bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extremely and very preterm‐born children <1500 g show different weight development in childhood compared to their peers
Authors: Geisler Inga , Rausch Tanja Katrin , Göpel Wolfgang , Spiegler Juliane 
Published: February 2021

AbstractAimTo develop reference growth charts for body mass index (BMI), weight, length and head circumference in children born extremely preterm (EPT) or very preterm (VPT) with a birth weight <1500 g.MethodsWe analysed EPT and VPT children from the German Neonatal Network born between 2009 and 2013 without chronic diseases or medications influencing growth. These data of EPT and VPT datasets were split into a training dataset and a validation dataset. In the validation dataset, data from 385 EPT and 491 VPT children from birth to age 6 years were analysed to calculate growth charts.ResultsThe percentiles of length of EPT and VPT children were comparable to German reference percentiles. The BMI peak in infancy was attenuated, and BMI was lower in all the EPT and VPT children analysed. From 2 years until 6 years of age, head circumference was lower in EPT and VPT boys and girls.ConclusionDeficits in height described in EPT cohorts born during the 1980 s and 1990 s were not seen in our cohort. However, EPT and VPT born children showed growth patterns that differed from national reference curves for BMI. The growth charts provided here can be used to judge the growth of EPT and VPT born children.
The effect of gluten‐free diet on body mass index in paediatric celiac disease
Authors: Anafy Adi , Cohen Shlomi , Ben Tov Amir , Amir Achiya , Weintraub Yael , Moran‐Lev Hadar , Dali Levy Margalit , Ankona Bussel Maayan , Yerushalmy Feler Anat 
Published: February 2021

AbstractAimMore normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten‐free diet (GFD) on BMI.MethodsData on all children diagnosed with CD during 7/2010–7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs <5%, 5%–85% and >85%, respectively).ResultsOf the 236 children [median age 7.87 (4.91–11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow‐up of 15.7 (0–85) months, but there was a significant shift of patients between the BMI categories (p < 0.001).ConclusionAlthough a shift of patients between the BMI categories was observed, following a GFD did not significantly affect the overall BMI in children with CD.
Prevalence of and factors influencing vitamin D deficiency in paediatric patients diagnosed with cancer at northern latitudes
Authors: Jackmann Natalja , Gustafsson Jan , Harila‐Saari Arja , Ljungman Gustaf , Nezirevic Dernroth Dzeneta , Frisk Per , Mäkitie Outi 
Published: February 2021

AbstractAimTo investigate the prevalence of vitamin D deficiency among children with non‐haematological malignancies and to explore possible causes of low vitamin D levels among these patients.MethodsWe performed a cross‐sectional study of 458 children diagnosed with solid tumours, brain tumours, non‐Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25‐hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25‐hydroxyvitamin D level below 50 nmol/L.ResultsThe prevalence rate of vitamin D deficiency among children with non‐haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25‐hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25‐hydroxyvitamin D and parathyroid hormone.ConclusionVitamin D deficiency is common among children diagnosed with cancer, particularly among school‐aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients.
Expression of the novel tumour suppressor sterile alpha motif and HD domain‐containing protein 1 is an independent adverse prognostic factor in classical Hodgkin lymphoma
Authors: Xagoraris Ioanna , Vassilakopoulos Theodoros P. , Drakos Elias , Angelopoulou Maria K. , Panitsas Fotios , Herold Nikolas , Medeiros L. Jeffrey , Giakoumis Xanthoula , Pangalis Gerassimos A. , Rassidakis George Z. 
Published: February 2021

SummaryThe expression patterns and prognostic significance of sterile alpha motif and HD domain‐containing protein 1 (SAMHD1) protein in the neoplastic Hodgkin and Reed Sternberg (HRS) cells of Hodgkin lymphoma (HL) were investigated in a cohort of 154 patients with HL treated with standard regimens. SAMHD1 expression was assessed by immunohistochemistry using diagnostic lymph node biopsies obtained prior to treatment. Using an arbitrary 20% cut‐off, SAMHD1 was positive in HRS cells of 48/154 (31·2%) patients. SAMHD1 expression was not associated with clinicopathologic parameters, such as age, gender, stage or histologic subtype. In 125 patients with a median follow‐up of 90 months (7–401 months), SAMHD1 expression in HRS cells significantly correlated with inferior freedom from progression (FFP) (P = 0·025), disease‐specific survival (DSS) (P = 0·013) and overall survival (OS) (P = 0·01). Importantly, in multivariate models together with disease stage, histology subtype and type of treatment as covariates, SAMHD1 expression retained an independent significant association with unfavourable FFP (P = 0·005) as well as DSS (P = 0·022) and OS (P = 0·018). These findings uncover the significance of a novel, adverse prognostic factor in HL that may have therapeutic implications since SAMHD1 inhibitors are now available for clinical use.
Cost‐effectiveness analysis of multiple imaging modalities in diagnosis and follow‐up of intermediate complex cystic renal lesions
Authors: Spiesecke Paul , Reinhold Thomas , Wehrenberg Yano , Werner Sven , Maxeiner Andreas , Busch Jonas , Fischer Thomas , Hamm Bernd , Lerchbaumer Markus Herbert 
Published: February 2021

ObjectivesTo compare health‐economic aspects of multiple imaging modalities used to monitor renal cysts, the present study evaluates costs and outcomes of patients with Bosniak IIF and III renal cysts detected and followed‐up by either contrast‐enhanced computed tomography (ceCT), contrast‐enhanced magnetic resonance imaging (ceMRI), or contrast‐enhanced ultrasonography (CEUS).Patients and MethodsA simulation using Markov models was implemented and performed with 10 cycles of 1 year each. Proportionate cohorts were allocated to Markov models by a decision tree processing specific incidences of malignancy and levels of diagnostic performance. Costs of imaging and surgical treatment were investigated using internal data of a European university hospital. Multivariate probabilistic sensitivity analysis was performed to confirm results considering input value uncertainties. Patient outcomes were measured in quality‐adjusted life years (QALY), and costs as averages per patient including costs of imaging and surgical treatment.ResultsCompared to the ‘gold standard’ of ceCT, ceMRI was more effective but also more expensive, with a resulting incremental cost‐effectiveness ratio (ICER) >€70 000 (Euro) per QALY gained. CEUS was dominant compared to ceCT in both Bosniak IIF and III renal cysts in terms of QALYs and costs. Probabilistic sensitivity analysis confirmed these results in the majority of iterations.ConclusionBoth ceMRI and CEUS can be used as alternatives to ceCT in the diagnosis and follow‐up of intermediately complex cystic renal lesions without compromising effectiveness, while CEUS is clearly cost‐effective. The economic results apply to a large university hospital and must be adapted for smaller hospitals.
Rostral cuneiform nucleus and the defence reaction: Direct and indirect midbrain–medullary 5‐HT mechanisms in baroreflex inhibition
Authors: Netzer Florence , Sévoz‐Couche Caroline 
Published: February 2021

Background and PurposeActivation of the defence reaction inhibits the baroreflex response via the intermediate rostro‐ventromedial medulla (B3 raphé) and nucleus tractus solitarius (NTS). Our aim was to determine whether and how baroreflex inhibition, induced by the disinhibition of the rostral cuneiform nucleus (part of the defence pathway), involves 5‐HT neurons in B3 and 5‐HT3 receptors in the NTS.Experimental ApproachWe performed immunohistochemistry and anatomical experiments to determine whether raphé 5‐HT cells expressing Fos were directly targeted by the rostral cuneiform nucleus. The effect of blocking raphé 5‐HT neurotransmission and NTS 5‐HT3 receptors on cuneiform‐induced inhibition of the baroreflex cardiac response were also analysed.Key ResultsBicuculline, microinjected into the rostral cuneiform nucleus, induced an increase of double‐labelled Fos‐5‐HT‐IR cells in both the lateral paragigantocellular nucleus (LPGi) and raphé magnus. The anterograde tracer Phaseolus vulgaris leucoaggutinin injected into the rostral cuneiform nucleus revealed a dense projection to the LPGi but not raphé magnus. Cuneiform‐induced baroreflex inhibition was prevented by B3 injection of 8‐OH‐DPAT, a selective 5‐HT1A receptor agonist. Cuneiform disinhibition also failed to inhibit the baroreflex bradycardia after NTS microinjection of the 5‐HT3 receptor antagonist granisetron and in 5‐HT3 receptor knockout mice.Conclusion and ImplicationsThe rostral cuneiform nucleus participates in the defence inhibition of the baroreflex bradycardia via direct activation of the LPGi and via a projection to the raphé magnus to activate NTS 5‐HT3 receptors and inhibit second‐order baroreflex neurons. These data bring new insights in primary and secondary mechanisms involved in vital baroreflex prevention during stress.
The multigene classifiers 95GC/42GC/155GC for precision medicine in ER‐positive HER2‐negative early breast cancer
Authors: Naoi Yasuto , Tsunashima Ryo , Shimazu Kenzo , Noguchi Shinzaburo 
Published: February 2021

AbstractIn clinical decision‐making, to decide the indication for adjuvant chemotherapy for estrogen receptor‐positive (ER+), human epidermal growth factor receptor‐2‐negative (HER2−), and node‐negative (n0) breast cancer patients, the accurate estimation of recurrence risk is essential. Unfortunately, conventional prognostic factors, such as tumor size, histological grade and ER, progesterone receptor (PR), and HER2 status as well as Ki67 index, are not sufficiently accurate for such estimation. Therefore, several multigene assays (MGAs) based on the mRNA expression analysis of multiple genes in tumor tissue have been developed to better predict patient prognosis. These assays include Oncotype DX, MammaPrint, PAM50, GGI, EndoPredict, and BCI. We developed Curebest™ 95‐Gene Classifier Breast (95GC) classifier, which is unique in that mRNA expression data of all 20 000 human genes are secondarily obtainable, as the 95GC assay is performed using Affymetrix microarray. This can capture mRNA expression of not only 95 genes but also every gene at once, and such gene expression data can be utilized by the other MGAs that we have developed, such as the 155GC, which is used for the prognostic prediction of ER+/HER2− breast cancer patients treated with neoadjuvant chemotherapy. We also developed the 42GC for predicting late recurrence in ER+/HER2− breast cancer patients. In this mini‐review, our recent attempt at the development of various MGAs, which is expected to facilitate the implementation of precision medicine in ER+/HER2− breast cancer patients, is presented with a special emphasis on 95GC.
Forty‐seven pathogenic variants causing autosomal recessive disorders are shared by Israeli and Saudi Arabian Arabs
Authors: Zlotogora Joël 
Published: February 2021

AbstractSeveral autosomal recessive disorders that are found among Arabs in Israel were also reported in Saudi Arabia. In a sytematic review of all the variants responsible for autosomal recessive disorders among Muslim Arabs Israel and in Saudi Arabia, 47 shared variants were found, many being known founder variants in both populations. Among the 21 shared variants that were reported among Bedouins 14 were founder variants representing 14% founder/assumed founder variants known in the Bedouins. Many of the common variants are ancient having a Bedouin origin probably linked to the migration from the Saudi Peninsula. It is probable that a similar phenomenon occurred along the route of the Bedouin migrations and indeed some of these variants are present in the corresponding populations.
Maintaining family stability in the age of digital technologies: An analysis of d/Discourse informing domestic screen media practices in three US families
Authors: Willett Rebekah , Wheeler Nathan 
Published: February 2021

AbstractThis article examines d/Discourses about screen media and parenting as reflected in parents' discursive construction of their decision‐making processes connected with domestic media practices. The analysis focuses on three parent interviews from a dataset of 51 parent interviews conducted in three states in the USA. The article illustrates ways d/Discourses connected with health, education, ethnicity and disability that are specific to these three households intersect with d/Discourses concerning children and media. The article argues that general categories describing parenting practices overlook the microcultures of households, erasing the emotional labour embedded in processes of decision‐making.
Evaluating institutional fit for the conservation of threatened species
Authors: Guerrero A. M. , Sporne I. , McKenna R. , Wilson K. A. 
Published: February 2021

AbstractRecovery and conservation of threatened species require adequate institutional responses. We tested an approach to systematically identify and measure how an institutional framework acknowledges threats and required responses for the recovery of endangered species. We measured institutional functional fit with a drivers‐pressure‐state‐impacts‐response (DPSIR) model integrated with a quantitative text mining method and qualitative analysis of statutory instruments to examine regulatory responses that support the recovery of 2 endangered species native to Australia, the bridled nailtail wallaby (Onychogalea fraenata) and the Eastern Bristlebird (Dasyornis brachypterus). The key components of the DPSIR model were present in the institutional framework at statutory and operational levels, but some institutional gaps remained in the protection and recovery of the Eastern Bristlebird, including feral predator control, weed control, and grazing management in some locations. However, regulatory frameworks varied in their geographic scope and the application and implementation of many instruments remained optional. Quantitative text mining can be used to quickly navigate a large volume of regulatory documents, but challenges remain in selection of terms, queries of co‐occurrence, and interpretation of word frequency counts. To inform policy, we recommend that quantitative assessments of institutional fit be complemented with qualitative analysis and interpreted in light of the sociopolitical and institutional context.
Striatal cholinergic transmission. Focus on nicotinic receptors’ influence in striatal circuits
Authors: Assous Maxime 
Published: February 2021

AbstractThe critical role of acetylcholine (ACh) in the basal ganglia is evident from the effect of cholinergic agents in patients suffering from several related neurological disorders, such as Parkinson's disease, Tourette syndrome, or dystonia. The striatum possesses the highest density of ACh markers in the basal ganglia underlying the importance of ACh in this structure. Striatal cholinergic interneurons (CINs) are responsible for the bulk of striatal ACh, although extrinsic cholinergic afferents from brainstem structures may also play a role. CINs are tonically active, and synchronized pause in their activity occurs following the presentation of salient stimuli during behavioral conditioning. However, the synaptic mechanisms involved are not fully understood in this physiological response. ACh modulates striatal circuits by acting on muscarinic and nicotinic receptors existing in several combinations both presynaptically and postsynaptically. While the effects of ACh in the striatum through muscarinic receptors have received particular attention, nicotinic receptors function has been less studied. Here, after briefly reviewing relevant results regarding muscarinic receptors expression and function, I will focus on striatal nicotinic receptor expressed presynaptically on glutamatergic and dopaminergic afferents and postsynaptically on diverse striatal interneurons populations. I will also review recent evidence suggesting the involvement of different GABAergic sources in two distinct nicotinic‐receptor‐mediated striatal circuits: the disynaptic inhibition of striatal projection neurons and the recurrent inhibition among CINs. A better understanding of striatal nicotinic receptors expression and function may help to develop targeted pharmacological interventions to treat brain disorders such as Parkinson's disease, Tourette syndrome, dystonia, or nicotine addiction.
Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control
Authors: Subba Rhea , Sandhir Rajat , Singh Surya Pratap , Mallick Birendra Nath , Mondal Amal Chandra 
Published: February 2021

AbstractDiabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic–pituitary–adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut–brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin‐sensitizing agents can help to manage the distressing condition. The possibility of glucagon‐like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.
Arginase 1+ IL‐10+ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response
Authors: Neri Davide , Carevic‐Neri Melanie , Brück Jürgen , Holstein Julia , Schäfer Iris , Solimani Farzan , Handgretinger Rupert , Hartl Dominik , Ghoreschi Kamran 
Published: February 2021

AbstractMyeloid‐derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which are characterized by their capability to suppress T‐cell responses. While MDSCs have been traditionally associated with cancer diseases, their role as regulators of autoimmune diseases is emerging. Pemphigus is a chronic autoimmune blistering skin disease characterized by dysregulated T‐cell responses and autoantibody production. The role of MDSCs in pemphigus disease has not been defined yet. The aim of this study was to characterize MDSCs in pemphigus patients and to dissect their relationship with CD4+ T‐cell subsets and clinical disease assessments. For this purpose, we performed a cross‐sectional analysis of 20 patients with pemphigus. Our results indicate that a population of CD66b+CD11b+ polymorphonuclear‐like MDSCs (PMN‐MDSCs) is expanded in the peripheral blood mononuclear cell fraction of pemphigus patients compared to age‐matched healthy donors. These PMN‐MDSCs have the capability of suppressing allogeneic T‐cell proliferation in vitro and show increased expression of characteristic effector molecules such as arginase I and interleukin‐10. We further demonstrate that PMN‐MDSCs are especially expanded in patients with active pemphigus, but not in patients in remission. Moreover, MDSC frequencies correlate with an increased Th2/Th1 cell ratio. In conclusion, the identification of a functional PMN‐MDSC population suggests a possible role of these cells as regulators of Th cell responses in pemphigus.
Optimal temperature of vegetation productivity and its linkage with climate and elevation on the Tibetan Plateau
Authors: Chen Anping , Huang Ling , Liu Qiang , Piao Shilong 
Published: February 2021

AbstractVegetation productivity first increases and then decreases with temperature; and temperature corresponding to the maximum productivity is called optimal temperature (Topt). In this study, we used satellite derived near‐infrared reflectance of vegetation (NIRv) data to map Topt of vegetation productivity at the spatial resolution of 0.1° on the Tibetan Plateau (TP), one of most sensitive regions in the climate system. The average Topt of non‐forest vegetation on the TP is about 14.7°C, significantly lower than the Topt value used in current ecosystem models. A remarkable geographical heterogeneity in Topt is observed over the TP. Higher Topt values generally appear in the north‐eastern TP, while the south‐western TP has relatively lower Topt (<10°C), in line with the difference of climate conditions and topography across different regions. Spatially, Topt tends to decrease by 0.41°C per 100 m increase in elevation, faster than the elevational elapse rate of growing season temperature, implying a potential CO2 regulation of Topt in addition to temperature acclimation. Topt increases by 0.66°C for each 1°C of rising mean annual temperature as a result of vegetation acclimation to climate change. However, at least at the decadal scale, there is no significant change in Topt between 2000s and 2010s, suggesting that the Topt climate acclimation may not keep up with the warming rate. Finally, future (2091–2100) warming could be close to and even surpass Topt on the TP under different RCP scenarios without considering potential climate acclimation. Our analyses imply that the temperature tipping point when the impact of future warming shifts from positive to negative on the TP is greatly overestimated by current vegetation models. Future research needs to include varying thermal and CO2 acclimation effects on Topt across different time scales in vegetation models.