bluuebunny/crossref_metadata_2025 huggingface dataset:
CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia‐related mutations in men
Authors: Zheng Huimei , Gong Chenjia , Li Jingping , Hou Jiaru , Gong Xinhan , Zhu Xinhai , Deng Huan , Wu Haoyue , Zhang Fengbin , Shi Qinghua , Zhou Jianteng , Shi Baolu , Yang Xiaohang , Xi Yongmei
Published: March 2024

Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21‐bp (g.30768132_30768152del21) and/or 24‐bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT‐like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head–tail coupling apparatus in the sperm of Ccdc157‐null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157‐deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.
Rapid review: A review of methods and recommendations based on current evidence
Authors: Guo Qiong , Jiang Guiyu , Zhao Qingwen , Long Youlin , Feng Kun , Gu Xianlin , Xu Yihan , Li Zhengchi , Huang Jin , Du Liang
Published: March 2024

Rapid review (RR) could accelerate the traditional systematic review (SR) process by simplifying or omitting steps using various shortcuts. With the increasing popularity of RR, numerous shortcuts had emerged, but there was no consensus on how to choose the most appropriate ones. This study conducted a literature search in PubMed from inception to December 21, 2023, using terms such as “rapid review” “rapid assessment” “rapid systematic review” and “rapid evaluation”. We also scanned the reference lists and performed citation tracking of included impact studies to obtain more included studies. We conducted a narrative synthesis of all RR approaches, shortcuts and studies assessing their effectiveness at each stage of RRs. Based on the current evidence, we provided recommendations on utilizing certain shortcuts in RRs. Ultimately, we identified 185 studies focusing on summarizing RR approaches and shortcuts, or evaluating their impact. There was relatively sufficient evidence to support the use of the following shortcuts in RRs: limiting studies to those published in English‐language; conducting abbreviated database searches (e.g., only searching PubMed/MEDLINE, Embase, and CENTRAL); omitting retrieval of grey literature; restricting the search timeframe to the recent 20 years for medical intervention and the recent 15 years for reviewing diagnostic test accuracy; conducting a single screening by an experienced screener. To some extent, the above shortcuts were also applicable to SRs. This study provided a reference for future RR researchers in selecting shortcuts, and it also presented a potential research topic for methodologists.
Effect of electromagnetic field‐assisted freezing on improving the stability of lemon juice after thawing
Authors: Huo Jingyi , Zhang Min , Chen Yiping
Published: March 2024

This study aims to reduce the production of flocculent material and stratification of lemon juice during freezing and thawing, using electric or magnetic fields to assist with the freezing of lemon juice. This study investigated the effect of 10–30 kV/cm electric field (EF) and 2–10 mT magnetic field (MF) on the quality of frozen lemon juice. Electromagnetic field treatment can shorten the freezing time and reduce its particle size, resulting in a lower polymer dispersion index and lower enzyme activity, thus improving its cloud stability. When the EF strength was 20 kV/cm and the MF strength was 6 mT, it resulted in the highest cloud stability, which increased by 15.50 and 16.95%, respectively. In addition, we studied the effect of electromagnetic fields on the physico‐chemical properties and bioactive components of lemon juice. The results showed that it did not affect its bioactive compounds activity and antioxidant activity, and did not cause loss of lemon juice flavor. The electromagnetic field treatment improved the quality of the juice and can be used as a potential novel processing technology for fruit juices.

Practical Applications

This study provides a simple and novel method to improve the stability of frozen lemon juice after thawing. The use of physical fields such as electric and magnetic field treatments to assist in freezing lemon juice improves the stability of lemon juice after thawing and provides a new method to improve the quality of fruit juice products.
Reconstruction of large scalp defect in a brown howler monkey (Alouatta guariba clamitans): A case report
Authors: Grings Germano Filipe , Surita Lívia Eichenberg , Nicknich Daniela , Torikachvili Marcela , dos Santos Eduardo Almeida Ruivo , Wartchow Barbara , Portinho Ciro Paz , Gomes Cristiano , Alievi Marcelo Meller
Published: March 2024

This case report describes different repair techniques used to reconstruct a large scalp defect in a brown howler monkey (Alouatta guariba clamitans) hit by a vehicle. Three reconstructive procedures were performed in two surgical stages. The repair techniques had successful outcomes on the patient's rehabilitation.
Transient and Long‐Term Linguistic Influences on Visual Perception: Shifting Brain Dynamics With Memory Consolidation
Authors: Maier Martin , Abdel Rahman Rasha
Published: March 2024

Linguistic categories can impact visual perception. For instance, learning that two objects have different names can enhance their discriminability. Previous studies have identified a typical pattern of categorical perception, characterized by faster discrimination of stimuli from different categories, a neural mismatch response during early visual processing (100–200 ms), and effects restricted to the right visual field. However, it remains unclear whether language affects perception online or through long‐term changes to mental representations in memory. To address this, we tested the impact of newly learned object categories with and without memory consolidation during sleep. We replicated the canonical pattern of categorical perception for categories that underwent consolidation. Without consolidation, linguistic categories still influenced early visual processing but with distinct neural dynamics. Therefore, we found evidence of both transient and long‐term effects of language on perception and conclude that memory consolidation plays a crucial role in shaping how linguistic categories modulate perception.
An RRM domain protein SOE suppresses transgene silencing in rice
Authors: Zhao Rui , Wu Wen‐Ai , Huang Yi‐Hua , Li Xin‐Kai , Han Jia‐Qi , Jiao Wu , Su Yin‐Na , Zhao He , Zhou Yang , Cao Wu‐Qiang , Zhang Xun , Wei Wei , Zhang Wan‐Ke , Song Qing‐Xin , He Xin‐Jian , Ma Biao , Chen Shou‐Yi , Tao Jian‐Jun , Yin Cui‐Cui , Zhang Jin‐Song
Published: March 2024

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear.

Here, through analysis of a suppressor for the OsEIN2 over‐expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre‐mRNA for efficient splicing and stabilization, allowing for subsequent DNG701‐mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre‐mRNA, leading to transgene silencing.

SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000‐grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele.

Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.
Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta‐analysis of randomized controlled trials
Authors: Wang Hao , Ma Qianqian , Chen Youpeng , Luo Ling , Ye Junzhao , Zhong Bihui
Published: March 2024

Background

Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta‐analysis of randomized controlled trials.

Data Source

The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness.

Results

A total of 174 studies with 10,183 patients were included in this meta‐analysis. In terms of improving BMI, Pan‐agonist of peroxisome proliferator‐activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = −3.40, 95% CI −5.55, −1.24) by the comparative effectiveness ranking. GLP‐1 (glucagon‐like peptide‐1) has the best effect in improving the liver fat content based on the MRI‐PDFF, steatosis score (SUCRA 99.7%, mean = −2.19, 95% CI −2.90, −1.48) and ballooning score (SUCRA 61.2%, mean = −0.82, 95% CI −4.46, 2.83).

Conclusions

Pan‐agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP‐1R agonists achieved the highest efficacy of steatosis improvement in this network meta‐analysis.
Physiological and psychological determinants of long‐term diet‐induced type 2 diabetes (T2DM) remission: A narrative review
Authors: Aksoy Ayse Nur , Abayomi Julie , Relph Nicola , Butler Thomas
Published: March 2024

Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease, causing a heavy burden on healthcare systems worldwide, with related complications and anti‐diabetes drug prescriptions. Recently, it was demonstrated that T2DM can be put into remission via significant weight loss using low‐carbohydrate diets (LCDs) and very low‐energy diets (VLEDs) in individuals with overweight and obesity. Clinical trials demonstrated remission rates of 25–77%, and metabolic improvements such as improved blood lipid profile and blood pressure were observed. In contrast, clinical trials showed that remission rate declines with time, concurrent with weight gain, or diminished weight loss. This review aims to discuss existing literature regarding underlying determinants of long‐term remission of T2DM including metabolic adaptations to weight loss (e.g., role of gastrointestinal hormones), type of dietary intervention (i.e., LCDs or VLEDs), maintaining beta (β)‐cell function, early glycemic control, and psychosocial factors. This narrative review is significant because determining the factors that are associated with challenges in maintaining long‐term remission may help in designing sustainable interventions for type 2 diabetes remission.
Identification of temporal shifts of oral bacteria in bone regeneration following mandibular bone defect injury and therapeutic surgery in a porcine model
Authors: Sanjar Fatemeh , Silliman David T. , Johnson Ian J. , Htut Zayer , Peacock Trent J. , Thompson Samira F. , Dion Gregory R. , Nahid Md A. , Decker John F. , Leung Kai P.
Published: March 2024

Background

Considered the second largest and most diverse microbiome after the gut, the human oral ecosystem is complex with diverse and niche‐specific microorganisms. Although evidence is growing for the importance of oral microbiome in supporting a healthy immune system and preventing local and systemic infections, the influence of craniomaxillofacial (CMF) trauma and routine reconstructive surgical treatments on community structure and function of oral resident microbes remains unknown. CMF injuries affect a large number of people, needing extensive rehabilitation with lasting morbidity and loss of human productivity. Treatment efficacy can be complicated by the overgrowth of opportunistic commensals or multidrug‐resistant pathogens in the oral ecosystem due to weakened host immune function and reduced colonization resistance in a dysbiotic oral microbiome.

Aims

To understand the dynamics of microbiota's community structure during CMF injury and subsequent treatments, we induced supra‐alveolar mandibular defect in Hanford miniature swine (n = 3) and compared therapeutic approaches of immediate mandibullar reconstructive (IMR) versus delayed mandibullar reconstructive (DMR) surgeries.

Methods

Using bacterial 16S ribosomal RNA gene marker sequencing, the composition and abundance of the bacterial community of the uninjured maxilla (control) and the injured left mandibula (lingual and buccal) treated by DMR were surveyed up to 70‐day post‐wounding. For the injured right mandibula receiving IMR treatment, the microbial composition and abundance were surveyed up to 14‐day post‐wounding. Moreover, we measured sera level of biochemical markers (e.g., osteocalcin) associated with bone regeneration and healing. Computed tomography was used to measure and compare mandibular bone characteristics such as trabecular thickness between sites receiving DMR and IMR therapeutic approaches until day 140, the end of study period.

Results

Independent of IMR versus DMR therapy, we observed similar dysbiosis and shifts of the mucosal bacteria residents after CMF injury and/or following treatment. There was an enrichment of Fusobacterium, Porphyromonadaceae, and Bacteroidales accompanied by a decline in Pasteurellaceae, Moraxella, and Neisseria relative abundance in days allotted for healing. We also observed a decline in species richness and abundance driven by reduction in temporal instability and inter‐animal heterogeneity on days 0 and 56, with day 0 corresponding to injury in DMR group and day 56 corresponding to delayed treatment for DMR or injury and immediate treatment for the IMR group. Analysis of bone healing features showed comparable bone‐healing profiles for IMR vs. DMR therapeutic approach.
How do we review coronectomies? A national survey
Authors: Turner Thomas , Cousins Matthew , Wemyss Callum , Goodall Christine
Published: March 2024

Introduction

Coronectomy of a mandibular third molar is a surgical procedure which aims to protect the inferior alveolar nerve (IAN) by removing the crown of the tooth, whilst leaving the roots in‐situ. There is an anecdotal variation in practice regarding the post‐operative clinical and radiographic review of patients who have undergone this procedure, which may be attributable to a lack of high‐quality evidence or guidance. The aim of this study was to establish current practice within the United Kingdom (UK) for a post‐operative review following a coronectomy.

Materials and Methods

An online survey was distributed to 50 Oral Surgery speciality registrars working within Oral Surgery and Oral and Maxillofacial departments across the UK during June 2022. Two reminder emails were sent, and participants were asked to respond on behalf of their departments.

Results

Twenty responses were received from trainees, on behalf of 20 separate departments. Fifty percent (n = 10) of the responding departments discharged patients without intra‐operative complications immediately following the procedure. The remaining 50% of departments discharged patients at points ranging from 2 weeks to 12 months. Departments who review patients who have undergone a coronectomy without intra‐operative complications do so between 1 and 3 times, with the most common time for the first review being at 1‐month post‐procedure (n = 3). When reviewing these patients, 54.5% (n = 6) of departments utilise face‐to‐face only reviews, whereas 36.4% (n = 4) of departments utilise a combination of face‐to‐face and remote reviews. Sixty‐five percent (n = 13) of departments do not routinely take postoperative imaging for these patients. Many departments also reported variation in practice within their departments, regarding discharge timing, clinical review and radiographic review.

Conclusion

This survey has suggested that there is variation in practice within the secondary and tertiary care Oral Surgery and Oral and Maxillofacial Surgery centres within the United Kingdom in relation to the post‐operative clinical and radiographic coronectomy review. Consideration should be given to further high‐quality research into these areas, including the merits of patient‐initiated reviews and the development of guidelines for post‐operative management of coronectomy patients.
Analytic shock‐fronted solutions to a reaction–diffusion equation with negative diffusivity
Authors: Miller Thomas , Tam Alexander K. Y. , Marangell Robert , Wechselberger Martin , Bradshaw‐Hajek Bronwyn H.
Published: March 2024

Reaction–diffusion equations (RDEs) model the spatiotemporal evolution of a density field according to diffusion and net local changes. Usually, the diffusivity is positive for all values of , which causes the density to disperse. However, RDEs with partially negative diffusivity can model aggregation, which is the preferred behavior in some circumstances. In this paper, we consider a nonlinear RDE with quadratic diffusivity that is negative for . We use a nonclassical symmetry to construct analytic receding time‐dependent, colliding wave, and receding traveling wave solutions. These solutions are multivalued, and we convert them to single‐valued solutions by inserting a shock. We examine properties of these analytic solutions including their Stefan‐like boundary condition, and perform a phase plane analysis. We also investigate the spectral stability of the and constant solutions, and prove for certain and that receding traveling waves are spectrally stable. In addition, we introduce a new shock condition where the diffusivity and flux are continuous across the shock. For diffusivity symmetric about the midpoint of its zeros, this condition recovers the well‐known equal‐area rule, but for nonsymmetric diffusivity it results in a different shock position.
The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes
Authors: Lundberg Tommy R. , Tucker Ross , McGawley Kerry , Williams Alun G. , Millet Grégoire P. , Sandbakk Øyvind , Howatson Glyn , Brown Gregory A. , Carlson Lara A. , Chantler Sarah , Chen Mark A. , Heffernan Shane M. , Heron Neil , Kirk Christopher , Murphy Marie H. , Pollock Noel , Pringle Jamie , Richardson Andrew , Santos‐Concejero Jordan , Stebbings Georgina K. , Christiansen Ask Vest , Phillips Stuart M. , Devine Cathy , Jones Carwyn , Pike Jon , Hilton Emma N.
Published: March 2024

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's “no presumption of advantage” principle disregards this reality. Studies show that transgender women (male‐born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of “meaningful competition” is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case‐by‐case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision‐making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.
Circa 1.9 Ga Rae‐Hearne collision from Lu–Hf garnet chronology in eclogites
Authors: Cutts J. A. , Regis D. , Pehrsson S. J. , Graziani R. , Petts D. C. , Smit M. A. , Knox B.
Published: March 2024

Canada's northern cratons record a complex poly‐metamorphic evolution in response to multiple orogenic events. The Snowbird Tectonic Zone (STZ), the principal suture between the Archean Rae and Hearne cratons, is a highly debated structure; it is argued to have accommodated modern‐style accretion in either the Neoarchean (2.6–2.5 Ga) or Palaeoproterozoic (ca. 1.9 Ga). To resolve this controversy, we use Lu–Hf garnet geochronology to date an eclogite collected from the East Athabasca mylonite triangle of the STZ. Garnet shows prograde trace‐element zoning, and we obtained an age of 1914.5 ± 3.4 Ma. The age is interpreted to date the timing of collision related to deep burial of crust along the STZ. This strongly supports Palaeoproterozoic terminal collision between the Rae and Hearne cratons, and that to constrain high‐pressure metamorphism during supercontinent assembly, dating eclogite itself is key.
Factors affecting physicians' decision to start prehospital blood product transfusion in blunt trauma patients: A cohort study of Helsinki Trauma Registry
Authors: Jama Timo , Lefering Rolf , Lauronen Jouni , Handolin Lauri
Published: March 2024

Background

Prehospital blood transfusions are increasing as a treatment for bleeding trauma patients at risk for exsanguination. Triggers for starting transfusion in the field are less studied. We analyzed the factors affecting the decision of physicians to start prehospital blood product transfusion (PHBT) in blunt adult trauma patients.

Study Design and Methods

Data of all adult blunt trauma patients from the Helsinki Trauma Registry between March 2016 and July 2021 were retrospectively analyzed. Univariate analysis for the identification of predictive factors and multivariate regression analysis for their importance as predictive factors for the initiation of PHBT were applied.

Results

There were 1652 patients registered in the database. A total of 556 of them were treated by a physician‐level prehospital emergency care unit, of which by transfusion‐capable unit in 394 patients. PHBT (red blood cells and/or plasma) was started in 19.8% of the patients. We identified three statistically highly important clinical triggers for starting PHBT: high crystalloid volume need, shock index ≥0.9, and need for prehospital pleural decompression.

Discussion

PHBT in blunt adult trauma patients is initiated in ~20% of the patients in Southern Finland. High crystalloid volume need, shock index ≥0.9 and prehospital pleural decompression are associated with the initiation of PHBT, probably reflecting patients at high risk for bleeding.
Image‐based non‐invasive assessment of suction blister wounds for clinical safety and efficacy
Authors: Wallblom Karl , Lundgren Sigrid , Saleh Karim , Schmidtchen Artur , Puthia Manoj
Published: March 2024

Recognising the need for objective imaging‐based technologies to assess wound healing in clinical studies, the suction blister wound model offers an easily accessible wound model that creates reproducible epidermal wounds that heal without scarring. This study provides a comprehensive methodology for implementing and evaluating photography‐based imaging techniques utilising the suction blister wound model. Our method encompasses a protocol for capturing consistent, high‐quality photographs and procedures for quantifying these images via a visual wound healing score and a computer‐assisted colour analysis of wound exudation and wound redness. We employed this methodology on 16 suction blister wounds used as controls in a clinical phase‐1 trial. Our method enabled us to discern and quantify subtle differences between individual wounds concerning healing progress, erythema and wound exudation. The wound healing score exhibited a high inter‐rater agreement. There was a robust correlation between the spectrophotometer‐measured erythema index and photography‐based wound redness, as well as between dressing protein content and photography‐based dressing yellowness. In conclusion, this study equips researchers conducting clinical wound studies with reproducible methods that may support future wound research and aid in the development of new treatments.
AYLLU : plataforma de cooperación mediada por agentes aplicada en un contexto de e-learning colaborativo : aprender a cooperar y cooperar para aprender
Authors:   Pontificia Universidad Javeriana, Ovalle Carranza Demetrio Arturo
Published: March 2024

Las propuestas innovadoras sobre estrategias de enseñanza y aprendizaje han permitido el avance de la educación buscando cambiar la clásica concepción de aprendizaje individual y competitivo por modelos como la enseñanza y aprendizaje colaborativos. Por tal motivo, para la validación de la plataforma AYLLU se desarrolló un entorno educativo que permite aplicar diferentes estrategias en las cuales los participantes de cada equipo asumen roles y responsabilidades que garantizan el éxito del aprendizaje. En el proyecto de investigación AYLLU se ha desarrollado una plataforma que proporciona mecanismos que faciliten la interacción entre las personas; en efecto, las personas son apoyadas por agentes de software que trabajan como mediadores y facilitadores de la colaboración. Por ello, y considerando las necesidades al realizar un proceso colaborativo, la plataforma AYLLU se focaliza en cubrir tres aspectos principales: la comunicación y cooperación entre personas, la diversidad y el contexto, y la gestión de los recursos compartidos. En un primer nivel, el modelo de agentes cooperativos asegura una comunicación estructurada y semántica en un marco en el cual los participantes tengan conciencia de grupo. En un segundo nivel, los componentes AES y MATEO proporcionan los mecanismos para personalizar, adaptarse al contexto y gestionar los grupos de trabajo, teniendo en cuenta las particularidades de los usuarios. En el tercer nivel, el gestor de recursos AYPUY administra el acceso y el almacenamiento de los recursos que comparten las personas en forma concurrente. Finalmente, los resultados obtenidos fueron satisfactorios: los procesos colaborativos se desarrollaron de manera fluida y efectiva.
Estimation of Injury Limits at Vulnerable Impact Locations Along the Forearm Via THUMS AM50 Finite Element Model at Airbag Loading Rates
Authors: Brewer Carson , Shakib Aryen , de Lange Julia E. , Quenneville Cheryl E.
Published: March 2024

Side and frontal airbag deployment represents the main injury mechanism to the upper extremity during automotive collisions. Previous dynamic injury limit research has been limited to testing the forearm at either the assumed most vulnerable location to fracture, the distal 1/3rd, or the midpoint. Studies have varied the surface to which impacts were applied, with no clear consensus on the site of greatest vulnerability. The unpredictability of airbag impact location, especially with altered hand positioning, limits the effectiveness of existing forearm injury limits determined from impacts at only one location. The current study quantified the effect of impacts at alternative locations on injury risk along the forearm using the THUMS FE model. Airbag-level impacts were simulated along the forearm on all four anatomical surfaces. Results showed the distal 1/3rd is not the most vulnerable location (for any side), indicating forearm fracture is not solely driven by area moment of inertia (as previously assumed). The posterior forearm was the weakest, suggesting that current test standards underestimate the fracture risk of the forearm. Linear regression models showed strong correlation between forearm fracture risk and bone geometry (cross-sectional area and area moment of inertia) as well as soft-tissue depth, potentially providing the ability to predict forearm injury tolerances for any location or forearm size. This study demonstrated the forearm's vulnerability to fracture from airbag deployments, indicating the need for safety systems to better address injury mechanisms for the upper limb to effectively protect drivers.
Using Social Learning Spaces to Think Beyond and Innovate Conventional Conferencing Formats
Authors: Santos Fernando , Camiré Martin , Pierce Scott , MacDonald Dany J. , Strachan Leisha , Newman Tarkington , Vella Stewart , Milistetd Michel
Published: March 2024

Across the academic landscape, scientific organizations host conferences that enable researchers to come together to foster learning, stimulate innovation, and promote change. Within the diverse field of kinesiology, conferences can help develop and disseminate knowledge on a range of issues such as athlete development and coach education. The purpose of the present article is to discuss the possibilities of thinking beyond conventional conferencing formats by creating dynamic social learning spaces that promote networking, critical thinking, and reflexivity. The theory underpinning social learning spaces is explained, followed by a narrative chronology of the three phases of evolution of the blue room group, an interdisciplinary collaboration of youth sport scholars who aim to foster innovation across subdisciplines of kinesiology. An interpretative summary of the blue room group as a social learning space is presented, in accordance with the principles of caring to make a difference, engaging uncertainty, and paying attention. The perceived benefits of kinesiology, as well as the challenges and limitations of the blue room, are discussed based on the authors’ experiences operating within a continuously evolving and shifting social learning space.
Evolution-inspired engineering of nonribosomal peptide synthetases
Authors: Bozhüyük Kenan A. J. , Präve Leonard , Kegler Carsten , Schenk Leonie , Kaiser Sebastian , Schelhas Christian , Shi Yan-Ni , Kuttenlochner Wolfgang , Schreiber Max , Kandler Joshua , Alanjary Mohammad , Mohiuddin T. M. , Groll Michael , Hochberg Georg K. A. , Bode Helge B.
Published: March 2024

Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired “eXchange Unit between T domains” (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.
Overcoming limitations in propanedehydrogenation by codesigning catalyst-membrane systems
Authors: Almallahi Rawan , Wortman James , Linic Suljo
Published: March 2024

Propylene production through propane dehydrogenation (PDH) is endothermic, and high temperatures required to achieve acceptable propane conversions lead to low selectivity and severe carbon-induced deactivation of conventional catalysts. We developed a catalyst-membrane system that removes the hydrogen by-product and can thus achieve propane conversions that exceed equilibrium limits. In this codesigned system, a silica/alumina (SiO
2
/Al
2
O
3
) hollow-fiber hydrogen membrane was packed with a selective platinum-tin (Pt
1
Sn
1
/SiO
2
) PDH catalyst on the tube side with hydrogen diffusing from the tube to the shell side. We demonstrate that the catalyst-membrane system can achieve propane conversions >140% of the nominal equilibrium conversion with a propylene selectivity >98% without deactivation of the system components. We also show that by introducing oxygen on the shell side of the catalyst-membrane system, we can couple the endothermic PDH reaction on the tube side with exothermic hydrogen oxidation on the shell side. This coupling results in higher rates of hydrogen transport, leading to further enhancements in the propane conversion as well as desired thermoneutral system operation.
Repeated co-option of HMG-box genes for sex determination in brown algae and animals
Authors: Luthringer Rémy , Raphalen Morgane , Guerra Carla , Colin Sébastien , Martinho Claudia , Zheng Min , Hoshino Masakazu , Badis Yacine , Lipinska Agnieszka P. , Haas Fabian B. , Barrera-Redondo Josué , Alva Vikram , Coelho Susana M.
Published: March 2024

In many eukaryotes, genetic sex determination is not governed by XX/XY or ZW/ZZ systems but by a specialized region on the poorly studied U (female) or V (male) sex chromosomes. Previous studies have hinted at the existence of a dominant male-sex factor on the V chromosome in brown algae, a group of multicellular eukaryotes distantly related to animals and plants. The nature of this factor has remained elusive. Here, we demonstrate that an HMG-box gene acts as the male-determining factor in brown algae, mirroring the role HMG-box genes play in sex determination in animals. Over a billion-year evolutionary timeline, these lineages have independently co-opted the HMG box for male determination, representing a paradigm for evolution’s ability to recurrently use the same genetic “toolkit” to accomplish similar tasks.
Modeling Heartland virus disease in mice and therapeutic intervention with 4′-fluorouridine
Authors: Westover Jonna B. , Jung Kie Hoon , Alkan Cigdem , Boardman Kirsten M. , Van Wettere Arnaud J. , Martens Craig , Rojas Inioska , Hicks Philip , Thomas Aaron J. , Saindane Manohar T. , Bluemling Gregory R. , Mao Shuli , Kolykhalov Alexander A. , Natchus Michael G. , Bates Paul , Painter George R. , Ikegami Tetsuro , Gowen Brian B.
Published: March 2024

Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses. We used this model to assess the efficacy of the ribonucleoside analog, 4′-fluorouridine (EIDD-2749), and showed that once-daily oral treatment with 3 mg/kg of drug, initiated after the onset of disease, protects mice against lethal MA-HRTV challenge and reduces viral loads in blood and tissues. Our findings provide insights into HRTV virulence and pathogenesis and support further development of EIDD-2749 as a therapeutic intervention for HRTV disease.

IMPORTANCE

More than 60 cases of HRTV disease spanning 14 states have been reported to the United States Centers for Disease Control and Prevention. The expanding range of the Lone Star tick that transmits HRTV, the growing population of at-risk persons living in geographic areas where the tick is abundant, and the lack of antiviral treatments or vaccines raise significant public health concerns. Here, we report the development of a new small-animal model of lethal HRTV disease to gain insight into HRTV pathogenesis and the application of this model for the preclinical development of a promising new antiviral drug candidate, EIDD-2749. Our findings shed light on how the virus causes disease and support the continued development of EIDD-2749 as a therapeutic for severe cases of HRTV infection.
The complete genomic sequencing of a
Klebsiella pneumoniae
isolated from a patient suffering from urinary tract infection
Authors: Di Lingfang , Gu Chunyan , Salman Sayyed , Li Yafei
Published: March 2024

The present study examines the genomic sequence of
Klebsiella pneumoniae
strain ACESH02121hy, which possesses a genome size of 5,281,767 bp. The strain was obtained from a patient’s urine sample presenting symptoms associated with urinary tract infection.
Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China
Authors: Huang Bingzhou , Deng Lishuang , Xu Tong , Jian Zhijie , Lai Siyuan , Ai Yanru , Xu Zhiwen , Zhu Ling
Published: March 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.

IMPORTANCE

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.
Flecainide causing elevated capture thresholds on pacemaker implantation
Authors: Leow Kevin Chee-Theng , Lim Wooi Ye , Lee Audrey , Rahman Moyazur , Tan Ren
Published: March 2024

Flecainide is a Vaughan Williams class 1c antiarrhythmic used to treat supraventricular and ventricular arrhythmias. It has been described as a rare cause for increased pacemaker capture thresholds. We describe a report of a patient, in her early 80s, presenting with tachy-brady syndrome on a background of permanent atrial fibrillation. She was treated with metoprolol and flecainide by her private cardiologist. Permanent right ventricular chamber pacing was recommended for her slow heart rate. At insertion of her single chamber pacemaker, she was noted to have elevated capture thresholds despite appropriate lead positioning. A flecainide level was elevated at 1.1 µg/mL, and it was subsequently ceased. This was associated with a rapid improvement in her capture threshold. Flecainide should be considered as a cause for elevated pacing thresholds at the time of implant. Particular care should be taken for at-risk groups such as the elderly and patients with renal impairment.
Investigation of divergent thinking among surgeons and surgeon trainees in Canada (IDEAS): a mixed-methods study
Authors: Thabane Alex , McKechnie Tyler , Arora Vikram , Calic Goran , Busse Jason W , Sonnadara Ranil , Bhandari Mohit
Published: March 2024

Objective

To assess the creative potential of surgeons and surgeon trainees, as measured by divergent thinking. The secondary objectives were to identify factors associated with divergent thinking, assess confidence in creative problem-solving and the perceived effect of surgical training on creative potential, and explore the value of creativity in surgery.

Design

We used a mixed-methods design, conducting a survey of divergent thinking ability using a validated questionnaire followed by two semi-structured interviews with top-scoring participants.

Participants & setting

Surgeons and surgeon trainees in the Department of Surgery at McMaster University.

Outcomes

The primary outcome was divergent thinking, assessed with the Abbreviated Torrance Test for Adults. Participants also self-assessed their confidence in creative problem-solving and the effect of surgical training on their creative potential. We performed descriptive analyses and multivariable linear regression to identify factors associated with divergent thinking. We conducted a thematic analysis of the interview responses.

Results

82 surgeons and surgeon trainees were surveyed; 43 were junior trainees and 28 were senior trainees. General surgery, orthopaedic surgery and plastic surgery represented 71.9% of the participants. The median participant age was 28 years (range 24–73), 51.2% of whom were female. Participants demonstrated levels of divergent thinking that were higher but not meaningfully different from the adult norm (62.39 (95% CI 61.25, 63.53), p<0.001). While participants scored significantly higher than the average adult on fluency (the ability to produce quantities of ideas) and flexibility (the ability to process information in different ways) (p<0.001 for both), they scored below average on originality (the ability to produce uncommon, new or unique ideas) (p<0.001). Regression analysis identified higher divergent thinking scores among females (estimated β=−3.58 (95% CI −6.25 to –0.90), p=0.010).

Conclusions

The divergent thinking ability among surgeons and surgeon trainees was not meaningfully different from the adult normative score; however, their ability to generate original ideas was below average.
Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke
Authors: Favilla Christopher G , Baird Grayson L , Grama Kedar , Konecky Soren , Carter Sarah , Smith Wendy , Gitlevich Rebecca , Lebron-Cruz Alexa , Yodh Arjun G , McTaggart Ryan A
Published: March 2024

Background

Early detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we investigated the ability of the portable Openwater optical blood flow monitor to detect LVO.

Methods

Patients were prospectively enrolled at two comprehensive stroke centers during stroke alert evaluation within 24 hours of onset with National Institutes of Health Stroke Scale (NIHSS) score ≥2. A 70 s bedside optical blood flow scan generated cerebral blood flow waveforms based on relative changes in speckle contrast. Anterior circulation LVO was determined by CT angiography. A deep learning model trained on all patient data using fivefold cross-validation and learned discriminative representations from the raw speckle contrast waveform data. Receiver operating characteristic (ROC) analysis compared the Openwater diagnostic performance (ie, LVO detection) with prehospital stroke scales.

Results

Among 135 patients, 52 (39%) had an anterior circulation LVO. The median NIHSS score was 8 (IQR 4–14). The Openwater instrument had 79% sensitivity and 84% specificity for the detection of LVO. The rapid arterial occlusion evaluation (RACE) scale had 60% sensitivity and 81% specificity and the Los Angeles motor scale (LAMS) had 50% sensitivity and 81% specificity. The binary Openwater classification (high-likelihood vs low-likelihood) had an area under the ROC (AUROC) of 0.82 (95% CI 0.75 to 0.88), which outperformed RACE (AUC 0.70; 95% CI 0.62 to 0.78; P=0.04) and LAMS (AUC 0.65; 95% CI 0.57 to 0.73; P=0.002).

Conclusions

The Openwater optical blood flow monitor outperformed prehospital stroke scales for the detection of LVO in patients undergoing acute stroke evaluation in the emergency department. These encouraging findings need to be validated in an independent test set and the prehospital environment.
Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex
Authors: Joseph Anna , Baslet Gaston , O’Neal Mary A , Polich Ginger , Gonsalvez Irene , Christoforou Andrea N , Dworetzky Barbara A , Spagnolo Primavera A
Published: March 2024

Background

Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging as one potential mechanism. To begin to understand the role of immune dysfunctions in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex.

Methods

Using a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by the presence of psychiatric comorbidities.

Results

The overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p= 0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p’s < 0.05).

Conclusions

This study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterised by distinct dysregulations in immune response.