bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
Authors: Jansson Malin , Lindberg Jessica , Rask Gunilla , Svensson Johan , Billing Ola , Nazemroaya Anoosheh , Berglund Anette , Wärnberg Fredrik , Sund Malin
Published: May 2022

Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (≤15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.
Analysis of Genetic Association Between ABCA7 Polymorphism and Alzheimer’s Disease Risk in the Southern Chinese Population
Authors: Wang Lijun , Jiao Yang , Zhao Aonan , Xu Xiaomeng , Ye Guanyu , Zhang Yichi , Wang Ying , Deng Yulei , Xu Wei , Liu Jun
Published: May 2022

Objective

The study aimed to clarify the association of the 21 single nucleotide polymorphisms (SNPs) with Alzheimer’s disease (AD) in the population of southern China.

Methods

A case-control study was conducted with a total sample size of 490 subjects (246 patients with AD and 244 age- and gender-matched healthy controls) enrolled in this study. Twenty-one selected SNPs were detected using SNaPshot assay and polymerase chain reaction (PCR) technique. Then, we assessed how these SNPs correlated with AD susceptibility.

Results

The results showed that rs3764650 of ABCA7 was closely correlated with risen AD morbidity in the allele [P = 0.010, odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.09–1.89], dominant (P = 0.004, OR = 1.71, 95% CI 1.19–2.46), and additive (P = 0.012, OR = 1.42, 95% CI 1.08–1.86) models. However, rs4147929 of ABCA7 was related to higher AD risk in the allele (P = 0.006, OR = 1.45, 95% CI 1.11–1.89), dominant (P = 0.012, OR = 1.59, 95% CI 1.11–2.27), and additive (P = 0.010, OR = 1.40, 95% CI 1.08–1.81) models. In addition, the frequencies of the G-allele at rs3764650 (P = 0.030) and the A-allele at rs4147929 (P = 0.001) in AD were statistically higher in APOE ε4 carriers in comparison to non-carriers.

Conclusion

This study demonstrated that the G-allele at rs3764650 and the A-allele at rs4147929 appeared at higher risk for developing AD, particularly in APOE ε4 carriers. Moreover, it was observed that rs3764650 and rs4147929 of ABCA7 were linked to AD. More in-depth research with a relatively large sample is needed to make the results more convincing.
Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
Authors: Wang Li-Ping , Geng Jieli , Liu Chang , Wang Yuyang , Zhang Zhijun , Yang Guo-Yuan
Published: May 2022

Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice (n = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism in vitro. The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group (p < 0.05). The diabetic mice had less exploratory behavior compared to the control (p < 0.05). However, the diabetic mice were more likely to show anxiety (p < 0.05) and depression (p < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment in vitro (p < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.
The Impact of Aerobic Exercise on Mood Symptoms in Trauma-Exposed Young Adults: A Pilot Study
Authors: Mizzi Allison L. , McKinnon Margaret C. , Becker Suzanna
Published: May 2022

Introduction

Physical activity has beneficial effects on mood in both healthy and clinical populations. Emerging literature suggests that physical activity may benefit psychological symptoms, such as depressive mood, in those with post-traumatic stress disorder (PTSD). It is estimated that 76% of Canadians have experienced a traumatic event during their lifetime (Van Ameringen et al., 2008). Thus, there is a large proportion of the population that does not meet criteria for PTSD but may still suffer from trauma-related symptoms such as depression and require support for their mental health. The current pilot study aimed to evaluate the impact of an aerobic exercise intervention on mood symptoms in trauma-exposed young adults.

Methods

Twenty-five low active young adults with subclinical trauma symptoms but no current or past diagnosis of PTSD were recruited. Participants were randomly assigned to participate in an 8-week exercise intervention group or a waitlist control group. Mood symptoms were assessed before and after the intervention. In addition, measures of aerobic fitness, trauma symptoms, emotion regulation, and trait mindfulness were assessed at both time points.

Results

The exercise intervention was effective at inducing the expected improvements in aerobic fitness. Overall, the exercise group had a significantly greater decrease in mood symptoms across the intervention compared to the waitlist control group.

Conclusion

The current pilot study is the first to evaluate the impact of aerobic exercise on mood in trauma-exposed young adults. An 8-week intervention significantly reduced mood symptoms in exercisers relative to waitlist controls. Our results are consistent with previous research indicating that physical activity reduced depressive symptoms in those with PTSD (Rosenbaum et al., 2015b). Importantly, we extend these findings to individuals with subclinical or undiagnosed PTSD symptoms, where exercise may be an effective intervention to improve mood and manage or prevent further decline in mental health in those at risk of developing PTSD.
Design Principles for Neurorobotics
Authors: Krichmar Jeffrey L. , Hwu Tiffany J.
Published: May 2022

In their book “How the Body Shapes the Way We Think: A New View of Intelligence,” Pfeifer and Bongard put forth an embodied approach to cognition. Because of this position, many of their robot examples demonstrated “intelligent” behavior despite limited neural processing. It is our belief that neurorobots should attempt to follow many of these principles. In this article, we discuss a number of principles to consider when designing neurorobots and experiments using robots to test brain theories. These principles are strongly inspired by Pfeifer and Bongard, but build on their design principles by grounding them in neuroscience and by adding principles based on neuroscience research. Our design principles fall into three categories. First, organisms must react quickly and appropriately to events. Second, organisms must have the ability to learn and remember over their lifetimes. Third, organisms must weigh options that are crucial for survival. We believe that by following these design principles a robot's behavior will be more naturalistic and more successful.
Evaluating the Abnormality of Bilateral Motor Cortex Activity in Subacute Stroke Patients Executing a Unimanual Motor Task With Increasing Demand on Precision
Authors: Revill Kate Pirog , Barany Deborah A. , Vernon Isabelle , Rellick Stephanie , Caliban Alexandra , Tran Julie , Belagaje Samir R. , Nahab Fadi , Haut Marc W. , Buetefisch Cathrin M.
Published: May 2022

Abnormal contralesional M1 activity is consistently reported in patients with compromised upper limb and hand function after stroke. The underlying mechanisms and functional implications of this activity are not clear, which hampers the development of treatment strategies targeting this brain area. The goal of the present study was to determine the extent to which contralesional M1 activity can be explained by the demand of a motor task, given recent evidence for increasing ipsilateral M1 activity with increasing demand in healthy age-matched controls. We hypothesized that higher activity in contralesional M1 is related to greater demand on precision in a hand motor task. fMRI data were collected from 19 patients with ischemic stroke affecting hand function in the subacute recovery phase and 31 healthy, right-handed, age-matched controls. The hand motor task was designed to parametrically modulate the demand on movement precision. Electromyography data confirmed strictly unilateral task performance by all participants. Patients showed significant impairment relative to controls in their ability to perform the task in the fMRI scanner. However, patients and controls responded similarly to an increase in demand for precision, with better performance for larger targets and poorer performance for smaller targets. Patients did not show evidence of elevated ipsilesional or contralesional M1 blood oxygenation level-dependent (BOLD) activation relative to healthy controls and mean BOLD activation levels were not elevated for patients with poorer performance relative to patients with better task performance. While both patients and healthy controls showed demand-dependent increases in BOLD activation in both ipsilesional/contralateral and contralesional/ipsilateral hemispheres, patients with stroke were less likely to show evidence of a linear relationship between the demand on precision and BOLD activation in contralesional M1 than healthy controls. Taken together, the findings suggest that task demand affects the BOLD response in contralesional M1 in patients with stroke, though perhaps less strongly than in healthy controls. This has implications for the interpretation of reported abnormal bilateral M1 activation in patients with stroke because in addition to contralesional M1 reorganization processes it could be partially related to a response to the relatively higher demand of a motor task when completed by patients rather than by healthy controls.
Genotype–Phenotype Correlation in Progressive Supranuclear Palsy Syndromes: Clinical and Radiological Similarities and Specificities
Authors: Ruiz-Barrio Iñigo , Horta-Barba Andrea , Illán-Gala Ignacio , Kulisevsky Jaime , Pagonabarraga Javier
Published: May 2022

The progressive supranuclear palsy (PSP) syndrome encompasses different entities. PSP disease of sporadic origin is the most frequent presentation, but different genetic mutations can lead either to monogenic variants of PSP disease, or to other conditions with a different pathophysiology that eventually may result in PSP phenotype. PSP syndrome of monogenic origin is poorly understood due to the low prevalence and variable expressivity of some mutations. Through this review, we describe how early age of onset, family history of early dementia, parkinsonism, dystonia, or motor neuron disease among other clinical features, as well as some neuroimaging signatures, may be the important clues to suspect PSP syndrome of monogenic origin. In addition, a diagnostic algorithm is proposed that may be useful to guide the genetic diagnosis once there is clinical suspicion of a monogenic PSP syndrome.
Characterization of Thyroid Hormones Antivertigo Effects in a Rat Model of Excitotoxically-Induced Vestibulopathy
Authors: Bringuier Claire M. , Hatat Bérenice , Boularand Romain , Chabbert Christian , Tighilet Brahim
Published: May 2022

Impaired vestibular function induces disabling symptoms such as postural imbalance, impaired locomotion, vestibulo-ocular reflex alteration, impaired cognitive functions such as spatial disorientation, and vegetative deficits. These symptoms show up in sudden attacks in patients with Ménière or neuritis and may lead to emergency hospitalizations. To date, however, there is no curative solution to these pathologies and the effectiveness of treatments used to reduce symptoms in the management of patients is discussed. Thus, elucidating the biological mechanisms correlated to the expression kinetics of the vestibular syndrome is useful for the development of potential therapeutic candidates with a view to relieving patients and limiting emergency hospitalizations. Recently, a robust antivertigo effect of thyroxine (T4) was demonstrated in a rodent model of impaired vestibular function induced by unilateral surgical section of the vestibular nerve. The aim of the present study was to assess thyroid hormones L-T4 and triiodothyronine (T3) as well as the bioactive thyroid hormone metabolite TRIAC on a rodent model of acute unilateral vestibulopathy more representative of clinical vestibular pathology. To this end, a partial and transient unilateral suppression of peripheral vestibular inputs was induced by an excitotoxic lesion caused by transtympanic injection of kainic acid (TTK) into the inner ear of adult rats. Vestibular syndrome and functional recovery were studied by semi-quantitative and quantitative assessments of relevant posturo-locomotor parameters. In contrast to the effect previously demonstrated in the complete and irreversible vestibular injury model, administration of thyroxine in the TTK rodent model did not display significant antivertigo effect. However, it is noteworthy that administration of thyroxine showed trends to prevent posturo-locomotor alterations. Furthermore, the results of the current study suggested that a single dose of thyroxine is sufficient to induce the same effects on vestibular syndrome observed with sub-chronic administration, and that reducing the T4 dose may more efficiently prevent the appearance of vestibular deficits induced by the excitotoxic type lesion. Finally, comparison of the antivertigo effect of T4 in different vestibulopathy models enables us to determine the therapeutic indication in which thyroxine could be a potential therapeutic candidate.
A New Sensitive Test Using Virtual Reality and Foam to Probe Postural Control in Vestibular Patients: The Unilateral Schwannoma Model
Authors: Oussou Grâce , Magnani Christophe , Bargiotas Ioannis , Lamas Georges , Tankere Frederic , Vidal Catherine
Published: May 2022

Vestibular schwannomas (VS) are benign tumors of the vestibular nerve that may trigger hearing loss, tinnitus, rotatory vertigo, and dizziness in patients. Vestibular and auditory tests can determine the precise degree of impairment of the auditory nerve, and superior and inferior vestibular nerves. However, balance is often poorly quantified in patients with untreated vestibular schwannoma, for whom validated standardized assessments of balance are often lacking. Balance can be quantified with the EquiTest. However, this device was developed a long time ago and is expensive, specific, and not sensitive enough to detect early deficits because it assesses balance principally in the sagittal plane on a firm platform. In this study, we assessed postural performances in a well-defined group of VS patients. We used the Dizziness Handicap Inventory (DHI) and a customized device consisting of a smartphone, a mask delivering a fixed or moving visual scene, and foam rubber. Patients were tested in four successive sessions of 25 s each: eyes open (EO), eyes closed (EC), fixed visual scene (VR0), and visual moving scenes (VR1) delivered by the HTC VIVE mask. Postural oscillations were quantified with sensors from an android smartphone (Galaxy S9) fixed to the back. The results obtained were compared to those obtained with the EquiTest. Vestibulo-ocular deficits were also quantified with the caloric test and vHIT. The function of the utricle and saccule were assessed with ocular and cervical vestibular-evoked myogenic potentials (o-VEMPs and c-VEMPs), respectively. We found that falls and abnormal postural oscillations were frequently detected in the VS patients with the VR/Foam device. We detected no correlation between falls or abnormal postural movements and horizontal canal deficit or age. In conclusion, this new method provides a simpler, quicker, and cheaper method for quantifying balance. It will be very helpful for (1) determining balance deficits in VS patients; (2) optimizing the optimal therapy indications (active follow-up, surgery, or gamma therapy) and follow-up of VS patients before and after treatment; (3) developing new rehabilitation methods based on balance training in extreme conditions with disturbed visual and proprioceptive inputs.
Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats
Authors: Koebele Stephanie V. , Poisson Mallori L. , Palmer Justin M. , Berns-Leone Claire , Northup-Smith Steven N. , Peña Veronica L. , Strouse Isabel M. , Bulen Haidyn L. , Patel Shruti , Croft Corissa , Bimonte-Nelson Heather A.
Published: May 2022

Oral contraceptives and hormone therapies require a progestogen component to prevent ovulation, curtail uterine hyperplasia, and reduce gynecological cancer risk. Diverse classes of synthetic progestogens, called progestins, are used as natural progesterone alternatives due to progesterone’s low oral bioavailability. Progesterone and several synthetic analogs can negatively impact cognition and reverse some neuroprotective estrogen effects. Here, we investigate drospirenone, a spironolactone-derived progestin, which has unique pharmacological properties compared to other clinically-available progestins and natural progesterone, for its impact on spatial memory, anxiety-like behavior, and brain regions crucial to these cognitive tasks. Experiment 1 assessed three drospirenone doses in young adult, ovariectomized rats, and found that a moderate drospirenone dose benefited spatial memory. Experiment 2 investigated this moderate drospirenone dose with and without concomitant ethinyl estradiol (EE) treatment, the most common synthetic estrogen in oral contraceptives. Results demonstrate that the addition of EE to drospirenone administration reversed the beneficial working memory effects of drospirenone. The hippocampus, entorhinal cortex, and perirhinal cortex were then probed for proteins known to elicit estrogen- and progestin- mediated effects on learning and memory, including glutamate decarboxylase (GAD)65, GAD67, and insulin-like growth factor receptor protein expression, using western blot. EE increased GAD expression in the perirhinal cortex. Taken together, results underscore the necessity to consider the distinct cognitive and neural impacts of clinically-available synthetic estrogen and progesterone analogs, and why they produce unique cognitive profiles when administered together compared to those observed when each hormone is administered separately.
Transcriptomic Characteristics Associated With Aging in the Thyroid Gland
Authors: Liu Chien-Liang , Chien Ming-Nan , Hsu Yi-Chiung , Cheng Shih-Ping
Published: May 2022

The aging thyroid is associated with a plethora of morphological and functional changes. Limited studies have addressed the gene expression signature in the aging thyroid, except for sporadic reports using data from postmortem samples in the Genotype-Tissue Expression (GTEx) project. In this investigation, we analyzed the RNA sequencing data of 58 samples of normal-appearing counterpart thyroid tissues from The Cancer Genome Atlas. Aging-correlated genes were identified by determining the Spearman rank-order correlation between patient age and gene expression level. Additionally, we performed gene set enrichment analysis and conducted a weighted correlation network analysis. The results were compared with those analyzed using the GTEx data. The over-represented protein class of aging-correlated genes is mainly metabolite interconversion enzymes. Our analyses identified alterations in immune and inflammatory responses, mitochondrial functions, cytoskeletal proteins, as well as amino acid and cytochrome P450 metabolism. There was no significant association between thyroid differentiation and age. Our findings may shed molecular light on thyroid disorders in the geriatric population.
The Risk Reduction Effect of a Nutritional Intervention With a Partially Hydrolyzed Whey-Based Formula on Cow's Milk Protein Allergy and Atopic Dermatitis in High-Risk Infants Within the First 6 Months of Life: The Allergy Reduction Trial (A.R.T.), a Multicenter Double-Blinded Randomized Controlled Study
Authors: Nicolaou Nicolaos , Pancheva Rouzha , Karaglani Eva , Sekkidou Mikaela , Marinova-Achkar Miglena , Popova Simoneta , Tzaki Margarita , Kapetanaki Anastasia , Iacovidou Nicoletta , Boutsikou Theodora , Iliodromiti Zoi , Papaevangelou Vassiliki , Sardeli Olympia , Xepapadaki Paraskevi , Papathoma Evangelia , Thijs-Verhoeven Inge , Kudla Urszula , Ulfman Laurien H. , Schaafsma Anne , Manios Yannis
Published: May 2022

Background

The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated.

Objective

To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life.

Materials and Methods

In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed.

Results

Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA (p = 0.186). AD incidence was significantly lower in those receiving pHF as compared to SF (10.6% vs. 18.7%, p = 0.024) with a relative risk (RR, 95% CI) of 0.54 (0.32, 0.92), in particular when adjusting for family history of AD [6.5% vs. 27.3%, RR 0.24 (0.07, 0.78), p = 0.018] representing a risk reduction of 76%. The PP analysis showed similar results.

Conclusion

This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect.
The Impact of Cereal Grain Composition on the Health and Disease Outcomes
Authors: Garutti Mattia , Nevola Gerardo , Mazzeo Roberta , Cucciniello Linda , Totaro Fabiana , Bertuzzi Carlos Alejandro , Caccialanza Riccardo , Pedrazzoli Paolo , Puglisi Fabio
Published: May 2022

Whole grains are a pivotal food category for the human diet and represent an invaluable source of carbohydrates, proteins, fibers, phytocompunds, minerals, and vitamins. Many studies have shown that the consumption of whole grains is linked to a reduced risk of cancer, cardiovascular diseases, and type 2 diabetes and other chronic diseases. However, several of their positive health effects seem to disappear when grains are consumed in the refined form. Herein we review the available literature on whole grains with a focus on molecular composition and health benefits on many chronic diseases with the aim to offer an updated and pragmatic reference for physicians and nutrition professionals.
Red Wine and Health: Approaches to Improve the Phenolic Content During Winemaking
Authors: Vejarano Ricardo , Luján-Corro Mariano
Published: May 2022

There is ample evidence regarding the health benefits of red wine consumption due to its content of phenolic compounds, as an alternative to improve the state of health and prevent various diseases, being the implementation of procedures that allow a greater extraction and stability of phenolic compounds during the elaboration a key aspect. The first part of this review summarizes some studies, mostly at the preclinical level, on the mechanisms by which phenolic compounds act in the human organism, taking advantage of their antioxidant, anti-inflammatory, antitumor, antithrombotic, antiatherogenic, antimicrobial, antiviral, and other activities. Although the migration of grape components into the must/wine occurs during the winemaking process, the application of new technologies may contribute to increasing the content of phenolic compounds in the finished wine. Some of these technologies have been evaluated on an industrial scale, and in some cases, they have been included in the International Code of Oenological Practice by the International Organization of Vine and Wine (OIV). In this sense, the second part of this review deals with the use of these novel technologies that can increase, or at least maintain, the polyphenol content. For example, in the pre-fermentative stage, phenolic extraction can be increased by treating the berries or must with high pressures, pulsed electric fields (PEF), ultrasound (US), e-beam radiation or ozone. At fermentative level, yeasts with high production of pyranoanthocyanins and/or their precursor molecules, low polyphenol absorption, and low anthocyanin-β-glucosidase activity can be used. Whereas, at the post-fermentative level, aging-on-lees (AOL) can contribute to maintaining polyphenol levels, and therefore transmitting health benefits to the consumer.
The Synergistic Role of Irreversible Electroporation and Chemotherapy for Locally Advanced Pancreatic Cancer
Authors: Gyftopoulos Argyrios , Ziogas Ioannis A. , Barbas Andrew S. , Moris Dimitrios
Published: May 2022

Irreversible electroporation (IRE) is a local ablative technique used in conjunction with chemotherapy to treat locally advanced pancreatic cancer (LAPC). The combination of IRE and chemotherapy has showed increased overall survival when compared to chemotherapy alone, pointing towards a possible facilitating effect of IRE on chemotherapeutic drug action and delivery. This review aims to present current chemotherapeutic regimens for LAPC and their co-implementation with IRE, with an emphasis on possible molecular augmentative mechanisms of drug delivery and action. Moreover, the potentiating mechanism of IRE on immunotherapy, M1 oncolytic virus and dendritic cell (DC)-based treatments is briefly explored. Investigating the synergistic effect of IRE on currently established treatment regimens as well as newer ones, may present exciting new possibilities for future studies seeking to improve current LAPC treatment algorithms.
Heterogeneous Expression and Subcellular Localization of Pyruvate Dehydrogenase Complex in Prostate Cancer
Authors: Nunes-Xavier Caroline E. , Mingo Janire , Emaldi Maite , Flem-Karlsen Karine , Mælandsmo Gunhild M. , Fodstad Øystein , Llarena Roberto , López José I. , Pulido Rafael
Published: May 2022

Background

Pyruvate dehydrogenase (PDH) complex converts pyruvate into acetyl-CoA by pyruvate decarboxylation, which drives energy metabolism during cell growth, including prostate cancer (PCa) cell growth. The major catalytic subunit of PDH, PDHA1, is regulated by phosphorylation/dephosphorylation by pyruvate dehydrogenase kinases (PDKs) and pyruvate dehydrogenase phosphatases (PDPs). There are four kinases, PDK1, PDK2, PDK3 and PDK4, which can phosphorylate and inactivate PDH; and two phosphatases, PDP1 and PDP2, that dephosphorylate and activate PDH.

Methods

We have analyzed by immunohistochemistry the expression and clinicopathological correlations of PDHA1, PDP1, PDP2, PDK1, PDK2, PDK3, and PDK4, as well as of androgen receptor (AR), in a retrospective PCa cohort of patients. A total of 120 PCa samples of representative tumor areas from all patients were included in tissue microarray (TMA) blocks for analysis. In addition, we studied the subcellular localization of PDK2 and PDK3, and the effects of the PDK inhibitor dichloroacetate (DCA) in the growth, proliferation, and mitochondrial respiration of PCa cells.

Results

We found heterogeneous expression of the PDH complex components in PCa tumors. PDHA1, PDP1, PDK1, PDK2, and PDK4 expression correlated positively with AR expression. A significant correlation of PDK2 immunostaining with biochemical recurrence and disease-free survival was revealed. In PCa tissue specimens, PDK2 displayed cytoplasmic and nuclear immunostaining, whereas PDK1, PDK3 and PDK4 showed mostly cytoplasmic staining. In cells, ectopically expressed PDK2 and PDK3 were mainly localized in mitochondria compartments. An increase in maximal mitochondrial respiration was observed in PCa cells upon PDK inhibition by DCA, in parallel with less proliferative capacity.

Conclusion

Our findings support the notion that expression of specific PDH complex components is related with AR signaling in PCa tumors. Furthermore, PDK2 expression associated with poor PCa prognosis. This highlights a potential for PDH complex components as targets for intervention in PCa.
Case Report: Dubin-Johnson Syndrome Presenting With Infantile Cholestasis: An Overlooked Diagnosis in an Extended Family
Authors: Kamal Naglaa M. , Saadah Omar , Alghamdi Hamdan , Algarni Ali , El-Shabrawi Mortada H. F. , Sherief Laila M. , Abosabie Salma A. S.
Published: May 2022

Dubin-Johnson syndrome (DJS) is an often-missed diagnosis of neonatal cholestasis. We report two patients with DJS, who presented with neonatal cholestasis. The first patient underwent extensive investigations for infantile cholestasis with no definitive etiology reached; the diagnosis of DJS was missed until the age of 14 years old. The diagnosis was confirmed genetically with c.2273G > T, p.G758V mutation in exon 18 of the ABCC2 gene. The 2nd patient is a 7-day-old baby, the son of the 1st patient who gave birth to him at the age of 21 years old. He was diagnosed with DJS at the age of 2 weeks based on normal clinical and laboratory workup apart from direct hyperbilirubinemia. He had the same mutation as his mother in homozygous status. The husband was heterozygous for the same mutation. DJS is one of the often-missed differential diagnoses of neonatal cholestasis. It should be suspected in patients of infantile cholestasis, who have an, otherwise, normal physical examination, and laboratory investigations to avoid unnecessary lengthy, invasive, and expensive workups.
Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study
Authors: Rodriguez Maria Jose , Martinez-Orgado Jose , Corredera Araceli , Serrano Irene , Arruza Luis
Published: May 2022

Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.

Aim

The aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate–severe HIE during TH and rewarming.

Method

Newborns at >36 weeks' gestation with moderate–severe HIE treated with TH were evaluated with targeted neonatal echocardiography (TNE), including TDI, within 24 h of TH initiation (T1), at 48–72 h of treatment (T2), and after rewarming (T3). These retrospective data were collected and compared with a control group of healthy babies at >36 weeks' gestation that was prospectively evaluated following the same protocol.

Results

A total of 21 patients with HIE + TH and 15 controls were included in the study. Myocardial relaxation before the onset of biventricular filling was prolonged in the HIE + TH group during TH with significantly longer isovolumic relaxation time (IVRT') in the left ventricle (LV), the septum, and the right ventricle (RV). This was associated with slower RV early diastolic velocity (e') and prolonged filling on T1. Total isovolumic time (t-IVT; isovolumic contraction time [IVCT'] + IVRT') and myocardial performance index (MPI') were globally increased in asphyxiated neonates. All these differences persisted after correction for heart rate (HR) and normalized after rewarming. TDI parameters assessing late diastole (a' velocity or e'/a' and E/e' ratios) did not differ between groups.

Conclusion

TDI evaluation in our study demonstrated a pattern of early diastolic dysfunction during TH that normalized after rewarming, whereas late diastole seemed to be preserved. Our data also suggest a possible involvement of impaired twist/untwist motion and dyssynchrony. More studies are needed to investigate the impact and therapeutic implication of diastolic dysfunction in these babies, as well as to clarify the role of TH in these findings.
Glycinergic Modulation of Pain in Behavioral Animal Models
Authors: Peiser-Oliver Julian M. , Evans Sally , Adams David J. , Christie Macdonald J. , Vandenberg Robert J. , Mohammadi Sarasa A.
Published: May 2022

Animal models of human pain conditions allow for detailed interrogation of known and hypothesized mechanisms of pain physiology in awake, behaving organisms. The importance of the glycinergic system for pain modulation is well known; however, manipulation of this system to treat and alleviate pain has not yet reached the sophistication required for the clinic. Here, we review the current literature on what animal behavioral studies have allowed us to elucidate about glycinergic pain modulation, and the progress toward clinical treatments so far. First, we outline the animal pain models that have been used, such as nerve injury models for neuropathic pain, chemogenic pain models for acute and inflammatory pain, and other models that mimic painful human pathologies such as diabetic neuropathy. We then discuss the genetic approaches to animal models that have identified the crucial glycinergic machinery involved in neuropathic and inflammatory pain. Specifically, two glycine receptor (GlyR) subtypes, GlyRα1(β) and GlyRα3(β), and the two glycine transporters (GlyT), GlyT1 and GlyT2. Finally, we review the different pharmacological approaches to manipulating the glycinergic system for pain management in animal models, such as partial vs. full agonism, reversibility, and multi-target approaches. We discuss the benefits and pitfalls of using animal models in drug development broadly, as well as the progress of glycinergic treatments from preclinical to clinical trials.
Comparative Metabolomics Analysis Reveals Key Metabolic Mechanisms and Protein Biomarkers in Alzheimer’s Disease
Authors: Dai Zhao , Hu Tian , Su Shijie , Liu Jinman , Ma Yinzhong , Zhuo Yue , Fang Shuhuan , Wang Qi , Mo Zhizhun , Pan Huafeng , Fang Jiansong
Published: May 2022

Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic changes in AD, which provides insight into the identification of potential biomarkers for diagnosis, treatment, and prognostic assessment. However, since different species may lead to systemic abnormalities in metabolomic profiles, it is urgently needed to perform a comparative metabolomics analysis between AD animal models and human patients. In this study, we integrated 78 metabolic profiles from public literatures, including 11 metabolomics studies in different AD mouse models and 67 metabolomics studies from AD patients. Metabolites and enrichment analysis were further conducted to reveal key metabolic pathways and metabolites in AD. We totally identified 14 key metabolites and 16 pathways that are both differentially significant in AD mouse models and patients. Moreover, we built a metabolite-target network to predict potential protein markers in AD. Finally, we validated HER2 and NDF2 as key protein markers in APP/PS1 mice. Overall, this study provides a comprehensive strategy for AD metabolomics research, contributing to understanding the pathological mechanism of AD.
Fusion of THz-TDS and NIRS Based Detection of Moisture Content for Cattle Feed
Authors: Huang Jinlei , Luo Bin , Cao Yaoyao , Li Bin , Qian Mengbo , Jia Nan , Zhao Wenwen
Published: May 2022

As an essential index to evaluate feed quality, feed moisture content which is too high or too low will impose an adverse impact on feed nutritional value. Therefore, the quantitative analysis of feed moisture content is significant. In this paper, the detection of feed moisture content based on terahertz (THz) and near-infrared (NIR) spectroscopy and data fusion technology of THz and NIR (THz-NIR) was investigated. First, feed samples with different water content (29.46%–49.46%) were prepared, and THz (50–3000 μm) and NIR (900–1700 nm) spectral data of samples was collected and preprocessed, and the feed samples were divided into correction set and verification set by 2:1. Second, the spectral data was fused through the head-to-tail splicing, and the feed moisture content prediction model was established combined with partial least squares regression (PLSR). Third, competitive adaptive reweighting sampling (CARS) was applied to extract spectral characteristic variables for feature layer fusion, and the feed moisture content prediction model in feature level was constructed combined with PLSR. Finally, the evaluation parameters validation set correlation coefficient (Rp), the root mean square error of prediction (RMSEP), and the residual predictive deviation (RPD) were employed to evaluate the prediction effect of the model. The results indicated that THz, NIR spectra, and data fusion technology could quickly and effectively predict feed moisture content. Among them, the characteristic layer spectral data fusion model achieved the optimal prediction effect while Rp, RMSEP, and RPD reached 0.9933, 0.0069, and 8.7386 respectively. In conclusion, compared with the prediction model established by single THz and NIR spectrum, THz-NIR spectrum data fusion could more accurately predict feed moisture content and provide certain theoretical and technical support for inspirations and methods for quantitative analysis of feed moisture content of livestock and poultry.
100 kHz Narrow-Linewidth Burst-Mode MOPA Laser System With Uniform Envelope
Authors: Yu Xin , Zhang Shanchun , Peng Jiangbo , Cao Zhen , Gao Long , Liu Wenbei
Published: May 2022

In this study, a 100-kHz narrow-linewidth burst-mode laser system combined with a master oscillator power amplifier (MOPA) structure was reported with a stable pulse burst profile over 2 ms duration. A theoretical model was established to characterize and compensate the variation characteristics of coefficient of variation (COV) within a burst envelope for the double-pass three-stage amplification system, in terms of different parameter factors. Simulated results yielded similar tendency with the measured ones. For a stable burst envelope with a COV of 2.72% and 2.93%, output pulse energy at a 100 kHz repetition rate was scaled up to 1.08 and 4.38 mJ in the case of an input average pulse energy of 8.6 and 116.51 nJ, respectively. Corresponding Mx2 and My2 values with 2.2 and 2.4 were endowed with 1.08 mJ output single-pulse energy and 2.7 and 2.1 for 4.38 mJ pulse energy. The spectral linewidth of amplified pulses was measured to be less than 83.1 and 67.9 MHz, with respect to output pulse duration of 10.3 and 96.1 ns, respectively.
Calculation of the Coupling Coefficient in Step-Index Multimode Polymer Optical Fibers Based on the Far-Field Measurements
Authors: Savović Svetislav , Djordjevich Alexandar , Drljača Branko , Simović Ana , Min Rui
Published: May 2022

Using the power flow equation (PFE), this article investigates mode coupling in step-index (SI) multimode (MM) polymer optical fiber (POF). This equation’s coupling coefficient was initially fine-tuned so that it could appropriately reconstruct previously recorded far-field (FF) power distributions. The equilibrium mode distribution (EMD) and steady-state distribution (SSD) in the SI MM POF were found to be obtained at lengths Lc = 15 m and zs = 41 m, respectively. These lengths are substantially shorter than their glass optical fiber counterparts. Such characterization of the investigated POF can be used in its employment as a part of the communication or sensory system. Namely, the POF’s bandwidth is inverse linear function of fiber length (z−1) below the coupling length Lc. However, it has a z−1/2 dependence beyond this equilibrium length. Thus, the shorter the coupling length Lc, the sooner transition to the regime of slower bandwidth decrease occurs. It is also important to be able to determine a modal distribution at a certain length of the POF employed as a part of optical fiber sensory system.
Effect of Darkness on Intrinsic Motivation for Undirected Singing in Bengalese Finch (Lonchura striata Domestica): A Comparative Study With Zebra Finch (Taeniopygia guttata)
Authors: Kim Yunbok , Mori Chihiro , Kojima Satoshi
Published: May 2022

The zebra finch (ZF) and the Bengalese finch (BF) are animal models that have been commonly used for neurobiological studies on vocal learning. Although they largely share the brain structure for vocal learning and production, BFs produce more complex and variable songs than ZFs, providing a great opportunity for comparative studies to understand how animals learn and control complex motor behaviors. Here, we performed a comparative study between the two species by focusing on intrinsic motivation for non-courtship singing (“undirected singing”), which is critical for the development and maintenance of song structure. A previous study has demonstrated that ZFs dramatically increase intrinsic motivation for undirected singing when singing is temporarily suppressed by a dark environment. We found that the same procedure in BFs induced the enhancement of intrinsic singing motivation to much smaller degrees than that in ZFs. Moreover, unlike ZFs that rarely sing in dark conditions, substantial portion of BFs exhibited frequent singing in darkness, implying that such “dark singing” may attenuate the enhancement of intrinsic singing motivation during dark periods. In addition, measurements of blood corticosterone levels in dark and light conditions provided evidence that although BFs have lower stress levels than ZFs in dark conditions, such lower stress levels in BFs are not the major factor responsible for their frequent dark singing. Our findings highlight behavioral and physiological differences in spontaneous singing behaviors of BFs and ZFs and provide new insights into the interactions between singing motivation, ambient light, and environmental stress.
Developmental-Based Classification of Enkephalin and Somatostatin Containing Neurons of the Chicken Central Extended Amygdala
Authors: Pross Alessandra , Metwalli Alek H. , Desfilis Ester , Medina Loreta
Published: May 2022

The central extended amygdala, including the lateral bed nucleus of the stria terminalis and the central amygdala, plays a key role in stress response. To understand how the central extended amygdala regulates stress it is essential to dissect this structure at molecular, cellular and circuit levels. In mammals, the central amygdala contains two distinct cell populations that become active (on cells) or inactive (off cells) during the conditioned fear response. These two cell types inhibit each other and project mainly unidirectionally to output cells, thus providing a sophisticated regulation of stress. These two cell types express either protein kinase C-delta/enkephalin or somatostatin, and were suggested to originate in different embryonic domains of the subpallium that respectively express the transcription factors Pax6 or Nkx2.1 during development. The regulation of the stress response by the central extended amygdala is poorly studied in non-mammals. Using an evolutionary developmental neurobiology approach, we previously identified several subdivisions in the central extended amygdala of chicken. These contain Pax6, Islet1 and Nkx2.1 cells that originate in dorsal striatal, ventral striatal or pallidopreoptic embryonic divisions, and also contain neurons expressing enkephalin and somatostatin. To know the origin of these cells, in this study we carried out multiple fluorescent labeling to analyze coexpression of different transcription factors with enkephalin or somatostatin. We found that many enkephalin cells coexpress Pax6 and likely derive from the dorsal striatal division, resembling the off cells of the mouse central amygdala. In contrast, most somatostatin cells coexpress Nkx2.1 and derive from the pallidal division, resembling the on cells. We also found coexpression of enkephalin and somatostatin with other transcription factors. Our results show the existence of multiple cell types in the central extended amygdala of chicken, perhaps including on/off cell systems, and set the basis for studying the role of these cells in stress regulation.