bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogenous NECTIN4 expression in urothelial high-risk non-muscle-invasive bladder cancer
Authors: Garczyk Stefan , Degener Stephan , Bischoff Felix , Schnitzler Tician , Salz Anne , Golz Reinhard , Buchner Alexander , Schulz Gerald B. , Schneider Ursula , Gaisa Nadine T. , Knüchel Ruth 
Published: April 2022

Abstract
High-grade non-muscle-invasive bladder cancer (HG NMIBC) patients are at high risk (HR) of progression to muscle-invasion. Bladder-preserving therapies for this patient subgroup are limited, and additional treatments are desirable. Recently, enfortumab vedotin, targeting cancer-associated NECTIN4, has been approved for the treatment of advanced urothelial carcinoma. However, data on the expression of NECTIN4 and its therapeutic potential for HR NMIBC are scarce. Here, NECTIN4 was immunohistochemically analyzed in urothelial HG NMIBC by studying cohorts of carcinoma in situ (CIS)/T1HG (N = 182 samples), HG papillary tumors from mixed-grade lesions (mixed TaHG) (N = 87) and papillary HG tumors without a history of low-grade disease (pure TaHG/T1HG) (N = 98) from overall 225 patients. Moreover, inter-lesional NECTIN4 heterogeneity in multifocal HG NMIBC tumors was determined. A high prevalence of NECTIN4 positivity was noted across HG NMIBC subgroups (91%, N = 367 samples), with 77% of samples showing moderate/strong expression. Heterogenous NECTIN4 levels were observed between HG NMIBC subgroups: non-invasive areas of CIS/T1HG and pure TaHG/T1HG samples showed NECTIN4 positivity in 96% and 99%, with 88% and 83% moderate/strong expressing specimens, respectively, whereas significantly lower NECTIN4 levels were detected in mixed TaHG lesions (72% positivity, 48% of samples with moderate/strong NECTIN4 expression). Moreover, higher NECTIN4 heterogeneity was observed in patients with multifocal mixed TaHG tumors (22% of patients) compared to patients with multifocal CIS/T1HG and pure TaHG/T1HG tumors (9% and 5%). Taken together, NECTIN4-directed antibody–drug conjugates might be promising for the treatment of HR NMIBC patients, especially for those exhibiting CIS/T1HG and pure TaHG/T1HG tumors without a history of low-grade disease.
Paediatric intestinal pseudo-obstruction: a scoping review
Authors: Nham Susan , Nguyen Alexander T. M. , Holland Andrew J. A. 
Published: April 2022

Abstract
Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a complex and resource-limited solution associated with its own morbidity and mortality. We conducted a scoping review to present a contemporary summary of the epidemiology, aetiology, pathophysiology, diagnosis, management and complications of PIPO.Conclusion: PIPO represents a rare disorder that is difficult to diagnose and challenging to treat, with significant morbitity and mortality. The only known cure is intestinal transplantation.

What is Known:• Paediatric intestinal pseudo-obstruction is a rare, heterogeneous disorder that confers a high rate of morbidity and mortality• Complications of paediatric intestinal pseudo-obstruction include chronic pain, small intestine bacterial overgrowth and malrotation. Other complications can occur related to its management, such as line infections with parenteral nutrition or cardiac side effects of prokinetic medications

What is New:• Progress in medical and surgical therapy in recent years has led to improved patient outcomes• Enteral autonomy has been reported in most patients at as early as 1 month post-transplantation
Clinical and genetic correlations of scoliosis in Rett syndrome
Authors: Rodocanachi Roidi Marina Luisa , Cozzi Francesca , Isaias Ioannis Ugo , Grange Francesca , Ferrari Elena Paola , Ripamonti Enrico 
Published: April 2022

Abstract
Aim
To identify the clinical features correlating with the presence and severity of scoliosis in girls with Rett syndrome (RTT).

Method
Seventy-five girls with a clinical and genetically determined diagnosis of RTT participated in this cross-sectional study. Clinical scales administered included the Rett assessment rating scale, the modified Ashworth scale, the Rett syndrome motor evaluation scale, the PainAD, and the scale of evaluation of purposeful hand function. Multivariable analyses, such as ordinal logistic regression and ANCOVA, were used to assess the correlation between these scales and a clinical score of scoliosis.

Results
About 60% of patients had scoliosis, in general mild or moderate. The severity of scoliosis correlated with age and important neurological factors such as muscular hypertonus and hyperreflexia, standing, walking (level walking and on stairs), and postural transitions. No association was found with global disease severity, hand function, pain, or type of genetic mutation.

Interpretation
Scoliosis is a relevant problem in RTT. It should be carefully monitored along the life span, especially in conjunction with (loco-)motor impairment in these patients.
The effect of metamorphism on the aggregate properties of gabbroic rocks
Authors: Urueña Cindy , Möller Charlotte , Andersson Jenny , Lindqvist Jan-Erik , Göransson Mattias 
Published: April 2022

Abstract
Granitic rocks are durable materials sought after for the production of road and railroad aggregates. Granitic bedrock commonly, however, includes gabbroic components, which may enhance or decrease the aggregate performance. This study evaluates the variation in resistance to fragmentation (Los Angeles value, LA) and wear/abrasion (micro-Deval value, MDE) for the fraction 10/14 mm of gabbro in different metamorphic states. Samples were collected along a 150-km profile where metamorphic conditions grade from epidote–amphibolite to high-pressure granulite-facies, and the degree of metamorphic recrystallization varies with the amount of hydrous fluid. Rocks with no or incipient metamorphic recrystallization preserving their primary igneous fabric and interlocking texture meet the criteria for both asphalt base course and track ballast in railroad, with LA and MDE values below 25% and 14%, respectively. Mafic granulite and fine-grained amphibolite have LA values below 25% and can be used in unbound layers. Mafic granulites crystallize at high temperatures but commonly preserve a relict igneous texture due to limited hydration. Coarse-grained amphibolite and migmatitic amphibolite have the poorest performance. They recrystallized at hydrous conditions, leading to complete recrystallization, grain coarsening, and loss of interlocking igneous texture. This study shows that both temperature and infiltration of hydrous fluids significantly affect the technical properties. Even at high metamorphic temperatures, gabbroic rocks may yield aggregates of high technical performance. At hydrous conditions, however, recrystallization results in rock aggregates suitable for unbound layers only. The variation in metamorphic grade and hydration is easily assessed by the geologist in the field and by using standard petrographic microscopy.
Circular economy for durable products and materials: the recycling of plastic building products in Germany—status quo, potentials and recommendations
Authors: Bendix Phillip , Achenbach Hermann , Weißhaupt Petra , Eckert Daniela , Oehme Ines , Berg Holger 
Published: April 2022

AbstractThe construction sector is the second largest area for the application for plastics. Due to the long life times of construction products, the implementation of the circular economy faces its own challenges. To investigate this challenge, the study covers a market study for Germany, voluntary take-back and recycling schemes of construction products, as well as the use of plastic recyclates in construction products. In addition, plastic packaging of construction products is covered. Opportunities and barriers to the use of recycled plastics in construction products are derived from the intersection of available technologies, recyclate supply, and technical requirements for construction products. The report concludes with recommendations to various stakeholders on how to promote the use of recyclates in construction products and their packaging. Important points here are the introduction of a recyclate quota for films as construction product packaging and the description of recycling possibilities and recyclate content in the technical documentation of construction products.
Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience
Authors: Wu Wen-Chi , Lin Tzu-Yuan , Chen Ming‑Huang , Hung Yi‑Ping , Liu Chien-An , Lee Rheun‑Chuan , Huang Yi‑Hsiang , Chao Yee , Chen San-Chi 
Published: April 2022

AbstractLenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%, p = 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months, p = 0.05) and OS (22.9 vs. 10.3 months, p = 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5–12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1–9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1–0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted.
Heavy elements
Authors: Hansen Camilla Juul 
Published: April 2022

AbstractHow are the heavy elements formed? This has been a key open question in physics for decades. Recent direct detections of neutron star mergers and observations of evolved stars show signatures of chemical elements in the blue range of their spectra that bear witness of recent nuclear processes that led to heavy element production. The formation of heavy elements typically takes place through neutron-capture reactions creating radioactive isotopes, which following beta-decay turn into the stable isotopes we today can measure indirectly in the surfaces of cool, low-mass stars or meteoritic grains. The conditions (such as the neutron density or entropy) of these n-capture reactions remain to date poorly constrained, and only through a multidisciplinary effort can we, by combining and comparing observations, experiments, and theoretical predictions, improve on one of the top 10 most important open physics questions posed at the turn of the century. This emphasises the need for detailed observations of the near-UV to blue wavelength region. The shortage of spectrographs and hence spectra covering this range with high-resolution and high signal-to-noise has for decades played a limiting factor in our understanding of how heavy elements form in the nuclear reactions as well as how they behave in the stellar surfaces. With CUBES (Cassegrain U-Band Efficient Spectrograph) we can finally improve the observations, by covering the crucial blue range in more remote stars and also achieve a higher signal-to-noise ratio (SNR). This is much needed to detect and accurately deblend the absorption lines and in turn derive more accurate and precise abundances of the heavy elements.
Similar distribution of 15N labeled cattle slurry and mineral fertilizer in soil after one year
Authors: Frick Hanna , Oberson Astrid , Cormann Michael , Wettstein Hans-Rudolf , Frossard Emmanuel , Bünemann Else Katrin 
Published: April 2022

AbstractTargeted use of animal manures as a nitrogen (N) fertilizer is challenging because of their poorly predictable N fertilizer value. An enhanced understanding of their N transformation processes in soil under field conditions is necessary to better synchronize N availability and crop N demand. 15N labeled cattle slurry, produced by feeding a heifer with 15N labeled ryegrass hay, was used in an on-farm trial on two neighboring fields, cropped with maize or grass-clover, in order to assess crop N uptake and N dynamics in the topsoil. Recovery of applied total N in plant biomass was higher for mineral fertilizer (Min) (45–48%) than for slurry (Slu) (17–22%) when applied at the same rate of mineral N. Also, N derived from fertilizer in plant biomass was higher for Min than for Slu, due to both greater NH3 emissions and greater initial immobilization of slurry N. Despite initial differences between the two in the relative distribution of residual fertilizer N in soil N pools, already in the following spring the majority (77–89%) of residual N from both fertilizers was found in the non-microbial organic N pool. Of the applied total N, 18–26% remained in the topsoil after the first winter for Min, compared to 32–52% for Slu. Thus, the proportion of fertilizer N not taken up by the first crop after application, enters the soil organic N pool and must be re-mineralized to become plant available.
Distinct Psychological Profiles Linking Childhood Adversity and Substance Misuse in High-Risk Young Adults
Authors: van Zyl Tara-Lynne , O’Neill Tara , Rushe Teresa 
Published: April 2022

AbstractAdverse childhood experiences (ACEs) constitute a key determinant in the development of substance misuse. However, the understanding of how ACEs cultivate this risk lacks the specificity needed to inform effective prevention and intervention practices. This issue may be remedied by exploring the distinction between ACEs and their effects on development. The present study investigated whether distinct patterns of adversity are differentially associated with substance misuse along unique profiles of psychological variables, namely anxiety and punishment sensitivity – an internalizing profile – versus reward sensitivity and executive functioning – an externalizing profile. Using a cross-sectional retrospective design, 124 high-risk young adults completed assessments of childhood adversity and psychological functioning. We employed the ACE-IQ to capture extended ACEs such as community and collective violence, as our sample grew up in the post-conflict society of Northern Ireland. Exploratory Factor Analysis revealed three patterns of adversity co-occurrence – Childhood Maltreatment, Household Dysfunction and Community Adversity, all of which independently predicted different types of substance misuse. Childhood Maltreatment was significantly associated with heavy drug use probability; Household Dysfunction was associated with cannabis dependence probability; and Community Adversity was associated with both cannabis dependence and heavy drug use probability. Logistic regressions (all p < .05) showed that heavy drug use probability was predicted by Childhood Maltreatment and anxiety in one model, and by Community Adversity and reduced punishment sensitivity in another, suggesting that different types of ACEs were associated with partially distinct outcomes in this sample. These results support the proposal that different ACE subtypes confer distinct effects, which carries clinical implications for substance misuse prevention and intervention.
Thermal behavior and antibacterial studies of a carbonate Mg–Al-based layered double hydroxide (LDH) for in vivo uses
Authors: Cardinale Anna Maria , Vecchio Ciprioti Stefano , Fortunato Marco , Catauro Michelina 
Published: April 2022

AbstractThe goal of this work is to study the thermal behavior and the antibacterial properties of a MgAl-CO3 layered double hydroxide (LDH), which demonstrated high efficiency in removing chromium (VI) from contaminated industrial wastewater. The compound has been synthesized via co-precipitation route (direct method) followed by hydrothermal treatment, obtaining nanoscopic crystallites with a partially disordered (turbostratic) structure. After its synthesis, the compound was characterized by means of X-ray powder diffraction, field emission scanning electron microscope, inductively coupled plasma atomic emission spectroscopy and analysis and Fourier transform infrared spectroscopy. On the other hand, with the view to check the drug delivery and surgical tools usage of MgAl-CO3, antibacterial tests, performed according to the Kirby–Bauer method, revealed the inability the growth of the pathogenic bacterial strains. Thermogravimetry and differential thermal analysis revealed that evolution of water from the material occurs in two stages upon heating and a noticeable interaction takes place between water (in the vapor phase) and MgAl-CO3. Kinetic analysis of both steps provides almost constant values of activation energy, with the following average values in the range 0.1 < a < 0.9: E1 = (66 ± 9) kJ mol‒1; E2 = (106 ± 7) kJ mol‒1. Finally, prediction of reasonable reaction times extrapolated at 25 and 37 °C has been made from kinetic parameters of the first step, while almost unrealistic reaction time values were determined using the same procedure with kinetic parameters related to the second step.
Beneficial effects of antisymmetric nonlinear damping with application to energy harvesting and vibration isolation under general inputs
Authors: Zhu Yun-Peng , Lang Z. Q. 
Published: April 2022

AbstractBeneficial effects of nonlinear damping on energy harvesting and vibration isolation under harmonic inputs have been investigated showing that the introduction of nonlinear damping can increase the harvested energy and reduce the vibration over both the resonant and higher frequency ranges. However, the scenario becomes more complicated when the loading inputs are of more general form such as multi-tone and random inputs, which can produce system responses that are induced by an interaction of system input components of different frequencies. In the present study, by introducing the concept of power transmissibility, the study of the beneficial effects of nonlinear damping is extended to the systems subject to general inputs including both multi-tone and random inputs. A rigorous analysis is conducted based on single degree of freedom systems subject to general inputs. The analysis reveals the conditions under which the antisymmetric nonlinear damping is beneficial for improving energy harvester performance and reducing of the power of system output in vibration isolation. Moreover, the beneficial effects are demonstrated by two case studies.
Amodal completion and relationalism
Authors: Nanay Bence 
Published: April 2022

AbstractAmodal completion is usually characterized as the representation of those parts of the perceived object that we get no sensory stimulation from. In the case of the visual sense modality, for example, amodal completion is the representation of occluded parts of objects we see. I argue that relationalism about perception, the view that perceptual experience is constituted by the relation to the perceived object, cannot give a coherent account of amodal completion. The relationalist has two options: construe the perceptual relation as the relation to the entire perceived object or as the relation to the unoccluded parts of the perceived object. I argue that neither of these options are viable.
Evolution of salt tolerance in Arabidopsis thaliana on siliceous soils does not confer tolerance to saline calcareous soils
Authors: Pérez-Martín Laura , Busoms Silvia , Almira Maria Jose , Azagury Nicole , Terés Joana , Tolrà Roser , Poschenrieder Charlotte , Barceló Juan 
Published: April 2022

Abstract
Purpose
Alkaline salinity constrains crop yield. Previously, we observed local adaptation of Arabidopsis thaliana to saline-siliceous soils (pH ≤ 7) and to non-saline carbonate soils. However, no natural population of A. thaliana was localized on saline-alkaline soils. This suggests that salinity tolerance evolved on saline-siliceous soils may not confer tolerance to alkaline salinity. This hypothesis was explored by addressing physiological and molecular responses to alkaline salinity of A. thaliana that differ in tolerance to either non-alkaline salinity or carbonate.

Methods
A. thaliana native to saline-siliceous soils (high salinity, HS), non-saline carbonate soils (high alkalinity, HA), or soils with intermediate levels of these factors (medium saline-alkalinity, MSA) were cultivated in common gardens on saline-siliceous or saline-calcareous substrates. Hydroponics and irrigation experiments confirmed the phenotypes. The growth, mineral concentrations, proline content, osmotic potential, genetic variation distribution, and expression levels of selected genes involved in salinity and alkalinity tolerance were assessed.

Results
HS performed best on saline-siliceous soil and in hydroponics with salinity (pH 5.9). However, HS was more sensitive to saline-alkaline conditions than HA and MSA. The fitness under saline-alkaline conditions was ranked according to MSA > HA > HS. Under alkaline salinity, MSA best maintained ion homeostasis, osmotic balance, and higher expression levels of key genes involved in saline or alkaline tolerance (AHA1, root HKT1 and FRO2, and shoot NHX1 and IRT1).

Conclusion
In A. thaliana, salinity tolerance evolved on saline-siliceous soils does not provide tolerance to alkaline salinity. Plants native to intermediate conditions (MSA) have more plasticity to adapt to alkaline salinity than those locally adapted to these individual stress factors.