bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster behavior in dental implant failure – A scoping review
Authors: Bidra Avinash S. , Volp Luiz Carlos , Iverson Marissa
Published: May 2024

Purpose

To provide an overview of cluster behavior in dental implant failure including the reported prevalence in modern roughened surface implants as well as the risk factors associated with cluster failures.

Material and Methods

An electronic search for articles in the English language literature published from January 1, 2000, to March 8, 2023, was performed using PubMed, Embase, Dentistry and Oral Sciences, ProQuest, and Central search engines. Using a standardized systematic search process and predetermined inclusion and exclusion criteria in three stages, the final list of selected articles reporting on cluster behavior in dental implant failure was obtained. Cluster behavior was defined as the failure of two or more implants in the same patient within a 2‐year period irrespective of the site. Data from the selected articles were reviewed, critically analyzed, interpreted, and reported.

Results

The initial electronic search resulted in 948 titles. After applying inclusion and exclusion criteria, the systematic search process resulted in five clinical studies reporting data on cluster behavior of dental implant failure with modern roughened surfaces. These five studies reported on a total of 9986 implants with 858 reported failures (early and late) over varying periods. Out of the 858 implant failures, 217 implants (25.2%) exhibited cluster behavior. The overall prevalence of cluster behavior of modern roughened surface implant failure was 2.1%.  The most common location risk factors reported were posterior maxilla, history of previous implant failures, poor bone quality, and occlusal overload.

Conclusions

Cluster behavior occurs in 25% of modern roughened surface implant failures which is significantly less than machined surface cluster implant failures. Nevertheless, the overall prevalence of cluster pattern of implant failure of modern roughened surface implants is reasonably low at 2%.
Microbiome of periodontitis and peri‐implantitis before and after therapy: Long‐read 16S rRNA gene amplicon sequencing
Authors: Yu Pei‐Shiuan , Tu Che‐Chang , Wara‐aswapati Nawarat , Wang Chen‐Ying , Tu Yu‐Kang , Hou Hsin‐Han , Ueno Takaaki , Chen I‐Hui , Fu Kuan‐Lun , Li Huei‐Ying , Chen Yi‐Wen
Published: May 2024

Aims

The microbial profiles of peri‐implantitis and periodontitis (PT) are inconclusive. The controversies mainly arise from the differences in sampling sites, targeted gene fragment, and microbiome analysis techniques. The objective of this study was to explore the microbiomes of peri‐implantitis (PI), control implants (CI), PT and control teeth (CT), and the microbial change of PI after nonsurgical treatment (PIAT).

Methods

Twenty‐two patients diagnosed with both PT and peri‐implantitis were recruited. Clinical periodontal parameters and radiographic bone levels were recorded. In each patient, the subgingival and submucosal plaque samples were collected from sites with PI, CI, PT, CT, and PIAT. Microbiome diversity was analyzed by high‐throughput amplicon sequencing using full‐length of 16S rRNA gene by next generation sequencing.

Results

The 16S rRNA gene sequencing analysis revealed 512 OTUs in oral microbiome and 377 OTUs reached strain levels. The PI and PT groups possessed their own unique core microbiome. Treponema denticola was predominant in PI with probing depth of 8–10 mm. Interestingly, Thermovirga lienii DSM 17291 and Dialister invisus DSM 15470 were found to associate with PI. Nonsurgical treatment for peri‐implantitis did not significantly alter the microbiome, except Rothia aeria.

Conclusion

Our study suggests Treponemas species may play a pivotal role in peri‐implantitis. Nonsurgical treatment did not exert a major influence on the peri‐implantitis microbiome in short‐term follow‐up. PT and peri‐implantitis possess the unique microbiome profiles, and different therapeutic strategies may be suggested in the future.
Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta‐analysis
Authors: Pimolbutr Kununya , Poomsawat Sopee , Na‐ek Nat , Warnakulasuriya Saman , Buajeeb Waranun
Published: May 2024

Objective

To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia.

Methods

A systematic search of four databases—MEDLINE/PubMed, EMBASE, Scopus, and ProQuest—was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random‐effects models, and subgroup analysis was performed to investigate the source of heterogeneity.

Results

A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9–28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV‐16 (9.1%) and HPV‐18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity.

Conclusions

Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub‐sites.
Effect of Insertional Direction of Pedicle Screw on Screw Loosening: A Biomechanical Study on Synthetic Bone Vertebra under a Physiology‐like Load
Authors: Zhan Xuqiang , Gao Feng , Yang Yangyang , Tsai Tsung‐Yuan , Wan Zongmiao , Yu Yan
Published: May 2024

Objectives

It is now understood that pedicle screw loosening at the implant‐bone interface can lead to poor screw–bone interface purchase and decreased fixation stability. Previous biomechanical tests used cadaveric vertebrae and pull‐out or torque loads to assess the effect of the insertional direction of pedicle screws on screw loosening. However, these tests faced challenges in matching biomechanical differences among specimens and simulating in vivo loads applied on pedicle screws. This study aimed to evaluate the effect of the insertional direction of pedicle screws on screw loosening using tension‐compression‐bending loads and synthetic bone vertebrae.

Methods

Polyaxial pedicle screws were inserted into nine synthetic bone vertebrae in three directions (three samples per group): cranial, parallel, and caudad (−10°, 0°, +10° of the pedicle screw rod to the upper plane of the vertebra, respectively). Pedicle screws in the vertebrae were loaded using a polyethylene block connected to a material testing machine. Tension‐compression‐bending loads (100N–250N) with 30,000 cycles were applied to the pedicle screws, and displacements were recorded and then cycle‐displacement curve was drawn based on cycle number. Micro‐CT scans were performed on the vertebrae after removing the pedicle screws to obtain images of the screw hole, and the screw hole volume was measured using imaging analysis software. Direct comparison of displacements was conducted via cycle‐displacement curve. Screw hole volume was analyzed using analysis of variance. The correlation between the displacement, screw hole volume and the direction of pedicle screw was assessed by Spearman correlation analysis.

Results

The smallest displacements were observed in the caudad group, followed by the parallel and cranial groups. The caudad group had the smallest screw hole volume (p < 0.001 and p = 0.009 compared to the cranial and parallel groups, respectively), while the volume in the parallel group was greater than that in the cranial group (p = 0.003). Correlation analysis revealed that the insertional direction of the pedicle screw was associated with the displacement (p = −0.949, p < 0.001) and screw hole volume (p = −0.944, p < 0.001).

Conclusion

Strong correlations were found between the insertional direction of the pedicle screw and relevant parameters, including displacement and screw hole volume. Pedicle screw insertion in the caudad direction resulted in the least pedicle screw loosening.
Individuals lack the ability to accurately detect emotional piloerection
Authors: McPhetres Jonathon , Han Ailin , Gao Halo H. , Kemp Nicole , Khati Bhakti , Pu Cathy X. , Smith Abbie , Shui Xinyu
Published: May 2024

Piloerection (e.g., goosebumps) is an essential thermoregulatory and social signaling mechanism in non‐human animals. Although humans also experience piloerection—often being perceived as an indicator of profound emotional experiences—its comparatively less effective role in thermoregulation and communication might influence our capacity to monitor its occurrence. We present three studies (total N = 617) demonstrating participants' general inability to detect their own piloerection events and their lack of awareness that piloerection occurs with a similar frequency on multiple anatomical locations. Self‐reported goosebumps were more frequent than observed piloerection. However, only 31.8% of self‐reports coincided with observable piloerection, a bias unrelated to piloerection intensity, anatomical location, heart‐rate variability, or interoceptive awareness. We also discovered a self‐report bias for the forearm, contradicting the observation that piloerection occurs with equal frequency on multiple anatomical locations. Finally, there was low correspondence between self‐reports of being “emotionally moved” and observed piloerection. These counterintuitive findings not only highlight a disconnect between an obvious physiological response and our capacity for self‐monitoring, but they underscore a fascinating divergence between human and non‐human species. Although piloerection is vital in non‐human organisms, the connection between piloerection and psychological experience in humans may be less significant than previously assumed, possibly due to its diminished evolutionary relevance.
Oral supplementation with Scabiosa artropurperea L. aqueous extract improves the in vivo sexual behaviour, sperm quality and androgen level in rams
Authors: Niama Wijden , Saïd Samia Ben , Aroua Mohamed , Amiri Sihem , Chograni Hnia , Ramé Christelle , Bouzid Kahena , Bartakiz Ahlem , Froment Pascal , Dupont Joelle , Mahouachi Mokhtar
Published: May 2024

The effects of an aqueous extract of Scabiosa atropurpurea L. (AES) on the reproduction potential of Queue Fine de l'Ouest rams were evaluated over 9 weeks. Eighteen mature (4–6 years old) rams (52.8 ± 2.6 kg) were divided into three groups. The control (C) group was fed oat hay ad libitum with 700 g of concentrate and the other two groups were fed the same diet supplemented with AES at 1 and 2 mg/kg body weight (AES1 and AES2, respectively). Ram sperm was collected with an artificial vagina (2 × 2 days/week) to evaluate sperm production and quality, antioxidant activity, the adenosine triphosphate (ATP) and calcium concentrations. Sexual behaviour and plasma testosterone concentrations were also investigated. The administration of AES improved sexual behaviour (the duration of contact and the number of lateral approaches). The addition of AES also improved individual spermatozoa motility (C: 71.7% ± 6.3%; AES1: 78.3% ± 4.9%; AES2: 83.8% ± 4.4%), the sperm concentration (C: 5.6 ± 0.36; AES1: 6.4 ± 0.81; AES2: 6.7 ± 0.52 × 109 spermatozoa/mL), the ATP ratio (C: 1 ± 0.08; AES1: 2.1 ± 0.08; AES2: 3.3 ± 0.08) and the calcium concentration (C: 5.6 ± 0.24; AES1: 7.7 ± 0.21; AES2: 8.1 ± 0.24 mmol/L). AES treatment decreased the percentage of abnormal sperm (C: 18.5% ± 1.2%; AES1: 16.2% ± 1.1%; AES2: 14.8% ± 0.94%) and DNA damage (C: 62%; AES1: 27%; AES2: 33%) and was associated with elevated seminal fluid antioxidant activity (C: 22 ± 0.27; AES1: 27.1 ± 1.08 and AES2: 27.5 ± 0.36 mmol Trolox equivalents/L) and plasma testosterone (C: 8.3 ± 0.7; AES1: 11.7 ± 0.4; AES2: 15 ± 0.7 ng/L). In conclusion, our study suggests that S. atropurpurea may be potentially useful to enhance libido and sperm production and quality in ram.
Labour market trajectories and unemployment of older workers in Europe after the Great Recession
Authors: Trentini Marco
Published: May 2024

Many European countries want to overcome the early exit from labour market which was widespread since the 1970s through pension reform and labour policies. The extension of working life is hindered by factors that the literature overlooks. This article focuses on the discontinuity of the late‐career caused by unemployment. The aim is to investigate whether older workers are at risk of unemployment and what are the transitions after spells of unemployment. The labour market trajectories of workers over 50s in 11 European countries from 2006 to 2019 were analysed, specifically after the Great Recession and before the Covid‐19 epidemic. It is based on longitudinal survey data from the generated Survey of Health, Ageing and Retirement in Europe Job Episodes Panel. Event history analysis and sequence analysis were performed. Older employees are unlikely to face unemployment. The transition rate highlights the difficulty for older workers into re‐employment. A low education level increases the risk of unemployment and remaining unemployed. Data by country confirm the trend towards overcoming the transition from unemployment to early exit. Divergences concern the higher risk of being trapped in unemployment in Southern European countries such as Greece and Italy.
Three major challenges in the shift to electric vehicles: Industrial organization, industrial policy, and a just transition
Authors: Jeong Jun Ho , Kim Chulsik , Jo Hyung Je
Published: May 2024

This article aims to comprehensively review current research on the transformation within the automotive industry, with a specific focus on electrification, which has driven structural shifts. The exploration of three key dimensions forms the crux of this review: the technical aspects of the transition to electric vehicles (EVs) and the diverse perspectives on EVs as an innovative icon; the array of policy interventions linked to the transition and their distinctive features; and the intricate interplay of discourse and practices integral to the concept of a just transition. Examining these dimensions reveals a disparity between aspirational ideals and current realities in the transformative phase. While the shift to EVs revolutionizes automobile design, the mirroring hypothesis of a concomitant revolution in production and organizational paradigms lacks empirical support. The socio‐ecological transition encounters conflicts between transformative advocates, arguing for robust interventionist policies to overhaul the prevailing social‐technical automotive regime, and status quo upholders favoring an ecological modernization of the regime. Furthermore, the article underscores nuanced tensions in negotiating a just transition amid diverse stakeholder positions.
American Rural–Nonrural Differences in Motherhood Wage Penalties
Authors: Li Xiao
Published: May 2024

A rich body of literature has studied variances in motherhood wage penalties. Yet studies have not explored American rural–nonrural differences in this phenomenon. The spatial differences in women's experiences deserve exploration. Based on prior studies, rural mothers may experience greater wage penalties than nonrural mothers because of their high marriage rates, low educational levels, and the traditional gender attitudes and norms in rural communities. However, they may experience smaller penalties because rural job structures lack diversity and jobs there tend to be low‐paid. This paper uses fixed‐effects models to examine the rural–nonrural differences in motherhood wage penalties, with data from the National Longitudinal Survey of Youth (NLSY79). The results show that although rural women reported lower education levels and higher marriage rates than nonrural women, they experienced smaller motherhood wage penalties than nonrural women partially because they were more likely to work in low‐paid occupations and industries.
Incentives for plasma donation
Authors: Koch Elena , Leiße Antonia , Veseli Besarta , Jensen Johannes , Spekman Marloes , Merz Eva‐Maria , Shehu Edlira , Thibert Jean‐Baptiste , Beurel‐Trehan Antoine , Leblond Marion , Oesterer Martin , Kluge Philipp , Forioso Donata , Clement Michel
Published: May 2024

Background and Objectives

This work provides an overview of the incentives used for plasma donation in Europe and beyond. The overview can provide new ideas to blood establishments.

Materials and Methods

We conducted a systematic online search of incentives used and asked national experts to validate the data across all European Union countries as well as other European and non‐European countries. We categorized the data into level of incentive (using the Nuffield Council on Bioethics' rungs [2011]) and country.

Results

We analysed more than 490 organizations across 26 countries. Our findings reveal different incentives used in these countries. Snacks and pre‐donation health checks are commonly provided. In addition, loyalty programmes, small gifts, vouchers, lotteries, travel compensations and time off from work extend the strategic incentive portfolio. Only seven countries offer financial compensation ranging from the equivalent of 10–35€ for European countries. In countries with a decentralized model, where more than one organization collects plasma, we observe that more diversified incentive strategies are generally used, including monetary and non‐monetary incentives. In countries with a centralized model, where only one organization is allowed to collect plasma, financial compensation is usually not offered. Centralized plasma collection without financial compensation relies on a wider range of non‐monetary incentives than with financial compensation.

Conclusion

The country group analysis offers valuable insights into the relationship between incentive strategies and the prevailing centralized versus decentralized plasma collection model. This overview provides a broader understanding of incentives used by blood establishments and offers avenues for future practice.
Exploring attitudes toward xenotransplantation: A scoping review of healthcare workers, healthcare students, and kidney patients
Authors: Rodger Daniel , Smith Jonathan A.
Published: May 2024

Background

Recent advances mean that formal clinical trials of solid organ xenotransplantation are increasingly likely to begin and patients requiring a kidney transplant could be the first participants. Healthcare workers and healthcare students constitute the current and future workforce that will influence public opinion of xenotransplantation. The attitudes of these populations are important to consider before recruitment for formal clinical trials begins.

Methods

This scoping review was reported according to the PRISMA extensions for scoping reviews checklist and the Joanna Briggs Institute methodology for scoping reviews. The Scopus, PubMed, and ScienceDirect databases were searched to identify articles that studied the attitudes of healthcare workers, healthcare students, or kidney patients toward xenotransplantation.

Results

The search generated 816 articles, of which 27 met the eligibility criteria. The studies were conducted in 14 different countries on five different continents. Participants from the 27 studies totaled 29,836—this was constituted of 6,223 (21%) healthcare workers, 21,067 (71%) healthcare students, and 2,546 (8%) kidney patients. All three groups had an overall positive attitude toward xenotransplantation. However, in studies where participants were asked to consider xenotransplantation when the risks and results were not equal to allotransplantation—the overall attitude switched from positive to negative. The results also found that Spanish‐speaking populations expressed more favorable views toward xenotransplantation compared to English‐speaking populations.

Conclusion

The results of this review suggest that while attitudes of the three groups toward xenotransplantation are—on the face of it—positive, this positivity deteriorates when the risks and outcomes are framed in more clinically realistic terms. Only formal clinical trials can determine how the risks and outcomes of xenotransplantation compare to allotransplantation.
Equidistribution of high traces of random matrices over finite fields and cancellation in character sums of high conductor
Authors: Gorodetsky Ofir , Kovaleva Valeriya
Published: May 2024

Let be a random matrix distributed according to uniform probability measure on the finite general linear group . We show that equidistributes on as as long as and that this range is sharp. We also show that nontrivial linear combinations of equidistribute as long as and this range is sharp as well. Previously equidistribution of either a single trace or a linear combination of traces was only known for , where depends on , due to work of the first author and Rodgers. We reduce the problem to exhibiting cancellation in certain short character sums in function fields. For the equidistribution of , we end up showing that certain explicit character sums modulo exhibit cancellation when averaged over monic polynomials of degree in as long as . This goes far beyond the classical range due to Montgomery and Vaughan. To study these sums, we build on the argument of Montgomery and Vaughan but exploit additional symmetry present in the considered sums.
Warm Air Bending of AZ31B Sheets Based on an Online Local Contact Heating Method
Authors: Wang Xu , Wen Tong , Liu Feng , Zhou Yin
Published: May 2024

Warm forming holds significant potential in shaping challenging materials due to its comprehensive advantages compared to cold and hot forming. Effective heating is crucial for precise warm forming processes. This study explored an innovative warm air bending technique employing an online local contact heating method. Heat transfer during the preheating stage and the air bending of AZ31B sheets were investigated through experiments and finite element analysis at temperatures ranging from room temperature (24 °C) to 250 °C, considering the thermomechanical coupling effect. The results indicate a significant increase in the bending center angle, advancing from 69.8 deg to more than 119 deg as the heating temperature rises from room temperature to 250 °C. Fractures were effectively eliminated when the sheet heating temperatures exceeded 150 °C. Simultaneously, as the localized heating temperature increases, a corresponding decrease in the rebound angle is observed, reducing from 10.6 deg to 2.3 deg. The findings validate the feasibility of warm air bending using online local contact heating in industrial applications, with regard to forming quality and production efficiency.
Chatter Stability of Orthogonal Turn-Milling Process in Frequency and Discrete-Time Domains
Authors: Berenji Kaveh Rahimzadeh , Tehranizadeh Faraz , Budak Erhan
Published: May 2024

As the industry seeks better quality and efficiency, multitasking machine tools are becoming increasingly popular owing to their ability to create complex parts in one setup. Turn-milling, a type of multi-axis machining, combines milling and turning processes to remove material through simultaneous rotations of the cutter and workpiece with the translational feed of the tool. While turn-milling can be advantageous for large parts made of hard-to-cut materials, it also offers challenges in terms of surface form errors and process stability. Because tool eccentricity and workpiece rotation lead to more complexity in process mechanics and dynamics, traditional milling stability models cannot predict the stability of turn-milling processes. This study presents a mathematical model based on process mechanics and dynamics by incorporating the unique characteristics of the orthogonal turn-milling process to avoid self-excited chatter vibrations. A novel approach was employed to model time-varying delays considering the simultaneous rotation of the tool and workpiece. Stability analysis of the system was performed in both the discrete-time and frequency domains. The effects of eccentricity and workpiece speed on stability diagrams were demonstrated and validated through experiments. The results show that the tool eccentricity and workpiece speed alter the engagement geometry and delay in the regeneration mechanism, respectively, leading to significant stability diagram alterations. The proposed approach offers a comprehensive framework for the stability of orthogonal turn-milling and guidance for the selection of process conditions to achieve stable cuts with enhanced productivity.
DesignFusion: Integrating Generative Models for Conceptual Design Enrichment
Authors: Chen Liuqing , Jing Qianzhi , Tsang Yixin , Wang Qianyi , Sun Lingyun , Luo Jianxi
Published: May 2024

Conceptual design is a pivotal phase of product design and development, encompassing user requirement exploration and informed solution generation. Recent generative models with their powerful content generation capabilities have been applied to conceptual design to support designers’ ideation. However, the lack of transparency in their generation process and the shallow nature of their generated solutions constrain their performance in complex conceptual design tasks. In this study, we first introduce a conceptual design generation approach that combines generative models with classic design theory. This approach decomposes the conceptual design task based on design process and design attributes, and uses the who, what, where, when, why, how (5W1H) method, function-behavior-structure model, and Kansei Engineering to guide generative models to generate conceptual design solutions through multi-step reasoning. Then we present an interactive system using a mind-map layout to visualize multi-step reasoning, called DesignFusion. This empowers designers to track the generation process and control inputs/outputs at each reasoning step. Two user studies show that our approach significantly enhances the quality of generated design solutions and enriches designer experience in human–artificial intelligence co-creation.
Discrete Structural Design Synthesis: A Hierarchical-Inspired Deep Reinforcement Learning Approach Considering Topological and Parametric Actions
Authors: Ororbia Maximilian E. , Warn Gordon P.
Published: May 2024

Structural design synthesis considering discrete elements can be formulated as a sequential decision process solved using deep reinforcement learning, as shown in prior work. By modeling structural design synthesis as a Markov decision process (MDP), the states correspond to specific structural designs, the discrete actions correspond to specific design alterations, and the rewards are related to the improvement in the altered design’s performance with respect to the design objective and specified constraints. Here, the MDP action definition is extended by integrating parametric design grammars that further enable the design agent to not only alter a given structural design’s topology, but also its element parameters. In considering topological and parametric actions, both the dimensionality of the state and action space and the diversity of the action types available to the agent in each state significantly increase, making the overall MDP learning task more challenging. Hence, this paper also addresses discrete design synthesis problems with large state and action spaces by significantly extending the network architecture. Specifically, a hierarchical-inspired deep neural network architecture is developed to allow the agent to learn the type of action, topological or parametric, to apply, thus reducing the complexity of possible action choices in a given state. This extended framework is applied to the design synthesis of planar structures considering both discrete elements and cross-sectional areas, and it is observed to adeptly learn policies that synthesize high performing design solutions.
Perinuclear damage from nuclear envelope deterioration elicits stress responses that contribute toLMNAcardiomyopathy
Authors: Sikder Kunal , Phillips Elizabeth , Zhong Zhijiu , Wang Nadan , Saunders Jasmine , Mothy David , Kossenkov Andrew , Schneider Timothy , Nichtova Zuzana , Csordas Gyorgy , Margulies Kenneth B. , Choi Jason C.
Published: May 2024

Mutations in theLMNAgene encoding lamins A/C cause an array of tissue-selective diseases, with the heart being the most commonly affected organ. Despite progress in understanding the perturbations emanating fromLMNAmutations, an integrative understanding of the pathogenesis underlying cardiac dysfunction remains elusive. Using a novel conditional deletion model capable of translatome profiling, we observed that cardiomyocyte-specificLmnadeletion in adult mice led to rapid cardiomyopathy with pathological remodeling. Before cardiac dysfunction,Lmna-deleted cardiomyocytes displayed nuclear abnormalities, Golgi dilation/fragmentation, and CREB3-mediated stress activation. Translatome profiling identified MED25 activation, a transcriptional cofactor that regulates Golgi stress. Autophagy is disrupted in the hearts of these mice, which can be recapitulated by disrupting the Golgi. Systemic administration of modulators of autophagy or ER stress significantly delayed cardiac dysfunction and prolonged survival. These studies support a hypothesis wherein stress responses emanating from the perinuclear space contribute to theLMNAcardiomyopathy development.
MRGPRX4 mediates phospho-drug–associated pruritus in a humanized mouse model
Authors: Chien Daphne Chun-Che , Limjunyawong Nathachit , Cao Can , Meixiong James , Peng Qi , Ho Cheng-Ying , Fay Jonathan F. , Roth Bryan L. , Dong Xinzhong
Published: May 2024

The phosphate modification of drugs is a common chemical strategy to increase solubility and allow for parenteral administration. Unfortunately, phosphate modifications often elicit treatment- or dose-limiting pruritus through an unknown mechanism. Using unbiased high-throughput drug screens, we identified the Mas-related G protein–coupled receptor X4 (MRGPRX4), a primate-specific, sensory neuron receptor previously implicated in itch, as a potential target for phosphate-modified compounds. Using both G
q
-mediated calcium mobilization and G protein–independent GPCR assays, we found that phosphate-modified compounds potently activate MRGPRX4. Furthermore, a humanized mouse model expressing MRGPRX4 in sensory neurons exhibited robust phosphomonoester prodrug–evoked itch. To characterize and confirm this interaction, we further determined the structure of MRGPRX4 in complex with a phosphate-modified drug through single-particle cryo–electron microscopy (cryo-EM) and identified critical amino acid residues responsible for the binding of the phosphate group. Together, these findings explain how phosphorylated drugs can elicit treatment-limiting itch and identify MRGPRX4 as a potential therapeutic target to suppress itch and to guide future drug design.
T6SS nuclease effectors in
Pseudomonas syringae
act as potent antimicrobials in interbacterial competition
Authors: Yu Xun , Yan Yubo , Zeng Jie , Liu Yongxuan , Sun Xiaowen , Wang Zhiyong , Li Lin
Published: May 2024

Type VI secretion system (T6SS) is a potent weapon employed by various
Pseudomonas
species to compete with neighboring microorganisms for limited nutrients and ecological niches. However, the involvement of T6SS effectors in interbacterial competition within the phytopathogen
Pseudomonas syringae
remains unknown. In this study, we examined two T6SS clusters in a wild-type
P. syringae
MB03 and verified the involvement of one cluster, namely, T6SS-1, in interbacterial competition. Additionally, our results showed that two T6SS DNase effectors, specifically Tde1 and Tde4, effectively outcompeted antagonistic bacteria, with Tde4 playing a prominent role. Furthermore, we found several cognate immunity proteins, including Tde1i
a
, Tde1i
b
, and Tde4i, which are located in the downstream loci of their corresponding effector protein genes and worked synergistically to protect MB03 cells from self-intoxication. Moreover, expression of either Tde1 or C-terminus of Tde4 in
Escherichia coli
cells induced DNA degradation and changes in cell morphology. Thus, our results provide new insights into the role of the T6SS effectors of
P. syringae
in the interbacterial competition in the natural environment.

IMPORTANCE

The phytopathogen
Pseudomonas syringae
employs an active type VI secretion system (T6SS) to outcompete other microorganisms in the natural environment, particularly during the epiphytic growth in the phyllosphere. By examining two T6SS clusters in
P. syringae
MB03, T6SS-1 is found to be effective in killing
Escherichia coli
cells. We highlight the excellent antibacterial effect of two T6SS DNase effectors, namely, Tde1 and Tde4. Both of them function as nuclease effectors, leading to DNA degradation and cell filamentation in prey cells, ultimately resulting in cell death. Our findings deepen our understanding of the T6SS effector repertoires used in
P. syringae
and will facilitate the development of effective antibacterial strategies.
Degradation of TRIM32 is induced by RTA for Kaposi’s sarcoma-associated herpesvirus lytic replication
Authors: Zhang Yulin , Dong Zhongwei , Gu Feng , Xu Yifei , Li Ying , Sun Wen , Rao Wutian , Du Shujuan , Zhu Caixia , Wang Yuyan , Wei Fang , Cai Qiliang
Published: May 2024

TRIM32 is often aberrantly expressed in many types of cancers. Kaposi’s sarcoma-associated herpesvirus (KSHV) is linked with several human malignancies, including Kaposi’s sarcoma and primary effusion lymphomas (PELs). Increasing evidence has demonstrated the crucial role of KSHV lytic replication in viral tumorigenesis. However, the role of TRIM32 in herpesvirus lytic replication remains unclear. Here, we reveal that the expression of TRIM32 is upregulated by KSHV in latency, and reactivation of KSHV lytic replication leads to the inhibition of TRIM32 in PEL cells. Strikingly, RTA, the master regulator of lytic replication, interacts with TRIM32 and dramatically promotes TRIM32 for degradation via the proteasome systems. Inhibition of TRIM32 induces cell apoptosis and in turn inhibits the proliferation and colony formation of KSHV-infected PEL cells and facilitates the reactivation of KSHV lytic replication and virion production. Thus, our data imply that the degradation of TRIM32 is vital for the lytic activation of KSHV and is a potential therapeutic target for KSHV-associated cancers.

IMPORTANCE

TRIM32 is associated with many cancers and viral infections; however, the role of TRIM32 in viral oncogenesis remains largely unknown. In this study, we found that the expression of TRIM32 is elevated by Kaposi’s sarcoma-associated herpesvirus (KSHV) in latency, and RTA (the master regulator of lytic replication) induces TRIM32 for proteasome degradation upon viral lytic reactivation. This finding provides a potential therapeutic target for KSHV-associated cancers.
Ectomycorrhizal fungi alter soil food webs and the functional potential of bacterial communities
Authors: Berrios Louis , Bogar Glade D. , Bogar Laura M. , Venturini Andressa M. , Willing Claire E. , Del Rio Anastacia , Ansell T. Bertie , Zemaitis Kevin , Velickovic Marija , Velickovic Dusan , Pellitier Peter T. , Yeam Jay , Hutchinson Chelsea , Bloodsworth Kent , Lipton Mary S. , Peay Kabir G.
Published: May 2024

Most of Earth’s trees rely on critical soil nutrients that ectomycorrhizal fungi (EcMF) liberate and provide, and all of Earth’s land plants associate with bacteria that help them survive in nature. Yet, our understanding of how the presence of EcMF modifies soil bacterial communities, soil food webs, and root chemistry requires direct experimental evidence to comprehend the effects that EcMF may generate in the belowground plant microbiome. To this end, we grew
Pinus muricata
plants in soils that were either inoculated with EcMF and native forest bacterial communities or only native bacterial communities. We then profiled the soil bacterial communities, applied metabolomics and lipidomics, and linked omics data sets to understand how the presence of EcMF modifies belowground biogeochemistry, bacterial community structure, and their functional potential. We found that the presence of EcMF (i) enriches soil bacteria linked to enhanced plant growth in nature, (ii) alters the quantity and composition of lipid and non-lipid soil metabolites, and (iii) modifies plant root chemistry toward pathogen suppression, enzymatic conservation, and reactive oxygen species scavenging. Using this multi-omic approach, we therefore show that this widespread fungal symbiosis may be a common factor for structuring soil food webs.

IMPORTANCE

Understanding how soil microbes interact with one another and their host plant will help us combat the negative effects that climate change has on terrestrial ecosystems. Unfortunately, we lack a clear understanding of how the presence of ectomycorrhizal fungi (EcMF)—one of the most dominant soil microbial groups on Earth—shapes belowground organic resources and the composition of bacterial communities. To address this knowledge gap, we profiled lipid and non-lipid metabolites in soils and plant roots, characterized soil bacterial communities, and compared soils amended either with or without EcMF. Our results show that the presence of EcMF changes soil organic resource availability, impacts the proliferation of different bacterial communities (in terms of both type and potential function), and primes plant root chemistry for pathogen suppression and energy conservation. Our findings therefore provide much-needed insight into how two of the most dominant soil microbial groups interact with one another and with their host plant.
Supplemental Material: Insights into the Phanerozoic evolution of the São Francisco Craton based on detrital zircon thermochronology and U-Pb-Hf geochronology
Authors: Dias Airton N.C. , al. et
Published: May 2024

Table S1: Stratigraphic unit, coordinates, and lithological information from collected samples. Table S2: Detailed zircon fission-track thermochronology and U-Pb detrital zircon data from samples obtained by LA-ICP-MS from São Francisco Craton and Brasilia and Araçuaí belts. Table S3: U-Pb detrital zircon data from samples obtained by the LA-ICP-MS method. Table S4: Lu-Hf zircon data from the southern São Francisco Craton.  
Congenital cystic neck mass of thymic origin
Authors: Almalki Zohour Awadh , Alsheef Hussain , Alnemari Farah Salman , Aljuaid Sarah Owaidh
Published: May 2024

Neck masses are frequently seen in children. The differential diagnosis includes infectious, congenital and neoplastic lesions. We report a case of rare thymic neck mass in a boy in his middle childhood presented with a history of a left anterolateral neck mass not associated with fever, dysphagia or shortness of breath. The radiographic evaluation showed a picture of a thymopharyngeal duct cyst. Thymic remnant and thymopharyngeal duct cyst are caused by the failure of obliteration and might appear as a lateral neck mass in children. The most effective treatment for a thymopharyngeal duct cyst is total surgical excision. This particular case highlights the importance for clinicians to have a high index of suspicion for a broad differential diagnosis when evaluating paediatric patients who present with neck mass. Additionally, we emphasise the importance of consistently considering thymopharyngeal cyst as differential diagnosis.
Large retroperitoneal lymphangioma
Authors: Chiang Jessica , Woo Jacqueline Elise , Vu Alexander Hien , Sirsi Sandeep
Published: May 2024

Abnormal cystic lymphangioma is a rare, benign tumour of lymphatic origin that often presents with subtle clinical symptoms. A man in his 20s sought medical attention for a progressively tender mass located in the right lower quadrant. Following ultrasound and CT imaging, surgical pathology confirmed the presence of abnormal cystic lymphangioma. This case is noteworthy because of the patient’s young age and the retroperitoneal location. An exploratory laparotomy was performed, mitigating the risk of recurrence. In the future, if imaging identifies a cystic mass, consideration of abnormal cystic lymphangioma within the differential diagnosis is imperative. Despite its predominantly subtle symptoms and non-malignant nature, the mass effect by the abnormal cystic lymphangioma can compromise surrounding structures. Overall, clinicians confronted with a cystic mass should adopt a comprehensive diagnostic approach, encompassing abnormal cystic lymphangioma in the differential diagnosis due to its unknown and complex nature.
Difficulties in investigating and treating fibrosing thyroid disorder (overlap of fibrosing variant of Hashimoto’s thyroiditis and Riedel’s thyroiditis)
Authors: Clifford Liam Mahoney , Joseph Flavian
Published: May 2024

A gentleman in his 90s presented with a slowly enlarging goitre over 18 months, causing manifestations of superior vena cava obstruction, dysphagia and hoarseness of voice. Investigations were suggestive of a fibrosing thyroid pathology. Surgical management was avoided due to high surgical risk. Treatment included prednisolone and tamoxifen with palliative management in the event of further medical deterioration. This article illustrates the difficulties in diagnosing and managing fibrosing thyroid diseases.
Study protocol for assessment of the efficacy of calcium dobesilate versus placebo on SARS-CoV-2 viral load in outpatients with COVID-19 (CADOVID study): a randomised, placebo-controlled, double-blind, monocentric phase II trial
Authors: Salamun Julien , Da Silva Tamara , Ustero Pilar , Gosmain Yvan , Guessous Idris , Calmy Alexandra , Spechbach Herve
Published: May 2024

Introduction

SARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a well-established, widely available vasoactive and angioprotective drug interacting with heparan sulphate, with the potential to interfere with the uptake of SARS-CoV-2 by epithelial cells. The CADOVID trial aims to evaluate the efficacy and safety of CaD in reducing the SARS-CoV-2 viral load in non-hospitalised adult patients diagnosed with COVID-19, confirmed by a positive SARS-CoV-2 PCR, including its efficacy to reduce the impact of persistent COVID-19 symptoms.

Methods and analysis

This is a randomised, placebo-controlled, double-blind, monocentric phase II trial. Enrolment began in July 2022. A total of 74 adult patients will be randomly allocated to the CaD arm or the placebo group with a 1:1 ratio, respectively. Participants in the intervention arm will receive two capsules of CaD 500 mg two times per day and the placebo arm will receive two matching capsules of mannitol 312.5 mg two times per day, with a treatment period of 7 days for both arms, followed by a 77-day observational period without treatment administration. Participants will be asked to complete secured online questionnaires using their personal smartphone or other electronic device. These include a COVID-19 questionnaire (assessing symptoms, temperature measurement, reporting of concomitant medication and adverse events), a COVID-19 persistent symptoms’ questionnaire and the Short Form 12-Item (SF-12) survey. SARS-CoV-2 PCR testing will be performed on nasopharyngeal swabs collected on days 1, 4, 8 and 21. The primary endpoint is the reduction from baseline of SARS-CoV-2 viral load determined by RT-PCR at day 4.

Ethics and dissemination

This trial has received approval by the Geneva Regional Research Ethics Committee (2022-00613) and Swissmedic (701339). Dissemination of results will be through presentations at scientific conferences and publication in scientific journals.

Trial registration number

NCT05305508; Clinicaltrials.gov; Swiss National Clinical Portal Registry (SNCTP 000004938).
Patient, caregiver and other knowledge user engagement in consensus-building healthcare initiatives: a scoping review protocol
Authors: Munce Sarah E. P. , Wong Elliott , Luong Dorothy , Rao Justin , Cunningham Jessie , Bailey Katherine , John Tomisin , Barber Claire , Batthish Michelle , Chambers Kyle , Cleverley Kristin , Crabtree Marilyn , Diaz Sanober , Dimitropoulos Gina , Gorter Jan Willem , Grahovac Danijela , Grimes Ruth , Guttman Beverly , Hébert Michèle L , Henze Megan , Higgins Amanda , Khodyakov Dmitry , Li Elaine , Lo Lisha , Macgregor Laura , Mooney Sarah , Severino Samadhi Mora , Mukerji Geetha , Penner Melanie , Pidduck Jacklynn , Shulman Rayzel , Stromquist Lisa , Trbovich Patricia , Wan Michelle , Williams Laura , Yates Darryl , Toulany Alene
Published: May 2024

Introduction

Patient engagement and integrated knowledge translation (iKT) processes improve health outcomes and care experiences through meaningful partnerships in consensus-building initiatives and research. Consensus-building is essential for engaging a diverse group of experienced knowledge users in co-developing and supporting a solution where none readily exists or is less optimal. Patients and caregivers provide invaluable insights for building consensus in decision-making around healthcare, policy and research. However, despite emerging evidence, patient engagement remains sparse within consensus-building initiatives. Specifically, our research has identified a lack of opportunity for youth living with chronic health conditions and their caregivers to participate in developing consensus on indicators/benchmarks for transition into adult care. To bridge this gap and inform our consensus-building approach with youth/caregivers, this scoping review will synthesise the extent of the literature on patient and other knowledge user engagement in consensus-building healthcare initiatives.

Methods and analysis

Following the scoping review methodology from Joanna Briggs Institute, published literature will be searched in MEDLINE, EMBASE, CINAHL and PsycINFO databases from inception to July 2023. Grey literature will be hand-searched. Two independent reviewers will determine the eligibility of articles in a two-stage process, with disagreements resolved by a third reviewer. Included studies must be consensus-building studies within the healthcare context that involve patient engagement strategies. Data from eligible studies will be extracted and charted on a standardised form. Abstracted data will be analysed quantitatively and descriptively, according to specific consensus methodologies, and patient engagement models and/or strategies.

Ethics and dissemination

Ethics approval is not required for this scoping review protocol. The review process and findings will be shared with and informed by relevant knowledge users. Dissemination of findings will also include peer-reviewed publications and conference presentations. The results will offer new insights for supporting patient engagement in consensus-building healthcare initiatives.

Protocol registration

https://osf.io/beqjr