bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
Authors: Louisse Jochem , Mulder Patrick P. J. , Gerssen Arjen , Stoopen Geert , Rijkers Deborah , van de Schans Milou G. M. , Peijnenburg Ad A. C. M. 
Published: May 2022

AbstractPyrrolizidine alkaloids (PAs) are produced by various plant species and have been detected as contaminants in food and feed. Monitoring programmes should include PAs that are present in relevant matrices and that exhibit a high toxic potential. The aim of the present study was to use a bioassay-directed analysis approach to identify relevant PAs not yet included in monitoring programmes. To that end, extracts ofHeliotropium europaeumandH. popoviiwere prepared and analysed with LC–MS/MS for the presence of 35 PAs included in monitoring programmes, as well as for genotoxic activity in the HepaRG/γH2AX assay. Europine, heliotrine and lasiocarpine were found to be the most abundant PAs. The extracts showed a higher γH2AX activity than related artificial mixtures of quantified known PAs, which might point to the presence of unknown toxic PAs. TheH. europaeumextract was fractionated and γH2AX activities of individual fractions were determined. Fractions were further analysed applying LC–Orbitrap-MS analysis and Compound Discoverer software, identifying various candidate PAs responsible for the non-explained genotoxic activity. Altogether, the results obtained show that bioassay-directed analysis allows identification of candidate PAs that can be included in monitoring programmes.
Efficient workflow for suspect screening analysis to characterize novel and legacy per- and polyfluoroalkyl substances (PFAS) in biosolids
Authors: Dickman Rebecca A. , Aga Diana S. 
Published: May 2022

AbstractLand application of treated sewage sludge (also known as biosolids) is considered a sustainable route of disposal because it reduces waste loading into landfills while improving soil health. However, this waste management practice can introduce contaminants from biosolids, such as per- and polyfluoroalkyl substances (PFAS), into the environment. PFAS have been observed to be taken up by plants, accumulate in humans and animals, and have been linked to various negative health effects. There is limited information on the nature and amounts of PFAS introduced from biosolids that have undergone different treatment processes. Therefore, this study developed analytical techniques to improve the characterization of PFAS in complex biosolid samples. Different clean-up techniques were evaluated and applied to waste-activated sludge (WAS) and lime-stabilized primary solids (PS) prior to targeted analysis and suspect screening of biosolid samples. Using liquid chromatography with high-resolution mass spectrometry, a workflow was developed to achieve parallel quantitative targeted analysis and qualitative suspect screening. This study found that concentrations of individual PFAS (27 targeted analytes) can range from 0.6 to 84.6 ng/g in WAS (average total PFAS = 241.4 ng/g) and from 1.6 to 33.8 ng/g in PS (average total PFAS = 72.1 ng/g). The suspect screening workflow identified seven additional PFAS in the biosolid samples, five of which have not been previously reported in environmental samples. Some of the newly identified compounds are a short-chain polyfluorinated carboxylate (a PFOS replacement), a diphosphate ester (a PFOA precursor), a possible transformation product of carboxylate PFAS, and an imidohydrazide which contains a sulfonate and benzene ring.
Enhancement of cranial nerves in Lyme neuroborreliosis: incidence and correlation with clinical symptoms and prognosis
Authors: Lindland Elisabeth S. , Solheim Anne Marit , Dareez Muhammad Nazeer , Eikeland Randi , Ljøstad Unn , Mygland Åse , Reiso Harald , Lorentzen Åslaug R. , Harbo Hanne F. , Beyer Mona K. 
Published: May 2022

Abstract
Purpose
Symptoms of cranial neuritis are a common presentation of Lyme neuroborreliosis (LNB). Imaging studies are scarce and report contradictory low prevalence of enhancement compared to clinical studies of cranial neuropathy. We hypothesized that MRI enhancement of cranial nerves in LNB is underreported, and aimed to assess the prevalence and clinical impact of cranial nerve enhancement in early LNB.

Methods
In this prospective, longitudinal cohort study, 69 patients with acute LNB were examined with MRI of the brain. Enhancement of cranial nerves III–XII was rated. MRI enhancement was correlated to clinical findings of neuropathy in the acute phase and after 6 months.

Results
Thirty-nine of 69 patients (57%) had pathological cranial nerve enhancement. Facial and oculomotor nerves were most frequently affected. There was a strong correlation between enhancement in the distal internal auditory canal and parotid segments of the facial nerve and degree of facial palsy (gamma = 0.95, p < .01, and gamma = 0.93, p < .01), despite that 19/37 nerves with mild-moderate enhancement in the distal internal auditory canal segment showed no clinically evident palsy. Oculomotor and abducens nerve enhancement did not correlate with eye movement palsy (gamma = 1.00 and 0.97, p = .31 for both). Sixteen of 17 patients with oculomotor and/or abducens nerve enhancement had no evident eye movement palsy.

Conclusions
MRI cranial nerve enhancement is common in LNB patients, but it can be clinically occult. Facial and oculomotor nerves are most often affected. Enhancement of the facial nerve distal internal auditory canal and parotid segments correlate with degree of facial palsy.
Conventional MRI features can predict the molecular subtype of adult grade 2–3 intracranial diffuse gliomas
Authors: Lasocki Arian , Buckland Michael E. , Drummond Katharine J. , Wei Heng , Xie Jing , Christie Michael , Neal Andrew , Gaillard Frank 
Published: May 2022

Abstract
Purpose
Molecular biomarkers are important for classifying intracranial gliomas, prompting research into correlating imaging with genotype (“radiogenomics”). A limitation of the existing radiogenomics literature is the paucity of studies specifically characterizing grade 2–3 gliomas into the three key molecular subtypes. Our study investigated the accuracy of multiple different conventional MRI features for genotype prediction.

Methods
Grade 2–3 gliomas diagnosed between 2007 and 2013 were identified. Two neuroradiologists independently assessed nine conventional MRI features. Features with better inter-observer agreement (κ ≥ 0.6) proceeded to consensus assessment. MRI features were correlated with genotype, classified as IDH-mutant and 1p/19q-codeleted (IDHmut/1p19qcodel), IDH-mutant and 1p/19q-intact (IDHmut/1p19qint), or IDH-wildtype (IDHwt). For IDHwt tumors, additional molecular markers of glioblastoma were noted.

Results
One hundred nineteen patients were included. T2-FLAIR mismatch (stratified as > 50%, 25–50%, or < 25%) was the most predictive feature across genotypes (p < 0.001). All 30 tumors with > 50% mismatch were IDHmut/1p19qint, and all seven with 25–50% mismatch. Well-defined margins correlated with IDHmut/1p19qint status on univariate analysis (p < 0.001), but this related to correlation with T2-FLAIR mismatch; there was no longer an association when considering only tumors with < 25% mismatch (p = 0.386). Enhancement (p = 0.001), necrosis (p = 0.002), and hemorrhage (p = 0.027) correlated with IDHwt status (especially “molecular glioblastoma”). Calcification correlated with IDHmut/1p19qcodel status (p = 0.003). A simple, step-wise algorithm incorporating these features, when present, correctly predicted genotype with a positive predictive value 91.8%.

Conclusion
T2-FLAIR mismatch strongly predicts IDHmut/1p19qint even with a lower threshold of ≥ 25% mismatch and outweighs other features. Secondary features include enhancement, necrosis and hemorrhage (predicting IDHwt, especially “molecular glioblastoma”), and calcification (predicting IDHmut/1p19qcodel).
Interactions of Fungi and Algae from the Greenland Ice Sheet
Authors: Perini L. , Gostinčar C. , Likar M. , Frisvad J. C. , Kostanjšek R. , Nicholes M. , Williamson C. , Anesio A. M. , Zalar P. , Gunde-Cimerman N. 
Published: May 2022

AbstractHeavily pigmented glacier ice algae Ancylonema nordenskiöldii and Ancylonema alaskanum (Zygnematophyceae, Streptophyta) reduce the bare ice albedo of the Greenland Ice Sheet, amplifying melt from the largest cryospheric contributor to eustatic sea-level rise. Little information is available about glacier ice algae interactions with other microbial communities within the surface ice environment, including fungi, which may be important for sustaining algal bloom development. To address this substantial knowledge gap and investigate the nature of algal-fungal interactions, an ex situ co-cultivation experiment with two species of fungi, recently isolated from the surface of the Greenland Ice Sheet (here proposed new species Penicillium anthracinoglaciei Perini, Frisvad and Zalar, Mycobank (MB 835602), and Articulospora sp.), and the mixed microbial community dominated by glacier ice algae was performed. The utilization of the dark pigment purpurogallin carboxylic acid-6-O-β-D-glucopyranoside (C18H18O12) by the two fungi was also evaluated in a separate experiment. P. anthracinoglaciei was capable of utilizing and converting the pigment to purpurogallin carboxylic acid, possibly using the sugar moiety as a nutrient source. Furthermore, after 3 weeks of incubation in the presence of P. anthracinoglaciei, a significantly slower decline in the maximum quantum efficiency (Fv/Fm, inverse proxy of algal stress) in glacier ice algae, compared to other treatments, was evident, suggesting a positive relationship between these species. Articulospora sp. did uptake the glycosylated purpurogallin, but did not seem to be involved in its conversion to aglycone derivative. At the end of the incubation experiments and, in conjunction with increased algal mortality, we detected a substantially increasing presence of the zoosporic fungi Chytridiomycota suggesting an important role for them as decomposers or parasites of glacier ice algae.
Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy
Authors: Zboralski Dirk , Hoehne Aileen , Bredenbeck Anne , Schumann Anne , Nguyen Minh , Schneider Eberhard , Ungewiss Jan , Paschke Matthias , Haase Christian , von Hacht Jan L. , Kwan Tanya , Lin Kevin K. , Lenore Jan , Harding Thomas C. , Xiao Jim , Simmons Andrew D. , Mohan Ajay-Mohan , Beindorff Nicola , Reineke Ulrich , Smerling Christiane , Osterkamp Frank 
Published: May 2022

Abstract
Purpose
Fibroblast activation protein (FAP) is a membrane-bound protease that has limited expression in normal adult tissues but is highly expressed in the tumor microenvironment of many solid cancers. FAP-2286 is a FAP-binding peptide coupled to a radionuclide chelator that is currently being investigated in patients as an imaging and therapeutic agent. The potency, selectivity, and efficacy of FAP-2286 were evaluated in preclinical studies.

Methods
FAP expression analysis was performed by immunohistochemistry and autoradiography on primary human cancer specimens. FAP-2286 was assessed in biochemical and cellular assays and in in vivo imaging and efficacy studies, and was further evaluated against FAPI-46, a small molecule–based FAP-targeting agent.

Results
Immunohistochemistry confirmed elevated levels of FAP expression in multiple tumor types including pancreatic, breast, and sarcoma, which correlated with FAP binding by FAP-2286 autoradiography. FAP-2286 and its metal complexes demonstrated high affinity to FAP recombinant protein and cell surface FAP expressed on fibroblasts. Biodistribution studies in mice showed rapid and persistent uptake of 68Ga-FAP-2286, 111In-FAP-2286, and 177Lu-FAP-2286 in FAP-positive tumors, with renal clearance and minimal uptake in normal tissues. 177Lu-FAP-2286 exhibited antitumor activity in FAP-expressing HEK293 tumors and sarcoma patient-derived xenografts, with no significant weight loss. In addition, FAP-2286 maintained longer tumor retention and suppression in comparison to FAPI-46.

Conclusion
In preclinical models, radiolabeled FAP-2286 demonstrated high tumor uptake and retention, as well as potent efficacy in FAP-positive tumors. These results support clinical development of 68Ga-FAP-2286 for imaging and 177Lu-FAP-2286 for therapeutic use in a broad spectrum of FAP-positive tumors.
Natural variation MeMYB108 associated with tolerance to stress-induced leaf abscission linked to enhanced protection against reactive oxygen species in cassava
Authors: Wang Bin , Li Shuxia , Zou Liangping , Guo Xin , Liang Jiaxin , Liao Wenbin , Peng Ming 
Published: May 2022

Abstract
Key Message
Natural variation of the MeMYB108 exon was associated with reactive oxygen scavengers led to alleviate leaf abscission under drought in cassava.

Abstract
The reactive oxygen scavengers play important roles in regulating the cassava (Manihot esculenta Crantz) leaf abscission induced by stresses. To date, the relationship between natural variations of MYB genes and reactive oxygen scavengers under drought in cassava genotypes remains unclear. Here, we reported the transcription factor MeMYB108 played an important role in regulating leaf abscission exposed to drought in cassava. The expression levels of MeMYB108 in abscission zones of cassava leaf pulvinus were higher in cassava genotype SC124, which were less easy to shed leaves under stress than cassava genotype SC8 when the leaf abscission induced by the same drought condition. Compared with wild type and interference expression plants, overexpression of MeMYB108 significantly reduced the drought-induced leaf abscission rate under drought. The consecutively 2-year analysis of reactive oxygen scavengers showed significant differences among different cassava genotypes under drought-induced leaf abscission, indicating the relevance between reactive oxygen scavengers and leaf abscission. Correlation analysis revealed the natural variation of the MeMYB108 exon was associated with reactive oxygen scavengers during drought-induced leaf abscission. Association analysis between pairwise LD of DNA polymorphism indicated the MeMYB108 allele enhanced the tolerance of cassava to drought-induced leaf abscission. Complementation transgenic lines containing the elite allele of MeMYB108SC124 decreased the leaf abscission rate induced by drought conditions, demonstrating natural variation in MeMYB108 contributed to leaf abscission tolerance induced by drought in cassava. Further studies showed MeMYB108 played an active role in the tolerance of cassava to drought-induced leaf abscission by inducing scavenging of reactive oxygen species.
Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson’s disease
Authors: He Yijing , Peng Kangwen , Li Ruoyu , Zhang Zhuoyu , Pan Lizhen , Zhang Tianyu , Lin Ao , Hong Ronghua , Nie Zhiyu , Guan Qiang , Jin Lingjing 
Published: May 2022

AbstractT lymphocytes are involved in the pathogenesis of Parkinson’s disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO−) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28− CD27−), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.
Temporal patterns of weekly births and conceptions predicted by meteorology, seasonal variation, and lunar phases
Authors: Gudziunaite Sandra , Moshammer Hanns 
Published: May 2022

Summary
Background
Data reporting the number of births given by women resident in Vienna for each week between 1999 and 2019, and the duration (in weeks) of their pregnancies, were used to estimate the week of conception. When preliminary examinations detected cyclical patterns for births and conceptions, a series of Poisson regressions for births and conceptions were performed to assess whether these cycles could be associated with lunar or solar phases.

Methods
To that end 2 sine-cosine functions, 1 with a wavelength of 1 year (365.25 days) and 1 with a wavelength of 29.529 days, the latter resembling the average length of a lunar cycle, were constructed. In addition, also average weekly temperatures were included in the models.

Results
Same week temperature was a strong non-linear predictor for both births and conceptions. Extreme temperatures, especially hot temperatures, increased the number of births while the numbers of successful conceptions were decreased by extreme temperatures. Regarding annual variation in conceptions, the lowest values were found in May and the highest in late autumn and early winter. Therefore, the highest numbers of births are observed in the summer. As per lunar variations, the highest numbers of conceptions occurred at the full moon and the highest numbers of births at the waxing crescent to first quarter moon.

Discussion
The latter results should be treated with caution, as they are not hypothesis driven. Furthermore, literature reports on this topic are conflicting. Nevertheless, these findings will be useful in further analyses examining air pollution effects.
Therapeutic opportunities and clinical outcome measures in Duchenne muscular dystrophy
Authors: Ricci Giulia , Bello Luca , Torri Francesca , Schirinzi Erika , Pegoraro Elena , Siciliano Gabriele 
Published: May 2022

Abstract

Introduction
Duchenne muscular dystrophy (DMD) is a devastatingly severe genetic muscle disease characterized by childhood-onset muscle weakness, leading to loss of motor function and premature death due to respiratory and cardiac insufficiency.

Discussion
In the following three and half decades, DMD kept its paradigmatic role in the field of muscle diseases, with first systematic description of disease progression with ad hoc outcome measures and the first attempts at correcting the disease-causing gene defect by several molecular targets. Clinical trials are critical for developing and evaluating new treatments for DMD.

Conclusions
In the last 20 years, research efforts converged in characterization of the disease mechanism and development of therapeutic strategies. Same effort needs to be dedicated to the development of outcome measures able to capture clinical benefit in clinical trials.
Lower serum triglyceride levels linked to more severe motor performance in Parkinson’s disease
Authors: Zhang Meimei , Chen Huimin , Liu Genliang , Wang Xuemei , Wang Zhan , Feng Tao , Zhang Yumei 
Published: May 2022

Abstract

Introduction
Emerging evidence has suggested that lipid metabolism is correlated with Parkinson’s disease (PD) onset and progression. However, the effect of lipid metabolism on motor performance in PD patients is still unknown. This study estimated the association between lipid profiles and the severity of motor performance in PD.

Methods
This cross-sectional study enrolled 279 idiopathic PD patients from the Department of Neurology of Beijing Tiantan Hospital from May 2016 to August 2018. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and apolipoprotein B (Apo-B) levels were detected in fast serum samples. Motor performance was assessed by Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) total scores and subscores in these patients. The associations of lipid profiles with motor performance were analyzed using multivariable linear regression models.

Results
Compared to males, females with PD exhibited significantly higher serum TC, LDL-C, HDL-C, Apo-A1, and Apo-B levels. When accounting for covariates, lower serum TG levels were significantly associated with higher MDS-UPDRS III total scores and gait/postural instability subscores. Additionally, the univariate linear regression model showed that in males with PD, serum HDL-C or Apo-A1 levels were significantly associated with tremor subscores.

Conclusion
Lower serum TG levels were associated with more severe motor performance in patients with PD and TG may be a potential predictive biomarker for motor performance in PD patients.
Cognition and motor phenotypes in ALS: a retrospective study
Authors: Aiello Edoardo Nicolò , Pain Debora , Radici Alice , Aktipi Kalliopi Marinou , Sideri Riccardo , Appollonio Ildebrando , Mora Gabriele 
Published: May 2022

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is phenotypically heterogeneous in motor manifestations, and the extent of upper vs. lower motor neuron involvement is a widespread descriptor. This study aimed to examine cognition across different ALS motor phenotypes.

Methods
ALS patients (N = 124) were classified as classical (N = 66), bulbar (N = 13), predominant-upper motor neuron (PUMN; N = 19), and predominant-lower motor neuron (PLMN; N = 26) phenotypes. Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and function with the ALS Functional Rating Scale—Revised (ALSFRS-R). Revised ALS-FTD consensus criteria were applied for cognitive/behavioral phenotyping.

Results
Defective ECAS-total scores were detected in all groups — bulbar: 15.4%, classical: 30.3%, PLMN: 23.1%, and PUMN: 36.8%. Classical and PUMN ALS patients performed worse than PLMN ones on ECAS-total, ALS-specific, Fluency, and Executive measures. No other difference was detected. Worse ASLFRS-R scores correlated with poorer ECAS-total scores in classical ALS patients.

Conclusions
Frontotemporal cognitive deficits are more prevalent in PUMN and classical ALS and linked to disease severity in the latter, but occur also in PLMN phenotypes.