bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence (AI) adaptation: Analysis of determinants among Small to Medium-sized Enterprises (SME’s)
Authors: Ingalagi Sanjeev S , Mutkekar R R , Kulkarni P M
Published: November 2023

Implementation of Artificial Intelligences changes the way of doing business in small and medium enterprises. The determinants for success or failures for implementation of artificial intelligences systems in small firms remain very unclear in India. Hence, the paper attempts to analyse various perceptive of AI implementations from a management point of view. Data analysis was carried out of 167 small and medium firms located in Karnataka state (India) from two tier towns. Existing literature review revealed top management’s commitment, organisational readiness, external support, employee adoption and competitive pressure influence adoption of artificial intelligence technologies substantially. The study confirms influences of AI technology in small and medium firm’s management. Clear understanding of drivers for AI implementation helps managers and owners of SMEs to take up appropriate initiatives. The results provide assorted perceptive to AI services providers to integrate business proposals for small and medium enterprises needs.
Modification of streamer-to-leader transition model based on radial thermal expansion in the sphere-plane gap discharge at high altitude
Authors: GENG 耿 Jianghai 江海 , LIN 林 Guo 果 , WANG 王 Ping 平 , DING 丁 Yujian 玉剑 , DING 丁 Yang 杨 , YU 俞 Hua 华
Published: November 2023

Historically, streamer-to-leader transition studies mainly focused on the rod-plane gap and low altitude analysis, with limited attention paid to the sphere-plane gap at high altitude analysis. In this work, sphere-plane gap discharge tests were carried out under the gap distance of 5 m at the Qinghai Ultra High Voltage (UHV) test base at an altitude of 2200 m. The experiments measured the physical parameters such as the discharge current, electric field intensity and instantaneous optical power. The duration of the dark period and the critical charge of streamer-to-leader transition were obtained at high altitude. Based on radial thermal expansion of the streamer stem, we established a modified streamer-to-leader transition model of the sphere-plane gap discharge at high altitude, and calculated the stem temperature, stem radii and the duration of streamer-to-leader transition. Compared with the measured duration of sphere-plane electrode discharge at an altitude of 2200 m, the error rate of the modified model was 0.94%, while the classical model was 6.97%, demonstrating the effectiveness of the modified model. From the comparisons and analysis, several suggestions are proposed to improve the numerical model for further quantitative investigations of the leader inception.
Invisible Stripes? A Field Experiment on the Disclosure of a Criminal Record in the British Labour Market and the Potential Effects of Introducing Ban-The-Box Policies
Authors: Rovira Marti
Published: November 2023

Labour market discrimination against individuals with criminal records may be unfair, ineffective and counterproductive. This article describes a field experiment designed to indicate whether job applicants disclosing a criminal record in the British labour market have a lower probability of success than equivalent applicants not disclosing criminal records. The research also provides insights into the potential effects of introducing a Ban-The-Box (BTB) policy in the United Kingdom, which would prohibit questions on prior convictions in the first stages of the recruitment process. The results confirm the existence of criminal record discrimination and suggest that introducing a BTB policy would increase job prospects for White applicants with criminal records, but not for members of ethnic minorities.
Deciphering the impact of coding and non-coding SCN1A gene variants on RNA splicing
Authors: Sparber Peter , Sharova Margarita , Davydenko Ksenia , Pyankov Denis , Filatova Alexandra , Skoblov Mikhail
Published: November 2023

Variants that disrupt normal pre-mRNA splicing are increasingly being recognized as a major cause of monogenic disorders. The SCN1A gene, a key epilepsy gene that is linked to various epilepsy phenotypes, is no exception. Approximately 10% of all reported variants in the SCN1A gene are designated as splicing variants, with many located outside of the canonical donor and acceptor splice sites, and most have not been functionally investigated. However, given its restricted expression pattern, functional analysis of splicing variants in the SCN1A gene could not be routinely performed. In this study, we conducted a comprehensive analysis of all reported SCN1A variants and their potential to impact SCN1A splicing and conclude that splicing variants are substantially misannotated and under-represented.

We created a splicing reporter system consisting of 18 splicing vectors covering all 26 protein-coding exons with different genomic contexts and several promoters of varying strengths in order to reproduce the wild-type splicing pattern of the SCN1A gene, revealing cis-regulatory elements essential for proper recognition of SCN1A exons. Functional analysis of 95 SCN1A variants was carried out, including all 68 intronic variants reported in the literature, located outside of the splice sites canonical dinucleotides; 21 exonic variants of different classes (synonymous, missense, nonsense and in-frame deletion) and six variants observed in patients with epilepsy. Interestingly, almost 20% of tested intronic variants had no influence on SCN1A splicing, despite being reported as causative in the literature. Moreover, we confirmed that the majority of predicted exonic variants affect splicing unravelling their true molecular mechanism. We used functional data to perform genotype-phenotype correlation, revealing distinct distribution patterns for missense and splice-affecting ‘missense’ variants and observed no difference in the phenotype severity of variants leading to in-frame and out-of-frame isoforms, indicating that the Nav1.1 protein is highly intolerant to structural variations.

Our work demonstrates the importance of functional analysis in proper variant annotation and provides a tool for high-throughput delineation of splice-affecting variants in SCN1A in a whole-gene manner.
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

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

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

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

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

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

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

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

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

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 < .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

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

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

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 >3 days after symptom onset, and with CD4 counts <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

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

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.
Small bowel obstruction caused by a mango phytobezoar within a Meckel’s diverticulum
Authors: Hulf Toby , Ben-David Matan
Published: November 2023

A fit and well gentleman in his 40s presented with vomiting and obstipation. His only relevant history being recent ingestion of a large quantity of mangoes. A computer tomography demonstrated a small bowel obstruction with a transition point in the right iliac fossa, but no other pathological findings. After a short period of non-operative management he proceeded to surgery, where a phytobezoar was identified at a Meckel’s diverticulum causing a pantaloon shaped intra-luminal obstruction. A small bowel resection and primary anastomosis was performed and the patient had an uncomplicated post-operative course. Meckel’s diverticuli are a relatively common phenomenon and may pre-dispose to bowel obstructions through a number of different mechanisms. This unusual case highlights the importance of considering this as a differential, and one that will likely require timely operative intervention.
Coeliac artery avulsion secondary to high velocity blunt abdominal trauma: a case report
Authors: Kay Tegan J , Rahman Zafreen , Musicki Korana , Atkinson Noel , Martin Katherine
Published: November 2023

Coeliac artery (CA) injuries are an extremely rare subset of blunt abdominal trauma with a reported incidence of only 0.01%. Patterns of CA injury include intimal tear, dissection, thrombosis and pseudoaneurysm, with the most rare being complete CA avulsion. These complex injuries pose a treatment challenge due to rapid blood loss and anatomical difficultly in achieving proximal and multiple points of distal vascular control. To our knowledge, this case of CA avulsion from blunt polytrauma is only the 7th case reported in the literature. To assist in management, we report a case of blunt traumatic CA avulsion managed successfully with open ligation following endovascular balloon occlusion of the juxta-coeliac aorta for haemorrhage control.
Cultural specificities of online dictionaries for English learners: Evidence from a user survey and a multimodal discourse analysis
Authors: Zhong Shuneng , Liu Xiqin
Published: November 2023

This study examines three popular e-dictionary platforms using a quantitative user survey coupled with a qualitative multimodal discourse analysis (MDA): Chinese Youdao, Cambridge English-Mandarin Chinese Dictionary (Cambridge), and the Free Dictionary (FD). The survey (N = 478) revealed that, despite its language flaws, Youdao was preferred by most Chinese EFL (English as a Foreign Language) learners mainly due to its search functionality and personalization. In contrast, English majors and postgraduates preferred Cambridge for its reliability and multimodal resources. FD ranked the lowest in popularity mainly for perceived inconvenience of searching and less accessibility of personalized functions. Multinomial logistic regressions and structural equation modelling showed that dictionary selection by users was contingent upon their perception of its features and their use strategies. Furthermore, MDA revealed how each dictionary contributed to the construction of a cultural identity. Youdao seemed to be a toolbox for personal use, with raw texts of varying quality, but with a clear and practical vision, in addition to customization options. Cambridge portrayed itself as a welcoming language community through appealing imagery, interactive options, and diverse navigational styles. FD was comparable to a dynamic and cluttered library, archiving large blocks of hyperlinked texts and word lists accompanied by musical animations. In brief, multimodal and cultural factors partially explained Chinese EFL learners’ preferences for a specific dictionary, highlighting the importance of adaptation to the linguistic and cultural background of the user, including customization. A general cultural and semiotic framework is proposed to examine the representation of cultural identity in e-dictionaries.
Statistical Comparison of Substructures in Pure Aluminum Before and After Creep Deformation, Based on EBSD Image Data
Authors: Rieder Philipp , Petrich Lukas , Serrano-Munoz Itziar , Fernández Ricardo , Bruno Giovanni , Schmidt Volker
Published: November 2023

Electron backscatter diffraction (EBSD) images of extruded pure aluminum were statistically analyzed to investigate creep-induced subgrain structures after applying two different levels of creep stress, corresponding to the power law (PL) and power-law breakdown (PLB) regimes. Kernel average misorientation analysis of EBSD measurements revealed 2D morphologies, which were subdivided by a multi-step segmentation procedure into subgranular arrangements. Various descriptors were employed to characterize the “subgrains” quantitatively, including their size, shape, spatial arrangement, and crystallographic orientation. In particular, the analysis of the orientations of subgrains was conducted by neglecting rotations around the loading axis. This approach facilitated the individual investigation of the {001} and {111} subgrain families with respect to the loading axis for two investigated stress levels plus a reference specimen. For the PL regime, the statistical analysis of subgrain descriptors computed from segmented image data revealed a similar degree of strain accumulation for {111} and {001} subgrains. In contrast, for the PLB regime, the analyzed descriptors indicate that {111} subgrains tend to accumulate significantly more strain than {001} ones. These observations suggest that the mechanisms leading to PLB may be associated with strain localization dependent on intergranular stress, hindering the recovery process within {111} grains.
A Short Historical Review of Water-Soluble Aminoplastic Resin Use for Lipid Ultrastructure Research
Authors: Gao Johnson K
Published: November 2023

In 1982, a water-soluble aminoplastic resin embedding method for electron microscopy (EM) was developed to study lipids. It involves a silylation technique for processing cured resins by converting them from hydrophilic to hydrophobic status, facilitating ultra-thin sectioning. The technique offers better preservation of lipovitellin material in frog (Rana amurensis) yolk platelets, and it shows membrane ultrastructure better than traditional epoxy embedding methods. An early (1982) pseudo-colored TEM image processing technique applied to the micrographs obtained by EM of silylated aminoplastic thin sections revealed the lipovitellin molecules, in relation to the biosynthesis of new membranes in the first cleavage of the egg, with remarkable clarity and explains the lipovitellin molecules in relation to the biosynthesis of new membranes. Because the original article was written in Chinese and published in China before its open policy, many scientists may not be aware of the publication. Thus, in this short review, the essential components of the procedure are presented in English to help guide investigators who might be interested in the use of water-soluble embedding methods for lipid research.
Tissue Clearing: An Overview of Methods, Considerations, and Applications
Authors: Padgett Caleb A
Published: November 2023

Since the advent of confocal microscopy, advances in tissue clearing have allowed researchers to push the limits of imaging depth and dive deeper into the precise 3D structures of biological specimens. As clearing methods are discovered, refined, and retired, it behooves the prudent microscopist to consider the pros and cons of various tissue clearing methods and systematically evaluate whether tissue clearing is beneficial to answer their research questions. Herein, I will briefly discuss the evolution of tissue clearing, pros and cons of more popular methods and techniques related to fluorescence microscopy, and key considerations for selecting a method most likely to yield experimental success.
Igniting New Confocal Imaging Potential – Nikon AX R Series with NSPARC
Authors: Delattre Sabrina
Published: November 2023

The Nikon AX/AX R microscope with the recently developed Nikon Spatial Array Detector (NSPARC) provides rapid, super-resolution image acquisition of fixed and living cells. Here, we discuss the structure and function of the NSPARC, which provides excellent resolution and signal-to-noise (S/N) capabilities, and show applications related to in vitro neutrophil movement within pancreatic blood vessels and dynamic changes in mitochondrial morphology occurring over a matter of seconds. The large field-of-view and associated AI software facilitates acquisition and analysis of large 3D samples.
Addressing Burnout in the Primary Care Setting: The Impact of an Evidence-Based Mindfulness Toolkit
Authors: Christensen Andrew J , Virnig Jonathan P , Case Nicole L , Hayes Stephanie S , Heyne Rebecca , Taylor Laura A , Allen Micheal P
Published: November 2023

Background

Burnout is insidious and manifests over prolonged, repeated exposure to occupational stressors. There is a growing crisis among health care workers (HCWs) due to high levels of burnout and associated adverse outcomes. Identifying and addressing burnout can be problematic due to extensive variances of perceived occupational stressors across HCWs.

Purpose

Mindfulness-based training can enhance individual HCWs’ abilities to perceive and constructively respond to stresses endemic in the health care environment. It can reduce the prevalence of burnout in the primary care setting. An evidence-based multimodal Mindfulness-Based Stress Reduction toolkit (MBSR TK) was designed, implemented, and evaluated for its impact on HCWs’ self-reported stress levels (SRSL).

Implementation Strategies

A pre-post-program evaluation explored the impact of a multimodal toolkit program on HCW SRSL with the Mini-Z burnout survey (MZBS). The MBSR TK program, consisting of a 45 minute introduction and 4 biweekly 15 minute mindfulness sessions offering acupressure, meditation, journaling for gratitude, and self-compassion was designed, delivered, and evaluated with HCWs across 2 military primary care clinics in South Texas.

Results

All HCWs across 2 Air Force family practice clinics were invited to participate in all toolkit components. Seventy percent of all HCWs (N = 90) attended the introduction session. Thirty-seven (41%) HCWs completed pre and post MZBSs, and these responses are included in the data analysis section. The most represented HCWs were registered nurses, physician assistants, and technicians, respectively, at 24%, 21%, and 18%. The Wilcoxon Signed-Rank test examined changes in HCWs’ SRSL after participation in the MBSR TK program. HCWs who attended the introduction plus one biweekly session showed statistically significant decreases in self-reported stress (P = 0.018) and burnout (P = 0.045) and a significant increase in electronic health record proficiency (P = 0.033).

Conclusions

Multimodal mindfulness toolkits to address SRSL burnout are practical, accessible, easily implemented, adaptive to any environment, and can decrease burnout with participation with just one 15 minute session. This MBSR TK implementation effectively lowered self-reported stress in HCWs who are repeatedly challenged to adapt to various settings around the world during peacetime, wars, natural disasters, humanitarian crises, and now, pandemics.
Discovery of a one-sided radio filament of PSR J0538+2817 in S147: escape of relativistic PWN leptons into surrounding supernova remnant?
Authors: Khabibullin I I , Churazov E M , Bykov A M , Chugai N N , Zinchenko I I
Published: November 2023

We report the discovery of a faint radio filament near PSR J0538+2817 in the NVSS, CGPS, and the Rapid ASKAP Continuum Survey data. This pulsar is plausibly associated with the supernova that gave rise to the Spaghetti nebula (Simeis 147). The structure is one-sided and appears to be almost aligned (within 17 degrees) with the direction of the pulsar’s proper motion, but in contrast to the known cases of pulsar radio tails, it is located ahead of the pulsar. At the same time, this direction is also approximately (within 5 degrees) perpendicular to the axis of the extended non-thermal X-ray emission around the pulsar. No X-ray or optical emission is detected from the filament region, although the end point of the radio filament appears to be adjacent to a filament of Hα emission. We speculate that this structure might represent a filament connecting pulsar wind nebula (PWN) with the ambient interstellar medium filled with relativistic electrons escaping the pulsar nebula, i.e. a radio analogue of X-ray filaments of Guitar and Lighthouse PWNs and filaments of non-thermal radio emission in the Galactic Centre.
Uridine–cytidine kinase 2 potentiates the mutagenic influence of the antiviral β-d-N4-hydroxycytidine
Authors: Xu Zhen , Flensburg Christoffer , Bilardi Rebecca A , Majewski Ian J
Published: November 2023

Molnupiravir (EIDD-2801) is an antiviral that received approval for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Treatment of bacteria or cell lines with the active form of molnupiravir, β-d-N4-hydroxycytidine (NHC, or EIDD-1931), induces mutations in DNA. Yet these results contrast in vivo genotoxicity studies conducted during registration of the drug. Using a CRISPR screen, we found that inactivating the pyrimidine salvage pathway component uridine–cytidine kinase 2 (Uck2) renders cells more tolerant of NHC. Short-term exposure to NHC increased the mutation rate in a mouse myeloid cell line, with most mutations being T:A to C:G transitions. Inactivating Uck2 impaired the mutagenic activity of NHC, whereas over-expression of Uck2 enhanced mutagenesis. UCK2 is upregulated in many cancers and cell lines. Our results suggest differences in ribonucleoside metabolism contribute to the variable mutagenicity of NHC observed in cancer cell lines and primary tissues.
VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023
Authors: Alvarez-Jarreta Jorge , Amos Beatrice , Aurrecoechea Cristina , Bah Saikou , Barba Matthieu , Barreto Ana , Basenko Evelina Y , Belnap Robert , Blevins Ann , Böhme Ulrike , Brestelli John , Brown Stuart , Callan Danielle , Campbell Lahcen I , Christophides George K , Crouch Kathryn , Davison Helen R , DeBarry Jeremy D , Demko Richard , Doherty Ryan , Duan Yikun , Dundore Walter , Dyer Sarah , Falke Dave , Fischer Steve , Gajria Bindu , Galdi Daniel , Giraldo-Calderón Gloria I , Harb Omar S , Harper Elizabeth , Helb Danica , Howington Connor , Hu Sufen , Humphrey Jay , Iodice John , Jones Andrew , Judkins John , Kelly Sarah A , Kissinger Jessica C , Kittur Nupur , Kwon Dae Kun , Lamoureux Kristopher , Li Wei , Lodha Disha , MacCallum Robert M , Maslen Gareth , McDowell Mary Ann , Myers Jeremy , Nural Mustafa Veysi , Roos David S , Rund Samuel S C , Shanmugasundram Achchuthan , Sitnik Vasily , Spruill Drew , Starns David , Tomko Sheena Shah , Wang Haiming , Warrenfeltz Susanne , Wieck Robert , Wilkinson Paul A , Zheng Jie
Published: November 2023

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes.
Inter-generational nuclear crosstalk links the control of gene expression to programmed genome rearrangement during the Paramecium sexual cycle
Authors: Bazin-Gélis Mélanie , Eleftheriou Evangelia , Zangarelli Coralie , Lelandais Gaëlle , Sperling Linda , Arnaiz Olivier , Bétermier Mireille
Published: November 2023

Multinucleate cells are found in many eukaryotes, but how multiple nuclei coordinate their functions is still poorly understood. In the cytoplasm of the ciliate Paramecium tetraurelia, two micronuclei (MIC) serving sexual reproduction coexist with a somatic macronucleus (MAC) dedicated to gene expression. During sexual processes, the MAC is progressively destroyed while still ensuring transcription, and new MACs develop from copies of the zygotic MIC. Several gene clusters are successively induced and switched off before vegetative growth resumes. Concomitantly, programmed genome rearrangement (PGR) removes transposons and their relics from the new MACs. Development of the new MACs is controlled by the old MAC, since the latter expresses genes involved in PGR, including the PGM gene encoding the essential PiggyMac endonuclease that cleaves the ends of eliminated sequences. Using RNA deep sequencing and transcriptome analysis, we show that impairing PGR upregulates key known PGR genes, together with ∼600 other genes possibly also involved in PGR. Among these genes, 42% are no longer induced when no new MACs are formed, including 180 genes that are co-expressed with PGM under all tested conditions. We propose that bi-directional crosstalk between the two coexisting generations of MACs links gene expression to the progression of MAC development.