published: January 2021

Mammalian eggs are surrounded by an extracellular matrix called the zona pellucida (ZP). This envelope participates in processes such as acrosome reaction induction, sperm binding, protection of the oviductal embryo, and may be involved in speciation. In eutherian mammals, this coat is formed of three or four glycoproteins (ZP1–ZP4). WhileMus musculushas been used as a model to study the ZP for more than 35 years, surprisingly, it is the only eutherian species in which the ZP is formed of three glycoproteins Zp1, Zp2, and Zp3,Zp4being a pseudogene.Zp4was lost in theMuslineage after it diverged fromRattus, although it is not known when precisely this loss occurred. In this work, the status of Zp4 in several murine rodents was tested by phylogenetic, molecular, and proteomic analyses. Additionally, assays of crossin vitrofertilization between three and four ZP rodents were performed to test the effect of the presence of Zp4 in murine ZP and its possible involvement in reproductive isolation. Our results showed thatZp4pseudogenization is restricted to the subgenusMus, which diverged around 6 MYA. Heterologousin vitrofertilization assays demonstrate that a ZP formed of four glycoproteins is not a barrier for the spermatozoa of species with a ZP formed of three glycoproteins. This study identifies the existence of several mouse species with four ZPs that can be considered suitable for use as an experimental animal model to understand the structural and functional roles of the four ZP proteins in other species, including human.
miRNAs and Müller Glia Reprogramming During Retina Regeneration
Authors: Konar Gregory J. , Ferguson Claire , Flickinger Zachary , Kent Matthew R. , Patton James G.
Published: January 2021

The use of model systems that are capable of robust, spontaneous retina regeneration has allowed for the identification of genetic pathways and components that are required for retina regeneration. Complemented by mouse models in which retina regeneration can be induced after forced expression of key factors, altered chromatin accessibility, or inhibition of kinase/signaling cascades, a clearer picture of the key regulatory events that control retina regeneration is emerging. In all cases, Müller glia (MG) serve as an adult retinal stem cell that must be reprogrammed to allow for regeneration, with the end goal being to understand why regenerative pathways are blocked in mammals, but spontaneous in other vertebrates such as zebrafish. miRNAs have emerged as key gene regulatory molecules that control both development and regeneration in vertebrates. Here, we focus on a small subset of miRNAs that control MG reprogramming during retina regeneration and have the potential to serve as therapeutic targets for treatment of visual disorders and damage.
RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I
Authors: Huang Lingtong , Fang Xueling , Zhang Xuan , Wu Weifang , Yao Hangping , Fang Qiang
Published: January 2021

The macrophage stimulating protein (MSP)–Recepteur d’origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic dendritic cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.
Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
Authors: Kargaran Parisa K. , Mosqueira Diogo , Kozicz Tamas
Published: January 2021

Mitochondrial medicine is an exciting and rapidly evolving field. While the mitochondrial genome is small and differs from the nuclear genome in that it is circular and free of histones, it has been implicated in neurodegenerative diseases, type 2 diabetes, aging and cardiovascular disorders. Currently, there is a lack of efficient treatments for mitochondrial diseases. This has promoted the need for developing an appropriate platform to investigate and target the mitochondrial genome. However, developing these therapeutics requires a model system that enables rapid and effective studying of potential candidate therapeutics. In the past decade, induced pluripotent stem cells (iPSCs) have become a promising technology for applications in basic science and clinical trials, and have the potential to be transformative for mitochondrial drug development. Engineered iPSC-derived cardiomyocytes (iPSC-CM) offer a unique tool to model mitochondrial disorders. Additionally, these cellular models enable the discovery and testing of novel therapeutics and their impact on pathogenic mtDNA variants and dysfunctional mitochondria. Herein, we review recent advances in iPSC-CM models focused on mitochondrial dysfunction often causing cardiovascular diseases. The importance of mitochondrial disease systems biology coupled with genetically encoded NAD+/NADH sensors is addressed toward developing an in vitro translational approach to establish effective therapies.
Stochastic Modeling of Explosive Eruptive Events at Galeras Volcano, Colombia
Authors: Sandri Laura , Garcia Alexander , Costa Antonio , Guerrero Lopez Alejandra , Cordoba Gustavo
Published: January 2021

A statistical analysis of explosive eruptive events can give important clues on the behavior of a volcano for both the time- and size-domains, producing crucial information for hazards assessment. In this paper, we analyze in these domains an up-to-date catalog of eruptive events at Galeras volcano, collating data from the Colombian Geological Survey and from the Smithsonian Institution. The dataset appears to be complete, stationary and consisting of independent events since 1820, for events of magnitude ≥2.6. In the time-domain, Inter-Event Times are fitted by various renewal models to describe the observed repose times. On the basis of the Akaike Information Criterion, the preferred model is the Lognormal, with a characteristic time scale of ∼1.6 years. However, a tendency for the events to cluster in time into “eruptive cycles” is observed. Therefore, we perform a cluster analysis, to objectively identify clusters of events: we find three plausible partitions into 6, 8 and 11 clusters of events with magnitude≥2.6the 6-cluster partition being the preferred. The Inter-Event Times between cluster onsets (inter-cluster) and between events belonging to the same cluster (intra-cluster) are also modeled by renewal models. For inter-cluster data, the preferred model is the Brownian Passage Time, describing a periodical occurrence (mean return time ∼36 years) perturbed by a Gaussian noise. For the intra-cluster explosions, the preferred model is the Lognormal, with a characteristic time scale of ∼0.9 years. In the size-domain, we analyze only single events, due to the low number of clusters. Considering two independent parts of the catalog, we cannot reject the null hypothesis of the erupted mass being described by a power law, implying no characteristic eruption size. Finally, looking for time- and size-predictability, we find a significant inverse linear relationship between the logarithm of the erupted mass during a cycle and the time to the subsequent one. These results suggest that, presently, Galeras is still in the eruption cycle started in 2007; a new eruptive cycle may be expected in a few decades, unless the present cluster resumes to activity with magnitude ≥2.6.
Molecular Signatures and Their Clinical Utility in Pancreatic Neuroendocrine Tumors
Authors: Chatani Praveen Dilip , Agarwal Sunita Kishore , Sadowski Samira Mercedes
Published: January 2021

Pancreatic neuroendocrine tumors (PNETs) are classified based on their histologic differentiation and proliferative indices, which have been used extensively to determine prognosis. Advances in next-generation sequencing and other high-throughput techniques have allowed researchers to objectively explore tumor specimens and learn about the genetic alterations associated with malignant transformation in PNETs. As a result, targeted, pathway-specific therapies have been emerging for the treatment of unresectable and metastatic disease. As we continue to trial various pharmaceutical products, evidence from studies using multi-omics approaches indicates that clinical aggressiveness stratifies along other genotypic and phenotypic demarcations, as well. In this review, we explore the clinically relevant and potentially targetable molecular signatures of PNETs, their associated trials, and the overall differences in reported prognoses and responses to existing therapies.
Hypogonadism, Type-2 Diabetes Mellitus, and Bone Health: A Narrative Review
Authors: Russo Vittoria , Chen Rui , Armamento-Villareal Reina
Published: January 2021

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could be at risk. To date, there is very little information on the bone health men with both hypogonadism and T2DM. Insulin resistance, which is the primary defect in T2DM, is associated with low testosterone (T) levels in men and may play a role in the bidirectional relationship between these two conditions, which together may portend a worse outcome for bone. The present manuscript aims to review the available evidences on the effect of the combination of hypogonadism and T2DM on bone health and metabolic profile, highlights the possible metabolic role of the skeleton, and examines the pathways involved in the interplay between bone, insulin resistance, and gonadal steroids.
Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases
Authors: Zhang Keyi , Shou Xuefei , Chen Hong , Qiao Nidan , He Wenqiang , Chen Zhengyuan , Shen Ming , Li Shiqi , Zhao Yao , Zhang Zhaoyun , Li Yiming , Ye Hongying , Wang Yongfei
Published: January 2021

Purpose

To investigate the different clinical characteristics of silent corticotroph adenomas (SCAs) with positive and negative adrenocorticotropic hormone (ACTH) immunostaining, and to explore the value of pituitary-restricted transcription factor (Tpit) immunostaining for diagnosing SCAs.

Methods

The clinical materials of patients with SCAs who had a typical pathological feature with positive Tpit immunostaining and positive/negative ACTH immunostaining, and without clinical features and biochemical evidence for Cushing’s Syndrome in our center from April 2018 to March 2019 were analyzed retrospectively. The differences in clinical characteristics and surgical results between ACTH-positive and -negative SCAs were explored.

Results

A total of one hundred and five patients (94.3% female) with SCAs were included. There were 66 SCAs with ACTH-negative (66/105, 62.9%), and 39 SCAs with ACTH-positive (39/105, 37.1%). Cases with ACTH-negative SCAs were more likely to have lower ACTH levels (27.5 ± 24.0 vs. 54.4 ± 58.6, P = 0.011), more multiple microcysts (81.8% vs. 61.5%, P = 0.022) and lower levels of Ki-67 expression (low expression rate 90.9% vs. 74.4%, P = 0.023). No statistical significant differences were observed between patients with ACTH-positive and -negative SCAs regarding gender (97.0% vs. 89.7%, P = 0.192), age (50.3 ± 10.3 vs. 49.0 ± 11.2, P = 0.543), surgical history (16.7% vs. 23.1%, P = 0.419), suprasellar extension (66.7% vs. 74.4%, P = 0.408), sphenoid sinus extension (51.5% vs. 56.4%, P = 0.627), cavernous sinus invasion (75.8% vs. 66.7%, P = 0.314), large cyst on Magnetic Resonance Imaging (MRI) (47.0% vs. 61.5%, P = 0.149), or gross total resection rate (42.4% vs. 51.3%, P = 0.379).

Conclusions

ACTH-negative SCAs were observed to be more clinically silent and more likely to demonstrate multiple microcysts on MRI. The prevalence of SCAs, especially ACTH-negative SCAs, proved to be substantially underestimated and thus they should be given enough attention in consideration of the high aggressiveness of this subtype of refractory pituitary adenoma (PA).
Generating Hexahedral Mesh for Wire-wrapped Fuel Assembly With RBF Mesh Deformation Method
Authors: Wang X. A. , Zhang Dalin , Wang Mingjun , Liu Yapeng , Zhou Lei , Wang Shibao , Liang Yu , Tian Wenxi , Qiu Suizheng , Su G. H.
Published: January 2021

Fuel assemblies with wire spacer are widely used in Generation IV liquid nuclear reactors. With the rapid development of computational power, the Computational Fluid Dynamic (CFD) method is becoming an effective tool to investigate the detailed three-dimensional thermal hydraulic characteristics in wire-wrapped fuel assemblies. Due to the complexity of geometry, most of the published researches are performed with large number tetrahedron or polyhedral cells. The simulation is quite time-consuming and is generally limited to assemblies with small number of fuel pins. In this paper, a hexahedron meshing strategy is developed based on the Radial Basis Function (RBF) theory in present paper. This strategy would be beneficial for the modeling for the wire-wrapped fuel assemblies in real nuclear reactor core with large number of fuel pins. To validate this strategy, two experiments are simulated and detailed flow parameter distributions within the bundle, including the pressure distribution and the temperature distribution, have been compared. Good agreements have been achieved between the simulation results and the experimental results.
Mechanosensing and Plant Growth Regulators Elicited During the Thigmomorphogenetic Response
Authors: Telewski Frank W.
Published: January 2021

The influence of mechanical bending or flexing of trees, due primarily to wind, on tree growth and development has been observed and reported for hundreds of years. This response was defined as the thigmomorphogenetic response in 1973. In general, the response of trees and other plants to bending is a reduction in extension/height growth, increase in radial growth, and increased allocation from above-ground to below-ground tissues accompanied by changes in biomechanical properties of the xylem. Within the last 50 years, significant advancements have been reported in characterizing the response of trees to this mechanical perturbation. Current research has advanced the understanding of how plants respond after mechanopreception via molecular signaling and physiological changes in growth regulation. This review provides insight into these subcellular reactions of thigmomorphogenesis and a summary of recent advances.
Identification of a Five-Gene Prognostic Model and Its Potential Drug Repurposing in Colorectal Cancer Based on TCGA, GTEx and GEO Databases
Authors: Yang Feng , Cai Shaoyi , Ling Li , Zhang Haiji , Tao Liang , Wang Qin
Published: January 2021

Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Unfortunately, many CRC patients are still being diagnosed at an advanced stage of the cancer, and the 5-year survival rate is only ~30%. Effective prognostic markers of CRC are therefore urgently needed. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases to identify prognostic biomarkers for CRC, which in turn help in exploring potential drug-repurposing. We identified five hub genes (PGM2, PODXL, RHNO1, SCD, and SEPHS1), which had good performance in survival prediction and might be involved in CRC through three key pathways (“Cell cycle,” “Purine metabolism,” and “Spliceosome” KEGG pathways) identified by a KEGG pathway enrichment analysis. What is more, we performed a co-expression analysis between five hub genes and transcription factors to explore the upstream regulatory region. Furthermore, we screened the potential drug-repurposing for the five hub genes in CRC according to the Binding DB and ZINC15 databases. Taking together, we constructed a five-gene signature to predict overall survival of CRC and found the potential drug-repurposing, which may improve the outcome of CRC in the future.
Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation
Authors: Matos Tiago R. , Hirakawa Masahiro , Alho Ana C. , Neleman Lars , Graca Luis , Ritz Jerome
Published: January 2021

CD4+Regulatory T cells (Treg) play a critical role in maintaining immune homeostasis. Various Treg subsets have been identified, however the heterogeneity of Treg subpopulations during development remains uncharacterized. Using mass cytometry we obtained single cell data on expression of 35 functional markers to examine the heterogeneity of Treg cells at birth and in adults. Unsupervised clustering algorithms FlowSOM and ACCENSE were used to quantify Treg heterogeneity. As expected, Treg in umbilical cord blood were predominately naïve while Treg in adult blood were predominately central memory and effector memory cells. Although umbilical cord blood Treg are mostly naïve cells, we observed multiple phenotypic Treg subsets in cord blood. Nevertheless, peripheral blood in adults contained higher percentages of Treg and the heterogeneity of Treg was significantly increased in adults. We also studied Treg heterogeneity throughout a 2-year period after allogeneic hematopoietic stem cell transplantation (alloHSCT) and in patients with chronic graft-versus-host disease (cGVHD). Treg heterogeneity recovered rapidly after alloHSCT and gradually increased in the first two years post-transplant. However, patients with cGVHD had significantly fewer distinct Treg subpopulations, proposing a correlation between a disrupted Treg heterogeneity and cGVHD. Our study is the first to compare human Treg heterogeneity at birth, in healthy adults and in patients after alloHSCT with and without cGVHD. This approach to characterize Treg heterogeneity based on expression of a large panel of functional markers may enable future studies to identify specific Treg defects that contribute to immune dysfunction.
Donor-Derived Myeloid Heme Oxygenase-1 Controls the Development of Graft-Versus-Host Disease
Authors: Spilleboudt Chloé , De Wilde Virginie , Lewalle Philippe , Cabanne Ludovic , Leclerc Mathieu , Beckerich Florence , Bories Dominique , Cardoso Silvia , Soares Miguel P. , Vokaer Benoît , Hougardy Jean-Michel , Flamand Véronique , Racapé Judith , Abramowicz Marc , Maury Sébastien , Le Moine Alain
Published: January 2021

Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by HMOX1) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the Hmox1 allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT)n repeat polymorphism (L/L) in the HMOX1 promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT)n repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human HMOX1 (GT)n microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD.
VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp
Authors: Eckert Ina N. , Ribechini Eliana , Jarick Katja J. , Strozniak Sandra , Potter Sarah J. , Beilhack Andreas , Lutz Manfred B.
Published: January 2021

Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) onin vitroGM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1−/−) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4+T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increasedin vitrosuppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IVin vitro. However, interaction times ofItga1−/−A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substratein vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs fromItga1−/−mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression.
R848 Is Involved in the Antibacterial Immune Response of Golden Pompano (Trachinotus ovatus) Through TLR7/8-MyD88-NF-κB-Signaling Pathway
Authors: Zhou Yongcan , Chen Xiaojuan , Cao Zhenjie , Li Jianlong , Long Hao , Wu Ying , Zhang Zhengshi , Sun Yun
Published: January 2021

R848 is an imidazoquinoline compound that is a specific activator of toll-like receptor (TLR) 7/8 and is often used in immunological research in mammals and teleosts. However, the immune responses initiated by R848 through the TLR7/8 pathway in response to bacterial infection remain largely unexplored in teleosts. In the current study, we investigated the antibacterial response and the participating signaling pathway initiated by R848 in golden pompano (Trachinotus ovatus). We found that R848 could stimulate the proliferation of head kidney lymphocytes (HKLs) in a dose-dependent manner, enhance the survival rate of HKLs, and inhibit the replication of bacteria in vivo. However, these effects induced by R848 were significantly reduced when chloroquine (CQ) was used to blocked endosomal acidification. Additionally, an in vivo study showed that R848 strengthened the antibacterial immunity of fish through a TLR7/8 and Myd88-dependent signaling pathway. A cellular experiment showed that Pepinh-MYD (a Myd88 inhibitor) significantly reduced the R848-mediated proliferation and survival of HKLs. Luciferase activity analysis showed that R848 enhanced the nuclear factor kappa B (NF-κB) activity, whereas this activity was reduced when CQ and Pepinh-MYD were present. Additionally, when an NF-κB inhibitor was present, the R848-mediated pro-proliferative and pro-survival effects on HKLs were significantly diminished. An in vivo study showed that knockdown of TLR7, TLR8, and Myd88 expression in golden pompano via siRNA following injection of R848 resulted in increased bacterial dissemination and colonization in fish tissues compared to that of fish injection of R848 alone, suggesting that R848-induced antibacterial immunity was significantly reduced. In conclusion, these results indicate that R848 plays an essential role in the antibacterial immunity of golden pompano via the TLR7/8-Myd88-NF-κB- signaling pathway.
Small Scale Factors Modify Impacts of Temperature, Ice Scour and Waves and Drive Rocky Intertidal Community Structure in a Greenland Fjord
Authors: Sejr Mikael K. , Mouritsen Kim N. , Krause-Jensen Dorte , Olesen Birgit , Blicher Martin Emil , Thyrring Jakob
Published: January 2021

Understanding the influence of physical drivers and their scale-dependent interactions on ecosystem structure and function is becoming increasingly relevant as ecologists are challenged to quantify and predict the biological implications of anthropogenic activities and climate changes. Here, we aim to quantify the impact of multiple physical drivers (ice scour, wave exposure, and air temperature) and their interactions with small scale modifying factors (tidal level, substrate rugosity, and canopy forming macroalgae) on rocky intertidal community structure. We did this by quantifying intertidal biomass, cover and species richness at three tidal levels (high, mid, and low) at four sites in a sub-arctic Greenland fjord. We found a well-developed intertidal community, with a total of 16 macroalgae and 20 invertebrate species. At one locality, the total biomass was dominated by canopy forming algae exceeding 16 kg wet weight per m–2. Physical stress from ice scour, waves, and air exposure had negative effects on all three community metrics but important interactions and modifying processes were identified. The effect of tidal level differed between sites ranging from an absence of organisms at both high- and mid-intertidal level at the most ice- and wave exposed site to extensive cover across all three tidal levels at the wave and ice sheltered site. Canopy forming macroalgae and substrate rugosity both modified the impacts of physical stress. In the absence of ice scour, canopy forming algae formed extensive cover that modified extreme air temperatures, and the abundance of dominant invertebrate species were all positively related to the biomass of macroalgae. Rugosity provided refuge from ice scour, facilitating increased species richness and cover at exposed sites. Moreover, we detected no negative effects of fast ice, and ice scour impacts were primarily found where presence of glacial ice was combined with wave exposure. Our results provide an example of how large-scale physical factors pass through a filter of several modifying smaller scale processes before their impact on plot scale community structure is manifested.
Macrofauna Inhabiting Massive Demosponges From Shallow and Mesophotic Habitats Along the Israeli Mediterranean Coast
Authors: Goren Liron , Idan Tal , Shefer Sigal , Ilan Micha
Published: January 2021

Sponges have long been considered as “living hotels” due to the great diversity and abundance of other taxonomic groups often found in association with them. Sponges are the dominant components of benthic communities in the Levant Sea; and especially in the recently discovered mesophotic sponge grounds off the coast of Israel. However, almost no data exist regarding their associated macrofauna. The current study sought to identify the macrofauna associated with massive sponges along the Israeli Mediterranean coast; and to compare the role of sponges, as ecosystem engineers, or “living hotels,” in both the shallow-water and mesophotic habitats. Sixty-four massive sponge specimens, from 10 different species, were collected from shallow and mesophotic habitats by SCUBA diving and Remotely Operated Vehicle, respectively. Sponge volume was estimated, specimens were dissected, and the associated macrofauna were identified. Our results reveal that the sponges supported a diverse assemblage of associated macrofauna. A total of 61 associated taxa were found, including species reported for the first time in Israel. A clear, differentiation existed in the structure of the associated assemblage between the two habitats, which is mainly attributed to four species (two polychaetes, a crustacean, and a brittle star). The trophic composition remained stable across the two habitats. No correlation was found between sponge volume and the associated fauna community parameters. The highest richness of associated fauna was found in the mesophotic habitat, where sponge diversity is also higher. In contrast, a greater endobiont abundance and density were recorded in the shallow habitat, where massive sponges may be a limiting factor due to their lower richness and abundance. Our findings emphasize the importance of sponges as ecosystem engineers, and suggest that sponge diversity may be an important factor that contribute to benthic biodiversity in these regions.