bluuebunny/crossref_metadata_2025 huggingface dataset:
Classroom learning environments and dropout prevention in Hungary
Authors: Tókos Katalin , Kárász Judit Takácsné , Rapos Nóra , Lénárd Sándor , Szivák Judit
Published: November 2023

Early school leaving is an outcome of complex and long‐term processes comprising personal, institutional, and systemic factors. Studies on individuals in Hungary have identified a connection between early school leaving and teaching practices at schools. The creation of supportive learning environments in turn can contribute to preventing early school leaving. This article reports on findings from a cross‐sectional study conducted in Hungary between 2018 and 2021 in the context of the project HRDOP–3.1.2‐16‐2016‐0000 Renewal of the public education methodology to reduce early school leaving. The primary focus of the study was to investigate the characteristics of the learning environment in participating schools. The study sought to identify risk factors as well as mitigating factors that are relevant to early school leaving. Sampling was based on availability; the sample contained the responses of 9892 students and 6034 teachers and heads from 473 educational institutions. Respondents were asked about their opinions about the characteristic features of the learning environment in the classroom and at school. This article presents our comparison of results from: (1) a research panel on teacher and student perceptions of the attributes of the classroom learning environment; (2) analysis on differences in teacher and student perceptions; and (3) analysis on possible differences between the results of the questionnaires administered to different groups of respondents in different years. Besides outlining characteristic features of how learning environments were perceived in Hungary, the article offers a conceptual framework and tool for understanding and contributing to the development of supportive learning environments.
Impact of movie and video game elements on tic manifestation in children
Authors: Raz Gal , Davidovitch Shiri , Halevi Mor , Zuckerman Maya , Ben‐Haim Yael , Koryto Yuval , Steinberg Tamar , Leitner Yael , Rotstein Michael S.
Published: November 2023

Background and purpose

Children in developed countries spend a significant portion of their waking hours engaging with audiovisual content and video games. The impact of media consumption on children's health and well‐being has been widely studied, including its effects on tic disorders. Previous studies have shown that tic frequency can both increase and decrease during activities like gaming and television watching, resulting in mixed findings.

Methods

To better understand the impact of audiovisual media on tics, we conducted a fine‐grained tic manifestation analysis. We focused on the effects of the impact of a movie scene with suspensful elements and a video game designed to heighten anticipation, thought to stimulate phasic and striatal dopamine release. We closely monitored tic frequency throuhghout these experiences based on moment‐to‐moment tic annotation. The study included 20 participants (19 males aged 7‐16) diagnosed with tic disorders (Yale Global Tic Severity Scale≥8), and we tested the replicability of our findings with an independent group of 36 children (15 females, aged 7‐15) with tic disorders.

Results

During film viewing, we observed significant synchronization in the temporal tic patterns of various individuals despite diversity in their tic profiles. Furthermore, employing a video game developed for our study, we found that tic frequency increases during anticipation of a pending reward. This finding was replicated in a second experiment with an independent cohort.

Conclusions

Our results indicate that tic frequency is affected by media elements in the short‐term, and call for further investigation of the long‐term impacts of exposure to such tic triggers.
Efficacy and safety of TM5614 in combination with paclitaxel in the treatment of paclitaxel‐resistant cutaneous angiosarcoma: Phase II study protocol
Authors: Fujimura Taku , Yoshino Koji , Nakamura Motoki , Kato Hiroshi , Ito Takamichi , Maekawa Takeo , Fujisawa Yasuhiro , Matsushita Shigeto , Amagai Ryo , Yamazaki Emi , Takahashi Manami , Tamabuchi Erika , Hashimoto Akira , Kambayashi Yumi , Yamazaki Naoya , Miyata Toshio , Asano Yoshihide
Published: November 2023

Cutaneous angiosarcoma (CAS) is an endothelial cell‐derived, highly aggressive type of vascular tumour. Although chemoradiotherapy with paclitaxel (PTX) is recognized as a first‐line therapy for CAS, second‐line therapy for CAS remains controversial, and there is no standard therapy for taxane‐resistant CAS. Plasminogen activator inhibitor‐1 (PAI‐1) is associated with poor clinical outcomes, and elevated levels of PAI‐1 in both tissue and serum are correlated with poor response to therapy in various cancers, including skin cancers. Since PAI‐1 protects endothelial cells from Fas ligand‐mediated apoptosis, PAI‐1 inhibition might induce apoptosis of endothelial cell‐derived tumours such as CAS. This is a single‐arm, open‐label, multi‐institutional, Phase 2 clinical trial to assess the efficacy and safety of PTX in combination with TM5614 (PAI‐1 inhibitor) in patients with PTX‐resistant CAS. PTX will be administered for 28 weeks, with oral administration of TM5614. The primary endpoint of this study will be the overall response rate (ORR) at 28 weeks after starting treatment (central image evaluation). The secondary endpoint will include the ORR at 28 weeks after starting treatment (investigator evaluation), ORR at 8 weeks and 16 weeks after initiation of treatment (central and investigator evaluation), progression‐free survival, overall survival, disease control rate and safety profiles. Assuming the null hypothesis of a response rate of 13.6% and an alternative hypothesis of 45%, a minimum of 15 patients are required to achieve a two‐sided, Type I error of 5% and power of 70% based on the exact binomial distribution. Data quality control will be conducted by a combination of centralized (remote) and on‐site monitoring. This study will contribute to the development of novel combination therapy for PTX‐resistant CAS patients, which remains an unmet clinical need.
The appendicularian Oikopleura dioica can enhance carbon export in a high CO2 ocean
Authors: Taucher Jan , Lechtenbörger Anna Katharina , Bouquet Jean‐Marie , Spisla Carsten , Boxhammer Tim , Minutolo Fabrizio , Bach Lennart Thomas , Lohbeck Kai T. , Sswat Michael , Dörner Isabel , Ismar‐Rebitz Stefanie M. H. , Thompson Eric M. , Riebesell Ulf
Published: November 2023

Gelatinous zooplankton are increasingly recognized to play a key role in the ocean's biological carbon pump. Appendicularians, a class of pelagic tunicates, are among the most abundant gelatinous plankton in the ocean, but it is an open question how their contribution to carbon export might change in the future. Here, we conducted an experiment with large volume in situ mesocosms (~55–60 m3 and 21 m depth) to investigate how ocean acidification (OA) extreme events affect food web structure and carbon export in a natural plankton community, particularly focusing on the keystone species Oikopleura dioica, a globally abundant appendicularian. We found a profound influence of O. dioica on vertical carbon fluxes, particularly during a short but intense bloom period in the high CO2 treatment, during which carbon export was 42%–64% higher than under ambient conditions. This elevated flux was mostly driven by an almost twofold increase in O. dioica biomass under high CO2. This rapid population increase was linked to enhanced fecundity (+20%) that likely resulted from physiological benefits of low pH conditions. The resulting competitive advantage of O. dioica resulted in enhanced grazing on phytoplankton and transfer of this consumed biomass into sinking particles. Using a simple carbon flux model for O. dioica, we estimate that high CO2 doubled the carbon flux of discarded mucous houses and fecal pellets, accounting for up to 39% of total carbon export from the ecosystem during the bloom. Considering the wide geographic distribution of O. dioica, our findings suggest that appendicularians may become an increasingly important vector of carbon export with ongoing OA.
Influence of pulse energy, tip design and insertion depth during Er:YAG‐activated irrigation on cleaning efficacy in simulated severely curved complex root canal systems in vitro
Authors: Bürklein Sebastian , Abdi Izzeddin , Schäfer Edgar , Appel Carsten , Donnermeyer David
Published: November 2023

Aim

To investigate the influence of pulse energy, tip geometry and tip position in simulated 3D‐printed root canals with multiple side canals at different levels in all directions on the cleaning performance of laser‐activated irrigation (LAI) compared to sonic activation (EDDY) and conventional needle irrigation (NI).

Methodology

3D‐printed root canal models (25/.06, length 20 mm, curvature 60°, radius 5 mm) with side canals (diameter 0.2 mm) at 2, 5 and 8 mm from the apex were filled with coloured biofilm‐mimicking hydrogel. LAI (Morita AdvErL Evo, Kyoto, Japan) was performed with six settings (n = 20; pulse‐energy, pulses per second [PPS], tip position): LAI1 (50 mJ, 25 PPS, P400FL, canal entrance [CE]), LAI2 (same as LAI1, but insertion depth 9 mm before the apical endpoint [AE] [corresponding to 1 mm above the first lateral canals]), LAI3 (80 mJ, 25 PPS, P400FL, 9 mm before AE), LAI4 (same as LAI 3, but at CE) for 3 × 20 s each, LAI5 (50 mJ, 25 PPS, P400FL 2 × 20 s, CE & R200T (30 mJ, 25 PPS, 1 × 20 s, 9 mm before AE), LAI6 (30 mJ, 25 PPS, R200T, 9 mm before AE, 3 × 20 s). A continuous irrigation (3 mL/20 s) using distilled water accompanied the irrigation cycles. NI and EDDY (3 × 20 s each; 3 mL/20 s irrigation, insertion AE minus 1 mm, amplitude 4 mm) served as control groups. Biofilm‐mimicking hydrogel removal (ImageJ, NIH) was assessed for the entire system, the central canal and the lateral canals using standardized photographs with a microscope (Expert DN, Müller‐Optronic) and statistically analysed was performed using Kruskal–Wallis and Dunn tests (p = .05). Irrigant extrusion beyond the foramina was also recorded.

Results

LAI2 (99.08%; interquartile range [IQR]: 96.85–100.00) and LAI3 (97.50%; 96.24–100.00) achieved the significantly best and LAI6 (80.08%; 73.41–84.69) the significantly worst removal of hydrogel from the entire root canal system amongst all LAI configurations (p < .05). There were no significant differences between LAI6, EDDY (72.89%; 67.49–76.22) and manual irrigation (54.39%; 51.01–56.94) (p > .05). R200T laser tip caused significantly more often irrigant extrusion than all other techniques (p < .05).

Conclusion

Tip design, energy settings, and the positioning of the laser tip below the canal entrance caused an improvement in cleaning performance of the LAI. However, the small R200T tip created significantly more procedural errors (irrigant extrusion) due to higher concentrated energy.
Behind the creative canvas: An innovative trauma‐informed art‐based educational approach using an immersive learning pedagogy
Authors: Milasan Lucian H. , Farr Andy , Turnbull Isabel , Scott‐Purdy Daniel
Published: November 2023

Trauma has been increasingly considered in mental health policies and strategies worldwide. However, the implementation of such initiatives into practice remains inconsistent resulting in a fragmented approach to trauma‐informed care. One explanation for the current state of trauma services is the unpreparedness of mental health nurses in line with emerging traumagenic theoretical frameworks. We addressed this gap by implementing an innovative pedagogic project co‐produced with people with lived experience of trauma. The aim of this qualitative study was to explore mental health nursing students' perspective on the usefulness of an art‐based approach to learning about, and working with, trauma in a non‐interactive virtual reality (VR) environment. Ten mental health nursing students have been conveniently selected to take part in a focus group. The thematic analysis revealed authenticity, the power of arts, and underutilisation of arts in mental health nursing as key themes following students' reflections and critical discussions. Recommendations to enhance trauma‐informed nursing education and practice are made to support an approach that has the potential to instil positive changes in the way mental health nursing students perceive and work with trauma in their practice.
The morphology and physiology of bacteriophages as revealed by the electron microscope
Authors: BRADLEY D. E.
Published: November 2023

SYNOPSIS

The electron microscope can reveal details of both the infective process and the morphology of bacteriophages. Various standard specimen‐preparation methods are available for these studies: negative staining is the most valuable method for morphological aspects and the sectioning of bacteria for studying intracellular multiplication. Phages fall into six distinct morphological groups. Detailed examination of these reveals a variety of forms showing variations within each group. All phages have one thing in common, the possession of symmetry; the heads have recognisable geometrical shapes and the tails, when present, possess morphological subunits usually clearly arranged in a regular fashion.

Phage morphology is important not only as a fundamental characteristic, but also as a major criterion for taxonomic purposes. However, some phages, which are morphologically similar, can infect bacterial hosts in different genera or families so that additional criteria such as host range have to be used in considering a possible system for the classification of bacteriophages.

The electron microscope is particularly suitable for providing information about the adsorption and intracellular multiplication stages of the infective process. Shadowing and negative staining show that tailed phages adsorb tail first, and that tail‐less ribonucleic acid phages attach to bacterial fimbriae in large numbers. Sections of infected bacteria reveal cytological changes within the cell during intracellular multiplication.

In addition, the electron microscope can be used to investigate the natural habitats of phages. In one of these a particle with an unusual “life cycle” was found associated with the genus Bacillus. It normally exists in the prophage state in a lysogenic host. It is active on indicator strains, but only kills them and cannot multiply within them.

These various aspects are reviewed in detail with particular reference to information provided by the electron microscope.
Principles and limitations of immunohistochemical methods
Authors: MAYERSBACH H. V.
Published: November 2023

SYNOPSIS

Immunofluorescence is an ingenious method in histochemical research as it is possible to solve problems which are impossible to approach with other methods. Everyone using this method must be aware that immunohistochemistry is a field still developing and full of weeds and thorns. In particular, one must be aware that the method consumes a great amount of time when all the factors involved are taken into account. An uncritical use of this method will not only give wrong results but also bring it into discredit.
Etablissement des relations de dominance‐soumission chez les bovins domestiques III. Effet de l'expérience sociale
Authors: Bouissou Marie‐France , Lavenet Colette , Orgeur P.
Published: November 2023

An evaluation of social experience in the establishment of dominance‐submission relationships was attempted using 20 animals in various constellations of 4.

The establishment of rank‐order in 5 groups of inexperienced heifers upon their first contact with strangers was compared with that in 20 groups consisting of the same animals in different arrangements upon their second to their fifth encounter with strangers.

With experience, the various types of agonistic interactions were differently utilized, contact‐forming and fighting time were reduced, the social order was more rapidly and firmly established, and fighting often dispensed with.
A comparison of end‐of‐life care quality for Veterans receiving hospice in VA nursing homes and community nursing homes
Authors: Wachterman Melissa W. , Smith Dawn , Carpenter Joan G. , Griffin Hillary L. , Thorpe Joshua , Feder Shelli L. , Hoelter Jillian , Ersek Mary , Shreve Scott , Kutney‐Lee Ann
Published: November 2023

Background

While the Veterans Health Administration (VA) has long provided hospice care within VA community living centers (CLCs, i.e., VA nursing homes), an increasing number of Veterans are receiving hospice in VA‐contracted community nursing homes (CNHs). However, little data exist about the quality of end‐of‐life (EOL) care provided in CNHs. The aim of this study was to compare family ratings of the quality of EOL care provided to Veterans receiving hospice in VA CLCs and VA‐contracted CNHs.

Methods

We conducted a retrospective analysis of national data from VA's electronic medical record and Bereaved Family Survey (BFS) for Veterans who received hospice in VA CLCs or VA‐contracted CNHs between October 2021 and March 2022. The final sample included 1238 Veterans who died in either a CLC (n = 1012) or a CNH (n = 226) and whose next‐of‐kin completed the BFS. Our primary outcome was the BFS global rating of care received in the last 30 days of life. Secondary outcomes included BFS items related to symptom management, communication, emotional and spiritual support, and information about burial and survivor benefits. We compared unadjusted and adjusted proportions for all BFS outcomes between those who received hospice in CLCs and CNHs.

Results

The adjusted proportion of family members who gave the best possible rating (a score of 9 or 10 out of a possible 10) for the overall care received near EOL was more than 13 percentage points higher for Veterans who received hospice in VA CLCs compared to VA‐contracted CNHs. Our findings also revealed quality gaps of even greater magnitude in specific EOL care‐focused domains.

Conclusions

Our findings document inadequacies in the quality of multiple aspects of EOL care provided to Veterans in CNH‐based hospice and illuminate the urgent need for policy and practice interventions to improve this care.
Electric currents of 448 kHz upregulate anti‐senescence pathways in human dermal fibroblasts
Authors: Toledano‐Macías Elena , Martínez‐Pascual María Antonia , Hernández‐Bule María Luisa
Published: November 2023

Background

Currently, finding new therapeutic strategies that reduce skin aging is a challenge for dermatologists and aesthetic doctors. In recent years, physical therapies have been included in the options for antiaging treatments; however, the biological bases of such treatments have scarcely been studied. One of these physical therapies is capacitive–resistive electric transfer (CRET) therapy. Previous studies have shown that subthermal treatment with CRET promotes the proliferation and migration of various cell types involved in skin regeneration, such as human ADSC (stem cells), fibroblasts, or keratinocytes.

Objective

This study investigates the effects of in vitro treatment with CRET‐Std (standard, non‐modulated signal) or CRET‐Mod (modulated signal) on cell proliferation and migration, markers of aging, and extracellular matrix production.

Methods

Three types of human dermal fibroblasts were used: neonatal fibroblasts (HFn), replicative senescent fibroblasts (HFs), and adult fibroblasts (HFa). The effects of electric stimulation on cell proliferation and migration were studied through XTT and wound closure assays, respectively. The expression of the aging marker β‐galactosidase was assessed using a colorimetric assay, whereas immunoblot, immunofluorescence, and ELISAs were carried out to analyze the expression levels of migration, aging, and extracellular matrix proteins.

Results

The treatment with CRET‐Std increased HFn and HFa proliferation, as well as migration in the three types of fibroblasts studied compared to those of the controls. Conversely, CRET‐Mod did not modify either of these two processes with respect to the controls. Additionally, CRET‐Std also reduced the cellular senescence markers β‐gal, vimentin, p53, and p21 in all three types of human skin fibroblasts. In addition, the application of CRET‐Std also induced fibronectin production in HFn and was able to stimulate ECM neocollagenesis.

Conclusion

CRET treatment improves a number of functions related to migration and proliferation, and it reduces age‐related cellular changes in human dermal fibroblasts. Therefore, the use of this CRET therapy to reduce the signs of dermal aging and to promote tissue regeneration could be of interest.
Progesterone after mifepristone: A pilot prospective single arm clinical trial for women who have changed their mind after commencing medical abortion
Authors: Turner Joseph V. , Garratt Deborah , McLindon Lucas A. , Barwick Anna , Spark M. Joy
Published: November 2023

Aim

This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy.

Methods

The Progesterone‐After‐Mifepristone—pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single‐arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web‐based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment.

Results

Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40–70 days of gestation, with progesterone being commenced within 5.7–72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events.

Conclusion

This small study demonstrated a clinically sound protocol for researching the use of progesterone‐after‐mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field.
The eco‐evolutionary importance of reproductive system variation in the macroalgae: Freshwater reds as a case study
Authors: Krueger‐Hadfield Stacy A. , Shainker‐Connelly Sarah J. , Crowell Roseanna M. , Vis Morgan L.
Published: November 2023

The relative frequency of sexual versus asexual reproduction governs the distribution of genetic diversity within and among populations. Most studies on the consequences of reproductive variation focus on the mating system (i.e., selfing vs. outcrossing) of diploid‐dominant taxa (e.g., angiosperms), often ignoring asexual reproduction. Although reproductive systems are hypothesized to be correlated with life‐cycle types, variation in the relative rates of sexual and asexual reproduction remains poorly characterized across eukaryotes. This is particularly true among the three major lineages of macroalgae (green, brown, and red). The Rhodophyta are particularly interesting, as many taxa have complex haploid–diploid life cycles that influence genetic structure. Though most marine reds have separate sexes, we show that freshwater red macroalgae exhibit patterns of switching between monoicy and dioicy in sister taxa that rival those recently shown in brown macroalgae and in angiosperms. We advocate for the investigation of reproductive system evolution using freshwater reds, as this will expand the life‐cycle types for which these data exist, enabling comparative analyses broadly across eukaryotes. Unlike their marine cousins, species in the Batrachospermales have macroscopic gametophytes attached to filamentous, often microscopic sporophytes. While asexual reproduction through monospores may occur in all freshwater reds, the Compsopogonales are thought to be exclusively asexual. Understanding the evolutionary consequences of selfing and asexual reproduction will aid in our understanding of the evolutionary ecology of all algae and of eukaryotic evolution generally.
Vascular persistence following precision micropuncture
Authors: Horchler Summer N. , Hancock Patrick C. , Sun Mingjie , Liu Alexander T. , Massand Sameer , El‐Mallah Jessica C. , Goldenberg Dana , Waldron Olivia , Landmesser Mary E. , Agrawal Shailaja , Koduru Srinivas V. , Ravnic Dino J.
Published: November 2023

Objective

The success of engineered tissues continues to be limited by time to vascularization and perfusion. Recently, we described a simple microsurgical approach, termed micropuncture (MP), which could be used to rapidly vascularize an adjacently placed scaffold from the recipient macrovasculature. Here we studied the long‐term persistence of the MP‐induced microvasculature.

Methods

Segmental 60 μm diameter MPs were created in the recipient rat femoral artery and vein followed by coverage with a simple Type 1 collagen scaffold. The recipient vasculature and scaffold were then wrapped en bloc with a silicone sheet to isolate intrinsic vascularization. Scaffolds were harvested at 28 days post‐implantation for detailed analysis, including using a novel artificial intelligence (AI) approach.

Results

MP scaffolds demonstrated a sustained increase of vascular density compared to internal non‐MP control scaffolds (p < 0.05) secondary to increases in both vessel diameters (p < 0.05) and branch counts (p < 0.05). MP scaffolds also demonstrated statistically significant increases in red blood cell (RBC) perfused lumens.

Conclusions

This study further highlights that the intrinsic MP‐induced vasculature continues to persist long‐term. Its combination of rapid and stable angiogenesis represents a novel surgical platform for engineered scaffold and graft perfusion.
Effect of chlorhexidine gel on the prevention of alveolar osteitis and post‐operative pain following transalveolar extraction of impacted mandibular third molars: A randomized study
Authors: Erinoso Olufemi , Ogunbayo Olakunle , Adesina Ayodele , James Olutayo , Ladeinde Akin , Ogunlewe Olugbemiga , Olaitan Ademola
Published: November 2023

Objective

This study aimed to compare the efficacy of 0.2% chlorhexidine gel with warm saline mouth rinse (WSMR) in the prevention of alveolar osteitis (AO) following transalveolar impacted mandibular third molar (IMTM) extraction after accounting for surgical operative confounding factors.

Materials and Methods

We conducted a parallel design randomized study. Participants were consenting adults randomly assigned to 0.9% WSMR and 0.2% chlorhexidine gel (administered twice daily post‐operatively) groups. All participants were followed up daily post‐operatively for one week. The primary outcome was an incidence of AO, assessed using Blum's criteria. Fischer's exact tests and regression models were used to investigate the effect of interventions on AO.

Results

One hundred participants were enrolled in the study, with 50 participants in each group. A higher incidence of AO was observed in the WSMR group than the chlorhexidine group (16% vs. 2%, p = 0.01). However, after adjusting for duration of extraction (aOR: 0.18; 95% CI: 0.02, 1.71) and bone operating time (aOR: 0.16; 95% CI: 0.02, 1.47), the difference was not statistically significant.

Conclusions

In conclusion, the study demonstrates that the application of the 0.2% chlorhexidine gel was not significantly more effective in preventing AO compared with the use of WSMR following transalveolar IMTM extraction after controlling for operative factors.
Decoding speech sounds from neurophysiological data: Practical considerations and theoretical implications
Authors: Sarrett McCall E. , Toscano Joseph C.
Published: November 2023

Machine learning techniques have proven to be a useful tool in cognitive neuroscience. However, their implementation in scalp‐recorded electroencephalography (EEG) is relatively limited. To address this, we present three analyses using data from a previous study that examined event‐related potential (ERP) responses to a wide range of naturally‐produced speech sounds. First, we explore which features of the EEG signal best maximize machine learning accuracy for a voicing distinction, using a support vector machine (SVM). We manipulate three dimensions of the EEG signal as input to the SVM: number of trials averaged, number of time points averaged, and polynomial fit. We discuss the trade‐offs in using different feature sets and offer some recommendations for researchers using machine learning. Next, we use SVMs to classify specific pairs of phonemes, finding that we can detect differences in the EEG signal that are not otherwise detectable using conventional ERP analyses. Finally, we characterize the timecourse of phonetic feature decoding across three phonological dimensions (voicing, manner of articulation, and place of articulation), and find that voicing and manner are decodable from neural activity, whereas place of articulation is not. This set of analyses addresses both practical considerations in the application of machine learning to EEG, particularly for speech studies, and also sheds light on current issues regarding the nature of perceptual representations of speech.
Hiding in plain sight: Phylogenomics reveals a new branch on the Noctuoidea tree of life
Authors: St Laurent Ryan A. , Goldstein Paul Z. , Miller Scott E. , Robbins Robert K.
Published: November 2023

We analyse anchored hybrid enrichment data from densely sampled tribes and subfamilies of Notodontidae (Prominent Moths). Notodontidae are monophyletic except for an assemblage of genera related to Thacona Walker (=Scrancia Holland), which had been recognized at either the tribal or subfamilial rank within Notodontidae. We elevate and re‐describe Scranciidae stat. nov. as a family distinct from the six currently recognized noctuoid families (Noctuidae, Erebidae, Euteliidae, Nolidae, Notodontidae and Oenosandridae). Scranciidae include 22 genera comprising approximately 100 species—distributed in Africa, Asia and Australia. We re‐interpret morphological synapomorphies previously proposed for Notodontidae (including Scranciidae) and for the trifid Noctuoidea more broadly. Deep‐level relationships within Noctuoidea are not well resolved outside the clade comprising the four quadrifid families (Noctuidae, Erebidae, Euteliidae and Nolidae). The phylogenetic position of Scranciidae relative to Notodontidae, Oenosandridae and the quadrifids varied markedly depending on data type (amino acid vs. nucleotide) and analytical framework (maximum likelihood, multi‐species coalescent and parsimony). We discuss the possible roles of missing data and short branch lengths in resolving the placement of Scranciidae. In the topology best supported by the most available data, Scranciidae are sister to the remaining Noctuoidea, highlighting their phylogenetic significance. We provide a provisional list of the genera included in Scranciidae.
Characterization of the novel HLA‐B*08:312 allele by sequencing‐based typing
Authors: Blandin Lucie , Ralazamahaleo Mamy , Guidicelli Gwendaline , Rouzaire Paul , Lemal Richard
Published: November 2023

HLA‐B*08:312 differs from HLA‐B*08:01:01:01 by one nucleotide substitution in codon 324 in exon 6.
Whole‐genome resequencing facilitates the development of a 50K single nucleotide polymorphism genotyping array for Scots pine (Pinus sylvestris L.) and its transferability to other pine species
Authors: Estravis Barcala Maximiliano , van der Valk Tom , Chen Zhiqiang , Funda Tomas , Chaudhary Rajiv , Klingberg Adam , Fundova Irena , Suontama Mari , Hallingbäck Henrik , Bernhardsson Carolina , Nystedt Björn , Ingvarsson Pär K. , Sherwood Ellen , Street Nathaniel , Gyllensten Ulf , Nilsson Ove , Wu Harry X.
Published: November 2023

Scots pine (Pinus sylvestris L.) is one of the most widespread and economically important conifer species in the world. Applications like genomic selection and association studies, which could help accelerate breeding cycles, are challenging in Scots pine because of its large and repetitive genome. For this reason, genotyping tools for conifer species, and in particular for Scots pine, are commonly based on transcribed regions of the genome. In this article, we present the Axiom Psyl50K array, the first single nucleotide polymorphism (SNP) genotyping array for Scots pine based on whole‐genome resequencing, that represents both genic and intergenic regions. This array was designed following a two‐step procedure: first, 192 trees were sequenced, and a 430K SNP screening array was constructed. Then, 480 samples, including haploid megagametophytes, full‐sib family trios, breeding population, and range‐wide individuals from across Eurasia were genotyped with the screening array. The best 50K SNPs were selected based on quality, replicability, distribution across the draft genome assembly, balance between genic and intergenic regions, and genotype–environment and genotype–phenotype associations. Of the final 49 877 probes tiled in the array, 20 372 (40.84%) occur inside gene models, while the rest lie in intergenic regions. We also show that the Psyl50K array can yield enough high‐confidence SNPs for genetic studies in pine species from North America and Eurasia. This new genotyping tool will be a valuable resource for high‐throughput fundamental and applied research of Scots pine and other pine species.
Fiscal and current account imbalances: The cases of Germany and Portugal
Authors: Afonso António , Coelho José Carlos
Published: November 2023

We investigate the bilateral relationship between government budget balances and current account balances for Germany and Portugal. We find that the response of the current account balance to the budget balance is greater in Portugal than in Germany. On the other hand, the response of the budget balance to the current balance is higher in Germany than in Portugal. In Germany and Portugal, a fiscal rules index has a negative impact on the current account balance and the government effectiveness index has a positive impact on the government balance. The public debt‐to‐GDP ratio positively affects the current account balance in Portugal while the output gap has a negative influence, and that is not the case in Germany. During the period of implementation of the external assistance programme in Portugal, the current account balance improved, while the government balance did not. Finally, Germany's output gap positively influences Portugal's fiscal position.
GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study
Authors: Yadav Harsh , Pandit Depanshi , Singh Sidhartha , Sharma Parul , Garg Kranti , Girdhar Nidhi , Sharma Karan , Chopra Vishal , Chopra Siddharth , Sharma Siddharth
Published: November 2023

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S‐transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S‐transferase T1 (GSTT1) and glutathione S‐transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross‐sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(−) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30–3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(−) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43–5.87, P = 0.003). The GSTT1(−) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(−) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(−) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(−) null genotype in the North Indian population.
Directional and amplitude characteristics of pulsed call sequences in captive free-swimming Pacific white-sided dolphins (Lagenorhynchus obliquidens)
Authors: Mishima Yuka , Matsuo Ikuo , Karasawa Yuu , Ishii Marina , Morisaka Tadamichi
Published: November 2023

We investigated the directional properties and gain control of a pulsed call sequence that functions as a contact call in Pacific white-sided dolphins (Lagenorhynchus obliquidens). The pulsed call sequences were stereotyped patterns composed of three or more pulsed call elements and were collected from two dolphins, separated into adjacent pools, and allowed to swim freely. Eight hydrophones and an overhead camera were used to determine the positions and directions of the participants. The mean peak frequency and source levels were 8.4 ± 4.4 (standard deviation)–18.7 ± 12.7 kHz and 160.8 ± 3.8 to 176.4 ± 7.9 dB re 1 μPa (peak-to-peak), respectively, depending on the element types. The elements were omnidirectional, with mean directivity index of 0.9 ± 3.4 dB. The dolphins produced sequences, regardless of their relative position and direction to the lattice, leading to the adjacent pool where the conspecific was housed. They increased the amplitude by 6.5 ± 4.6 dB as the distance from the caller to an arbitrary point in the adjacent pool doubled. These results suggest that callers broadcast pulsed call sequences in a wide direction to reach dispersed conspecifics. However, they can adjust the acoustic active space by controlling the source levels.
Eukaryotic genomes from a global metagenomic data set illuminate trophic modes and biogeography of ocean plankton
Authors: Alexander Harriet , Hu Sarah K. , Krinos Arianna I. , Pachiadaki Maria , Tully Benjamin J. , Neely Christopher J. , Reiter Taylor
Published: November 2023

Metagenomics is a powerful method for interpreting the ecological roles and physiological capabilities of mixed microbial communities. Yet, many tools for processing metagenomic data are neither designed to consider eukaryotes nor are they built for an increasing amount of sequence data. EukHeist is an automated pipeline to retrieve eukaryotic and prokaryotic metagenome-assembled genomes (MAGs) from large-scale metagenomic sequence data sets. We developed the EukHeist workflow to specifically process large amounts of both metagenomic and/or metatranscriptomic sequence data in an automated and reproducible fashion. Here, we applied EukHeist to the large-size fraction data (0.8–2,000 µm) from Tara Oceans to recover both eukaryotic and prokaryotic MAGs, which we refer to as TOPAZ (Tara Oceans Particle-Associated MAGs). The TOPAZ MAGs consisted of >900 environmentally relevant eukaryotic MAGs and >4,000 bacterial and archaeal MAGs. The bacterial and archaeal TOPAZ MAGs expand upon the phylogenetic diversity of likely particle- and host-associated taxa. We use these MAGs to demonstrate an approach to infer the putative trophic mode of the recovered eukaryotic MAGs. We also identify ecological cohorts of co-occurring MAGs, which are driven by specific environmental factors and putative host-microbe associations. These data together add to a number of growing resources of environmentally relevant eukaryotic genomic information. Complementary and expanded databases of MAGs, such as those provided through scalable pipelines like EukHeist, stand to advance our understanding of eukaryotic diversity through increased coverage of genomic representatives across the tree of life.

IMPORTANCE

Single-celled eukaryotes play ecologically significant roles in the marine environment, yet fundamental questions about their biodiversity, ecological function, and interactions remain. Environmental sequencing enables researchers to document naturally occurring protistan communities, without culturing bias, yet metagenomic and metatranscriptomic sequencing approaches cannot separate individual species from communities. To more completely capture the genomic content of mixed protistan populations, we can create bins of sequences that represent the same organism (metagenome-assembled genomes [MAGs]). We developed the EukHeist pipeline, which automates the binning of population-level eukaryotic and prokaryotic genomes from metagenomic reads. We show exciting insight into what protistan communities are present and their trophic roles in the ocean. Scalable computational tools, like EukHeist, may accelerate the identification of meaningful genetic signatures from large data sets and complement researchers’ efforts to leverage MAG databases for addressing ecological questions, resolving evolutionary relationships, and discovering potentially novel biodiversity.
Development of a CRISPR-Cas12a system for efficient genome engineering in clostridia
Authors: Zhang Yanchao , Kubiak Aleksandra M. , Bailey Tom S. , Claessen Luuk , Hittmeyer Philip , Dubois Ludwig , Theys Jan , Lambin Philippe
Published: November 2023

Clostridium
species have gained attention in industrial and medical applications, and the development of genetic tools has enabled the advancement of the CRISPR-Cas systems for these bacteria. Compared to the primarily used Cas9 from
Streptococcus pyogenes
, the utilization of Cas12a (previously known as Cpf1) proteins remains incomplete in clostridia, although they exhibit potential advantages, including T-rich recognition for
Clostridium
genomes and lower toxicity. In this study, we expanded the CRISPR-Cas tools in clostridia by establishing a CRISPR-Cas12a system with two different
cas12a
genes (
Ascas12a
from
Acidaminococcus
and
Fncas12a
from
Francisella novicida
). The optimized tetracycline-inducible systems were initially determined by the glucuronidase reporter and were used to drive expression of the
cas12a
genes and crRNAs. Our results demonstrate that the CRISPR-FnCas12a system offers flexible target selection in clostridia, and a specific folding pattern of the precursor crRNA is important to enable high mutation generation efficiency. By using
sacB
(encoding levansucrase) as a negative marker for plasmid curing and determining the optimal size of the donor DNA template for gene integration in the CRISPR-FnCas12a system, we achieved highly efficient and rapid genome modification, exemplified by the successful engineering of clostridia (
Clostridium butyricum
and
Clostridium sporogenes
) to produce near-infrared fluorescence from biliverdin and hemin.

IMPORTANCE

Continued efforts in developing the CRISPR-Cas systems will further enhance our understanding and utilization of
Clostridium
species. This study demonstrates the development and application of a genome-engineering tool in two
Clostridium
strains,
Clostridium butyricum
and
Clostridium sporogenes
, which have promising potential as probiotics and oncolytic agents. Particular attention was given to the folding of precursor crRNA and the role of this process in off-target DNA cleavage by Cas12a. The results provide the guidelines necessary for efficient genome engineering using this system in clostridia. Our findings not only expand our fundamental understanding of genome-engineering tools in clostridia but also improve this technology to allow use of its full potential in a plethora of biotechnological applications.
CD4
+
T cells reverse surface antigen persistence in a mouse model of HBV replication
Authors: Bailey Jacob T. , Moshkani Safiehkhatoon , Rexhouse Catherine , Cimino Jesse L. , Robek Michael D.
Published: November 2023

Hepatitis B virus (HBV) is responsible for over 800,000 deaths yearly worldwide. While chronic HBV infection currently has no highly effective cure, immunotherapy has generated interest as a potential therapeutic solution due to the connection between viral chronicity and the magnitude of HBV-specific immune responses. Suitable animal models for studying successful immune responses to HBV are limited due to the lack of natural viral tropism for rodents. Using a mouse model of HBV replication, we found that CD4
+
T cells are essential for the antibody-mediated clearance of hepatitis B surface antigen (HBsAg) and that early transient inhibition of the CD4
+
T cell-B cell axis imparts HBsAg persistence through CD4
+
T cell functional impairment. HBsAg resolution in BALB/c mice transduced with an adeno-associated virus encoding the HBV genome (AAV-HBV) depended on B cells, MHCII, and CD4
+
T cells, but not CD8
+
T cells, indicative of antibody-mediated control. Furthermore, disrupting the CD40-CD40L interaction blunted HBsAg clearance and the generation of HBsAg-specific B cells. Finally, HBsAg persistence induced by transient CD4 depletion was reversible by the transfer of total splenocytes or purified CD4
+
T cells from immunized mice. These findings demonstrate the T cell-dependent nature of HBsAg-resolving antibody responses as well as the ability of CD4
+
T cells to reverse HBsAg persistence.

IMPORTANCE

Hepatitis B virus (HBV) is a leading causative agent of viral hepatitis. A preventative vaccine has existed for decades, but only limited treatment options are available for people living with chronic HBV. Animal models for studying HBV are constrained due to narrow viral tropism, impeding understanding of the natural immune response to the virus. Here, using a vector to overcome the narrow host range and establish HBV replication in mice, we identified the role of helper T cells in controlling HBV. We show that helper T cells promote the B cell’s ability to generate antibodies that remove HBV and its associated surface antigen from the blood and that transfer of purified helper T cells from HBV-immunized mice can reverse the accumulation of virus and antigen, furthering our understanding of the immune response to HBV.
Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study
Authors: Pradhan Richeek , Yu Oriana H Y , Platt Robert W , Azoulay Laurent
Published: November 2023

Introduction

The dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.

Research design and methods

Using the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96 739 DPP-4 inhibitor users and 209 341 sulfonylurea users, and 96 411 DPP-4 inhibitor users and 208 626 sulfonylurea users for non-melanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs of melanoma and non-melanoma skin cancer, separately.

Results

Overall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs 65.3 per 100 000 person-years, respectively; HR 0.77, 95% CI 0.61 to 0.96). The HR progressively reduced with increasing cumulative duration of use (0–2 years HR 1.14, 95% CI 0.84 to 1.54; 2.1–5 years HR 0.44, 95% CI 0.29 to 0.66; >5 years HR 0.33, 95% CI 0.14 to 0.74). In contrast, these drugs were not associated with the incidence of non-melanoma skin cancer, compared with sulfonylureas (448.1 vs 426.1 per 100 000 person-years, respectively; HR 1.06, 95% CI 0.98 to 1.15).

Conclusions

In this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not non-melanoma skin cancer, compared with sulfonylureas.