bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Latent Constructs through Multimodal Data Analysis
Authors: Wang Shiyu , Wu Shushan , Chen Yinghan , Fang Luyang , Xiao Liang , Li Feiming
Published: August 2024

This study presents a comprehensive analysis of three types of multimodal data‐response accuracy, response times, and eye‐tracking data‐derived from a computer‐based spatial rotation test. To tackle the complexity of high‐dimensional data analysis challenges, we have developed a methodological framework incorporating various statistical and machine learning methods. The results of our study reveal that hidden state transition probabilities, based on eye‐tracking features, may be contingent on skill mastery estimated from the fluency CDM model. The hidden state trajectory offers additional diagnostic insights into spatial rotation problem‐solving, surpassing the information provided by the fluency CDM alone. Furthermore, the distribution of participants across different hidden states reflects the intricate nature of visualizing objects in each item, adding a nuanced dimension to the characterization of item features. This complements the information obtained from item parameters in the fluency CDM model, which relies on response accuracy and response time. Our findings have the potential to pave the way for the development of new psychometric and statistical models capable of seamlessly integrating various types of multimodal data. This integrated approach promises more meaningful and interpretable results, with implications for advancing the understanding of cognitive processes involved in spatial rotation tests.
The influence of tobacco smoking on the outcomes achieved by root coverage procedures: An updated systematic review
Authors: Chambrone Leandro , Coccaro Miguelángel , Montaño Andrea Juliana , Lafaurie Gloria Inés
Published: August 2024

Objective

This updated version of a systematic review (SR) originally published in 2009 evaluated the effect of smoking on the clinical outcomes achieved with root coverage (RC) procedures in the treatment of gingival recession (GR) defects.

Materials and Methods

This SR includes randomized controlled trials, controlled clinical trials, and case series with a minimum follow‐up of 6 months. Eligible studies involved GR defects without interproximal tissue loss submitted to RC procedures, as well as outcome measures from smokers (i.e., those smoking 10 or more cigarettes per day at baseline) and nonsmokers, recorded separately. Three electronic databases were searched up to March 31, 2024. Random effects meta‐analyses were conducted thoroughly.

Results

A total of 12 studies reporting on 181 smokers and 162 nonsmokers, submitted to different RC procedures, were included. Half of these trials were originally included in the 2009 SR, whereas the other half (six studies) were included in this update. Nonsmokers experienced greater reductions in GR and gains in clinical attachment level compared to smokers. Pooled estimates comparing smokers and nonsmokers who received coronally advanced flap (CAF) alone and subepithelial connective tissue graft (SCTG) + CAF showed that nonsmokers achieved greater mean root coverage (MRC) in both treatments. Significant differences in MRC of 10.85% (95% CI, 1.92 to 19.77) and 22.04 (95% CI, 14.25 to 29.83), favoring nonsmokers, were identified for CAF and SCTG + CAF, respectively. Similarly, nonsmokers treated with SCTG + CAF displayed superior number of sites exhibiting complete root coverage (CRF) when compared with smokers (risk ratio, 4.12; 95% CI, 1.73 to 9.80).

Conclusions

Smoking negatively impacts the outcomes of RC procedures, particularly those achieved by SCTG‐based procedures.

Clinical Significance

Smoking was linked to poorer RC outcomes. These outcomes highlight the critical need to integrate smoking cessation into periodontal treatment plans.
Assessing robustness of consequential LCA: Insights from a multiregional economic model tailored to the cement industrial symbiosis
Authors: Lessard Jean‐Martin , Habert Guillaume , Tagnit‐Hamou Arezki , Amor Ben
Published: August 2024

One of the key challenges in conducting consequential life cycle assessment (LCA) is to identify and quantify what is likely to be affected by changes in market behavior—so‐called marginal effects. Although the critical importance of uncertainty and sensitivity assessments in attributional LCA is recognized, they are rarely conducted in consequential studies. Thus, this paper aims to address two objectives: first, to examine the uncertainty and robustness of marginal effects in consequential LCA and second, to identify the most influential group of inputs contributing to the overall variance in climate change impact scores. To accomplish this, the study employs an enhanced consequential LCA framework that integrates a multiregional economic optimization model with consequential LCA tools. The framework is applied to assess the climate implications of a 6% increase in clinker substitution within average Eastern North American cement production by 2030, relative to 2020 levels. Through this framework, a Monte Carlo simulation is conducted to evaluate the dispersion of the results. Subsequently, a variance‐based one‐at‐a‐time sensitivity analysis is performed to rank the most influential groups of inputs affecting the robustness of result across macroeconomic, material flow, economic, transport, and consequential life cycle inventory databases. Afterward, a conceptual framework is proposed to guide practitioners in prioritizing areas for testing consequential LCA results based on region‐specific information. This work aims to contribute to decision‐makers' access to more reliable information to support the development of effective environmental regulatory measures.
Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy
Authors: Roggenbuck Jennifer , Morales Ana , Ellis Colin A. , Dratch Laynie , Stetler Molly , Tan Christopher A. , Bucknor Brianna , Hatchell Kathryn E. , Aradhya Swaroop , Esplin Edward D. , Ting Yi‐Lee , Scherer Steven S.
Published: August 2024

Background and Aims

Prior to next‐generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory.

Methods

A cohort of 6849 adult patients underwent clinician‐ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis.

Results

A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines.

Interpretation

Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.
The relationship between swallowing oral hesitation and cognition in frontal lobe stroke
Authors: Yun Yeo Joon , Han Seung Hoon
Published: August 2024

Background & Objective

Oral stage dysphagia mostly caused by frontal lobe lesions. We investigated the relationship between oral hesitation and cognitive impairment after frontal lobe stroke.

Methods

We consecutively collected 946 patients with stroke from January 2016 to December 2020. Among them, 38 patients had only frontal lobe lesions. Video fluoroscopic swallowing study (VFSS) was performed in 5 stages from water to solid food. Patients who progressed to solid food are very rare, so we focused on liquid and soft food. Diagnosis of stroke was limited to cases in which cerebral infarction or haemorrhage had been verified by magnetic resonance imaging (MRI). Cognitive impairment was evaluated by MMSE in patients with frontal lobe lesions.

Result

Of the total 946 patients, 35 patients with frontal lobe lesions were enrolled in the study. Of them, 22 were judged to have cognitive impairment. The oral hesitation of the liquid component was analysed, and a conclusion was drawn that the group with cognitive impairment showed significant oral hesitation than the group without cognitive impairment. On the other hand, in the case of soft food, it was found that there was no correlation between cognition and oral hesitation.

Conclusion

It was confirmed that oral hesitation during swallowing in patients with frontal lobe stroke had a meaningful relationship with cognition, and oral hesitation during swallowing was significantly higher in liquid swallowing rather than soft food.
Impact of adding papain to sous vide cooking on texture and sensorial traits of marinated semitendinosus beefsteaks
Authors: de Oliveira Thales Leandro Coutinho , Tanaka Marcelo Stefanini , Rezende Jeferson Leandro , Rodrigues Lorena Mendes , Ramos Alcinéia de Lemos Sousa , Ramos Eduardo Mendes
Published: August 2024

Sous vide meat is an emerging food category, the consumption of which has increased owing to greater convenience, sensory traits, elderly consumers acceptance, and low‐cost cuts use. However, required prolonged thermal treatment to achieve desired tenderness, impact energy‐consumption besides triggering lipid oxidation, undesired off‐flavors, and cooked meat profiles. Using a response surface methodology (RSM), this study evaluated the effects of the vegetal proteolytic papain (0 to 20 mg/kg) and low‐temperature sous vide cooking (SVC) time (1 to 8 h at 65°C) in low‐value marinated M. semitendinosus beefsteaks on technological characteristics associated with tenderness, and lipid oxidation. Additionally, the sensory profile traits of the pre‐selected treatments were described using check‐all‐that‐apply (CATA) and preference mapping. Shear force (WBsSF) was reduced with greater papain addition, whereas higher cooking losses (CL) were observed with longer SVC cooking times. Both the released total collagen and TBARS values increased with increasing papain concentrations and SVC times. Combining high levels of papain (>10 mg/kg) and SVC time (>6 h) resulted in lower WBsSF values (<20 N) but higher CL (>27%) and the CATA descriptors “aftertaste” and “mushy.” The optimized conditions (14 mg/kg papain; 2 h SVC) also reduced WBsSF values (<26 N) with lower CL (<20%) and were most preferred and described as “juicy” and “tender” by consumers. Observed results suggest that combined mild SVC and papain may potentiate tenderness, conjointly favor juiciness and oxidation, further representing a promising tool for reducing SVC time without compromising valued sous vide sensory traits.
Salinity/ionic balance interactions on the zootechnical performance and histology of Litopenaeus vannamei and water quality in a biofloc system
Authors: Ueno Fukura Mitsuaki , Collazos Lasso Luis Felipe , Vinatea Arana Luis Alejandro , Baldisserotto Bernardo
Published: August 2024

This study aimed to evaluate the interactions between two low salinities (S = 4 and 8 g L−1) and two ionic balances (Na+/Mg+2/Ca+2/K+ ratio, IB1 = 27.6/3.6/1.05/1 and IB2 = 40.6/4.7/1.98/1) on zootechnical performance and histology of Litopenaeus vannamei postlarvae (0.0073 ± 0.0007 g) and juveniles (0.2163 ± 0.0080 g) reared in a biofloc system at stocking density of 1500 and 300 individuals m−3, respectively, over two culture phases: nursery (30 days) and grow‐out (60 days). High nitrification processes were detected at lower salinity treatments, with the lowest ammonia and nitrite concentration in those. There were no significant differences on shrimp survival between treatments; however, the best final weights were observed in the S8IB2 (0.24 ± 0.01 g) and S4IB1 (2.80 ± 0.12 g) treatments for the nursery and grow‐out stages, respectively. The most frequent histological lesions were the absence of lipid vacuoles in the hepatopancreas and abundant organic debris in the gill lamellae. The viability of rearing L. vannamei juveniles in biofloc at low salinity is still relatively weak because of their low growth and low efficiency to store fatty acids in the hepatopancreas; however, higher postlarvae productivity was found at 8 g L−1 and Na+/Mg+2/Ca+2/K+ ratio of 40.6/4.7/1.98/1 in the nursery stage.
Factors associated with progression of non‐motor symptoms and deterioration in quality of life in Parkinson's disease: Results of J‐FIRST, a 1‐year observational study
Authors: Kashihara Kenichi , Chiu Shih‐Wei , Tsuboi Yoshio , Hattori Nobutaka , Nomoto Masahiro , Watanabe Hirohisa , Maeda Tetsuya , Saiki Hidemoto , Shimo Yasushi , Yamaguchi Takuhiro ,   the J‐FIRST Group
Published: August 2024

Background

Worsening motor symptoms are associated with deteriorations in health‐related quality of life (HrQOL) in patients with Parkinson's disease (PD).

Aim

Because few studies have examined whether non‐motor symptoms (NMSs) predict worsening of overall NMSs and HrQOL, we investigated whether NMSs are associated with the changes in these outcomes in patients with PD.

Methods

We used data from J‐FIRST, a 52‐week study of patients with PD, ≥1 NMS, and wearing‐off under levodopa treatment. Changes in Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part I and 8‐item Parkinson's Disease Questionnaire (PDQ‐8) total scores during the observation period were compared between patients with and without individual NMSs at baseline. Relationships among NMSs were analyzed by cluster analysis.

Results

The analyses comprised 996 patients. The MDS‐UPDRS Part I total scores significantly increased in patients with cognitive impairment, depressed mood, and apathy, but significantly decreased in patients with features of dopamine dysregulation syndrome, relative to the changes in patients without these NMSs at baseline. The PDQ‐8 total scores significantly increased in patients with cognitive impairment, hallucinations and psychosis, depressed mood, apathy, pain and other sensations, urinary problems, and fatigue relative to the changes in patients without these NMSs at baseline. NMSs were broadly clustered into cognitive/mental functions, and autonomic functions and sleep. Light headedness on standing, fatigue, and pain and other sensations were closely related.

Conclusion

We observed significant deteriorations in the NMS burden and HrQOL in patients with cognitive, mental, or autonomic‐related NMSs.
Bridges between two medical realities: Perspectives of Indigenous medical and nursing students on snakebite care in the Brazilian Amazon
Authors: de Farias Altair Seabra , Viana Guilherme Pinto , Cristino Joseir Saturnino , Farias Franciane Ribeiro , Farias Lara Francisca Ribeiro , de Freitas Raquel Nascimento , Murta Felipe , Machado Vinícius Azevedo , Sachett Jacqueline de Almeida Gonçalves , Monteiro Wuelton M.
Published: August 2024

In the Brazilian Amazon, snakebite envenomations (SBEs) disproportionately affect Indigenous populations, and have a significantly higher incidence and lethality than in non‐Indigenous populations. This qualitative study describes the Indigenous and biomedical healthcare domains for SBE care from the perspective of the Indigenous medical and nursing students in Manaus, Western Brazilian Amazon. In‐depth interviews were conducted with five Indigenous students from the Amazonas State University, between January and December 2021. The interviews were analyzed using inductive content analysis. We organized an explanatory model with five themes: (1) participants' identities; (2) causality levels in Indigenous and biomedical systems; (3) therapeutic itineraries in Indigenous and biomedical systems; (4) ideological implications of adding biomedical devices to Indigenous healing systems; and (5) therapeutic failure in and efficacy of Indigenous and biomedical systems. From a noncolonial perspective and seeking to increase the quality and acceptability of health care for the Indigenous populations of the Brazilian Amazon, the training of Indigenous health professionals presents itself as a promising strategy. For this goal, universities should serve as empowering settings for Indigenous health students that support them in their growth and development, raise their awareness of injustice, and catalyze change toward a culturally adapted and effective service for the users.
Postoperative ileus—Establishing a porcine model
Authors: Martensen A. K. , Moen E. V. , Brock C. , Funder J. A.
Published: August 2024

Background

Postoperative ileus (POI), characterized by absent gastrointestinal motility, is a frequent complication following major abdominal surgery, with no current effective treatment possibilities. For further research in the treatment of this condition, we aimed to establish a porcine model of POI.

Methods

A total of 12 Landrace pigs, weighing 60 kg, were included. Five animals were used as pilots to establish the surgical procedure, five animals received the same reproducible surgical procedure developed in the pilot experiments, while two animals were used as control. The primary endpoint was number of days to first stool. Intestinal motility was monitored using the SmartPill system.

Key Results

Four of the five pigs who underwent the final surgical procedure passed first stool on the third postoperative day (POD), and one passed first stool on the fifth POD. SmartPill data showed retention of the capsule in the stomach in four of five pigs with usable traces.

Conclusion and Inferences

An experimental porcine model of POI was established, forming the basis for future studies in POI.
Comparative Study of Preoperative Sagittal Spinal Pelvic Alignment in Patients with Cervical Spondylotic Radiculopathy, Ossification of the Posterior Longitudinal Ligament, and Cervical Spondylotic Myelopathy
Authors: Wang Shuo , Yuan Suomao , Liu Ping , Qi Feng , Tian Yonghao , Zhang Yuchen , Li Changzhen , Li Jiale , Liu Xinyu , Wang Lianlei
Published: August 2024

Objectives

Cervical spondylosis may lead to changes in the sagittal parameters of the neck and trigger compensatory alterations in systemic sagittal parameters. However, there is currently a dearth of comparative research on the changes and compensatory alterations to sagittal parameters resulting from different types of cervical spondylosis. This study compared the preoperative sagittal alignment sequences among patients with cervical spondylotic radiculopathy (CSR), ossification of the posterior longitudinal ligament (OPLL), and cervical spondylotic myelopathy (CSM) caused by factors resulting from non‐OPLL factors.

Materials and Methods

Full length lateral X‐ray of the spine and cervical computed tomography (CT) of 256 patients (134 men, 122 women; mean age, 56.9 ± 9.5 years) were analyzed retrospectively. A total of 4096 radiomics features were measured through the lateral X‐ray by two spinal surgeons with extensive experience. The clinical symptoms measures were the Japanese Orthopaedic Association (JOA) score, number of hand actions in 10 s, hand‐grip strength, visual analog scale (VAS) score. Normally distributed data was compared using one‐way analysis of variance (ANOVA) for parametric variables and χ2 test were used to analyze the categorical data.

Results

In the OPLL group, the C2‐C7 Cobb angle was greater than in the CSR and CSM groups (19.8 ± 10.4°, 13.3 ± 10.3°, and 13.9 ± 9.9°, respectively, p < 0.001). Additionally, the C7‐S1 SVA measure was found to be situated in the anterior portion with regards to the CSM and CSR groups (19.7 ± 58.4°, −6.3 ± 34.3° and −26.3 ± 32.9°, p < 0.001). Moreover, the number of individuals with C7‐S1 SVA >50 mm was significantly larger than the CSM group (26/69, 11/83, p < 0.001). In the CSR group, the TPA demonstrated smaller values compared to the OPLL group (8.8 ± 8.5°, 12.7 ± 10.2°, p < 0.001). Furthermore, the SSA was comparatively smaller as opposed to both the OPLL and CSM groups (49.6 ± 11.2°, 54.2 ± 10.8° and 54.3 ± 9.3°, p < 0.05).

Conclusion

Patients with OPLL exhibit greater cervical lordosis than those with CSR and CSM. However, OPLL is more likely to result in spinal imbalance when compared to the CSM group. Furthermore, OPLL and CSM patients exhibit anterior trunk inclination and worse global spine sagittal parameters in comparison to CSR patients.
Institutional pressures and the prevalence of nonprofit sector support organizations
Authors: Liu Zejin
Published: August 2024

This study focuses on the prevalence of nonprofit sector support organizations (NSSOs)—a form of nonprofit organization (NPO) devoted to providing services and resources to support grassroots development. Contrary to previous studies that emphasize the importance of institutions in shaping the NPO population through their effect on citizens and nonprofit managers, this study links three institutional pressures—coercive, mimetic, and normative pressures—to the decisions of public agencies to establish NSSOs. This study examines this claim using a newly constructed dataset of NSSOs across 330 Chinese cities between 2012 and 2021 (N = 2385). The results indicate that cities with greater pressure from provincial governments, neighboring cities, and professional associations are more likely to promote the establishment of NSSOs. This study advances the understanding of the impact of institutions on the dynamics of the NPO population by demonstrating their effect on public agencies.
Lung cancer (internet‐based) Delphi (LUCiD): A modified eDelphi consensus process to establish Australasian clinical quality indicators for thoracic cancer
Authors: Nash Jessica , Stone Emily , Vinod Shalini , Leong Tracy , Dawkins Paul , Stirling Rob G. , Harden Susan , Bolton Alison , McWilliams Annette , O'Byrne Kenneth , Wright Gavin M. , Brunelli Vanessa N. , Guan Tracey , Philpot Shoni , Navani Neal , Brims Fraser ,   the LUCAP investigator team
Published: August 2024

Background and Objective

Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand.

Methods

Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting.

Results

The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking.

Conclusion

Twenty‐seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia.
Phagolysosomal resistance hypothesized to be a danger signal
Authors: Forden Christopher A.
Published: August 2024

Antigen presenting cells sometimes require T cell “help” to kill and decompose microbes they capture, especially when those microbes resist effector molecules including nitric oxide and reactive oxygen species. Pathogens are more likely to resist those effectors, shared by the innate and adaptive immune systems, than are commensals. Does such resistance alert the immune system to the danger posed by those pathogens? Several lines of evidence suggest this occurs. Mouse studies showed a surprising exacerbation, not alleviation of experimental autoimmune encephalomyelitis, by suppression of nitric oxide production, but only when the suppression was applied to animals undergoing vaccination with myelin. In contrast, animals receiving T cells activated by vaccination without suppression of nitric oxide benefitted from reduced autoimmune cytotoxicity when nitric oxide production was suppressed after adoptive transfer. Vaccinia and adenovirus suppress nitric oxide production and have been successful vaccine platforms, also consistent with the above phagolysosomal resistance hypothesis. The hypothesis solves a long‐standing quandary—how can nitric oxide protect against both infection and autoimmunity, especially autoimmune diseases for which it seems a major effector? The importance of physical linkage between epitopes, first proposed in Bretscher's Two‐Step, Two‐Signal theory dependent on B cells, is extended to include phagolysosomal resistance in general, plus a corollary proposition that the immune system detects resistance to dissociation of high‐affinity pathogenic ligands from host binding sites to make neutralizing antibodies.
Taking the next step: How student reflective essays about difficult clinical encounters demonstrate professional identity formation
Authors: Freeman Nicholas , Shapiro Johanna , Paguio Marvin , Lorkalantari Yasaman , Nguyen Alexis
Published: August 2024

Background

Difficult clinical encounters pose emotional and behavioural challenges for medical students. Unless resolved, they threaten students' professional competence and well‐being. Learning how to humanistically interact with patients perceived as “difficult” is an important component of the developmental process that underlies professional identity formation (PIF).

Methods

This study used thematic analysis to examine reflective essay data from the same set of students (N = 69), first in their third year and then in their fourth year of training at a US public medical school. Analysis focused on how student perceptions of patients', preceptors', and their own behaviour, attitudes, and emotions in difficult patient care situations evolved over time, and how such evolution contributed to their professional growth.

Findings

Students identified clinical predicaments influenced by their own emotions and behaviour, as well as those of patients and preceptors. In response to patients perceived as angry, rude, and uncooperative, students described themselves and their preceptors primarily as engaging in routine medical behaviours, followed by expressions of empathy. These encounters resulted in residual emotions as well as lessons learned. Fourth‐year students reported more empathy, patient‐centeredness, and patient ownership than third‐year students. While student‐physicians grew in professionalism and compassion, they also noted unresolved distressing emotions post‐encounter.

Conclusions

From third to fourth year, medical students undergo a process of professional growth that can be documented at a granular level through their perceptions of themselves, their patients, and their preceptors. Despite positive professional growth, students' lingering negative affect merits attention and support from clinical teachers.
When transfusion causes a splitting headache: A case report and rapid review of transfusion‐associated reversible cerebral vasoconstriction syndrome
Authors: Pelham‐Webb Bobbie , Guo Yin , Ramirez Alejandra , Waldron Evan , Emmanuele Valentina , Vargas Wendy , Kahn Justine , Stone Elizabeth F.
Published: August 2024

KEY IDEAS

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare and understudied transfusion reaction most commonly seen in adult females after correction of chronic, severe anemia.

Transfusion‐associated RCVS (TA‐RCVS) typically presents with thunderclap headaches and one or more systemic (hypertension, nausea/vomiting) or neurologic (seizure, stroke, visual changes) symptoms within a week after red blood cell transfusion.

Treatment of RCVS is based on blood pressure control; a recent study suggested that early use of nimodipine could shorten the disease course.
Global value chains and inward FDI: An empirical investigation of European firms
Authors: Imbruno Michele , Pittiglio Rosanna , Reganati Filippo , Szymczak Sabina , Wolszczak‐Derlacz Joanna
Published: August 2024

This paper empirically investigates whether and how the level of GVC integration of a given market may explain the presence of foreign‐owned firms. Using firm‐level data from 28 European Union countries during the period 2008–2014, we provide evidence that a greater country‐sector‐level GVC participation, via both backward and forward linkages, exerts a positive effect on a firm's likelihood to receive FDI. These findings appear particularly strong for new EU Member States and services industries when looking at the differences across countries and sectors. Interestingly, when exploring the role of country‐sector position along the GVC, we find that FDI gains from backward GVC integration are more prominent if the markets are associated with the final stages of the supply chain, whereas those from forward GVC integration are greater when the markets are associated with the initial stages, in line with the smile curve hypothesis.
Analysis of the immunomodulatory properties of mycobacterium cell wall fraction on the cytokine production of peripheral blood mononuclear cells of healthy dogs
Authors: Ward Robert , Wood Geoffrey A. , Pye Charlotte , Karimi Khalil , Yu Anthony , St‐Denis Myles , Blake Katherine , Raj Sugandha , Oladokun Samson , Sharif Shayan
Published: August 2024

Background

Mycobacterium cell wall fraction (MCWF) is derived from nonpathogenic Mycobacterium phlei and is used as an immunomodulatory compound in clinical practice, yet its mode‐of‐action requires further research.

Objective

To evaluate the host response to MCWF in canine peripheral blood mononuclear cells (PBMCs) by using enzyme‐linked immunosorbent assays (ELISA) and quantitative reverse transcription (qRT)‐PCR for assessment of cytokines.

Animals

Eight healthy Labrador retrievers.

Materials and Methods

PBMCs were isolated from whole blood using density centrifugation. The cells were cultured with different concentrations of MCWF or a potent stimulator of cytokine production, phorbol 12‐myristate 13‐acetate/ionomycin, or left in cell culture medium for 24, 48 and 72 h. Cytokines were measured by ELISA for interleukin (IL)‐4, IL‐10 and interferon‐gamma (IFN‐γ), and by qRT‐PCR for IL‐4, IL‐10, IL‐13, IFN‐γ, tumour necrosis factor alpha (TNF‐α) and transforming growth factor‐beta.

Results

A significant increase of IL‐10 messenger ribonucleic acid (mRNA) was detected at all time points for all concentrations of MCWF (p < 0.05). Protein analysis reflected this finding, with a maximum IL‐10 concentration of 300.6 ± 38.3 μg/mL. Compared to the negative control, post‐stimulation elevation of IFN‐γ mRNA was noted at 24 h with all concentrations of MCWF (p < 0.01), and TNF‐α mRNA was increased for 0.5 μg/dL MCWF only at 72 h (p < 0.05).

Conclusions and Clinical Relevance

MCWF stimulation of PBMCs results in the elevation of both proinflammatory and regulatory cytokine mRNA. Further research into the role of MCWF as a systemically administered regulatory immunomodulator or adjuvant to allergen‐specific immunotherapy should be considered.
An Enhanced Predictive Method for Large Droplet Breakage Based on the Discrete Particle Model
Authors: Ju Hongyu , Suo Jianqin , Li Yue
Published: August 2024

In high-speed flows, a single droplet undergoes fragmentation, yielding numerous child droplets. Conventional breakup models usually group these droplets into a single parcel, neglecting the postbreakup spatial distribution. To address this limitation, detailed numerical simulations have been conducted focusing on the bag and bag–stamen breakup modes of 200 μm-diameter droplet at Weber numbers of 15 and 30. The result shows that the largest length of the child-droplets cloud can reach up to 29 times the original diameter. Importantly, if the grid size is less than 29 times the droplet diameter, traditional models that use a single parcel for child droplets could produce inaccurate results. To overcome this limitation, a disk-like breakup (DLB) model was introduced. With this model, multiple parcels replace the original droplet and are initialized on a virtual disk. Additionally, partitioned breakup modeling was employed for both bag and bag–stamen breakups. Calculations using the DLB model were compared with the Taylor analogy breakup (TAB), Kelvin–Helmholtz Rayleigh–Taylor (KH–RT), and enhanced Taylor analogy breakup (ETAB) models. The result indicates that the DLB model is capable of simulating the spatial distribution of the droplet cloud postbreakup, achieving better agreement with the detailed numerical simulations using the volume of fluid (VOF) method in this paper and experiments in the literature.
Revealing the Effect of Dynamic Structural Evolution on Triple Junction Deformation Mechanism: Molecular Dynamics Simulations and an Energetic Model
Authors: Wan Panpan , Zhang Zhenghao , Huang Qishan , Zhou Haofei
Published: August 2024

Triple junction (TJ) migration is a plastic deformation mechanism in polycrystalline metals mediated by the interplay between neighboring grain boundaries (GBs). Compared with GB migration, the dynamic change of TJ structure during migration and its impact on subsequent TJ behavior is often overlooked. In this study, we explore the effect of dynamic TJ structure evolution on TJ deformation mechanism in a face-centered cubic metal Au model using molecular dynamics simulations. Our analysis reveals that the dislocation accumulation at TJ due to inconsistent disconnection nucleation from neighboring GBs can influence the stick-slip behavior of TJ migration. With the dynamic change of TJ structure, the velocity of TJ migration is gradually reduced, leading to a transition from TJ migration to dislocation emission from TJ. We have developed an energetic model to evaluate the critical stresses required for TJ migration and dislocation emission, providing an explanation of the competition between TJ migration and dislocation emission. Our findings deepen the understanding of TJ-governed plastic deformation mechanisms in polycrystalline materials.
Baseball and Culture: A Case-Study Examination of the Korean Baseball Organization Documentary Full Count
Authors: Hull Kevin , Choi Minhee
Published: August 2024

During the 2022 season, a documentary crew followed the teams and players in the Korean Baseball Organization, resulting in a 10-episode series Full Count that debuted the following year. The series was broadcast initially in South Korea; however, a later international release through a streaming platform allowed for increased worldwide exposure for the league, teams, players, and, perhaps somewhat uniquely, the culture and traditions in the home country. Therefore, even though the focus was baseball, this program provided a unique opportunity for the world to learn about the people and values of South Korea. Using constant comparative methodology, the following themes emerged: (a) emphasizing team over individual, (b) respecting elders, (c) overcoming adversity, and (d) playing with honor.
BLADE-ON-PETIOLE interacts with CYCLOIDEA to fine-tune
CYCLOIDEA
-mediated flower symmetry in monkeyflowers (
Mimulus
)
Authors: Gao Yuan , Li Jingjian , He Jiayue , Yu Yaqi , Qian Zexin , Geng Zhiqiang , Yang Liuhui , Zhang Yumin , Ke Yujie , Lin Qiaoshan , Wang Jing , Chen Sumei , Chen Fadi , Yuan Yao-Wu , Ding Baoqing
Published: August 2024

Morphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increase flower morphological diversity. We isolated three allelic mutants from two
Mimulus
species displaying altered floral symmetry and identified the causal gene as the ortholog of
Arabidopsis BLADE-ON-PETIOLE
. We found that MlBOP and MlCYC2A physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses
MlCYC2A
self-activation. MlCYC2A, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2A fine-tunes the expression of
MlCYC2A
, contributing to the formation of bilateral symmetry in flowers, a key trait in angiosperm evolution.
Single neuron responses to perceptual difficulty in the mouse auditory cortex
Authors: Haimson Baruch , Gilday Omri David , Lavi-Rudel Amichai , Sagi Hadar , Lottem Eran , Mizrahi Adi
Published: August 2024

Perceptual learning leads to improvement in behavioral performance, yet how the brain supports challenging perceptual demands is unknown. We used two photon imaging in the mouse primary auditory cortex during behavior in a Go-NoGo task designed to test perceptual difficulty. Using general linear model analysis, we found a subset of neurons that increased their responses during high perceptual demands. Single neurons increased their responses to both Go and NoGo sounds when mice were engaged in the more difficult perceptual discrimination. This increased responsiveness contributes to enhanced cortical network discriminability for the learned sounds. Under passive listening conditions, the same neurons responded weaker to the more similar sound pairs of the difficult task, and the training protocol by itself induced specific suppression to the learned sounds. Our findings identify how neuronal activity in auditory cortex is modulated during high perceptual demands, which is a fundamental feature associated with perceptual improvement.
Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier
Authors: Barker Scarlett J. , Thayer Mai B. , Kim Chaeyoung , Tatarakis David , Simon Matthew J. , Dial Rebekah , Nilewski Lizanne , Wells Robert C. , Zhou Yinhan , Afetian Megan , Akkapeddi Padma , Chappell Alfred , Chew Kylie S. , Chow Johann , Clemens Allisa , Discenza Claire B. , Dugas Jason C. , Dwyer Chrissa , Earr Timothy , Ha Connie , Ho Yvonne S. , Huynh David , Lozano Edwin I. , Jayaraman Srini , Kwan Wanda , Mahon Cathal , Pizzo Michelle , Robles-Colmenares Yaneth , Roche Elysia , Sanders Laura , Stergioulis Alexander , Tong Raymond , Tran Hai , Zuchero Y. , Estrada Anthony A. , Gadkar Kapil , Koth Christopher M. M. , Sanchez Pascal E. , Thorne Robert G. , Watts Ryan J. , Sandmann Thomas , Kane Lesley A. , Rigo Frank , Dennis Mark S. , Lewcock Joseph W. , DeVos Sarah L.
Published: August 2024

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfR
mu/hu
KI) mice and nonhuman primates. Intravenous injection and systemic delivery of OTV to TfR
mu/hu
KI mice resulted in sustained knockdown of the ASO target RNA,
Malat1
, across multiple mouse CNS regions and cell types, including endothelial cells, neurons, astrocytes, microglia, and oligodendrocytes. In addition, systemic delivery of OTV enabled
Malat1
RNA knockdown in mouse quadriceps and cardiac muscles, which are difficult to target with oligonucleotides alone. Systemically delivered OTV enabled a more uniform ASO biodistribution profile in the CNS of TfR
mu/hu
KI mice and greater knockdown of
Malat1
RNA compared with a bivalent, high-affinity TfR antibody. In cynomolgus macaques, an OTV directed against
MALAT1
displayed robust ASO delivery to the primate CNS and enabled more uniform biodistribution and RNA target knockdown compared with intrathecal dosing of the same unconjugated ASO. Our data support systemically delivered OTV as a potential platform for delivering therapeutic ASOs across the BBB.
Expanding the genetic toolbox for
Neisseria meningitidis
with efficient tools for unmarked gene editing, complementation, and labeling
Authors: Wuckelt Morgane , Laurent Audrey , Mouville Clémence , Meyer Julie , Jamet Anne , Lecuyer Hervé , Nassif Xavier , Bille Emmanuelle , Pelicic Vladimir , Coureuil Mathieu
Published: August 2024

The efficient natural transformation of
Neisseria meningitidis
allows the rapid construction of bacterial mutants in which the genes of interest are interrupted or replaced by antibiotic-resistance cassettes. However, this proved to be a double-edged sword, i.e., although facilitating the genetic characterization of this important human pathogen, it has limited the development of strategies for constructing markerless mutants without antibiotic-resistance markers. In addition, efficient tools for complementation or labeling are also lacking in
N. meningitidis
. In this study, we significantly expand the meningococcal genetic toolbox by developing new and efficient tools for the construction of markerless mutants (using a dual counterselection strategy), genetic complementation (using integrative vectors), and cell labeling (using a self-labeling protein tag). This expanded toolbox paves the way for more in-depth genetic characterization of
N. meningitidis
and might also be useful in other
Neisseria
species.

IMPORTANCE

Neisseria meningitidis
and
Neisseria gonorrhoeae
are two important human pathogens. Research focusing on these bacteria requires genetic engineering, which is facilitated by their natural ability to undergo transformation. However, the ease of mutant engineering has led the
Neisseria
community to neglect the development of more sophisticated tools for gene editing, particularly for
N. meningitidis
. In this study, we have significantly expanded the meningococcal genetic toolbox by developing novel and efficient tools for markerless mutant construction, genetic complementation, and cell tagging. This expanded toolbox paves the way for more in-depth genetic characterization of
N. meningitidis
and might also be useful in other
Neisseria
species.
CD81 fusion alters SARS-CoV-2 Spike trafficking
Authors: Cone Allaura S. , Zhou Yijun , McNamara Ryan P. , Eason Anthony. B. , Arias Gabriel F. , Landis Justin T. , Shifflett Kyle W. , Chambers Meredith G. , Yuan Runjie , Willcox Smaranda , Griffith Jack D. , Dittmer Dirk P.
Published: August 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the biggest public health crises in recent history. Many expect future coronavirus introductions into the human population. Hence, it is essential to understand the basic biology of these viruses. In natural infection, the SARS-CoV-2 Spike (S) glycoprotein is co-expressed with all other viral proteins, which modify cellular compartments to maximize virion assembly. By comparison, most of S is degraded when the protein is expressed in isolation, as in current molecular vaccines. To probe the maturation pathway of S, we redirected its maturation by fusing S to the tetraspanin protein CD81. CD81 is a defining constituent of extracellular vesicles (EVs) or exosomes. EVs are generated in large numbers by all cells, extruded into blood and lymph, and transfer cargo between cells and systemically (estimated 10
12
EVs per mL plasma). EVs, like platelets, can be transfused between unrelated donors. When fusing the proline-stabilized form of strain Delta S into the flexible, large extracellular loop of CD81 rather than being degraded in the lysosome, S was extruded into EVs. CD81-S fusion containing EVs were produced in large numbers and could be isolated to high purity. Purified CD81::S EVs bound ACE2, and S displayed on individual EV was observed by cryogenic electron microscopy (EM). The CD81::S-fusion EVs were non-toxic and elicited an anti-S trimer and anti-RBD antibody response in mice. This report shows a design path to maximize viral glycoprotein assembly and release without relying on the co-expression of potentially pathogenic nonstructural viral proteins.

IMPORTANCE

The severe acute respiratory syndrome coronavirus 2 pandemic caused the biggest public health crises in recent history. To understand the maturation pathway of S, we fused S to the tetraspanin protein CD81. The resulting molecule is secreted in extracellular vesicles and induces antibodies in mice. This may be a general design path for viral glycoprotein vaccines.
Recognition of crustal extension in the Basin and Range Province: A history
Authors: Osborn Gerald
Published: August 2024

The Basin and Range Province of the western United States has inspired or augmented many important geological ideas but is most famous for the concept of crustal extension. Acceptance of the concept was a slow process. Prior to the recognition of plate tectonics, extension was unexpected and hard to understand; when mapping of the region began in the 1860s, mountain ranges were assumed to be the products of crustal compression due to contraction of the Earth. The first mapping suggested that ranges are anticlinal folds, but the idea of uplift along vertical range-bounding faults arose shortly thereafter. There was recognition starting in the 1880s that at least some faults were normal-sense rather than vertical, which implied extension, but there were decades of dissent by geologists who still promoted the anticlinal-folding idea, thought that inclined faults were reverse faults, or believed that the basins and ranges were created by water or wind or glacial erosion rather than tectonics. Normal faulting gradually became widely accepted, but comprehension of its meaning was hindered by apparent thrust faults in parts of the province that suggested contractional deformation. These faults would later be interpreted as low-angle normal faults, and crustal extension became widely, though not universally, accepted in the 1960s as magnetic anomalies confirmed seafloor spreading. Roughly a century elapsed between the first geologic mapping and general acceptance of crustal extension. A parallel evolution of thought occurred in Africa as a consensus arose that rift valleys were products of extension.
Characterization of Tracking Modules Based on DSSD Sensors at the SC-1000 Accelerator for the BM@N Project
Authors: Dementev D. V. , Sheremetev A. D. , Shitenkov M. O. , Leontiev V. V. , Rufanov I. A. , Murin Yu. A.
Published: August 2024

The results of studying characteristics of modules based on double-sided microstrip silicon sensors, which are designed to create the wide-aperture Silicon Tracking System for the BM@N facility, are presented. The main module features are the use of fast readout electronics based on the STS-XYTER chip and the application of ultralight (0.23% X0) aluminum microcables for transmitting analog signals from the sensor strips to the input channels of the readout electronics. The results of testing different configurations of tracking modules on the extracted beam of protons at the SC-1000 accelerator in the PNPI are presented. The stable operation of readout electronics is demonstrated at loads close to the maximum values of 360 kHz s–1 cm–2. The signal-to-noise ratio was no less than 23. The measured coordinate resolution of the modules within the beam telescope was 17 ± 0.4 μm, and the detector efficiency of recording for protons with energy of 1 GeV was no less than 99%.