bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hypothesis to derive the shape of the dose–response curve for teratogenic radiation effects
Authors: Körblein Alfred 
Published: February 2022

AbstractReports of adverse pregnancy outcomes after in utero exposure to very low levels of ionizing radiation are inconsistent with a threshold dose of 100 mSv for teratogenic effects in humans. In the present study, it is hypothesized that the shape of the dose–response relationship for teratogenic effects is a cumulative lognormal distribution without threshold. This hypothesis relies on the assumption that both doses and radiosensitivities in human populations exposed to ionizing radiation are random variables, modeled by lognormal density functions. Here, radiosensitivity is defined as the dose limit up to which radiation damage can be repaired by the cellular repair systems, in short, the repair capacity. Monte Carlo simulation is used to generate N pairs of individual doses and repair capacities. Radiation damage occurs whenever the dose exceeds the related repair capacity. The rate of radiation damage is the number of damages, divided by the number N of pairs. Monte Carlo simulation is conducted for a sufficient number of ascending median doses. The shape of the dose–response relationship is determined by regression of damage rates on mean dose. Regression with a cumulative lognormal distribution function yields a perfect fit to the data. Acceptance of the hypothesis means that studies of adverse health effects following in-utero exposure to low doses of ionizing radiation should not be discarded primarily because they contradict the concept of a threshold dose for teratogenic effects.
Human spatial memory is biased towards high-calorie foods: a cross-cultural online experiment
Authors: de Vries Rachelle , Boesveldt Sanne , de Vet Emely 
Published: February 2022

AbstractBackgroundHuman memory appears to prioritise locations of high-calorie foods, likely as an adaptation for foraging within fluctuating ancestral food environments. Importantly, this “high-calorie bias” in human spatial memory seems to yield consequences for individual eating behaviour in modern food-abundant settings. However, as studies have mainly been conducted in European (Dutch) populations to date, we investigated whether the existence of the cognitive bias can be reasonably generalised across countries that vary on culturally-relevant domains, such as that of the USA and Japan. Furthermore, we investigated whether sociodemographic factors moderate the expression of the high-calorie spatial memory bias in different populations.MethodsIn a cross-cultural online experiment, we measured the food location memory of diverse participants from the USA (N = 72; 44.4% Male; 54 ± 15.99 years) and Japan (N = 74; 56.8% Male; 50.85 ± 17.32 years), using a validated computer-based spatial memory task with standardised images of high-calorie and low-calorie foods. To directly compare the magnitude of the high-calorie spatial memory bias in a broader cultural scope, we also included data from a previous online experiment that identically tested the food spatial memory of a Dutch sample (N = 405; 56.7% Male; 47.57 ± 17.48 years).ResultsIn the US sample, individuals more accurately recalled (i.e. had lower pointing errors for) locations of high-calorie foods versus that of low-calorie alternatives (Mean difference = -99.23 pixels, 95% CI = [-197.19, -1.28]) – regardless of one’s hedonic preferences, familiarity with foods, and encoding times. Likewise, individuals in the Japanese sample displayed an enhanced memory for locations of high-calorie (savoury-tasting) foods (Mean difference = -40.41 pixels, 95% CI = [-76.14, -4.68]), while controlling for the same set of potential confounders. The magnitude of the high-calorie bias in spatial memory was similar across populations (i.e. the USA, Japan, and the Netherlands), as well as across diverse sociodemographic groups within a population.ConclusionsOur results demonstrate that the high-calorie bias in spatial memory transcends sociocultural boundaries. Since the cognitive bias may negatively impact on our dietary decisions, it would be wise to invest in strategies that intervene on our seemingly universal ability to efficiently locate calorie-rich foods.
B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages
Authors: Nobari Shirin Teymouri , Nojadeh Jafar Nouri , Talebi Mehdi 
Published: February 2022

AbstractB cell maturation antigen (BCMA), a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17), highly expressed on the plasma cells of Multiple myeloma (MM) patients, as well as the normal population. BCMA is used as a biomarker for MM. Two members of the TNF superfamily proteins, including B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), are closely related to BCMA and play an important role in plasma cell survival and progression of MM. Despite the maximum specificity of the monoclonal antibody technologies, introducing the tumor-specific antigen(s) is not applicable for all malignancies, such as MM that there plenty of relatively specific antigens such as GPCR5D, MUC1, SLAMF7 and etc., but higher expression of BCMA on these cells in comparison with normal ones can be regarded as a relatively exclusive marker. Currently, different monoclonal antibody (mAb) technologies applied in anti-MM therapies such as daratuzumab, SAR650984, GSK2857916, and CAR-T cell therapies are some of these tools that are reviewed in the present manuscript. By the way, the structure, function, and signaling of the BCMA and related molecule(s) role in normal plasma cells and MM development, evaluated as well as the potential side effects of its targeting by different CAR-T cells generations. In conclusion, BCMA can be regarded as an ideal molecule to be targeted in immunotherapeutic methods, regarding lower potential systemic and local side effects.
Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study
Authors: Lewis Kimberly A. , Osier Nico , Carrasco Ruy , Chiou Jennifer , Carter Patricia , Garcia Alexandra , Flowers Elena , Gennatas Efstathios D. , Nguyen Christina , Rana Ambreen , Brown Sharon A. , Tiziani Stefano 
Published: February 2022

Abstract
Background
In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition’s underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population.

Methods
A sample of 20 adolescents with JIA and 20 controls aged 13–17 years were recruited to complete surveys, provide medical histories and biospecimens, and undergo assessments. Fasting morning plasma samples were processed with liquid chromatography–mass spectrometry. Data were centered, scaled, and analyzed using generalized linear models accounting for age, sex, and medications (p-values adjusted for multiple comparisons using the Holm method). Spearman’s correlations were used to evaluate relationships among metabolites, time since diagnosis, and disease severity.

Results
Of 72 metabolites identified in the samples, 55 were common to both groups. After adjustments, 6 metabolites remained significantly different between groups. Alpha-glucose, alpha-ketoglutarate, serine, and N-acetylaspartate were significantly lower in the JIA group than in controls; glycine and cystine were higher. Seven additional metabolites were detected only in the JIA group; 10 additional metabolites were detected only in the control group. Metabolites were unrelated to disease severity or time since diagnosis.

Conclusions
The metabolic signature of adolescents with JIA relative to controls reflects a disruption in oxidative stress; neurological health; and amino acid, caffeine, and energy metabolism pathways. Serine and N-acetylaspartate were promising potential biomarkers, and their metabolic pathways are linked to both JIA and cardiovascular disease risk. The pathways may be a source of new diagnostic, treatment, or prevention options. This study’s findings contribute new knowledge for systems biology and precision health approaches to JIA research. Further research is warranted to confirm these findings in a larger sample.
Pulmonary large cell carcinoma with neuroendocrine morphology shows genetic similarity to large cell neuroendocrine carcinoma
Authors: Liang Zuoyu , Wang Weiya , Hu Qianrong , Zhou Ping , Zhang Ying , Tang Yuan , Wu Qian , Fu Yiyun , Li Xue , Shao Yang , Jiang Lili 
Published: February 2022

Abstract
Background
Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics.

Methods
31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS.

Results
Compared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly.

Conclusions
We consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation.
Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy for non-metastatic locally advanced pancreatic cancer: a single-center retrospective study
Authors: Ogura Yuta , Terashima Kazuki , Nanno Yoshihide , Park SungChul , Suga Masaki , Takahashi Daiki , Matsuo Yoshiro , Sulaiman Nor Shazrina , Tokumaru Sunao , Okimoto Tomoaki , Toyama Hirochika , Fukumoto Takumi 
Published: February 2022

Abstract
Background
Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC.

Methods
The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes.

Results
The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P < 0.001). LAPCs with anterior peripancreatic invasion had more peritoneal recurrence within 6 months after GTP than those without anterior peripancreatic invasion (P = 0.039).

Conclusions
GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.
Awareness and agreement with neurofibromatosis care guidelines among U.S. neurofibromatosis specialists
Authors: Merker Vanessa L. , Knight Pamela , Radtke Heather B. , Yohay Kaleb , Ullrich Nicole J. , Plotkin Scott R. , Jordan Justin T. 
Published: February 2022

Abstract
Introduction
The neurofibromatoses (NF) are a group of rare, genetic diseases sharing a predisposition to develop multiple benign nervous system tumors. Given the wide range of NF symptoms and medical specialties involved in NF care, we sought to evaluate the level of awareness of, and agreement with, published NF clinical guidelines among NF specialists in the United States.

Methods
An anonymous, cross-sectional, online survey was distributed to U.S.-based NF clinicians. Respondents self-reported demographics, practice characteristics, awareness of seven NF guideline publications, and level of agreement with up to 40 individual recommendations using a 5-point Likert scale. We calculated the proportion of recommendations that each clinician rated “strongly agree”, and assessed for differences in guideline awareness and agreement by respondent characteristics.

Results
Sixty-three clinicians (49% female; 80% academic practice) across > 8 medical specialties completed the survey. Awareness of each guideline publication ranged from 53%-79% of respondents; specialists had higher awareness of publications endorsed by their medical professional organization (p < 0.05). The proportion of respondents who “strongly agree” with individual recommendations ranged from 17%-83%; for 16 guidelines, less than 50% of respondents “strongly agree”. There were no significant differences in overall agreement with recommendations based on clinicians’ gender, race, specialty, years in practice, practice type (academic/private practice/other), practice location (urban/suburban/rural), or involvement in NF research (p > 0.05 for all).

Conclusions
We identified wide variability in both awareness of, and agreement with, published NF care guidelines among NF experts. Future quality improvement efforts should focus on evidence-based, consensus-driven methods to update and disseminate guidelines across this multi-specialty group of providers. Patients and caregivers should also be consulted to proactively anticipate barriers to accessing and implementing guideline-driven care. These recommendations for improving guideline knowledge and adoption may also be useful for other rare diseases requiring multi-specialty care coordination.
Diagnostic value of fetal hemoglobin Bart’s for evaluation of fetal α-thalassemia syndromes: application to prenatal characterization of fetal anemia caused by undiagnosed α-hemoglobinopathy
Authors: Singha Kritsada , Yamsri Supawadee , Chaibunruang Attawut , Srivorakun Hataichanok , Sanchaisuriya Kanokwan , Fucharoen Goonnapa , Fucharoen Supan 
Published: February 2022

AbstractBackgroundTo evaluate whether the quantification of fetal hemoglobin (Hb) Bart’s is useful for differentiation of α-thalassemia syndromes in the fetus and to characterize the fetal anemia associated with fetal α-hemoglobinopathy.MethodsA total of 332 fetal blood specimens collected by cordocentesis were analyzed using capillary electrophoresis and the amount of Hb Bart’s was recorded. The result was evaluated against thalassemia genotypes determined based on Hb and DNA analyses. Prenatal Hb and DNA characterization of the fetal anemia observed in two families was done.ResultsAmong 332 fetuses investigated, Hb and DNA analyses identified 152 fetuses with normal genotypes. The remaining 180 fetuses carried α-thalassemia with several genotypes. Variable amounts of Hb Bart’s were identified in all fetuses with α-thalassemia, which could be used for simple differentiation of fetal α-thalassemia genotypes. These included α+- and α0-thalassemia traits, homozygous α+-thalassemia and Hb Constant Spring (CS), Hb H disease, Hb H-CS and Hb H-Quong Sze diseases, homozygous α0-thalassemia causing the Hb Bart’s hydrops fetalis and a remain uncharacterized α-thalassemia defect. The previously undescribed interactions of Hb Queens Park and Hb Amsterdam A1 with Hb E were detected in two fetuses with Hb Bart’s of 0.5%. The Hb Queens Park-AEBart’s disease was also noted in one pregnant woman. Prenatal analysis of the fetuses with severe fetal anemia and cardiomegaly with Hb Bart’s of 9.0% and 13.6% revealed unexpectedly the homozygous Hb CS and a compound heterozygosity of Hb CS/Hb Pakse’ with Hb E heterozygote, respectively.ConclusionsThe usefulness of detecting and differentiation of fetal α-thalassemia syndromes by quantifying of Hb Bart’s was demonstrated. Apart from the fatal condition of Hb Bart’s hydrops fetalis associated with homozygous α0-thalassemia, homozygous Hb CS and a compound Hb CS/Hb Pakse’ could result in severe fetal anemia and fetal complications, prenatal diagnosis is highly recommended. The simple Hb Bart’s quantification of fetal blood should prove helpful in this matter.
iSuc-ChiDT: a computational method for identifying succinylation sites using statistical difference table encoding and the chi-square decision table classifier
Authors: Zeng Ying , Chen Yuan , Yuan Zheming 
Published: February 2022

Abstract
Background
Lysine succinylation is a type of protein post-translational modification which is widely involved in cell differentiation, cell metabolism and other important physiological activities. To study the molecular mechanism of succinylation in depth, succinylation sites need to be accurately identified, and because experimental approaches are costly and time-consuming, there is a great demand for reliable computational methods. Feature extraction is a key step in building succinylation site prediction models, and the development of effective new features improves predictive accuracy. Because the number of false succinylation sites far exceeds that of true sites, traditional classifiers perform poorly, and designing a classifier to effectively handle highly imbalanced datasets has always been a challenge.

Results
A new computational method, iSuc-ChiDT, is proposed to identify succinylation sites in proteins. In iSuc-ChiDT, chi-square statistical difference table encoding is developed to extract positional features, and has a higher predictive accuracy and fewer features compared to common position-based encoding schemes such as binary encoding and physicochemical property encoding. Single amino acid and undirected pair-coupled amino acid composition features are supplemented to improve the fault tolerance for residue insertions and deletions. After feature selection by Chi-MIC-share algorithm, the chi-square decision table (ChiDT) classifier is constructed for imbalanced classification. With a training set of 4748:50,551(true: false sites), ChiDT clearly outperforms traditional classifiers in predictive accuracy, and runs fast. Using an independent testing set of experimentally identified succinylation sites, iSuc-ChiDT achieves a sensitivity of 70.47%, a specificity of 66.27%, a Matthews correlation coefficient of 0.205, and a global accuracy index Q9 of 0.683, showing a significant improvement in sensitivity and overall accuracy compared to PSuccE, Success, SuccinSite, and other existing succinylation site predictors.

Conclusions
iSuc-ChiDT shows great promise in predicting succinylation sites and is expected to facilitate further experimental investigation of protein succinylation.
Identifying targets for increased biogas production through chemical and organic matter characterization of digestate from full-scale biogas plants: what remains and why?
Authors: Ekstrand Eva-Maria , Björn Annika , Karlsson Anna , Schnürer Anna , Kanders Linda , Yekta Sepehr Shakeri , Karlsson Martin , Moestedt Jan 
Published: February 2022

AbstractBackgroundThis study examines the destiny of macromolecules in different full-scale biogas processes. From previous studies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential, but the factors dictating the size and composition of this residual fraction and how they correlate with the residual methane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of the composition of residual digestate fractions and to understand how they correlate with various operational and chemical parameters. The organic composition of both the substrates and digestates from nine biogas plants operating on food waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked to substrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.ResultsCarbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, in the digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). The degradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%). High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from the substrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradation efficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates also triggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kg VS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mg NH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative to the slow digestion of agricultural waste and manure.ConclusionsOperation at unstable conditions was one reason for the high residual macromolecule content and high RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteins represents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment or post-digestion of digestates, targeting microbial biomass or recalcitrant protein fractions, is a potential way to achieve increased protein degradation.