bluuebunny/crossref_metadata_2025_split huggingface dataset:
T‐cell‐derived Hodgkin lymphoma has motility characteristics intermediate between Hodgkin and anaplastic large cell lymphoma
Authors: Bein Julia , Flinner Nadine , Häupl Björn , Mathur Aastha , Schneider Olga , Abu‐Ayyad Marwa , Hansmann Martin‐Leo , Piel Matthieu , Oellerich Thomas , Hartmann Sylvia 
Published: May 2022

AbstractClassic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T‐cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T‐cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T‐cell‐derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility‐associated proteins were regarded, T‐cell‐derived cHL cell lines showed the highest similarity to ALK− ALCL cell lines. In contrast, T‐cell‐derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T‐cell‐derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T‐cell‐derived cHL. In summary, our cell line‐derived data suggest that based on proteomics and migration behaviour, T‐cell‐derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted.
Glucose‐dependent insulinotropic polypeptide secretion after oral macronutrient ingestion: The human literature revisited and a systematic study in model experiments in mice
Authors: Ahrén Bo 
Published: May 2022

AbstractAims/IntroductionThe incretin hormone glucose‐dependent insulinotropic polypeptide (GIP) is secreted after meal ingestion. This study explored the relative influence of classes of macronutrients on GIP secretion.Materials and MethodsThe human literature was revisited by identifying articles from PubMed using key words GIP, macronutrients, carbohydrates, fat, protein, healthy subjects. In model experiments in anesthetized mice, glucose (25–125 mg), protein (15–120 mg), fat emulsion (6–100 mg) or saline was given orally with determination of GIP levels.ResultsThe literature survey identified 15 studies in which glucose, protein or fat was administered to healthy subjects. All three classes of macronutrients stimulated GIP secretion with a 30–45 min peak after glucose and protein, and a more prolonged release after fat. Limitations in study designs preclude firm conclusions on the relative potency of the macronutrients. In mice, glucose was more potent to stimulate GIP secretion than fat and protein, with no significant difference between protein and fat. By co‐administration of the macronutrients at moderate caloric combinations, a synergistic stimulation of GIP secretion was observed. In contrast, when raising the glucose challenge together with protein and fat, no synergy, but an additive effect, was evident.ConclusionsGlucose, protein and fat all stimulate GIP secretion in humans and mice. In mice, glucose is more potent than fat and protein, and there is also a synergy between the macronutrients on GIP secretion at moderate caloric doses. Further studies are warranted in humans to explore the relative potency of macronutrients.
The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion‐related organelle
Authors: Santos Herbert J. , Nozaki Tomoyoshi 
Published: May 2022

AbstractThe simplest class of mitochondrion‐related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms. The identification of enzymes responsible for sulfate activation (AS, IPP, and APSK) and a number of lineage‐specific proteins such as the outer membrane beta‐barrel protein (MBOMP30), and transmembrane domain‐containing proteins that bind to various organellar proteins (ETMP1, ETMP30, EHI_170120, and EHI_099350) showcased the remarkable divergence of this organelle compared to the other MROs of anaerobic protozoa. Here, we summarize the findings regarding the biology of the mitosomes in E. histolytica, from their discovery up to the present understanding of its roles and interactions. We also include current advances and future perspectives on the biology, biochemistry, and evolution of the mitosomes of E. histolytica.
Altered PVN‐to‐CA2 hippocampal oxytocin pathway and reduced number of oxytocin‐receptor expressing astrocytes in heart failure rats
Authors: Althammer Ferdinand , Roy Ranjan K. , Lefevre Arthur , Najjar Rami S. , Schoenig Kai , Bartsch Dusan , Eliava Marina , Feresin Rafaela G. , Hammock Elizabeth A. D. , Murphy Anne Z. , Charlet Alexandre , Grinevich Valery , Stern Javier E. 
Published: May 2022

AbstractOxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN‐to‐CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR‐Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (~15%), this expression was much more abundant in CA2 astrocytes (~40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN‐to‐CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, they provide the first evidence for an altered PVN‐to‐CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.
2‐kDa hyaluronan ameliorates human facial wrinkles through increased dermal collagen density related to promotion of collagen remodeling
Authors: Abe Yukina , Seino Satoshi , Kurihara Hitoshi , Kage Madoka , Tokudome Yoshihiro 
Published: May 2022

AbstractBackground/AimsHyaluronan (HA) oligosaccharides are involved in several biological processes, primarily collagen remodeling and wound healing. Collagen remodeling is retarded in aging skin and causes wrinkles. The aim of this study was to evaluate the effect of 2‐kDa HA oligosaccharides (HA2k) on wrinkles by permeation through the stratum corneum and promotion of collagen remodeling.MethodsA 3D skin model and excised human skin were used to evaluate the permeation of fluorescein‐labeled HA2k. The effect of HA2k on collagen metabolism was evaluated by measuring the protein level of type 1 pro‐collagen (COL1A1) and matrix metalloproteinase‐1 (MMP‐1) in the 3D skin model. 0.1% HA2k solution and vehicle control was applied to the human forearm for 8 weeks to evaluate dermal collagen density. To evaluate the effect of HA2k on depth of facial wrinkles, a randomized controlled trial was conducted with 0.1% HA2k lotion and vehicle lotion for 8 weeks.ResultsHA2k was confirmed to permeate through the stratum corneum by fluorescent microscopy. Both COL1A1 and MMP‐1 were upregulated by HA2k application in a 3D skin model culture. The collagen density was higher for the HA2k‐treated forearm than for the vehicle control‐treated forearm after 4 weeks. The maximum wrinkle depths in the nasolabial fold and crow's feet area were significantly shallower in the HA2k lotion group than in the control group.ConclusionHA2k permeated the stratum corneum, activated collagen synthesis and degradation simultaneously, and ameliorated wrinkles.
The Long‐Term Effectiveness of a Multisetting Lifestyle Intervention on Tobacco‐Related Habits in Adolescent Boys and Girls: Tehran Lipid and Glucose Study
Authors: Masihay‐Akbar Hasti , Amiri Parisa , Rezaei Marjan , Jalali‐Farahani Sara , Cheraghi Leila , Momenan Amir Abbas , Azizi Fereidoun 
Published: May 2022

ABSTRACTBACKGROUNDThis study assesses the long‐term effectiveness of a lifestyle intervention on cigarette, passive, and hookah smoking in adolescent boys and girls.METHODSOne thousand one hundred and fifty‐nine adolescent participants of Tehran Lipid and Glucose Study (TLGS) (2001‐2004) were followed for 12 years. Participants in the intervention area received lifestyle interventions in family, schools, and community settings, with the largest part implemented in schools. After excluding those with missing baseline parental data (n = 66), complete parental data of 1093 adolescents was used for cluster analysis. Families were classified as low‐ and high‐risk. Two hundred and ninety‐six individuals who did not complete intervention/follow‐ups were excluded, GEE was performed on 797 adolescents (369 boys, 192 intervention) to assess the intervention effect on tobacco‐related habits.RESULTSAdolescents' mean baseline age was 15.21 ± 1.95. Those living in high‐risk families were more at risk of cigarette, passive, and hookah smoking. Intervention decreased odds of cigarette and passive smoking by 38% and 57%, respectively. Intervention did not reduce hookah smoking in adolescents. After sex‐specific analysis, the intervention reduced current cigarette smoking by 40% only in boys and passive smoking in both sexes.CONCLUSIONSTargeting lifestyle behaviors in school‐aged adolescents and their families reduces cigarette smoking in boys and protects both sexes from secondhand smoke.
Effects of different dietary protein levels on intestinal aquaporins in weaned piglets
Authors: Ren Zhihua , Zhang Xinyue , Fan Haoyue , Yu Yueru , Yao Shuhua , Wang Yuqian , Dong Yanqiang , Deng Huidan , Zuo Zhicai , Deng Youtian , Wang Ya , Xu Zhiwen , Deng Junliang 
Published: May 2022

AbstractThis study was conducted to investigate the relationship between changes in intestinal aquaporins (AQPs) in piglets fed diets with different protein levels and nutritional diarrhoea in piglets. Briefly, 96 weaned piglets were randomly divided into four groups fed diets with crude protein (CP) levels of 18%, 20%, 22% and 24%. The small intestines and colons of the weaned piglets were collected, and several experiments were conducted. In the small intestine, AQP4 protein expression was higher in weaned piglets fed the higher‐CP diets (22% and 24% CP) than in those fed the 20% CP diet except at 72 h (p < 0.01). At 72 h, the AQP4 protein expression in the small intestine was lower in the 18% group than in the other three groups (p < 0.01). Under 20% CP feeding, AQP2, AQP4 and AQP9 protein expression in the colons of piglets peaked at certain time points. The AQP2 and AQP4 mRNA levels in the colon and the AQP4 and AQP4 mRNA levels in the distal colon were approximately consistent with the protein expression levels. However, the AQP9 mRNA content in the colon was highest in the 18% group, and the AQP2 mRNA content in the distal colon was significantly higher in the 24% group than in the 20% group. AQP2 and AQP4 were expressed mainly around columnar cells in the upper part of the smooth colonic intestinal villi, and AQP9 was expressed mainly on columnar cells and goblet cells in the colonic mucosa. In conclusion, 20% CP is beneficial to the normal expression of AQP4 in the small intestine, AQP2, AQP4 and AQP9 in the colon of weaned piglets, which in turn maintains the balance of intestinal water absorption and secretion in piglets.
Speed of onset of a new chewable formulation of oclacitinib maleate (Apoquel®) in a canine model of IL‐31‐induced pruritus
Authors: Fleck Timothy , Norris Lori , King Vickie , Lesman Steven , Gonzales Andrea J. 
Published: May 2022

AbstractOclacitinib maleate (Apoquel®, Zoetis Inc.) is commonly used around the world for the control/treatment of pruritus associated with allergic dermatitis and the control/treatment of atopic dermatitis in dogs at least 12 months of age. A new flavored chewable formulation of oclacitinib has been developed where more than 90% of doses offered to dogs were freely accepted when tested in clinical trials. The objective of this study was to determine whether the new chewable formulation of oclacitinib has a similar onset of anti‐pruritic activity as the original oclacitinib film‐coated tablets (FCT). Twenty‐one laboratory beagle dogs were randomized to treatment and received placebo, 0.4–0.6 mg/kg oclacitinib FCT or 0.4–0.6 mg/kg flavored chewable oclacitinib tablet (n = 7/group). Efficacy was measured by assessing reduction in pruritus 1–3 h post‐administration of treatments. Pruritus was induced by injecting canine IL‐31, intravenously (2.5 μg/kg), approximately 15 min prior to the pruritus observation window. Results from this study demonstrated both oclacitinib FCT and the flavored chewable oclacitinib tablet significantly reduced IL‐31‐induced pruritus within 1–3 h post‐dosing compared to placebo (p = .0069 and .0113, respectively), suggesting the new formulation of oclacitinib chewable tablets works as quickly to reduce pruritus in dogs as the oclacitinib FCT.
The loss of polyphenol oxidase function is associated with hilum pigmentation and has been selected during pea domestication
Authors: Balarynová Jana , Klčová Barbora , Sekaninová Jana , Kobrlová Lucie , Cechová Monika Zajacová , Krejčí Petra , Leonova Tatiana , Gorbach Daria , Ihling Christian , Smržová Lucie , Trněný Oldřich , Frolov Andrej , Bednář Petr , Smýkal Petr 
Published: May 2022

Summary

Seed coats serve as protective tissue to the enclosed embryo. As well as mechanical there are also chemical defence functions. During domestication, the property of the seed coat was altered including the removal of the seed dormancy.

We used a range of genetic, transcriptomic, proteomic and metabolomic approaches to determine the function of the pea seed polyphenol oxidase (PPO) gene. Sequencing analysis revealed one nucleotide insertion or deletion in the PPO gene, with the functional PPO allele found in all wild pea samples, while most cultivated peas have one of the three nonfunctional ppo alleles. PPO functionality cosegregates with hilum pigmentation. PPO gene and protein expression, as well as enzymatic activity, was downregulated in the seed coats of cultivated peas.

The functionality of the PPO gene relates to the oxidation and polymerisation of gallocatechin in the seed coat. Additionally, imaging mass spectrometry supports the hypothesis that hilum pigmentation is conditioned by the presence of both phenolic precursors and sufficient PPO activity.

Taken together these results indicate that the nonfunctional polyphenol oxidase gene has been selected during pea domestication, possibly due to better seed palatability or seed coat visual appearance.
The impact of modified fluid gelatin 4% in a balanced electrolyte solution on plasma osmolality in children—A noninterventional observational study
Authors: Rudolf Daniel , Witt Lars , Boethig Dietmar , Rigterink Vanessa , Zander Rolf , Sümpelmann Robert , Dennhardt Nils 
Published: May 2022

AbstractBackgroundIntravenous fluids for perioperative infusion therapy should be isotonic to maintain the body fluid homeostasis in children. Modified fluid gelatin 4% in a balanced electrolyte solution has a theoretical osmolarity of 284 mosmol L−1, and a real osmolality of 264 mosmol kg H2O−1. Because both values are lower than those of 0.9% saline or plasma, gelatin would be expected to be hypotonic in‐vitro and in‐vivo.AimWe thus hypothesized that the infusion of gelatin would be expected to decrease plasma osmolality. We performed an in‐vitro experiment and an in‐vivo study to evaluate the impact of gelatin on the osmolality in children.MethodsIn the in‐vitro experiment, full blood samples were diluted with gelatin 4% or albumin (50 g L−1) from 0% (pure blood) to 100% (pure colloid), and the osmolality was measured by freezing‐point depression. In the in‐vivo study, blood gas analyses from children undergoing major pediatric surgery were collected before and after gelatin infusion, and the osmolality was calculated by a modified version of Zander's formula.ResultsIn the in‐vitro experiment, 65 gradually diluted blood samples from five volunteers (age 25–55 years) were analyzed. The dilution with gelatin caused no significant changes in osmolality between 0% and 100%. Compared with gelatin, the osmolality in the albumin group was significantly lower between 50% and 100% dilution (p < .05). In the in‐vivo study, 221 children (age 21.4 ± 30 months) were included. After gelatin infusion, the osmolality increased significantly (mean change 4.3 ± 4.8 [95% CI 3.7–4.9] mosmol kg H2O−1; p < .01) within a normal range.ConclusionsGelatin in a balanced electrolyte solution has isotonic characteristics in‐vitro and in‐vivo, despite the low theoretical osmolarity, probably caused by the (unmeasured) negative charges in the gelatin molecules contributing to the plasma osmolality. For a better evaluation of the (real) tonicity of gelatin‐containing solutions, we suggest to calculate the osmolality (mosmol kg H2O−1) using Zander's formula.Trial registrationClinicalTrials.gov (ID: NCT02495285).
Oncogenic properties via MAPK signaling of the SOX5‐RAF1 fusion gene identified in a wild‐typeNRAS/BRAF giant congenital nevus
Authors: Vinyals Antònia , Ferreres Josep R. , Calbet‐Llopart Neus , Ramos Raquel , Tell‐Martí Gemma , Carrera Cristina , Marcoval Joaquim , Puig Susana , Malvehy Josep , Puig‐Butillé Joan Anton , Fabra Àngels 
Published: May 2022

AbstractWe recently reported an RAF rearrangement without NRAS or BRAF mutations in lesions from Giant Congenital Melanocytic Nevi (CMN). The new gene fusion involves the 5′‐end of the promoter‐containing N terminus of the SOX5 gene fused to exons 7–16 of the 3′‐end of RAF1 gene leading to a SOX5‐RAF1 fusion transcript which loses the auto‐inhibitory CR1 domain but retains the complete in‐frame coding sequence for the C‐Terminal kinase domain of the RAF1. Stable expression of SOX5‐RAF1 fusion induced growth factor‐independent cell growth in murine hematopoietic Ba/F3 cells and melan‐a immortalized melanocytes. Besides, it led to the transformation of both Ba/F3 and NIH 3T3 cells as revealed by colony formation assays. Furthermore, its expression results in MAPK activation assessed by increased levels of p‐ERK protein in the cytosol of transduced cells. Treatment with Sorafenib and UO126 inhibited proliferation of Ba/F3‐SOX5‐RAF1 cells in the absence of IL3 but not the PLX 4720, a specific inhibitor of BRAF. Moreover, the tumorigenic and metastatic capacities of SOX5‐RAF1 were assessed in vivo. These results indicate that SOX5‐RAF1, a driver event for CMN development, has oncogenic capacity. Thus, sequencing of CMN transcriptomes may lead to the identification of this druggable fusion and interfere with the progression toward melanoma.
Transcranial direct current stimulation does not improve clinical and neurophysiological outcomes in panic disorder: A randomized sham‐controlled trial
Authors: Aksu Serkan , Soyata Ahmet Zihni , Mursalova Zhala , Eskicioğlu Gaye , Tükel Raşit 
Published: May 2022

AimEmerging evidence suggests that transcranial direct current stimulation (tDCS) has anxiolytic effects and may enhance emotional processing of threat and reduce threat‐related attentional bias. Panic disorder (PD) is considered to be a fear network disorder along with prefrontal activity alterations. We aim to assess the effect of tDCS on clinical and physiological parameters in PD for the first time.MethodsIn this triple‐blind randomized sham‐controlled pilot study, 30 individuals with PD were allocated into active and sham groups to receive 10 sessions of tDCS targeting the dorsolateral prefrontal cortex bilaterally at 2 mA for 20‐min duration over 2 weeks. The clinical severity, threat‐related attentional bias, interoceptive accuracy, and emotional recognition were assessed before, immediately after, and 1 month after tDCS.ResultsActive tDCS, in comparison to sham, did not elicit more favorable clinical and neuropsychological/physiological outcomes in PD.ConclusionThe present study provides the first clinical and neurobehavioral results of prefrontal tDCS in PD and indicates that prefrontal tDCS was not superior to sham in PD.
Efficacy and safety of recombinant human growth hormone therapy in pediatric intestinal transplant recipients
Authors: Vo Hanh D. , Elrokhsi Salaheddin H. , Iverson Angela K. , Keck Megan A. 
Published: May 2022

AbstractBackgroundRecombinant human growth hormone (rhGH) is widely used to treat growth retardation in children. We aimed to examine the effect of rhGH therapy on growth and its impact on allograft function in children with growth retardation after intestinal transplant (IT).MethodsWe retrospectively included children younger than 19 years who had received an IT with or without the liver, were diagnosed with growth retardation, and have received rhGH between January 2010 and January 2021. Changes in the patient's anthropometric parameters between baseline and various time points were compared using the paired t‐test or Wilcoxon signed‐rank test, as appropriate.ResultsSeven patients (all males and prepubertal) received rhGH for the median duration of 2.3 years. The median age at rhGH start was 9.5 years. The median growth velocity z‐score improved from −0.95 before treatment to 2.3 (p = .04) and 1.9 (p = .06) after 1 and 2 years of treatment, respectively. The median height‐for‐age z‐score significantly improved from −3.4 at rhGH start to −1.3 (p = .005) at rhGH stop and remained above baseline at the last visit (−2.4, p = .002). The change in the first‐year growth velocity was negatively correlated with the change in the second‐year growth velocity (r = −.90, p = .04). No serious adverse effects or worsening allograft function were observed.ConclusionsSeverely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long‐term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.