bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroactive nanoinjection platform for intracellular delivery and gene silencing
Authors: Shokouhi Ali-Reza , Chen Yaping , Yoh Hao Zhe , Murayama Takahide , Suu Koukou , Morikawa Yasuhiro , Brenker Jason , Alan Tuncay , Voelcker Nicolas H. , Elnathan Roey
Published: August 2023

Background

Nanoinjection—the process of intracellular delivery using vertically configured nanostructures—is a physical route that efficiently negotiates the plasma membrane, with minimal perturbation and toxicity to the cells. Nanoinjection, as a physical membrane-disruption-mediated approach, overcomes challenges associated with conventional carrier-mediated approaches such as safety issues (with viral carriers), genotoxicity, limited packaging capacity, low levels of endosomal escape, and poor versatility for cell and cargo types. Yet, despite the implementation of nanoinjection tools and their assisted analogues in diverse cellular manipulations, there are still substantial challenges in harnessing these platforms to gain access into cell interiors with much greater precision without damaging the cell’s intricate structure. Here, we propose a non-viral, low-voltage, and reusable electroactive nanoinjection (ENI) platform based on vertically configured conductive nanotubes (NTs) that allows for rapid influx of targeted biomolecular cargos into the intracellular environment, and for successful gene silencing. The localization of electric fields at the tight interface between conductive NTs and the cell membrane drastically lowers the voltage required for cargo delivery into the cells, from kilovolts (for bulk electroporation) to only ≤ 10 V; this enhances the fine control over membrane disruption and mitigates the problem of high cell mortality experienced by conventional electroporation.

Results

Through both theoretical simulations and experiments, we demonstrate the capability of the ENI platform to locally perforate GPE-86 mouse fibroblast cells and efficiently inject a diverse range of membrane-impermeable biomolecules with efficacy of 62.5% (antibody), 55.5% (mRNA), and 51.8% (plasmid DNA), with minimal impact on cells’ viability post nanoscale-EP (> 90%). We also show gene silencing through the delivery of siRNA that targets TRIOBP, yielding gene knockdown efficiency of 41.3%.

Conclusions

We anticipate that our non-viral and low-voltage ENI platform is set to offer a new safe path to intracellular delivery with broader selection of cargo and cell types, and will open opportunities for advanced ex vivo cell engineering and gene silencing.

Graphical abstract
Cerebrospinal fluid levels of neuroinflammatory biomarkers are increased in athletes with persistent post-concussive symptoms following sports-related concussion
Authors: Gard Anna , Vedung Fredrik , Piehl Fredrik , Khademi Mohsen , Wernersson Maria Portonova , Rorsman Ia , Tegner Yelverton , Pessah-Rasmussen Hélène , Ruscher Karsten , Marklund Niklas
Published: August 2023

A sports-related concussion (SRC) is often caused by rapid head rotation at impact, leading to shearing and stretching of axons in the white matter and initiation of secondary inflammatory processes that may exacerbate the initial injury. We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS preventing sports participation as well as limiting work, school and/or social activities for ≥ 6 months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Following a spinal tap, we analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age- and sex-matched controls exercising ≤ 2 times/week at low-to-moderate intensity. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17 months prior to the investigation. CSF cytokines and chemokines levels were significantly increased in eight (IL-2, TNF-α, IL-15, TNF-β, VEGF, Eotaxin, IP-10, and TARC), significantly decreased in one (Eotaxin-3), and unaltered in 16 in SRC athletes when compared to controls, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (Z < − 1.5) on cognitive testing. Individual biomarker concentrations did not strongly correlate with symptom rating or cognitive function. Limitations include evaluation at a single post-injury time point in relatively small cohorts, and no control group of concussed athletes without persisting symptoms was included. Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.
Third-party intervention and post-conflict behaviour in agonistic encounters of pigs (Sus scrofa)
Authors: Maffezzini Nicole , Turner Simon P. , Bolhuis J. Elizabeth , Arnott Gareth , Camerlink Irene
Published: August 2023

Background

Third-party interference in agonistic contests entails a deliberate intervention in an ongoing fight by a bystanding individual (third party) and may be followed by post-conflict social behaviour to provide support to a specific individual. The mechanisms behind third-party intervention are, however, still largely understudied. The aim of this study was to investigate third-party interference, with the predictions that (1) the interferer derives benefits from its action by winning a fight, (2) that patterns of intervention depend on familiarity, (3) that dyadic fights last longer than triadic fights, and (4) that interferers engage in non-agonistic social behaviours afterwards. Pre-pubertal pigs (Sus scrofa) (n = 384) were grouped with one familiar and four unfamiliar conspecifics (all non-kin) to elicit contests for dominance rank. Third-party interference was analysed for the first 30 min after grouping, along with the behaviour (nosing or aggression), contest duration, contest outcome, and interferer behaviour after the fight (post-conflict social behaviour).

Results

Three types of interference were observed: non-agonistic involvement (nose contact) by the interferer in a dyadic fight; a triadic fight with each of three contestants fighting one opponent at a time; and triadic fights with two opponents jointly attacking the third one (two-against-one fights). The likelihood of a third-party intervention to occur did not depend on the presence of a familiar animal in the fight. However, once intervention was triggered, interferers attacked unfamiliar fight initiators more than familiar ones. Two-against-one fights lasted longer than other triadic fights and occurred more often when both initial contestants were females. Results of 110 triadic fights (out of 585 fights in total) revealed that interferers were more likely to win compared to the initial opponents at equal body weight. The most common post-conflict behaviour displayed by the interferer was agonistic behaviour towards another group member, independently of familiarity.

Conclusions

The general lack of discrimination for familiarity suggests interference is not driven by support to familiar individuals in pigs. The results show that intervening in an ongoing fight gives the interferer a high chance of contest success and may be a strategy that is beneficial to the interferer to increase its dominance status.
Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study
Authors: Sun Yan-Qun , Chen Jin-Jin , Liu Mei-Chen , Zhang Yuan-Yuan , Wang Tao , Che Tian-Le , Li Ting-Ting , Liu Yan-Ning , Teng Ai-Ying , Wu Bing-Zheng , Hong Xue-Geng , Xu Qiang , Lv Chen-Long , Jiang Bao-Gui , Liu Wei , Fang Li-Qun
Published: August 2023

Background

Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking.

Methods

We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 − 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined.

Results

As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89–6.71), Brazil (3.45, 95% CI: 1.62–7.00) and the United States (2.44, 95% CI: 1.62–3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland.

Conclusions

The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.
Effectiveness of bladder filling control during online MR-guided adaptive radiotherapy for rectal cancer
Authors: Feng Xi , Tang Bin , Yao Xinghong , Liu Min , Liao Xiongfei , Yuan Ke , Peng Qian , Orlandini Lucia Clara
Published: August 2023

Background

Magnetic resonance-guided adaptive radiotherapy (MRgART) treatment sessions at MR-Linac are time-consuming and changes in organs at risk volumes can impact the treatment dosimetry. This study aims to evaluate the feasibility to control bladder filling during the rectum MRgART online session and its effectiveness on plan dosimetry.

Methods

A total of 109 online adaptive sessions of 24 rectum cancer patients treated at Unity 1.5 T MR-Linac with a short course radiotherapy (25 Gy, 5 Gy × 5) for whom the adaptive plan was optimized and recalculated online based on the daily magnetic resonance imaging (MRI) were analysed. Patients were fitted with a bladder catheter to control bladder filling; the bladder is emptied and then partially filled with a known amount of saline at the beginning and end of the online session. A first MRI ($${\mathrm{MRI}}_{\mathrm{i}}$$

MRI
i

) acquired at the beginning of the session was used for plan adaptation and the second ($${\mathrm{MRI}}_{\mathrm{f}}$$

MRI
f

) was acquired while approving the adapted plan and rigidly registered with the first to ensure the appropriateness of the isodoses on the ongoing delivery treatment. For each fraction, the time interval between the two MRIs and potential bladder changes were assessed with independent metrics, and the impact on the plan dosimetry was evaluated by comparing target and organs at risk dose volume histogram cut-off points of the plan adapted on $${\mathrm{MRI}}_{\mathrm{i}}$$

MRI
i

and recalculated on $${\mathrm{MRI}}_{\mathrm{f}}$$

MRI
f

.

Results

Median bladder volume variations, DSC, and HD of 8.17%, 0.922, and 2.92 mm were registered within a median time of 38 min between $${\mathrm{MRI}}_{\mathrm{i}}$$

MRI
i

and $${\mathrm{MRI}}_{\mathrm{f}}$$

MRI
f

; dosimetric differences < 0.65% were registered for target coverage, and < 0.5% for bladder, small bowel and femoral heads constraints, with a p value > 0.05.

Conclusion

The use of a bladder filling control procedure can help ensure the dosimetric accuracy of the online adapted treatment delivered.
Physiological effects of awake prone position in acute hypoxemic respiratory failure
Authors: Grieco Domenico Luca , Delle Cese Luca , Menga Luca S. , Rosà Tommaso , Michi Teresa , Lombardi Gianmarco , Cesarano Melania , Giammatteo Valentina , Bello Giuseppe , Carelli Simone , Cutuli Salvatore L. , Sandroni Claudio , De Pascale Gennaro , Pesenti Antonio , Maggiore Salvatore M. , Antonelli Massimo
Published: August 2023

Background

The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure.

Methods

Fifteen patients with acute hypoxemic respiratory failure and PaO2/FiO2 < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔPES), transpulmonary driving pressure (ΔPL), respiratory rate and esophageal pressure simplified pressure–time product per minute (sPTPES) by esophageal manometry, tidal volume (VT), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (VT/EELI) and pendelluft extent through electrical impedance tomography.

Results

Compared to supine position, prone position increased PaO2/FiO2 (median [Interquartile range] 104 mmHg [76–129] vs. 74 [69–93], p < 0.001), reduced respiratory rate (24 breaths/min [22–26] vs. 27 [26–30], p = 0.05) and increased ΔPES (12 cmH2O [11–13] vs. 9 [8–12], p = 0.04) with similar sPTPES (131 [75–154] cmH2O s min−1 vs. 105 [81–129], p > 0.99) and ΔPL (9 [7–11] cmH2O vs. 8 [5–9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmH2O s arbitrary units−3 [4–11] vs. 6 [4–9], p = 0.05; 0.53 s [0.32–61] vs. 0.40 [0.37–0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414–8547] vs. 1456 [959–2420], p = 0.002) and promoted VT distribution towards dorsal lung regions without affecting VT size and lung compliance: this generated lower dynamic strain (0.21 [0.16–0.24] vs. 0.38 [0.30–0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7–57] of VT in prone vs. 31% [14–55] in supine position, p > 0.99).

Conclusions

Prone position improves oxygenation, increases EELI and promotes VT distribution towards dependent lung regions without affecting VT size, ΔPL, lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔPES because of positional increases in airway resistance and prolonged expiratory time. Because high ΔPES is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔPES.

Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017.
Statistical analysis plan for a randomized controlled trial examining pedometer-based walking intervention in patients with heart failure with reduced ejection fraction: the WATCHFUL trial
Authors: Vetrovsky Tomas , Siranec Michal , Frybova Tereza , Gant Iulian , Semerad Miroslav , Miklikova Marie , Bunc Vaclav , Vesely Jiri , Stastny Jiri , Griva Martin , Precek Jan , Pelouch Radek , Parenica Jiri , Jarkovsky Jiri , Belohlavek Jan
Published: August 2023

Background

Physical activity is an effective management strategy for heart failure with reduced ejection fraction, but patients’ compliance is challenging. Walking is a suitable form of physical activity due to its convenience and sustainability, and it can potentially improve functional capacity in heart failure patients.

Objectives

The WATCHFUL trial aims to determine whether a pedometer-based walking intervention combined with face-to-face sessions and regular telephone contact improves functional capacity in heart failure patients.

Methods

The WATCHFUL trial is a 6-month multicenter, parallel-group, randomized, controlled, superiority trial with a 6-month follow-up. A total of 202 patients were recruited for the trial. The primary analysis will evaluate the change in distance walked during the 6-min walk test from baseline to 6 months based on the intention-to-treat population; the analysis will be performed using a linear mixed-effect model adjusted for baseline values. Missing data will be imputed using multiple imputations, and the impact of missing data will be assessed using a sensitivity analysis. Adverse events are monitored and recorded throughout the trial period.

Discussion

The trial has been designed as a pragmatic trial with a scalable intervention that could be easily translated into routine clinical care. The trial has been affected by the COVID-19 pandemic, which slowed patients’ recruitment and impacted their physical activity patterns.

Conclusions

The present publication provides details of the planned statistical analyses for the WATCHFUL trial to reduce the risks of reporting bias and erroneous data-driven results.

Trial registration

ClinicalTrials.gov (identifier: NCT03041610, registered: 3/2/2017).
Remodeling of the 3D chromatin architecture in the marine microalga Nannochloropsis oceanica during lipid accumulation
Authors: Yan Tongtong , Wang Kexin , Feng Kexin , Gao Xiangchen , Jin Yinghong , Wu Hongping , Zhang Wenfei , Wei Li
Published: August 2023

Background

Genomic three-dimensional (3D) spatial organization plays a key role in shaping gene expression and associated chromatin modification, and it is highly sensitive to environmental stress conditions. In microalgae, exposure to nitrogen stress can drive lipid accumulation, yet the associated functional alterations in the spatial organization of the microalgal genome have yet to be effectively characterized.

Results

Accordingly, the present study employed RNA-seq, Hi-C, and ChIP-seq approaches to explore the relationship between 3D chromosomal architecture and gene expression during lipid accumulation in the marine microalga Nannochloropsis oceanica in response to nitrogen deprivation (ND). These analyses revealed that ND resulted in various changes in chromosomal organization, including A/B compartment transitions, topologically associating domain (TAD) shifts, and the disruption of short-range interactions. Significantly higher levels of gene expression were evident in A compartments and TAD boundary regions relative to B compartments and TAD interior regions, consistent with observed histone modification enrichment in these areas. ND-induced differentially expressed genes (DEGs) were notably enriched in altered TAD-associated regions and regions exhibiting differential genomic contact. These DEGs were subjected to Gene Ontology (GO) term analyses that indicated they were enriched in the ‘fatty acid metabolism’, ‘response to stress’, ‘carbon fixation’ and ‘photosynthesis’ functional categories, in line with the ND treatment conditions used to conduct this study. These data indicate that Nannochloropsis cells exhibit a clear association between chromatin organization and transcriptional activity under nitrogen stress conditions. Pronounced and extensive histone modifications were evident in response to ND. Observed changes in chromatin architecture were linked to shifts in histone modifications and gene expression.

Conclusions

Overall, the reprogramming of many lipid metabolism-associated genes was evident under nitrogen stress conditions with respect to both histone modifications and chromosomal organization. Together these results revealed that higher-order chromatin architecture represents a new layer that can guide efforts to understand the transcriptional regulation of lipid metabolism in nitrogen-deprived microalgae.
Invasive hematophagous arthropods and associated diseases in a changing world
Authors: Cuthbert Ross N. , Darriet Frédéric , Chabrerie Olivier , Lenoir Jonathan , Courchamp Franck , Claeys Cecilia , Robert Vincent , Jourdain Frédéric , Ulmer Romain , Diagne Christophe , Ayala Diego , Simard Frédéric , Morand Serge , Renault David
Published: August 2023

Biological invasions have increased significantly with the tremendous growth of international trade and transport. Hematophagous arthropods can be vectors of infectious and potentially lethal pathogens and parasites, thus constituting a growing threat to humans—especially when associated with biological invasions. Today, several major vector-borne diseases, currently described as emerging or re-emerging, are expanding in a world dominated by climate change, land-use change and intensive transportation of humans and goods. In this review, we retrace the historical trajectory of these invasions to better understand their ecological, physiological and genetic drivers and their impacts on ecosystems and human health. We also discuss arthropod management strategies to mitigate future risks by harnessing ecology, public health, economics and social-ethnological considerations. Trade and transport of goods and materials, including vertebrate introductions and worn tires, have historically been important introduction pathways for the most prominent invasive hematophagous arthropods, but sources and pathways are likely to diversify with future globalization. Burgeoning urbanization, climate change and the urban heat island effect are likely to interact to favor invasive hematophagous arthropods and the diseases they can vector. To mitigate future invasions of hematophagous arthropods and novel disease outbreaks, stronger preventative monitoring and transboundary surveillance measures are urgently required. Proactive approaches, such as the use of monitoring and increased engagement in citizen science, would reduce epidemiological and ecological risks and could save millions of lives and billions of dollars spent on arthropod control and disease management. Last, our capacities to manage invasive hematophagous arthropods in a sustainable way for worldwide ecosystems can be improved by promoting interactions among experts of the health sector, stakeholders in environmental issues and policymakers (e.g. the One Health approach) while considering wider social perceptions.

Graphical abstract
Validating opioid use disorder diagnoses in administrative data: a commentary on existing evidence and future directions
Authors: Scherrer Jeffrey F. , Sullivan Mark D. , LaRochelle Marc R. , Grucza Richard
Published: August 2023

Background

A valid opioid use disorder (OUD) identification algorithm for use in administrative medical record data would enhance investigators’ ability to study consequences of OUD, OUD treatment seeking and treatment outcomes.

Main body

Existing studies indicate ICD-9 and ICD-10 codes for opioid abuse and dependence do not accurately measure OUD. However, critical appraisal of existing literature suggests alternative validation methods would improve the validity of OUD identification algorithms in administrative data. Chart abstraction may not be sufficient to validate OUD, and primary data collection via structured diagnostic interviews might be an ideal gold standard.

Conclusion and commentary

Generating valid OUD identification algorithms is critical for OUD research and quality measurement in real world health care settings.
Safety and efficacy of enterprise stenting for symptomatic atherosclerotic severe posterior circulation stenosis
Authors: Zhou Zhi-Long , Li Tian-Xiao , Zhu Liang-Fu , Wu Li-Heng , Guan Min , Ma Zhen-Kai , Liu Yang-Hui , Qin Jin , Gao Bu-Lang
Published: August 2023

Purpose

To investigate the safety and efficacy of Enterprise stent angioplasty and risk factors for the prognoses in treating symptomatic severe posterior circulation atherosclerotic stenosis (SSPCAS).

Materials and methods

Patients with SSPCAS who were treated with the Enterprise stent angioplasty were retrospectively enrolled. The clinical data, peri-procedural complications, postoperative residual stenosis, in-stent restenosis and recurrent stroke at follow-up were analyzed.

Results

262 patients with 275 stenotic lesions treated with the Enterprise stent angioplasty were enrolled. The stenosis degree was reduced from 86.3 ± 6.2% before to 19.3 ± 5.4% after stenting. Complications occurred in 14 (5.3%) patients. Clinical follow-up was performed in 245 (93.51%) patients for 16.5 ± 7.3 months. During 1 year follow-up, 7 patients (2.9%) had recurrent symptoms, including 4 patients with stenting in the intracranial vertebral artery and 3 in the basilar artery. Imaging follow-up was conducted in 223 (85.11%) patients. In-stent restenosis was present in 35 patients (15.7%), with the restenosis rate of 26.4% (n = 23) in the intracranial vertebral artery, which was significantly (P < 0.001) greater than in the basilar artery (8.8%). Six patients (17.1%) with in-stent restenosis were symptomatic. The stenotic length was the only significant (P = 0.026 and 0.024, respectively) independent risk factor for 1 year stroke or death events and in-stent restenosis.

Conclusion

The Enterprise stent can be safely and efficaciously applied in the treatment of symptomatic severe posterior circulation atherosclerotic stenosis, with a relatively low rate of in-stent restenosis and recurrent stroke within 1 year. The stenotic length was the only significant independent risk factor for 1 year stroke or death events and in-stent restenosis.
Research methods for heritage cotton fibres: case studies from archaeological and historical finds in a Finnish context
Authors: Suomela Jenni A. , Viljanen Mira , Svedström Kirsi , Wright Krista , Lipkin Sanna
Published: August 2023

Cotton (Gossypium species) was used as textile fibre already in the early Indus culture, and since then it has been cultivated in Tropical and Subtropical regions around the whole planet. The species G. hirsutum is nowadays the dominant cotton crop with more than 90% of the world market, while G. barbadense, G. herbaceum and G. arboreum combined, the other cultivated species of Gossypium genus total a minor part of world’s cotton production. Even in places where cotton was not cultivated, it could be an important trade item and income source for local textile centres, with the imported raw cotton lint being spun, woven and for some part exported from such sites around the globe. This all occurred far away from Finland, until changes brought by the development of long-distance trade and the Industrial Revolution. Based on archaeological finds, cotton as a textile material reached Finland relatively late, in the early Middle Ages. The article focuses on the problematic nature of identifying these cotton finds: whereas modern cotton fibres are easy to identify, the archaeological finds can at first sight be confused with bast or un-degummed silk fibres. This issue will be approached through reviewing recent Finnish cotton finds in heritage textiles. Additionally, the article examines whether the four cultivated cotton species could be differentiated using both classical and newly developed fibre identification methods, such as optical microscopy methods, a Scanning Electron Microscope (SEM), Fourier-transform infrared spectroscopy (FTIR) or Wide-Angle X-ray Scattering (WAXS).
Effect of a music intervention on anxiety in adult critically ill patients: a multicenter randomized clinical trial
Authors: Kakar Ellaha , Ottens Thomas , Stads Susanne , Wesselius Sanne , Gommers Diederik A. M. P. J. , Jeekel Johannes , van der Jagt Mathieu
Published: August 2023

Background

Previous studies show positive effect of music on reducing anxiety, pain, and medication requirement. Anxiety has become a more pertinent issue in the intensive care unit (ICU) since wakefulness is preferred according to recent guidelines. Nevertheless, evidence on the effect of music in ICU patients is scarce. Therefore, we studied the effect of music intervention on anxiety in ICU patients.

Methods

A multicenter randomized clinical trial was conducted between August 2020 and December 2021 in ICU’s at an academic medical centre and two regional hospitals. Adult critically ill patients were eligible when hemodynamically stable and able to communicate (Richmond agitation-sedation scale (RASS) of at least − 2). Patients in the intervention arm were offered music twice daily during three days for at least 30 min per session. Patients in the control group received standard care. The primary outcome was anxiety level assessed with the visual analogue scale for anxiety [VAS-A; range 0–10] twice daily (morning and evening). Secondary outcomes included; 6-item state-trait anxiety inventory (STAI-6), sleep quality, delirium, heart rate, mean arterial pressure, pain, RASS, medication, ICU length of stay, patients’ memory and experience of ICU stay.

Results

94 patients were included in the primary analysis. Music did not significantly reduce anxiety (VAS-A in the intervention group; 2.5 (IQR 1.0–4.5), 1.8 (0.0–3.6), and 2.5 (0.0–3.6) on day 1, 2, and 3 vs. 3.0 (0.6–4.0), 1.5 (0.0–4.0), and 2.0 (0.0–4.0) in the control group; p > 0.92). Overall median daily VAS-A scores ranged from 1.5 to 3.0. Fewer patients required opioids (21 vs. 29, p = 0.03) and sleep quality was lower in the music group on study day one [5.0 (4.0–6.0) vs. 4.5 (3.0–5.0), p = 0.03]. Other outcomes were similar between groups.

Conclusions

Anxiety levels in this ICU population were low, and music during 3 days did not decrease anxiety. This study indicates that efficacy of music is context and intervention-dependent, given previous evidence showing decreased anxiety.

Trial registration Netherlands Trial Register: NL8595, Registered, 1 April 2020. ClinicalTrials.gov ID: NCT04796389, Registered retrospectively, 12 March 2021
Spatial transcriptomics: recent developments and insights in respiratory research
Authors: Wang Wen-Jia , Chu Liu-Xi , He Li-Yong , Zhang Ming-Jing , Dang Kai-Tong , Gao Chen , Ge Qin-Yu , Wang Zhou-Guang , Zhao Xiang-Wei
Published: August 2023

The respiratory system’s complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.
Exploring student perceptions and use of face-to-face classes, technology-enhanced active learning, and online resources
Authors: Lewohl Joanne M.
Published: August 2023

The current cohort of undergraduate students is often said to value technology and is assumed to prefer immersive, interactive, and personalized learning experiences. In contrast, many educators recognise the value of face-to-face classes and believe that attending class positively impacts student performance. A novel teaching strategy, including traditional lectures and interactive workshops using an educational technology platform were implemented in an undergraduate neurobiology course. Attendance in class and use of lecture capture recording were associated with improved student performance. Further, student attitudes toward the teaching strategy were evaluated via a survey. The survey respondents included those that regularly attended class and those that did not. Overall, irrespective of attendance, students thought that face-to-face classes were beneficial to their learning and the use of active learning activities helped them to understand the course content. The most common reasons for non-attendance in class were attributed to factors such as the class schedule, work and family commitments and were not related to the availability of class recordings and other online resources. In contrast, the most common reasons for attendance in class included the perceived benefit, the standard of teaching and the level of interest in the course. The novel teaching strategy had a positive impact on student learning, and can be used for in-person, online and asynchronous learning, providing a mechanism for educators to cater for students who wish to attend in-person classes as well as providing options for flexible delivery.

Graphical Abstract
The Zn(II)2Cys6 transcription factor BcDIC affects the asexual reproduction of Botrytis cinerea by regulating pectinesterase genes
Authors: Lu Shasha , Zhang Xiaokang , He Chang , Li Guangjin , Chen Tong , Li Boqiang , Tian Shiping , Zhang Zhanquan
Published: August 2023

Botrytis cinerea is one of the most destructive plant pathogens, causing great economic losses in a wide variety of crops. It is difficult to control the pathogen because of its flexible mode of infection, high reproduction, genetic plasticity and strong stress resistance. There are more than 400 genes encoding transcription factors in the genome of B. cinerea, among which Zn(II)2Cys6(C6) transcription factors constitute the largest family. However, the mechanisms of Zn(II)2Cys6(C6) transcription factors regulating the development and pathogenicity of B. cinerea are largely unknown. In this study, we identified an important C6 transcription factor BcDIC that regulates the asexual reproduction and pathogenicity of B. cinerea. The virulence of the knockout mutant ΔBcDIC was reduced on various hosts. Especially, ΔBcDIC completely lost the ability of conidiation. By analyzing the transcriptome data, we found that deletion of ΔBcDIC enhanced the expression of pectinesterase family genes in B. cinerea. Furthermore, the results of yeast-one-hybrid and dual-LUC reporter assay suggested that BcDIC could bind to the promoter of two pectinesterase genes and suppress their expression. In this work, we identified a C6 transcription factor involved in the pathogenesis and asexual reproduction of B. cinerea, and the results implied that the capacity of pectin degradation was closely related with the reproduction process.
Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles
Authors: Kim Hyunjoon , Kirtane Ameya R. , Kim Na Yoon , Rajesh Netra Unni , Tang Chaoyang , Ishida Keiko , Hayward Alison M. , Langer Robert , Traverso Giovanni
Published: August 2023

mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (− 80 °C) and healthcare professionals to administer the vaccine through the parenteral route has somewhat limited their distribution in rural areas and developing countries. Overcoming these challenges stands to transform future deployment of mRNA vaccines. In this study, we developed an mRNA vaccine that can trigger a systemic immune response through administration via the gastrointestinal (GI) tract and is stable at 4 °C. A library of cationic branched poly(β-amino ester) (PBAE) polymers was synthesized and characterized, from which a polymer with high intracellular mRNA delivery efficiency and immune stimulation capacity was down-selected. mRNA vaccines made with the lead polymer-elicited cellular and humoral immunity in mice. Furthermore, lyophilization conditions of the formulation were optimized to enable storage under refrigeration. Our results suggest that PBAE nanoparticles are potent mRNA delivery platforms that can elicit B cell and T cell activation, including antigen-specific cellular and humoral responses. This system can serve as an easily administrable, potent oral mRNA vaccine.

Graphical Abstract
Central Disorders of Hypersomnolence
Authors: Blattner Margaret , Maski Kiran
Published: August 2023

Objective

The goals of this article are to describe the clinical approach to and management of patients with central disorders of hypersomnolence, and to understand and differentiate available diagnostic tools.

Latest Developments

Updated clinical practice guidelines for the treatment of central disorders of hypersomnolence and narcolepsy specifically highlight new treatment options. Approval for a lower-sodium oxybate formulation that contains 92% less sodium than the standard sodium oxybate for the treatment of narcolepsy and idiopathic hypersomnia adds to the number of medications available for these disorders, allowing for a more tailored management of symptoms.

Essential Points

Central disorders of hypersomnolence are characterized by excessive daytime sleepiness that impacts daily functions. These disorders can be differentiated by obtaining a detailed clinical sleep history and by a thoughtful interpretation of sleep diagnostic testing. Tailoring treatment approaches to meet the needs of individuals and accounting for medical and psychiatric comorbidities may improve quality of life.
REM Sleep Behavior Disorder and Other REM Parasomnias
Authors: Malkani Roneil
Published: August 2023

OBJECTIVE

This article reviews rapid eye movement (REM) sleep behavior disorder (RBD) and other REM sleep parasomnias, particularly recurrent isolated sleep paralysis and nightmare disorder.

LATEST DEVELOPMENTS

People with RBD have dream enactment behaviors that can be distressing and cause injuries to themselves or a bed partner. Diagnosis of RBD still requires video polysomnography but new evaluative techniques are emerging. Automatic scoring of REM sleep without atonia, the polysomnographic RBD feature, has led to clearer diagnostic cutoff values. Isolated RBD is strongly linked with neurodegenerative disorders, particularly α-synucleinopathies, with a median latency to neurodegenerative disease diagnosis of 8 years. Mounting imaging, electrophysiologic, and pathologic evidence supports neurodegenerative changes in patients with isolated RBD. Safety precautions should be reviewed with patients to reduce the risk of injury. Clonazepam and melatonin are first-line agents for RBD symptoms, and rivastigmine appears to be beneficial for RBD in people with mild cognitive impairment. For nightmare disorder, image rehearsal therapy is effective and can be delivered through online platforms.

ESSENTIAL POINTS

While RBD symptoms can often be managed, patients with isolated RBD should be monitored for signs and symptoms of impending neurodegenerative disease. Individuals who wish to know about the associated risk should be counseled accordingly to allow planning and involvement in research if they choose. Exercise may have some neuroprotective effects, although no treatment has been shown to modify the neurodegenerative risk.
Comparative Analysis of Surgical Working Corridors for Meckel Cave Trigeminal Schwannomas: A Quantitative Anatomic Study
Authors: Luzzi Sabino , Giotta Lucifero Alice , Baldoncini Matías , Galzio Renato , Campero Alvaro
Published: August 2023

BACKGROUND AND OBJECTIVES:

Volumetric analysis of the working corridors of the interdural approach to the Meckel cave may lead to a selection of routes which are anatomically more advantageous for trigeminal schwannoma resection. The herein-reported anatomic study quantitively compares the infratrochlear (IT) transcavernous, anteromedial (AM), and anterolateral (AL) corridors, highlighting their feasibility, indications, advantages, and limitations.

METHODS:

Anatomic boundaries and depth of Meckel cave, porus trigeminus, IT transcavernous, AM, and AL corridors were identified in 20 formalin-fixed latex-injected cadaveric heads and were subsequently measured. The corridor areas and volumes were derived accordingly. Each opening angle was also calculated. Angles and volumes were compared using analysis of variance. Statistical significance was set at a P-value <.05.

RESULTS:

The IT transcavernous corridor volume was greater than that of the AM and AL. The opening angle of the AM middle fossa triangle was wider than the other 2.

CONCLUSION:

The IT corridor can be advantageous for Meckel cave schwannomas invading the cavernous sinus and those with a notable extension into the posterior fossa because the transcavernous approach maximizes the working space into the retrosellar area. The AM middle fossa corridor is strategic in schwannomas confined to the Meckel cave with a minor extension into the posterior fossa. It raises the chance of total resection with a single approach involving the porus trigeminus opening.
The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation
Authors: Song Ran , Fond Aaron , Li Xiaohong , Tang Miao , Zhan Xiaoming , Gordillo Ruth , Moresco Eva Marie Y. , Beutler Bruce , Turer Emre E.
Published: August 2023

Intestinal immunity is dependent on barrier function to maintain quiescence. The mechanisms for the maintenance of this barrier are not fully understood. Delta 4-desaturase, sphingolipid 2 (DEGS2) is a lipid desaturase and hydroxylase that catalyzes the synthesis of ceramide and phytoceramide from dihydroceramide. Using a forward genetic approach, we found and validated a mutation in Degs2 as causative of increasing susceptibility to colitis and altering the phytoceramide balance in the colon. DEGS2 is expressed in the intestinal epithelium, and the colitis phenotype is dependent on the non-hematopoietic compartment of the mouse. In the absence of DEGS2, the colon lacks phytoceramides and accumulates large amounts of the precursor lipid dihydroceramide. In response to dextran sodium sulfate (DSS)-induced colitis, colonic epithelial cells in DEGS2-deficient mice had increased cell death and decreased proliferation compared to those in wild-type mice. These findings demonstrate that DEGS2 is needed to maintain epithelial integrity, protect against DSS-induced colitis and maintain lipid balance in vivo.
Visual guidance of honeybees approaching a vertical landing surface
Authors: Goyal Pulkit , Baird Emily , Srinivasan Mandyam V. , Muijres Florian T.
Published: August 2023

Landing is a critical phase for flying animals, whereby many rely on visual cues to perform controlled touchdown. Foraging honeybees rely on regular landings on flowers to collect food crucial for colony survival and reproduction. Here, we explored how honeybees utilize optical expansion cues to regulate approach flight speed when landing on vertical surfaces. Three sensory-motor control models have been proposed for landings of natural flyers. Landing honeybees maintain a constant optical expansion rate set-point, resulting in a gradual decrease in approach velocity and gentile touchdown. Bumblebees exhibit a similar strategy, but they regularly switch to a new constant optical expansion rate set-point. In contrast, landing birds fly at a constant time to contact to achieve faster landings. Here, we re-examined the landing strategy of honeybees by fitting the three models to individual approach flights of honeybees landing on platforms with varying optical expansion cues. Surprisingly, the landing model identified in bumblebees proved to be the most suitable for these honeybees. This reveals that honeybees adjust their optical expansion rate in a stepwise manner. Bees flying at low optical expansion rates tend to increase their set-point stepwise, while those flying at high optical expansion rates tend to decrease it stepwise. This modular landing control system enables honeybees to land rapidly and reliably under a wide range of initial flight conditions and visual landing platform patterns. The remarkable similarity between the landing strategies of honeybees and bumblebees suggests that this may also be prevalent among other flying insects. Furthermore, these findings hold promising potential for bioinspired guidance systems in flying robots.
The glutamatergic drive to breathe is reduced in severe but not moderate hypoxia in Damaraland mole-rats
Authors: Devereaux Maiah E. M. , Chiasson Sarah , Brennan Kate F. , Pamenter Matthew E.
Published: August 2023

Damaraland mole-rats (Fukomys damarensis) are a hypoxia-tolerant fossorial species that exhibit a robust hypoxic metabolic response (HMR) and blunted hypoxic ventilatory response (HVR). Whereas the HVR of most adult mammals is mediated by increased excitatory glutamatergic signalling, naked mole-rats, which are closely related to Damaraland mole-rats, do not utilize this pathway. Given their phylogenetic relationship and similar lifestyles, we hypothesized that the signalling mechanisms underlying physiological responses to acute hypoxia in Damaraland mole-rats are like those of naked mole-rats. To test this, we used pharmacological antagonists of glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs), combined with plethysmography, respirometry and thermal RFID chips, to non-invasively evaluate the role of excitatory AMPAR and NMDAR signalling in mediating ventilatory, metabolic and thermoregulatory responses, respectively, to 1 h of 5 or 7% O2. We found that AMPAR or NMDAR antagonism have minimal impacts on the HMR or hypoxia-mediated changes in thermoregulation. Conversely, the ‘blunted’ HVR of Damaraland mole-rats is reduced by either AMPAR or NMDAR antagonism such that the onset of the HVR occurs in less severe hypoxia. In more severe hypoxia, antagonists have no impact, suggesting that these receptors are already inhibited. Together, these findings indicate that the glutamatergic drive to breathe decreases in Damaraland mole-rats exposed to severe hypoxia. These findings differ from other adult mammals, in which the glutamatergic drive to breathe increases with hypoxia.