bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dispatches from Biotech beginning BeginNGS: Rapid newborn genome sequencing to end the diagnostic and therapeutic odyssey
Authors: Kingsmore Stephen F. ,   The BeginNGS Consortium
Published: October 2022

AbstractIn this Dispatch from Biotech, we briefly review the urgent need for extensive expansion of newborn screening (NBS) by genomic sequencing, and the reasons why early attempts had limited success. During the next decade transformative developments will continue in society and in the pharmaceutical, biotechnology, informatics, and medical sectors that enable prompt addition of genetic disorders to NBS by rapid whole genome sequencing (rWGS) upon introduction of new therapies that qualify them according to the Wilson and Jungner criteria (Wilson, J. M. G., & Jungner, G., World Health Organization. (1968). Principles and Practice of Screening for Disease. World Health Organization. Retrieved from https://apps.who.int/iris/handle/10665/37650). Herein we describe plans, progress, and clinical trial designs for BeginNGS (Newborn Genome Sequencing to end the diagnostic and therapeutic odyssey), a new international, pre‐competitive, public–private consortium that proposes to implement a self‐learning healthcare delivery system for screening all newborns for over 400 hundred genetic diseases, diagnostic confirmation, implementation of effective treatment, and acceleration of orphan drug development. We invite investigators and stakeholders worldwide to join the consortium in a prospective, multi‐center, international trial of the clinical utility and cost effectiveness of BeginNGS.
Olfactory Neuron Prokineticin‐2 as a Potential Target in Parkinson's Disease
Authors: Schirinzi Tommaso , Maftei Daniela , Passali Francesco M. , Grillo Piergiorgio , Zenuni Henri , Mascioli Davide , Maurizi Riccardo , Loccisano Laura , Vincenzi Martina , Rinaldi Anna Maria , Ralli Massimo , Di Girolamo Stefano , Stefani Alessandro , Lattanzi Roberta , Severini Cinzia , Mercuri Nicola B. 
Published: October 2022

ObjectiveThe objective of this study was to outline the dynamics of prokineticin‐2 pathway in relation to clinical‐pathological features of Parkinson's disease by examining olfactory neurons of patients.MethodsThirty‐eight patients (26 de novo, newly diagnosed) and 31 sex/age‐matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin‐2, prokineticin‐2 receptors type 1 and 2, and prokineticin‐2‐long peptide were measured in olfactory neurons by real‐time polymerase chain reaction (PCR); moreover, the prokineticin‐2 protein and α‐synuclein species (total and oligomeric) were quantified by immunofluorescence staining.ResultsProkineticin‐2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin‐2 levels, directly correlated with Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) part III motor score. In addition, oligomeric α‐synuclein was higher in Parkinson's disease and directly correlated with prokineticin‐2 protein levels. Total α‐synuclein did not differ between patients and controls.InterpretationProkineticin‐2 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin‐2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin‐2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α‐synuclein accumulation. These data, consistently with preclinical findings, support prokineticin‐2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196–204
Biological Effects of Black Phosphorus Nanomaterials on Mammalian Cells and Animals
Authors: Zhang Xuejiao , Donskyi Ievgen S. , Tang Weihao , Deng Shuo , Liu Daxu , Zhang Siyu , Zhao Qing , Xing Baoshan 
Published: October 2022

AbstractThe remarkable progress of applied black phosphorus nanomaterials (BPNMs) is attributed to BP's outstanding properties. Due to its potential for applications, environmental release and subsequent human exposure are virtually inevitable. Therefore, how BPNMs impact biological systems and human health needs to be considered. In this comprehensive Minireview, the most recent advancements in understanding the mechanisms and regulation factors of BPNMs’ endogenous toxicity to mammalian systems are presented. These achievements lay the groundwork for an understanding of its biological effects, aimed towards establishing regulatory principles to minimize the adverse health impacts.
Random‐effects meta‐analysis models for the odds ratio in the case of rare events under different data‐generating models: A simulation study
Authors: Jansen Katrin , Holling Heinz 
Published: October 2022

AbstractMeta‐analysis of binary data is challenging when the event under investigation is rare, and standard models for random‐effects meta‐analysis perform poorly in such settings. In this simulation study, we investigate the performance of different random‐effects meta‐analysis models in terms of point and interval estimation of the pooled log odds ratio in rare events meta‐analysis. First and foremost, we evaluate the performance of a hypergeometric‐normal model from the family of generalized linear mixed models (GLMMs), which has been recommended, but has not yet been thoroughly investigated for rare events meta‐analysis. Performance of this model is compared to performance of the beta‐binomial model, which yielded favorable results in previous simulation studies, and to the performance of models that are frequently used in rare events meta‐analysis, such as the inverse variance model and the Mantel–Haenszel method. In addition to considering a large number of simulation parameters inspired by real‐world data settings, we study the comparative performance of the meta‐analytic models under two different data‐generating models (DGMs) that have been used in past simulation studies. The results of this study show that the hypergeometric‐normal GLMM is useful for meta‐analysis of rare events when moderate to large heterogeneity is present. In addition, our study reveals important insights with regard to the performance of the beta‐binomial model under different DGMs from the binomial‐normal family. In particular, we demonstrate that although misalignment of the beta‐binomial model with the DGM affects its performance, it shows more robustness to the DGM than its competitors.
Therapist responsivity during disagreement in psychotherapy
Authors: Olson David A. , Westra Henny A. , Shukla Serena , Di Bartolomeo Alyssa A. 
Published: October 2022

AbstractObjectiveTherapist responsivity is recognised as an important factor for improved psychotherapy process and outcome. Previous research (Aviram et al., 2016) has found that increased therapist responsivity during key moments (e.g., disagreements) is particularly impactful to post‐treatment outcome. However, global scores of the observational coding system used in prior studies fail to capture more precise micromoments and specific therapist responsivity within disagreement episodes that may contribute to outcome. In response, this study analysed therapy disagreement episodes with more precise coding measures that capture moment‐to‐moment sequences of therapist and client utterances.MethodSixty disagreement episodes (segment beginning with clear client disagreement with therapist and ending once they shifted to a new topic) previously abstracted from early working phase sessions of a randomised controlled trial (RCT) of cognitive behavioural therapy with and without integrated motivational interviewing (Hara et al., 2022) were utilised. To gauge responsivity within these episodes, two therapist behaviours (demand and support) were examined in response to specific moments of client counter‐change talk (CCT) statements using microlevel, moment‐to‐moment coding systems. This resulted in indices of appropriate (CCT‐Support) and inappropriate/errors in responsivity (CCT‐Demand). Responsivity indices were compared with the gold standard observational coding measure for managing ambivalence and resistance, the Motivational Interviewing Treatment Integrity scale (MITI).ResultsWhile appropriate responsivity did not predict outcome, responsivity errors significantly predicted poorer outcome at one year post‐treatment. Additionally, the capacity of responsivity errors for predicting outcome was equivalent to that obtained from the global observational measure.ConclusionThese findings have significant implications for training by emphasising the need for therapists to be sensitive to context and to acquire skill at detecting and responsively managing specific moments to avoid responsivity errors and improve therapy outcomes.
Incidental finding of maternal malignancy in an unusual non‐invasive prenatal test and a review of similar cases
Authors: Moellgaard Maria Hammer , Lund Ida Charlotte Bay , Becher Naja , Skytte Anne‐Bine , Andreasen Lotte , Srebniak Malgorzata Ilona , Vogel Ida 
Published: October 2022

AbstractWe present a clinical case where a complex abnormal non‐invasive prenatal test (NIPT) result in a research project revealed carcinoma of the breast in the pregnant woman. Furthermore, the NIPT result did not demonstrate the same fetal chromosomal aberration as the chorion villus sample. A literature search for similar cases was performed identifying 43 unique cases, where abnormal NIPT results were related to maternal malignancy. Malignancy is a rare but important cause of complex abnormal non‐invasive prenatal test (NIPT) results and should be considered when fetal karyotype and abnormal NIPT results are discordant. Furthermore, a follow‐up invasive sample is essential for correct fetal diagnosis when abnormal NIPT results are found.
Lyme neuroborreliosis as a cause of sudden sensorineural hearing loss and facial palsy
Authors: Nitro Letizia , Martino Barbara , Fuccillo Emanuela , Felisati Giovanni , Saibene Alberto Maria 
Published: October 2022

AbstractWe present a case of sudden sensorineural hearing loss and rapidly progressive facial palsy in a female patient in her 40s with no, apparently, notable past medical or surgical history. Investigations revealed a positive serology for B. burgdoferi and the MRI allowed us to identify suggestive signs of Lyme meningitis with multiple cranial nerve involvement. After diagnosis, the patient was treated with intravenous ceftriaxone with a full recovery of sensorineural deafness and facial palsy. This case report highlights the importance of collecting a complete medical history in all cases of facial palsy and sudden hearing loss while presenting an infrequent clinical presentation of early disseminated Lyme disease with neuroborreliosis.
Silent challenge: Early kidney transplant failure and cardiomyopathy
Authors: Santana‐Estupiñán Raquel , Valga Francisco , Groba Marco María del Val , Quevedo‐Reina Juan Carlos , Bongiovanni David , Rodríguez‐Pérez José Carlos 
Published: October 2022

AbstractDifferentiation of hypertrophic cardiomyopathy phenotypes is challenging but crucial for appropriate management. We report a case of myocardial oxalate deposition as an infrequent cause of infiltrative cardiomyopathy.
Guillain–Barre Syndrome following lower segment caesarean section under spinal anesthesia: A case report
Authors: Luitel Prajjwol , Upadhyay Devansh , Neupane Nischal , Paudel Sujan , Gyawali Prashant , Gajurel Bikram Prasad , Karn Ragesh , Rajbhandari Reema , Gautam Niraj , Shrestha Ashish , Ojha Rajeev 
Published: October 2022

AbstractSymptoms of Guillain–Barre Syndrome (GBS) may be mistaken for typical puerperal changes, delaying diagnosis. Surgery and anesthesia may be triggers for GBS with an overall increase in pro‐inflammatory cytokines in the postpartum period. We report a unique case of GBS in the postpartum period who made a good recovery with supportive measures.
Case report of eosinophilic granulomatosis with polyangitis presenting as acute myocarditis
Authors: Björkenstam Marie , Bobbio Emanuele , Mellberg Tomas , Polte Christian L. , Bergh Niklas , Giallauria Francesco , Bollano Entela 
Published: October 2022

AbstractThis case presents a challenging diagnosis of EGPA presenting as eosinophilic myocarditis. It is a condition that can mimic many other diseases and where prompt diagnosis and early treatment is essential for recovery. The diagnosis was made after an endomyocardial biopsy (EMB) and showed the importance of EMB in the diagnostic work‐up.
Automatic pretreatment and multiblock analysis of flavor release and sensory temporal data simultaneously collected in vivo
Authors: Peltier Caroline , Visalli Michel , Labouré Hélène , Hélard Cantin , Andriot Isabelle , Cordelle Sylvie , Le Quéré Jean‐Luc , Schlich Pascal 
Published: October 2022

AbstractProton transfer reaction‐time‐of‐flight‐mass spectrometry (PTR‐ToF‐MS or PTR‐MS) is an analytical chemistry technique that can be used for measuring the concentration of volatile organic compounds directly in the subjects' noses (nosespace, in vivo analysis) during a tasting and over time. It can be combined with temporal sensory methods such as temporal dominance of sensations (TDS) or temporal check all that apply (TCATA) in order to obtain simultaneous sensory and physico‐chemical signals. This paper aims to provide a methodology to analyze in vivo PTR‐MS and temporal sensory data and illustrate it on a real dataset. First, relevant pretreatments of PTR‐MS data were established, including breathing correction, blank periods removal, and standardization. Then, a statistical multiblock analysis was presented: the regularized generalized canonical correlation analysis (RGCCA). The versality of the approach was demonstrated, as it can be used to answer most of problematics (exploratory or supervised). Finally, this methodology is illustrated on a dataset of PTR‐MS and TDS or TCATA data collected simultaneously. In this study, 16 semitrained subjects evaluated three chocolates in TDS and TCATA on six flavor attributes (Spicy, Cocoa, Woody, Fruity, Roasty, and Dry Fruits) with two replicates for each sensory method. Results showed that TCATA and TDS gave similar results, but TDS was shown to slightly better preserve the PTR‐MS observed product configuration than TCATA. All computing tools developed in this work are freely available.
Rational Design of a Triple Tumor Microenvironment‐Responsive Nanoplatform for Enhanced Tumor Theranostics
Authors: Zhang Shouqiang , Han Xin , Chen Xinran , Liu Yuxin , Zhou Jing 
Published: October 2022

AbstractThe development of responsive nanoplatforms based on the tumor microenvironment (TME) is critical for tumor diagnosis and treatment. Concentrating on a single TME‐responsive nanoplatform, however, may result in insufficient diagnostic accuracy and treatment efficacy. Herein, layered double‐hydroxides (LDHs) and rare earth nanomaterials (Er@Lu) were combined to create a triple TME‐responsive nanoplatform that was then modified with cypate (a fluorescent dye with strong absorbance) by a peptide chain and loaded with epigallocatechin gallate (EGCG), a chemotherapeutic drug. Multiple responses to TME occurred when Er@Lu/LDH‐EGCG reached the colorectal tumor region. Based on an acidic TME, the nanoplatform cracked and released Ni2+ and EGCG. NiS, which was produced by the reaction of Ni2+ with abundant H2S in tumor cells, was used for photothermal therapy and the released EGCG was used for chemotherapy. The MMP‐7 enzyme specifically expressed in tumor cells recognized and cut the peptide chain, resulting in cypate release. The fluorescence of the Er@Lu was then restored along with the release of cypate because of the absorption competition disappearance. Compared to a single TME response, Er@Lu/LDH‐EGCG with a triple TME response led to a better synergistic therapeutic effect in vitro and in vivo. This work has provided new approaches for developing multiple TME‐responsive therapeutic nanoplatforms for synergistic therapy with improved diagnosis and therapeutic efficiency.
Chiral‐at‐Metal Silver‐Mediated Base Pairs: Metal‐Centred Chirality versus DNA Helical Chirality
Authors: Lefringhausen Nils , Seiffert Victoria , Erbacher Catharina , Karst Uwe , Müller Jens 
Published: October 2022

AbstractWhen covalently incorporating ligands capable of forming chiral metal complexes into a DNA oligonucleotide duplex, an enantiospecific formation of metal‐mediated base pairs is possible. We have been investigating the chirality of the silver‐mediated base pair P−AgI−P (P, 1H‐imidazo[4,5‐f][1,10]phenanthroline) depending on the number of consecutive P : P pairs within a series of duplexes. Towards this end, both enantiomers of the nucleoside analogue 3‐(1H‐imidazo[4,5‐f][1,10]phenanthrolin‐1‐yl)propane‐1,2‐diol comprising an acyclic backbone were introduced into DNA duplexes, resulting in diastereomeric metal‐mediated base pairs. The same chiral‐at‐metal complex is formed inside the duplex for up to five neighbouring P−AgI−P pairs, irrespective of whether (S)‐P or (R)‐P is used. With six silver‐mediated base pairs, the chirality of the metal complex is inverted for (S)‐P but not for (R)‐P. This indicates an intricate balance of what determines the configuration of the metal complex, the intrinsically preferred metal‐centred chirality or the DNA helical chirality.
Synthesis, Post‐Functionalization and Properties of Diphosphapentaarenes
Authors: Regulska Elzbieta , Hindenberg Philip , Espineira‐Gutierrez Adrian , Romero‐Nieto Carlos 
Published: October 2022

AbstractLinearly‐fused polyarenes are an important class of compounds with high relevance in materials science. While modifying the shape and size represents a common means to fine‐tune their properties, the precise placement of heteroatoms is a strategy that is receiving an increasing deal of attention to overcome the intrinsic limitations of all‐carbon structures. Thus, linearly‐fused diphosphaarenes recently emerged as a novel family of molecules with striking optoelectronic properties and outstanding stability. However, the properties of diphosphaarenes are far from being benchmarked. Herein, we report the synthesis, phosphorus post‐functionalization and properties of new diphosphapentaarene derivatives. We describe their synthetic limitations and unveil their potential for optoelectronic applications.
On the Mechanism of the Formal [2+2] Cycloaddition – Retro‐electrocyclization (CA‐RE) Reaction
Authors: Hansen Jonathan Kirschner Solberg , Tortzen Christian G. , Sørensen Preben Graae , Brøndsted Nielsen Mogens 
Published: October 2022

AbstractThe [2+2] cycloaddition ‐ retro‐electrocyclization (CA‐RE) reaction is a “click‐like” protocol for facile synthesis of donor‐acceptor chromophores from an alkyne and tetracyanoethylene. Herein we shed light on the mechanism of this reaction by detailed kinetics studies using 1H NMR spectroscopy. By considering several experiments simultaneously, a variety of mechanistic models was evaluated. Surprisingly, a model in which the final 1,1,4,4‐tetracyanobuta‐1,3‐diene product promoted the first step was the only one that described well the experimental data. This autocatalysis model also involved a non‐concerted, stepwise formation of the cyclobutene cycloaddition adduct. By proper choice of conditions, we were able to generate the transient cyclobutene in sufficient amount to verify it as an intermediate using 13C NMR spectroscopy. For its final retro‐electrocyclization step, simple first‐order kinetics was observed and only minor solvent dependence, which indicates a concerted reaction.
Chromatic organization of retinal photoreceptors during eye migration of Atlantic halibut (Hippoglossus hippoglossus)
Authors: Bolstad Kennedy , Novales Flamarique Iñigo 
Published: October 2022

AbstractThe retinas of fishes often have single and double cone photoreceptors that are organized in lattice‐like mosaics. In flatfishes experiencing eye migration (i.e., the metamorphic process whereby one eye migrates to the other side of the head), the hexagonal lattice of single cones present in the larva undergoes major restructuring resulting in a dominant square mosaic postmetamorphosis consisting of four double cones surrounding each single cone. The expression of different opsin types during eye migration has not been examined despite its importance in understanding photoreceptor plasticity and whether cell fate (in terms of spectral phenotype) could influence square mosaic formation. Here, we probed the retina of Atlantic halibut undergoing eye migration for opsin expression using two antibodies, AHblue and AB5407, that labeled short wavelength sensitive 2 (SWS2) opsin and longer wavelength (predominantly middle wavelength sensitive, RH2) opsins, respectively. Throughout the retina, double and triple cones labeled with AB5407 exclusively, whereas the vast majority of single cones labeled with AHblue. A minority (<5%) of single cones in the square mosaic of the centroventral retina labeled with AB5407. In regions of mosaic transition and near peripheral growth zones, some single cones co‐expressed at least two opsins as they labeled with both antibodies. Short wavelength (SWS2 expressing, or S) cones formed a nonrandom mosaic gradient from central to dorsal retina in a region dominated by the larval single cone mosaic. Our results demonstrate the expression of at least two opsins throughout the postmetamorphic retina and suggest opsin switching as a mechanism to create new cone spectral phenotypes. In addition, the S cone gradient at the onset of eye migration may underlie a plastic, cell induction mechanism by which a cone's phenotype determines that of its neighbors and the formation of the square mosaic.
Two aspects of longevity are associated with rates of loss of telomeres in birds
Authors: Dobson F. Stephen , Schull Quentin , Criscuolo François 
Published: October 2022

AbstractTelomeres, the terminal repetitive DNA sequences at the ends of linear chromosomes, have strong associations with longevity in some major taxa. Longevity has been linked to rate of decline in telomere length in birds and mammals, and absolute telomere length seems to be associated with body mass in mammals. Using a phylogenetic comparative method and 30 species of birds, we examined longevity (reflected by maximum lifespan), absolute telomere length, the rate of change in telomere length (TROC), and body mass (often strongly associated with longevity) to ascertain their degree of association. We divided lifespan into two life‐history components, one reflected by body size (measured as body mass) and a component that was statistically independent of body mass. While both lifespan and body mass were strongly associated with a family tree of the species (viz., the phylogeny of the species), telomere measures were not. Telomere length was not significantly associated with longevity or body mass or our measure of mass‐independent lifespan. TROC, however, was strongly associated with mass‐independent lifespan, but only to a much lesser degree at best with body mass‐predicted lifespan. Our results supported an association of TROC and longevity, in particular longevity that was independent of body size and part of the pace‐of‐life syndrome of life histories.