bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroendoscopy-Assisted Entire-Process Visualization Technique of Ventricular Puncture for External Ventricular Drainage
Authors: Xu Yongqiang , Li Zhuoqun , Zhang Zhao , Zhang Haitao , Liu Pengfei
Published: June 2024

Objective:

This study aimed to investigate the feasibility, safety, and efficacy of the neuroendoscopy-assisted entire-process visualization technique (NEAEVT) of ventricular puncture for external ventricular drainage.

Methods:

Eighty-eight patients with cerebral hemorrhage who underwent unilateral ventricular puncture for external ventricular drainage in our hospital from June 2021 to June 2023 were analyzed. Patients were grouped according to puncture technique: NEAEVT (30 patients), freehand (30 patients), and laser-navigation-assisted (28 patients). Operation time, drainage tube placement, and catheter-related hemorrhage incidence were compared between the groups.

Results:

Mean operation time significantly differed between the freehand, NEAEVT, and laser-assisted groups (17.07, 18.37, and 34.04 min, respectively; P <0.0001). The position of the drainage tube was optimal or adequate in all patients of the NEAEVT group; optimal/adequate positioning was achieved in 80% of the freehand group. No catheter-related hemorrhage occurred in the NEAEVT group. Three freehand group patients and 2 laser-assisted group patients experienced catheter-related hemorrhage.

Conclusion:

The NEAEVT of ventricular puncture is accurate and achieves ventricular drainage without significantly increasing surgical trauma, operation time, or incidence of hemorrhage.
Global Research Trends and Focuses on Pierre Robin Sequence From 1992 to 2023: A Bibliometric Analysis of the Past 3 Decades
Authors: Liu Ziyang , Gong Beiwen , Li Xinru , Zhao Chenjie , Chen Yuxiang , Li Shuyuan , Abduwali Reza , Bai Yuxing , Teng Li , Lu Jianjian
Published: June 2024

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual’s growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.
Students Matriculating into Integrated Plastic Surgery: Are all Medical Schools Equal?
Authors: Yau Alice , Lentskevich Marina A. , Reddy Narainsai K. , Gutowski Kristof S. , Yau Irene , Gosain Arun K.
Published: June 2024

Introduction

Becoming a craniofacial/pediatric plastic surgeon depends on completing a plastic surgery (PS) residency. As medical school curricula for PS exposure are highly inconsistent, the authors investigated whether there was an association between the presence of PS elective rotations and/or home programs in medical schools with the proportion of students matriculating into integrated PS residency.

Methods:

A list of 198 medical schools was compiled from the Association for American Medical Colleges and the American Association of Colleges of Osteopathic Medicine. Plastic surgery residency programs were identified by the American Society of Plastic Surgery and the American Council of Educators in Plastic Surgery. Plastic surgery elective rotation offerings and recent matches (2021–2022) were obtained from school websites. Mean proportions of students matriculating into PS between schools that did versus did not have PS elective rotations and/or home PS residency programs were compared.

Results:

One hundred fifty-nine medical schools were included. Seventy-seven of 159 (48%) had both PS elective rotations and home program(s), 63/159 (40%) offered PS elective rotations only, and 19/159 (12%) had neither. The mean proportions of students matriculating differed significantly (P<0.001) among schools without PS electives or a home program [0.09%, 95% confidence interval (CI): −0.04% to 0.21%), PS elective only (0.51%, 95% CI: 0.25%–0.77%), and both PS elective and home program(s) (1.14%, 95% CI: 0.92%–1.37%).

Conclusion:

The presence of elective PS rotations and a home PS residency program significantly increase the chances of matriculation into integrated PS residency programs.
Middle Meningeal Arterial Embolization Combined With Drilling in the Treatment of Acute Epidural Hematoma
Authors: Wang Henglu , Wang Qingbo , Li Zefu
Published: June 2024

Objective:

The purpose of this study was to determine the technical feasibility and safety of middle meningeal arterial (MMA) embolization combined with drilling drainage in the treatment of acute epidural hematoma (AEDH) by comparing it with traditional craniotomy in the treatment.

Methods:

One hundred seventeen patients with AEDH treated for MMA embolization combined with drilling and drainage or craniotomy hematoma removal from January 2017 to September 2020 were retrospectively analyzed and divided into a craniotomy group (n=85) and a minimally invasive group (n=32). Hematoma removal was performed in the craniotomy group, and MMA embolization combined with drilling and drainage was performed in the minimally invasive group. The general clinical data, imaging data, surgery, and follow-up of the 2 groups were compared and analyzed.

Results:

Compared with the craniotomy group, the residual hematoma volume in the minimally invasive group was higher than in the craniotomy group. The average postoperative drainage duration in the minimally invasive group was longer than in the craniotomy group. Compared with the craniotomy group, the minimally invasive group was associated with shorter operative time, less intraoperative bleeding, and lower rates of postoperative rebleeding. In addition, the incidence of postoperative complications and length of hospitalization in the minimally invasive group were significantly shortened.

Conclusion:

Middle meningeal arterial embolization combined with drilling and drainage in the treatment of AEDH caused by MMA active bleeding is safe, effective, and more minimally invasive, and can be promoted and applied.
EnderScope: a low-cost 3D printer-based scanning microscope for microplastic detection
Authors: Burke Niamh , Müller Gesine , Saggiomo Vittorio , Hassett Amy Ruth , Mutterer Jérôme , Ó Súilleabháin Patrick , Zakharov Daniel , Healy Donal , Reynaud Emmanuel G. , Pickering Mark
Published: June 2024

Low-cost and scalable technologies that allow people to measure microplastics in their local environment could facilitate a greater understanding of the global problem of marine microplastic pollution. A typical way to measure marine microplastic pollution involves imaging filtered seawater samples stained with a fluorescent dye to aid in the detection of microplastics. Although traditional fluorescence microscopy allows these particles to be manually counted and detected, this is a resource- and labour-intensive task. Here, we describe a novel, low-cost microscope for automated scanning and detection of microplastics in filtered seawater samples—the EnderScope. This microscope is based on the mechanics of a low-cost 3D printer (Creality Ender 3). The hotend of the printer is replaced with an optics module, allowing for the reliable and calibrated motion system of the 3D printer to be used for automated scanning over a large area (>20 × 20 cm). The EnderScope is capable of both reflected light and fluorescence imaging. In both configurations, we aimed to make the design as simple and cost-effective as possible, for example, by using low-cost LEDs for illumination and lighting gels as emission filters. We believe this tool is a cost-effective solution for microplastic measurement.

This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.
Open instrumentation, like open data, is key to reproducible science. Yet, without incentives it won’t thrive
Authors: Stirling Julian
Published: June 2024

There is far more to open science than simply not shutting away your work. For example, a significant time investment must be made to collate, curate, explain and document precisely how an experiment can be reproduced or data can be reused. This time investment is currently poorly rewarded in our current model of open science where a bare minimum of openness is mandated, but further work is not recognized. As the open science movement looks beyond open access publications and open data towards ongoing detailed work such as open source software and open source hardware, it needs to consider how to properly encourage the extra work that is needed to properly document these projects. Without detailed documentation, the work cannot be replicated, reused and continually improved. If the work cannot be replicated or reused, is it really even open?

This article is part of the Theo Murphy meeting issue ‘Open, reproducible hardware for microscopy’.
Microbial-Derived Exerkines Prevent Skeletal Muscle Atrophy
Authors: Valentino Taylor R. , Burke Benjamin I. , Kang Gyumin , Goh Jensen , Dungan Cory M. , Ismaeel Ahmed , Mobley C. Brooks , Flythe Michael D. , Wen Yuan , McCarthy John J.
Published: June 2024

Regular exercise yields a multitude of systemic benefits, many of which may be mediated through the gut microbiome. Here, we report that cecal microbial transplants (CMTs) from exercise-trained vs. sedentary mice have modest benefits in reducing skeletal muscle atrophy using a mouse model of unilaterally hindlimb-immobilization. Direct administration of top microbial-derived exerkines from an exercise-trained gut microbiome preserved muscle function and prevented skeletal muscle atrophy.
Comprehensive Analysis of Juvenile Nasopharyngeal Angiofibromas via Whole Exome Sequencing
Authors: Kumari Kiran , Afroj Shariya , Madhry Deeksha , Verma Yash , Kairo Arvind K. , Thakar Alok , Sikka Kapil , Verma Hitesh , Verma Bhupendra
Published: June 2024

Objectives

The molecular basis and mechanisms of Juvenile Nasopharyngeal Angiofibromas (JNA) pathogenesis are still unknown. Despite being a rare and benign neoplasm, JNA is a locally aggressive and potentially destructive neoplasm among head and neck tumors, typically diagnosed in young males. The advancement of genome technologies and analytical tools has provided an unparalleled opportunity to explore the intricacy of JNA. The present study provides the first evidence of the involvement of chromosome Y genes in JNA.

Methods

Thirteen JNA patients at an advanced disease stage and 5 age-matched male controls were registered for this study. Whole-exome sequencing (WES) analysis was conducted followed by functional analysis to understand the molecular mechanism of the JNA.

Results

WES analysis revealed a high prevalence of mutations in 14 genes within the protein-coding, Male-Specific Region of the Y-chromosome of young males (mean age: 13.8 ± 2.4) with JNA. These mutations, occurring at 28 distinct positions, were characterized as moderate to high impact and were prevalent in 9 JNA patients but not in the control group. The most frequently mutated genes were USP9Y and UTY, followed by KDM5D, DDX3Y and TSPY4. The expression of USP9Y, UTY and DDX3Y was found to be co-modulated, implying their coordinated regulation as a complex. Furthermore, somatic mutations were detected in genes previously linked to JNA.

Conclusion

The wide array of genetic and somatic mutations identified in JNA provides novel insight into JNA pathophysiology.
Continent-wide drivers of spatial synchrony in age structure across wild great tit populations
Authors: Woodman Joe P. , Vriend Stefan J. G. , Adriaensen Frank , Álvarez Elena , Artemyev Alexander , Barba Emilio , Burgess Malcolm D. , Caro Samuel P. , Cauchard Laure , Charmantier Anne , Cole Ella F. , Dingemanse Niels , Doligez Blandine , Eeva Tapio , Evans Simon R. , Grégoire Arnaud , Lambrechts Marcel , Leivits Agu , Liker András , Matthysen Erik , Orell Markku , Park John S. , Rytkõnen Seppo , Senar Juan Carlos , Seress Gábor , Szulkin Marta , van Oers Kees , Vatka Emma , Visser Marcel E. , Firth Josh A. , Sheldon Ben C.
Published: June 2024

Spatio-temporal variation in age structure influences population dynamics, yet we have limited understanding of the spatial scale at which its fluctuations are synchronised between populations. Using 32 great tit populations, spanning 3200km and>130,000 birds across 67 years, we quantify spatial synchrony in breeding age structure and its drivers. We show that larger clutch sizes, colder winters and summers, and larger beech crops lead to younger populations. We report distant-dependent spatial synchrony of age structure, which is maintained at approximately 650km. Despite covariation with age structure, reproductive and environmental variables do not influence the scale of synchrony, except for a moderate effect of beech masting. We suggest that local ecological and density-dependent dynamics impact how environmental variation interacts with age structure, influencing estimates of the environment’s effect on spatial synchrony. Our analyses demonstrate the operation of synchrony in age structure over large scales, with implications for age-dependent demography in populations.
Dietary isoleucine content defines the metabolic and molecular response to a Western diet
Authors: Trautman Michaela E. , Green Cara L. , MacArthur Michael R. , Chaiyakul Krittisak , Alam Yasmine H. , Yeh Chung-Yang , Babygirija Reji , James Isabella , Gilpin Michael , Zelenovskiy Esther , Green Madelyn , Marshall Ryan N. , Sonsalla Michelle M. , Flores Victoria , Simcox Judith A. , Ong Irene M. , Malecki Kristen C. , Jang Cholsoon , Lamming Dudley W.
Published: June 2024

The amino acid composition of the diet has recently emerged as a critical regulator of metabolic health. Consumption of the branched-chain amino acid isoleucine is positively correlated with body mass index in humans, and reducing dietary levels of isoleucine rapidly improves the metabolic health of diet-induced obese male C57BL/6J mice. However, it is unknown how sex, strain, and dietary isoleucine intake may interact to impact the response to a Western Diet (WD). Here, we find that although the magnitude of the effect varies by sex and strain, reducing dietary levels of isoleucine protects C57BL/6J and DBA/2J mice of both sexes from the deleterious metabolic effects of a WD, while increasing dietary levels of isoleucine impairs aspects of metabolic health. Despite broadly positive responses across all sexes and strains to reduced isoleucine, the molecular response of each sex and strain is highly distinctive. Using a multi-omics approach, we identify a core sex- and strain-independent molecular response to dietary isoleucine, and identify mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype. Intriguingly, the metabolic effects of reduced isoleucine in mice are not associated with FGF21 – and we find that in humans plasma FGF21 levels are likewise not associated with dietary levels of isoleucine. Finally, we find that foods contain a range of isoleucine levels, and that consumption of dietary isoleucine is lower in humans with healthy eating habits. Our results demonstrate that the dietary level of isoleucine is critical in the metabolic and molecular response to a WD, and suggest that lowering dietary levels of isoleucine may be an innovative and translatable strategy to protect from the negative metabolic consequences of a WD.
Human skeletal muscle possesses an epigenetic memory of high intensity interval training
Authors: Pilotto AM , Turner DC , Crea E , Mazzolari R , Brocca L , Pellegrino MA , Miotti D , Bottinelli R , Sharples AP , Porcelli S
Published: June 2024

INTRODUCTION

Human skeletal muscle displays an epigenetic memory of resistance exercise induced by hypertrophy. It is unknown, however, whether high-intensity interval training (HIIT) also evokes an epigenetic muscle memory. This study employed repeated training intervention interspersed with a detraining period to assess epigenetic memory of HIIT.

METHODS

Twenty healthy subjects (25±5yrs) completed two HIIT interventions (training and retraining) lasting 2 months, separated by 3 months of detraining. Measurements at baseline, after training, detraining and retraining included maximal oxygen consumption (V̇O2max). Vastus lateralis biopsies were taken for genome-wide DNA methylation and targeted gene expression analyses. RESULTS: V̇O2maximproved during training and retraining (p<0.001) without differences between interventions (p>0.58). Thousands of differentially methylated positions (DMPs) predominantly demonstrated a hypomethylated state after training, retained even after 3-months exercise cessation and into retraining. Five genes; ADAM19, INPP5a, MTHFD1L, CAPN2, SLC16A3 possessed differentially methylated regions (DMRs) with retained hypomethylated memory profiles and increased gene expression. The retained hypomethylation during detraining was associated with an enhancement in expression of the same genes even after 3 months of detraining. SLC16A3, INPP5a, CAPN2 are involved in lactate transport and calcium signaling.

CONCLUSIONS

Despite similar physiological adaptations between training and retraining, memory profiles were found at epigenetic and gene expression level, characterized by retained hypomethylation and increased gene expression after training into long-term detraining and retraining. These genes were associated with calcium signaling and lactate transport. Whilst significant memory was not observed in physiological parameters, our novel findings indicate that human skeletal muscle possesses an epigenetic memory of HIIT.
High-dimensional multi-omics measured in controlled conditions are useful for maize platform and field trait predictions
Authors: Baber Ali , Bertrand Huguenin-Bizot , Maxime Laurent , François Chaumont , Maistriaux Laurie C , Stéphane Nicolas , Hervé Duborjal , Claude Welcker , François Tardieu , Tristan Mary-Huard , Laurence Moreau , Alain Charcosset , Daniel Runcie , Renaud Rincent
Published: June 2024

The effects of climate change in the form of drought, heat stress, and irregular seasonal changes threaten global crop production. The ability of multi-omics data, such as transcripts and proteins, to reflect a plant’s response to such climatic factors can be capitalized in prediction models to maximize crop improvement. Implementing multi-omics characterization in routine field evaluations is challenging due to high costs. It is, however, possible to do it on reference genotypes in controlled conditions. Using omics measured on a platform, we tested different multi-omics-based prediction approaches, with and without pedo-climatic data, using a high dimensional linear mixed model (MegaLMM) to predict genotypes for platform traits and agronomic field traits in a hybrid panel of 244 maize Dent lines crossed to a Flint tester. We considered two prediction scenarios: in the first one, new hybrids are predicted (CV1), and in the second one, partially observed hybrids are predicted (CV2). For both scenarios, all hybrids were characterized for omics on the platform. We observed that omics can predict both additive and non-additive genetic effects for the platform traits, resulting in much higher predictive abilities than GBLUP. This highlights their efficiency in capturing regulation processes in relation to the growth conditions. For the field traits, we observed that only the additive components of omics were useful and only slightly improved predictive abilities for predicting new hybrids (CV1, model MegaGAO) and for predicting partially observed hybrids (CV2, model GAOxW-BLUP) in comparison to GBLUP. We conclude that measuring the omics in the fields would be of considerable interest for predicting productivity, if the omics costs were to drop significantly. Our study confirms the potential of omics to predict additive and non-additive genetic effects, resulting in a potentially high increase in predictive abilities compared to standard genomic prediction models.

Key Message

Transcriptomics and proteomics information collected on a platform can predict additive and non-additive effects for platform traits and additive effects for field traits.
Systemic mRNA transport depends on m5C methylation, nuclear mRNA export factors and developmental phase changes
Authors: Xu Ying , Székely András , Ostendorp Steffen , Gupta Saurabh , Tomkins Melissa , Yang Lei , Apelt Federico , Zhao Yan , Mavrothalassiti Eleni , Wansing Linda , Kehr Julia , Saplaoura Eleftheria , Kragler Friedrich
Published: June 2024

In Arabidopis a high number of distinct mRNAs move from shoot to root. We previously reported on the correlation of m5C-methylation and lack of mRNA transport in juvenile plants depending on the RNA methyltransferasesDNMT2 NSUN2B. However, to our surprise we uncovered that lack ofDNMT2 NSUN2B(writer) activity did not abolished transport ofTCTP1andHSC70.1transcripts in flowering plants. We uncovered that transport of both transcripts is reinstated indnmt2 nsun2bmutants after commitment to flowering. This finding suggests that additional factors are seemingly involved in regulating / mediating mRNA transport. In search of such candidates, we identified the two ALY2 and ALY4 nuclear mRNA export factors belonging to the ALYREF family as bona fide m5C readers mediating mRNA transport. We show that both proteins are allocated along the phloem and that they bind preferentially to mobile mRNAs. MST measurements indicate that ALY2 and ALY4 bind to mobile mRNAs with relative high affinity with ALY4 showing higher affinity towards m5C-methylated mobile mRNAs. An analysis of the graft-mobile transcriptome of juvenile heterografted-grafted wild type,dnmt2 nsun2b,aly2andaly4mutants revealed that the nuclear export factors are key regulators of mRNA transport. We suggest that depending on the developmental stage m5C methylation has a negative and positive regulatory function in mRNA transport and acts together with ALY2 and ALY4 to facilitate mRNA transport in both juvenile and flowering plants.
TMAO miscompartmentalization is a reversible driver of autism pathophysiology
Authors: Launay Jean-Marie , Vodovar Nicolas
Published: June 2024

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder. Contrary to what has been reported for genetics and gut dysbiosis, ASD appears to be very homogeneous when considering tryptophan metabolism. Indeed, multiple biochemical anomalies have been observed in most individuals with ASD. Following up on these findings, we found that ASD is strongly associated with the miscompartmentalization of the chemical chaperone trimethylamineN-oxide (TMAO). Intracellular TMAO was markedly reduced in individuals with ASD as a result of altered fluid/electrolyte homeostasis and was responsible for numerous biochemical anomalies described in ASD. Administration of urea in a rat model of ASD that recapitulates the biochemical anomalies observed in humans not only restored biochemical parameters but also broadly improved all behaviours. Our results demonstrate the major role of TMAO in the pathophysiology of ASD and cellular physiology, although TMAO miscompartmentalization is not causal for ASD. We anticipate that urea, which is already clinically approved, offers a breakthrough therapeutic opportunity for ASD.
Lessons from combined metabolic model of mesophyll and guard cells
Authors: Sarkar Devlina , Kundu Sudip
Published: June 2024

Understanding of overall metabolisms of guard cell (GC) and mesophyll cell (MC), their possible interactions and roles in stomatal movement will help in designing crop plants with higher water use efficiencies. Although, previous constraint based modelling and analyses correctly predicted some known metabolic patterns of isolated C3MC, GC and Crassulacean Acid Metabolism (CAM) MC, quantitative estimations of combined metabolism of GC and MC and detailed analysis of GC metabolism in CAM are still awaiting. A six phase diel combined model of GC and MC is constructed integrating existing models of two different cell types with necessary modifications guided by known physiology. It is used to predict the similarities and dissimilarities of GC and MC metabolisms. In addition to previously predicted results, analysis of this new two-cell model successfully shows higher activities of some experimentally observed C4like enzymes in GC than MC in C3, the possible storage patterns of the osmolytes like K+, malate2-, sucrose etc., in CAM GC. Results also show different patterns of starch synthesis and accumulation, ATP production and utilization in GC and MC of C3and CAM. This combined model integrates stomatal opening, gaseous exchange and GC-MC metabolisms. It is a significant step towards understanding and quantitative estimation of the whole leaf tissue metabolism linking gaseous exchange with environment.

Significance statement

Our time-resolved combined metabolic model of guard and mesophyll cells integrates stomatal opening, gaseous exchange and cellular metabolisms in C3, CAM and partial CAM conditions; their analyses provide quantitative estimations of metabolic fluxes, ATP production and utilization, and different metabolic patterns of starch synthesis and accumulation of both the cells. It is a significant step towards understanding and quantitative estimation of the whole leaf tissue metabolism linking gaseous exchange with environment and phloem loading.
Efficient Seeding for Error-Prone Sequences with SubseqHash2
Authors: Li Xiang , Chen Ke , Shao Mingfu
Published: June 2024

Seeding is an essential preparatory step for large-scale sequence comparisons. Substring-based seeding methods such as kmers are ideal for sequences with low error rates but struggle to achieve high sensitivity while maintaining a reasonable precision for error-prone long reads. SubseqHash, a novel subsequence-based seeding method we recently developed, achieves superior accuracy to substring-based methods in seeding sequences with high mutation/error rates, while the only drawback is its computation speed. In this paper, we propose SubseqHash2, an improved algorithm that can compute multiple sets of seeds in one run by definingkorders over all length-ksubsequences and identifying the optimal subsequence under each of thekorders in a single dynamic programming framework. The algorithm is further accelerated using SIMD instructions. SubseqHash2 achieves a 10-50×speedup over repeating SubseqHash while maintaining the high accuracy of seeds. We demonstrate that SubseqHash2 drastically outperforms popular substring-based methods including kmers, minimizers, syncmers, and Strobemers for three fundamental applications. In read mapping, SubseqHash2 can generate adequate seed-matches for aligning hard reads that minimap2 fails on. In sequence alignment, SubseqHash2 achieves high coverage of correct seeds and low coverage of incorrect seeds. In overlap detection, seeds produced by SubseqHash2 lead to more correct overlapping pairs at the same false-positive rate. With all the algorithmic breakthroughs of SubseqHash2, we clear the path for the wide adoption of subsequence-based seeds in long-read analysis. SubseqHash2 is available athttps://github.com/Shao-Group/SubseqHash2.
How Error Correction Affects PCR Deduplication: A Survey Based on UMI Datasets of Short Reads
Authors: Ping Pengyao , Lan Tian , Su Shuquan , Liu Wei , Li Jinyan
Published: June 2024

Next-Generation Sequencing (NGS) data is widely utilised for various downstream applications in bioinformatics, and numerous techniques have been developed forPCR-deduplicationanderror-correctionto eliminate bias and errors introduced during the sequencing. This study first-time provides a joint overview of recent advances in PCR-deduplication and error-correction on short reads. In particular, we utilise UMI-based PCR-deduplication strategies and sequencing data to assess the performance of the solely-computational PCR-deduplication approaches and investigate how error correction affects the performance of PCR-deduplication. Our survey and comparative analysis reveal that the deduplicated reads generated by the solely-computational PCR-deduplication and error-correction methods exhibit substantial differences and divergence from the sets of reads obtained by the UMI-based deduplication methods. The existing solely-computational PCR-deduplication and error-correction tools can eliminate some errors but still leave hundreds of thousands of erroneous reads uncorrected. All the error-correction approaches raise thousands or more new sequences after correction which do not have any benefit to the PCR-deduplication process. Upon these discoveries, we offer practical suggestions to enhance the existing computational approaches for improving the quality of short-read sequencing data.
Development and Validation of the School in China REfusal EvaluatioN Scale (SCREEN): A Tool to Assess School Refusal in Chinese Adolescents
Authors: Xie Mingzhi , Bie Xiaoyuan , Sun Ye , Lu Guibin , Shu Peng , Wang Yingyu , Liu Mingming
Published: June 2024

The escalating phenomenon of school refusal (SR) in China has emerged as a significant psychological and educational crisis, with recent surveys revealing a disengagement rate exceeding 70% among students in primary and secondary education. This study introduces the novel School in China REfusal EvaluatioN Scale (SCREEN), specifically designed to assess the multifaceted nature of SR in the Chinese educational context, incorporating culturally relevant socio-psychological variables. Through a robust methodological framework, this research develops and validates the SCREEN, involving the generation and validation of an item pool followed by exploratory and confirmatory factor analyses. The reliability of the SCREEN was affirmed with a Cronbach’s alpha of 0.778, and its validity confirmed through satisfactory factor loadings across multiple dimensions of school engagement. The study’s findings highlight the prevalence and complexity of SR across various educational stages, emphasizing the necessity for holistic intervention strategies that address educational, familial, and societal contributors to SR. The SCREEN’s effectiveness in identifying specific psychological factors contributing to SR underscores the potential for targeted interventions and educational reforms tailored to the unique needs of Chinese students. This research not only contributes to the academic understanding of SR but also provides a practical tool for early detection and intervention, advocating for an integrated approach involving educators, psychologists, and families to mitigate this educational challenge. Future research should focus on longitudinal studies to evaluate intervention efficacy and further refine assessment tools for broader application.
An implantable biohybrid nerve model towards synaptic deep brain stimulation
Authors: Sifringer Léo , Fratzl Alex , Clément Blandine F. , Chansoria Parth , Mönkemöller Leah S. , Duru Jens , Ihle Stephan J. , Steffens Simon , Beltraminelli Anna , Ceylan Eylul , Hengsteler Julian , Maurer Benedikt , Weaver Sean M. , Tringides Christina M. , Vulić Katarina , Madduri Srinivas , Zenobi-Wong Marcy , Roska Botond , Vörös János , Ruff Tobias
Published: June 2024

Restoring functional vision in blind patients lacking a healthy optic nerve requires bypassing retinal circuits, ideally, by directly stimulating the visual thalamus. However, available deep brain stimulation electrodes do not provide the resolution required for vision restoration. We developed an implantable biohybrid nerve model designed for synaptic stimulation of deep brain targets. The interface combines a stretchable stimulation array with an aligned microfluidic axon guidance system seeded with neural spheroids to facilitate the development of a 3 mm long nerve-like structure. A bioresorbable hydrogel nerve conduit was used as a bridge between the tissue and the biohybrid implant. We demonstrated stimulation of spheroids within the biohybrid structurein vitroand used high-density CMOS microelectrode arrays to show faithful activity conduction across the device. Finally, implantation of the biohybrid nerve onto the mouse cortex showed that neural spheroids grow axonsin vivoand remain functionally active for more than 22 days post-implantation.
Present and future suitability of invasive and urban vectors through an environmentally-driven Mosquito Reproduction Number
Authors: Pardo-Araujo Marta , Eritja Roger , Alonso David , Bartumeus Frederic
Published: June 2024

1

Temperature and water availability significantly influence mosquito population dynamics. We’ve devised a method, integrating experimental data with insights from mosquito and thermal biology, to calculate the basic reproduction number (RM) for urban mosquito species,Aedes albopictusandAedes aegypti.RMrepresents the number of female mosquitoes produced by one female during her lifespan, indicating suitability for growth. Environmental conditions, including temperature, rainfall and human density influenceRMby altering key mosquito life cycle traits. Validation using data from Spain and Europe confirms the approach’s reliability. Our analysis suggests that temperature increases may not uniformly benefitAe. albopictusproliferation but could boostAe. aegyptiexpansion. We suggest using vectorRMmaps, leveraging climate and environmental data, to predict areas susceptible to invasive mosquito population growth. These maps aid in resource allocation for intervention strategies, supporting effective vector surveillance and management efforts.
Distinct Excitability Properties of Cardiac Calbindin Neurons: Identifying a Unique Neuronal Population
Authors: Lizot G. , Bescond J. , De Koninck Y. , Chahine M. , Bois P. , Faivre J-F. , Chatelier A.
Published: June 2024

The intrinsic cardiac nervous system is a complex system that plays a critical role in the regulation of cardiac physiological parameters and has been shown to contribute to cardiac arrhythmias. To date, several types of neurons with distinct neurochemical and electrophysiological phenotypes have been identified. However, no study has correlated the neurochemical phenotype to a specific electrophysiological behavior. Calbindin-D28k, a calcium binding protein, is expressed in numerous cardiac neurons. Given that changes in neuronal excitability have been associated with arrhythmia susceptibility and that calbindin expression has been associated with modulations of neuronal excitability, our objective is to assess whether the cardiac calbindin neuronal population has specific properties that could be involved in cardiac modulation and arrhythmias. By using a Cre-Lox mouse model to specifically target calbindin neurons with a fluorescent reporter, we characterized the neurochemical and the electrophysiological phenotype of this cardiac neuronal population. Calbindin neurons exhibit a specific neurochemical profile and a larger soma with shorter neurite length compared to other neurons. This was combined with a distinct electrophysiological signature characterized by a lower excitability with a predominantly phasic profile associated to a lower N-type calcium current density. These properties resemble to the cardiac neuronal remodeling observed in pathologies such as type II diabetes and heart failure. Therefore, we believe that this specific neuronal population deserves investigations in the context of these pathologies.
Coral hosts actively accumulate inorganic carbon for Symbiodiniaceae to maintain symbiotic relationships
Authors: Zhang Boya , Tang Si , Liu Lu , Xu Meiting , Liu Yaqing , Zhu Jianming , Xiao Weimin , Bi Hongsheng , Zhou Jin , Benfield Mark C. , Cai Zhonghua
Published: June 2024

High primary productivity of coral reefs is widely attributed to the mutualistic symbiosis between coral hosts and their microalgal partners (Symbiodiniaceae). Although the mechanisms maintaining this symbiosis have been considerable investigated, how the symbiont microalgae within coral get sufficient CO2for photosynthesis still remains inadquately explored. Here, we hypothesized that corals may actively accumulate dissolved inorganic carbon (DIC) for microalgae to maintain the symbiosis. Carbon (HCO3-and glucose) supply and consumption were evaluated in the scleractinian coral (Goniopora lobata) and its symbiont under light and dark conditions. Results suggest that Symbiodiniaceae were high DIC consumers, requiring about 2-3 fold more DIC than free-living species. The corals were high DIC producers, with internal concentrations up to 4.2 fold higher than in the surrounding seawater. In the absence of microalgae utilization, the excess DIC they produced appeared detrimental to their own growth. Moreover, transcriptomic analysis identified several DIC enrichment pathways are evolved in corals to attact the Symbiodiniaceae, including CO2concentrating mechanisms, respiration, calcification and phosphoenolpyruvate carboxylase. Increased the CO2dosage in seawater may induce coral symbiosis bleaching. Our findings can deeper reveal on the mechanisms sustaining coral symbiosis, and may help to predict how some corals respond to DIC imbalance under climate changes.
AKT2 modulates astrocytic nicotine responsesin vivo
Authors: Lombardi Andrew M. , Wong Helen , Bower Myra E. , Milstead Ryan , Borski Curtis , Schmitt Emily , Griffioen Mina , LaPlante Lauren , Ehringer Marissa A. , Stitzel Jerry , Hoeffer Charles A.
Published: June 2024

A better understanding of nicotine neurobiology is needed to reduce or prevent chronic addiction, ameliorate the detrimental effects of nicotine withdrawal, and increase successful cessation of use. Nicotine binds and activates two astrocyte-expressed nicotinic acetylcholine receptors (nAChRs), α4β2 and α7. We recently found thatProtein kinase B-β (Pkb-β orAkt2) expression is restricted to astrocytes in mice and humans. To determine if AKT2 plays a role in astrocytic nicotinic responses, we generated astrocyte-specificAkt2conditional knockout (cKO) and fullAkt2KO mice forin vivoandin vitroexperiments. Forin vivostudies, we examined mice exposed to chronic nicotine for two weeks in drinking water (200 μg/mL) and following acute nicotine challenge (0.09, 0.2 mg/kg) after 24 hrs. Ourin vitrostudies used cultured mouse astrocytes to measure nicotine-dependent astrocytic responses. We validated our approaches using lipopolysaccharide (LPS) exposure inducing astrogliosis. Sholl analysis was used to measure glial fibrillary acidic protein responses in astrocytes. Our data show that wild-type (WT) mice exhibit increased astrocyte morphological complexity during acute nicotine exposure, with decreasing complexity during chronic nicotine use, whereasAkt2cKO mice showed increased astrocyte morphology complexity. In culture, we found that 100μM nicotine was sufficient for morphological changes and blocking α7 or α4β2 nAChRs prevented observed morphologic changes. Finally, we performed conditioned place preference (CPP) inAkt2cKO mice and found that astrocytic AKT2 deficiency reduced nicotine preference compared to controls. These findings show the importance of nAChRs andAkt2signaling in the astrocytic response to nicotine.

Main Points

Nicotine regulates astrogliosisin vivo: acute exposure boosts complexity; chronic exposure diminishes it.

AKT2, expressed in astroglia, modulates morphological changes in response to nicotine and nicotine-dependent conditioned place preference.
Phase-separating MoSpa2 Complex Organizes Actin Nucleation Center forM.oryzaePlant Infection
Authors: He Danxia , Li Yuanbao , Ma Qianqian , Han Libo , Tang Dingzhong , Miao Yansong
Published: June 2024

Polarized actin cable from Spitzenkörper at the hyphal tip fuels filamentous growth in diverse biphasic fungal pathogens. This multi-component complex, featuring the actin nucleator Bni1 and other factors, initiates actin polymerization, guiding biphasic fungal growth and host infection. How dynamic assembly of Spitzenkörper and actin cable are achieved to support filamentous fungi that undergo multistage morphogenesis for host invasion remains unclear, includingMagnaporthe oryzae, which undergoes multistage morphological transition during rice infection. Here, we identified that the scaffolder MoSpa2 remodeling actin cable networks, in space and time, by assembling the polarisome complex via phase separation, supportingMagnaporthe oryzae’s polarized growth. Via N-terminal intrinsically disordered regions (IDRs), MoSpa2 first stimulates actin cable assembly through multivalent interactions with MoBni1 nucleator, and then also creates polarized actin cable bundles by F-actin association and a concurrent inhibition of cofilin-mediated F-actin depolymerization. MoSpa2 mutants exhibit impaired hyphal growth and reduced rice infection, underling its significance. This work elucidates the fundamental mechanisms underlying fungal morphogenesis, offering the potential for targeted interventions in pathogenesis.
Striatal cholinergic interneuron pause response requires Kv1 channels, is absent in dyskinetic mice, and is restored by dopamine D5 receptor inverse agonism
Authors: Tubert C , Paz RM , Stahl AM , Rela L , Murer MG
Published: June 2024

Striatal cholinergic interneurons (SCIN) exhibit pause responses conveying information about rewarding events, but the mechanisms underlying them remain elusive. Thalamic inputs induce a pause mediated by intrinsic mechanisms and regulated by dopamine D2 receptors, though the underlying membrane currents are unknown. Moreover, the role of D5 receptors (D5R) has not been addressed so far. We performed ex vivo studies that show that glutamate released by thalamic inputs in the dorsolateral striatum induces a burst in SCIN, followed by the activation of a Kv1-dependent delayed rectifier current responsible for the pause. Endogenous dopamine promotes the pause through D2R stimulation, while pharmacological stimulation of D5R suppresses it. Remarkably, the pause response is absent in parkinsonian mice rendered dyskinetic by chronic L-DOPA treatment but can be reinstated acutely by the inverse D5R agonist clozapine. Blocking the Kv1 current eliminates the pause reinstated by the D5R inverse agonist. In conclusion, the pause response is mediated by delayed rectifier Kv1 channels, which are tonically blocked in dyskinetic mice by a mechanism depending on D5R ligand-independent activity. Targeting these alterations may have therapeutic value in Parkinson’s disease.

Highlights

In brain slices, thalamostriatal input triggers a burst followed by a pause in SCIN.

Kv1, but not Kv7 or Kir2.2 channels, are necessary for the expression of the pause.

D2R stimulation promotes, and D5R stimulation inhibits the pause.

Thalamic bursts are not followed by a pause in SCIN from dyskinetic mice.

D5R inverse agonism restores a Kv1-dependent pause response in dyskinetic mice.
Frequency of antimicrobial-resistant bloodstream infections in Thailand, 2022
Authors: Tuamsuwan Krittiya , Chamawan Panida , Boonyarit Phairam , Srisuphan Voranadda , Klaytong Preeyarach , Rangsiwutisak Chalida , Wannapinij Prapass , Fongthong Trithep , Stelling John , Turner Paul , Limmathurotsakul Direk
Published: June 2024

Objectives

To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand

Methods

We analyzed data from 2022, generated by 111 public hospitals in health regions 1 to 12, using the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS) and submitted to the Ministry of Public Health, Thailand. Multilevel Poisson regression models were used.

Results

The most common cause of community-origin AMR BSI was third-generation cephalosporin-resistantEscherichia coli(3GCREC, 65.6%; 5,101/7,773 patients) and of hospital-origin AMR BSI was carbapenem-resistantAcinetobacter baumannii(CRAB, 51.2%, 4,968/9,747 patients). The percentage of patients tested for BSI was negatively associated with the frequency of community-origin 3GCREC BSI and hospital-origin CRAB BSI. Hospitals in health regions 4 (lower central) had the highest frequency of community-origin 3GCREC BSI per 100,000 tested patients (adjusted incidence rate ratio, 2.06; 95% confidence interval: 1.52-2.97). Health regions were not associated with the frequency of hospital-origin CRAB BSI, although between-hospital variation was high even adjusting for hospital level and size.

Conclusion

The high between-hospital variation of hospital-origin CRAB BSI suggests the importance of hospital-specific factors. Our approach and findings highlight health regions and hospitals where actions against AMR infection, including antimicrobial stewardship and infection control, should be prioritized.

Highlights

The frequency of AMR BSI in 111 public hospitals in Thailand in 2022 was studied.

The frequency of community-origin 3GCREC BSI was different by regions.

The frequency of hospital-origin CRAB BSI varied greatly among hospitals.

Underuse of BC was associated with the higher frequency of AMR BSI per tested patients.

Our findings contributed to actions against AMR at local and national levels.
Inferring genetic variant causal networks by leveraging pleiotropy
Authors: Tournaire Martin , Nouira Asma , Favre Moiron Mario , Rozenholc Yves , Verbanck Marie
Published: June 2024

Genetic variants have been associated with multiple traits through genome-wide association studies (GWASs), but pinpointing causal variants and their mechanisms remains challenging. Molecular phenotypes, such as eQTLs, are routinely used to interpret GWAS results. However, much concern has recently been raised about their weak overlap. Taking the opposite approach with PRISM (Pleiotropic Relationships to Infer the SNP Model), we leverage pleiotropy to pinpoint direct effects and build variant causal networks. PRISM clusters variant-trait effects into trait-mediated, confounder-mediated, and direct effects, and builds individual variant causal networks by cross-referencing results from all traits. In simulations, PRISM demonstrated high precision in identifying direct effects and reconstructing causal networks. Applying PRISM to 61 traits and diseases from UK Biobank, we found that direct effects accounted for less than 13% of significant effects, yet were highly enriched in heritability. Multiple lines of evidence showed that PRISM causal networks are consistent with established biological mechanisms.