bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of omalizumab in chronic urticaria during pregnancy: a real-life study
Authors: Patruno Cataldo , Guarneri Fabrizio , Nettis Eustachio , Bonzano Laura , Filippi Federica , Ribero Simone , Foti Caterina , Rubegni Pietro , Balato Anna , Miniello Andrea , Motolese Alfonso , Piraccini Bianca Maria , Quaglino Pietro , Romita Paolo , Lazzeri Laura , Buononato Dario , Dastoli Stefano , Raia Flavia , Napolitano Maddalena 
Published: November 2023

Abstract

Background
Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant.

Objectives
To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy.

Methods
We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception.

Results
Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks’ gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group.

Conclusions
Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.
Dynamic alternations of interhemispheric functional connectivity in brachial plexus avulsion injury patients with nerve transfer: a resting state fMRI study
Authors: Yang Yang , Li Tie , Deng Yan , Wang Junlong , Li Yajie , Liu Hanqiu , Wang Weiwei 
Published: November 2023

Abstract
Brachial plexus avulsion injury (BPAI) is a severe peripheral nerve injury that leads to functional reorganization of the brain. However, the interhemispheric coordination following contralateral cervical 7 nerve transfer remains unclear. In this study, 69 BPAI patients underwent resting-state functional magnetic resonance imaging examination to assess the voxel-mirrored homotopic connectivity (VMHC), which reveals the interhemispheric functional connection. The motor function of the affected upper extremity was measured using the Fugl–Meyer Assessment of Upper Extremity (FMA-UE) scale. The VMHC analysis showed significant differences between the bilateral precentral gyrus, supplementary motor area (SMA), middle frontal gyrus (MFG), and insula. Compared to the preoperative group, the VMHC of the precentral gyrus significantly increased in the postoperative short-term group (PO-ST group) but decreased in the postoperative long-term group (PO-LT group). Additionally, the VMHC of the SMA significantly increased in the PO-LT group. Furthermore, the VMHC of the precentral gyrus in the PO-ST group and the SMA in the PO-LT group were positively correlated with the FMA-UE scores. These findings highlight a positive relationship between motor recovery and increased functional connectivity of precentral gyrus and SMA, which provide possible therapeutic targets for future neuromodulation interventions to improve rehabilitation outcomes for BPAI patients.
Joint encoding of stimulus and decision in monkey primary visual cortex
Authors: Yiling Yang , Klon-Lipok Johanna , Singer Wolf 
Published: November 2023

Abstract
We investigated whether neurons in monkey primary visual cortex (V1) exhibit mixed selectivity for sensory input and behavioral choice. Parallel multisite spiking activity was recorded from area V1 of awake monkeys performing a delayed match-to-sample task. The monkeys had to make a forced choice decision of whether the test stimulus matched the preceding sample stimulus. The population responses evoked by the test stimulus contained information about both the identity of the stimulus and with some delay but before the onset of the motor response the forthcoming choice. The results of subspace identification analysis indicate that stimulus-specific and decision-related information coexists in separate subspaces of the high-dimensional population activity, and latency considerations suggest that the decision-related information is conveyed by top-down projections.
Dorsomedial frontal cortex damage impairs error-based, but not reinforcement-based motor learning in humans
Authors: Palidis Dimitrios J , Fellows Lesley K 
Published: November 2023

Abstract
We adapt our movements to new and changing environments through multiple processes. Sensory error-based learning counteracts environmental perturbations that affect the sensory consequences of movements. Sensory errors also cause the upregulation of reflexes and muscle co-contraction. Reinforcement-based learning enhances the selection of movements that produce rewarding outcomes. Although some findings have identified dissociable neural substrates of sensory error- and reinforcement-based learning, correlative methods have implicated dorsomedial frontal cortex in both. Here, we tested the causal contributions of dorsomedial frontal to adaptive motor control, studying people with chronic damage to this region. Seven human participants with focal brain lesions affecting the dorsomedial frontal and 20 controls performed a battery of arm movement tasks. Three experiments tested: (i) the upregulation of visuomotor reflexes and muscle co-contraction in response to unpredictable mechanical perturbations, (ii) sensory error-based learning in which participants learned to compensate predictively for mechanical force-field perturbations, and (iii) reinforcement-based motor learning based on binary feedback in the absence of sensory error feedback. Participants with dorsomedial frontal damage were impaired in the early stages of force field adaptation, but performed similarly to controls in all other measures. These results provide evidence for a specific and selective causal role for the dorsomedial frontal in sensory error-based learning.
Stochastic resonance in sparse neuronal network: functional role of ongoing activity to detect weak sensory input in awake auditory cortex of rat
Authors: Noda Takahiro , Takahashi Hirokazu 
Published: November 2023

Abstract
The awake cortex is characterized by a higher level of ongoing spontaneous activity, but it has a better detectability of weak sensory inputs than the anesthetized cortex. However, the computational mechanism underlying this paradoxical nature of awake neuronal activity remains to be elucidated. Here, we propose a hypothetical stochastic resonance, which improves the signal-to-noise ratio (SNR) of weak sensory inputs through nonlinear relations between ongoing spontaneous activities and sensory-evoked activities. Prestimulus and tone-evoked activities were investigated via in vivo extracellular recording with a dense microelectrode array covering the entire auditory cortex in rats in both awake and anesthetized states. We found that tone-evoked activities increased supralinearly with the prestimulus activity level in the awake state and that the SNR of weak stimulus representation was optimized at an intermediate level of prestimulus ongoing activity. Furthermore, the temporally intermittent firing pattern, but not the trial-by-trial reliability or the fluctuation of local field potential, was identified as a relevant factor for SNR improvement. Since ongoing activity differs among neurons, hypothetical stochastic resonance or “sparse network stochastic resonance” might offer beneficial SNR improvement at the single-neuron level, which is compatible with the sparse representation in the sensory cortex.
Masking effects on iso-valeric acid recognition by sub-threshold odor mixture
Authors: Huang Jianbo , Lin Jiehua , Yueng Rachel , Wu Shuyi , Solla Leto , Acree Terry 
Published: November 2023

Abstract
Masking unpleasant odors with pleasant-smelling odorants has a long history and is utilized in various industries, including perfumery and consumer products. However, the effectiveness of odor masking is idiosyncratic and temporary. In this study, we employed Sniff olfactometry (SO) to investigate the psychophysics of masking using brief 70 ms stimulations with mixtures of the mal-odorant iso-valeric acid (IVA) and different masking agents. IVA is a component of human sweat that can overpower its smell and is often associated with unpleasant descriptors such as “gym locker,” “smelly feet,” “dirty clothes,” and so on. Traditionally, high concentrations of pleasant-smelling odorants are used to mitigate the unpleasantness of IVA in situations involving clothing or environments contaminated with IVA. To examine the masking effects of sub-threshold levels of various masking agents (neohivernal, geraniol, florhydral, decanal, iso-longifolanone, methyl iso-eugenol, and s-limonene) on IVA, we conducted experiments using SO to measure the probability of recognizing IVA after 70 ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA suppressors. The study involved nine subjects, and on average, a single masking agent was found to decrease IVA recognition probability by 14–72%. Moreover, a sub-threshold odor mixture consisting of 6 masking agents demonstrated a substantial decrease in IVA recognition, with a reduction of 96%.
Genetic testing in prolactinomas: a cohort study
Authors: Boukerrouni Amina , Cuny Thomas , Anjou Thibaut , Raingeard Isabelle , Ferrière Amandine , Grunenwald Solange , Maïza Jean-Christophe , Marquant Emeline , Sahakian Nicolas , Fodil-Cherif Sarah , Salle Laurence , Niccoli Patricia , Randrianaivo Hanitra , Sonnet Emmanuel , Chevalier Nicolas , Thuillier Philippe , Vezzosi Delphine , Reynaud Rachel , Dufour Henry , Brue Thierry , Tabarin Antoine , Delemer Brigitte , Kerlan Véronique , Castinetti Frédéric , Barlier Anne , Romanet Pauline 
Published: November 2023

Abstract

Background
Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma.

Objective
We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas.

Materials and methods
A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients.

Results
About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas.

Conclusions
We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.
Performed poetry and all-round experience
Authors: Howarth Peter 
Published: November 2023

Abstract
The National Curriculum makes spoken poetry part of what children should know, but dramatically limits what it can do. Thinking of sound as a purely internal dimension of the poem, it ignores the way oral performance brings the context of the room, the person and the situation all into play with the meaning. Orality used to be much more important to English than it is now: Henry Newbolt put it at the centre of his 1921 English Report, arguing that sound and poetry are the primary medium in which children's loves might be formed. It is there for emotional aliveness, not cultural superiority, as Newbolt's critics have charged. But one of the missing contexts for Newbolt and for the curriculum itself is the twentieth-century change towards poets themselves reading. As Yeats, Pound, and Eliot met their audiences, they found that their poems were acquiring new meaning from the situations and places they were being read in. What we see with the oral turn is a space where aesthetic ‘form’, physical ‘context’, and social-cultural ‘occasion’ can briefly merge into one another, because the poem is being briefly inscribed, registered, or overlayed onto all of them. Oral delivery means the poem acquires some of the flavour of the place it is in – meaning that great care has to be taken to make classroom performance into real connection.
Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h
Authors: Becher Nina , Toennis Tobias , Bertaglia Emanuele , Blomström-Lundqvist Carina , Brandes Axel , Cabanelas Nuno , Calvert Melanie , Camm A John , Chlouverakis Gregory , Dan Gheorghe-Andrei , Dichtl Wolfgang , Diener Hans Christoph , Fierenz Alexander , Goette Andreas , de Groot Joris R , Hermans Astrid N L , Lip Gregory Y H , Lubinski Andrzej , Marijon Eloi , Merkely Béla , Mont Lluís , Ozga Ann-Kathrin , Rajappan Kim , Sarkozy Andrea , Scherr Daniel , Schnabel Renate B , Schotten Ulrich , Sehner Susanne , Simantirakis Emmanuel , Vardas Panos , Velchev Vasil , Wichterle Dan , Zapf Antonia , Kirchhof Paulus 
Published: November 2023

Abstract

Background and Aims
Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients.

Methods
This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation.

Results
Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P &lt; .001).

Conclusions
This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.
Germline mitotic quiescence and cell death are induced in Caenorhabditis elegans by exposure to pathogenic Pseudomonas aeruginosa
Authors: Bollen Daniel P , Reddy Kirthi C , Lascarez-Lagunas Laura I , Kim Dennis H , Colaiácovo Monica P 
Published: November 2023

Abstract
The impact of exposure to microbial pathogens on animal reproductive capacity and germline physiology is not well understood. The nematode Caenorhabditis elegans is a bacterivore that encounters pathogenic microbes in its natural environment. How pathogenic bacteria affect host reproductive capacity of C. elegans is not well understood. Here, we show that exposure of C. elegans hermaphrodites to the Gram-negative pathogen Pseudomonas aeruginosa causes a marked reduction in brood size with concomitant reduction in the number of nuclei in the germline and gonad size. We define 2 processes that are induced that contribute to the decrease in the number of germ cell nuclei. First, we observe that infection with P. aeruginosa leads to the induction of germ cell apoptosis. Second, we observe that this exposure induces mitotic quiescence in the proliferative zone of the C. elegans gonad. Importantly, these processes appear to be reversible; when animals are removed from the presence of P. aeruginosa, germ cell apoptosis is abated, germ cell nuclei numbers increase, and brood sizes recover. The reversible germline dynamics during exposure to P. aeruginosa may represent an adaptive response to improve survival of progeny and may serve to facilitate resource allocation that promotes survival during pathogen infection.
A Systematic Review of Potential Biomarkers for Bacterial Burden and Treatment Efficacy Assessment in Tuberculosis Platform-Based Clinical Trials
Authors: Espinosa-Pereiro Juan , Alagna Riccardo , Saluzzo Francesca , González-Moreno Jesús , Heinrich Norbert , Sánchez-Montalvá Adrián , Cirillo Daniela Maria 
Published: November 2023

Abstract
Adaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis. Platform trials can span different development phases. We grouped biomarkers as: α, bacterial load estimates used in phase 2a trials; β, early and end-of treatment end points, phase 2b-c trials; γ, posttreatment or trial-level estimates, phase 2c-3 trials. We considered as analysis unit (biomarker entry) each combination of biomarker, predicted outcome, and their respective measurement times or intervals. Performance metrics included: sensitivity, specificity, area under the receiver-operator curve (AUC), and correlation measures, and classified as poor, promising, or good. Eighty-six studies included 22 864 participants. From 1356 biomarker entries, 318 were reported with the performance metrics of interest, with 103 promising and 41 good predictors. Group results were: α, mycobacterial RNA and lipoarabinomannan (LAM) in sputum, and host metabolites in urine; β, mycobacterial RNA and host transcriptomic or cytokine signatures for early treatment response; and γ, host transcriptomics for recurrence. A combination of biomarkers from different categories could help in designing more efficient platform trials. Efforts to develop efficacy surrogates should be better coordinated.
Development and Pilot of an Mpox Severity Scoring System
Authors: Zucker Jason , McLean Jacob , Huang Simian , DeLaurentis Clare , Gunaratne Shauna , Stoeckle Kate , Glesby Marshall J , Wilkin Timothy J , Fischer William , Damon Inger , Brooks John T 
Published: November 2023

Abstract
Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting &gt;3 days after symptom onset, and with CD4 counts &lt;200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups.
Mpox Viral Lineage Analysis and Technique Development Using Next-generation Sequencing Approach
Authors: Kabir Farruk , Plaisance Erin , Portman Alexandra , Marfo Agnes , Cirrincione Kayle , Silva David , Amadi Victor , Stringer Joey , Short Luke 
Published: November 2023

Abstract

Background
In response to Mpox endemic and public health emergency, DCHHS aimed to develop NGS based techniques to streamline Mpox viral clade and lineage analysis.

Methods
The Mpox sequencing workflow started with DNA extraction and adapted Illumina's COVIDSeq assay using hMpox primer pools from Yale School of Public Health. Sequencing steps included cDNA amplification, tagmentation, PCR indexing, pooling libraries, sequencing on MiSeq, data analysis, and report generation. The bioinformatic analysis comprised read assembly and consensus sequence mapping to reference genomes and variant identification, and utilized pipelines including Illumina BaseSpace, NextClade, CLC Workbench, Terra.bio for data quality control (QC) and validation.

Results
In total, 171 mpox samples were sequenced using modified COVIDSeq workflow and QC metrics were assessed for read quality, depth, and coverage. Multiple analysis pipelines identified the West African clade IIb as the only clade during peak Mpox infection from July through October 2022. Analyses also indicated lineage B.1.2 as the dominant variant comprising the majority of Mpox viral genomes (77.7%), implying its geographical distribution in the United States. Viral sequences were uploaded to GISAID EpiPox.

Conclusions
We developed NGS workflows to precisely detect and analyze mpox viral clade and lineages aiding in public health genomic surveillance.
Clinical response of pancreatic cancer bearing a germline BRCA2 p.I3169M fs*48 variant for platinum-based drug and PARP inhibitor
Authors: Akahira Risa , Fukuda Koji , Shimazu Kazuhiro , Yoshida Taichi , Taguchi Daiki , Shinozaki Hanae , Nanjyo Hiroshi , Shibata Hiroyuki 
Published: November 2023

Abstract
Pancreatic cancer is a malignancy with a high mortality rate, accounting for 37 000 people annually in Japan. It is rarely diagnosed in a resectable state, and effective medicines for its advanced stage are scarce. Some pancreatic cancer is hereditary, and ~10% have germline mutations of Breast cancer 1/2 (BRCA1/2). BRCA1/2 are key molecules involved in homologous recombination to repair DNA double-strand break. Platinum-based drugs and poly Adenosine diphosphate ribose (ADP) ribose polymerase inhibitors that induce synthetic lethality would be theoretically effective in patients with loss-of-function mutations in BRCA1/2. Strictly speaking, some discrepancy between the pathogenicity of BRCA1/2 and their drug sensitivity might be expected. Hence, we report that platinum-based anticancer agents and poly ADP ribose polymerase inhibitors were effective against pancreatic cancer bearing BRCA2 p.I3169M fs*48.