bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term cause‐specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens—A nationwide Danish cohort study
Authors: Rossetti Sára , Juul Sidsel Jacobsen , Eriksson Frank , Warming Peder Emil , Glinge Charlotte , El‐Galaly Tarec Christoffer , Haaber Christensen Jacob , Kamper Peter , de Nully Brown Peter , Gislason Gunnar Hilmar , Vestmø Maraldo Maja , Tfelt‐Hansen Jacob , Hutchings Martin
Published: June 2024

The documented treatment‐induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995–2015 and aged 15–40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I–II and 33.5% had stage III–IV disease. With a median follow‐up of 14.76 years, 139 deaths occurred, yielding a 5‐year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL‐related death showed an initial sharp rise, with a plateau at 5.3% 10‐year post‐diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20‐year mark respectively. HL cases had a 7.5‐fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause‐specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.
Management of Refractory Anaphylaxis: An Overview of Current Guidelines
Authors: Pouessel Guillaume , Dribin Timothy E. , Tacquard Charles , Tanno Luciana Kase , Cardona Victoria , Worm Margitta , Deschildre Antoine , Muraro Antonella , Garvey Lene H. , Turner Paul J.
Published: June 2024

In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second‐line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta‐blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor‐acetyl hydrolase or hereditary alpha‐tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.
Management of Infant Atopic Eczema to Prevent Severe Eczema and Food Allergy
Authors: Yamamoto‐Hanada Kiwako , Ohya Yukihiro
Published: June 2024

Early intervention and active management of infant atopic eczema may play a crucial role in limiting eczema severity and preventing the onset of immediate‐type food allergy. Eczema management involves education, skincare and medications targeting skin inflammation and barrier repair. Topical corticosteroids are the mainstay of anti‐inflammatory therapy, with nonsteroidal options available for some infants. Proactive therapy, addressing subclinical inflammation, is useful for preventing eczema flares, especially in infants with recurrent eczema flares despite reactive therapy. In clinical practice, holistic consideration of overall infant and family health is essential. Providing advice on maternal stress management, nutritional guidance and recommendations for proper sleep and lifestyle is crucial for the well‐being of children and their families, not limited to eczema treatment alone.
Microglia in radiation‐induced brain injury: Cellular and molecular mechanisms and therapeutic potential
Authors: Wang Yafeng , Tian Jiayu , Liu Dandan , Li Tao , Mao Yanna , Zhu Changlian
Published: June 2024

Background

Radiation‐induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation‐induced brain injury.

Methods

This article critically examines recent developments in understanding the role of microglia activation in radiation‐induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition.

Results

Post‐irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation‐induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation‐induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation‐induced brain injury.

Conclusions

The intricate microenvironment and molecular mechanisms associated with radiation‐induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.
Characterising individuals with a substance use disorder accessing hospital‐based addiction care: Preliminary description of the outcomes for patients accessing addiction care prospective cohort study
Authors: James Hannah , Morgan Jeffrey , Nolan Seonaid
Published: June 2024

Introduction

Individuals with a substance use disorder (SUD) often face barriers to accessing health care, resulting in unmet needs and delayed care. Hospital‐based services have the potential to engage individuals with a SUD in ongoing treatment, but there is limited literature characterising this population.

Methods

The Outcomes for Patients Accessing Addiction Care study was a prospective hospital‐based cohort study conducted at St. Paul's Hospital in Vancouver, Canada. Participants were recruited from January 2018 to March 2020. Data were collected through an interviewer‐administered questionnaire, including socio‐demographic information, substance use history and mental health screening.

Results

The cohort included 536 participants, with 31% aged 30–39 years, 63% identifying as White and 74% reporting male sex at birth. Nearly half of the participants were either homeless or living in single room occupancy. Use of substances more than once per week was reported for tobacco/nicotine (86%), marijuana (43%), non‐medical use of prescription drugs (29%), illicit stimulants (52%) and illicit opioids (61%).

Discussion and Conclusion

This preliminary report provides a description of a hospital‐based cohort of individuals with a SUD accessing addiction care. The findings highlight demographic characteristics, mental health issues, substance use patterns and barriers to accessing services. Understanding these factors can inform the development of patient‐centred interventions and improve engagement and retention in addiction care. Further research is needed to explore interventions and program effectiveness in this population.
Novel three‐traction strings device with endoscopic submucosal dissection for the removal of a large rectal sessile serrated adenoma
Authors: Zhu Su‐zhu , Wu Ben‐hua , Li De‐feng
Published: June 2024

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Vindicating universalism: Pragmatic genealogy and moral progress
Authors: Blunden Charlie , Lane Benedict
Published: June 2024

How do we justify the normative standards to which we appeal in support of our moral progress judgments, given their historical and cultural contingency? To answer this question in a noncircular way, Elizabeth Anderson and Philip Kitcher appeal exclusively to formal features of the methodology by which a moral change was brought about; some moral methodologies are systematically less prone to bias than others and are therefore less vulnerable to error. However, we argue that the methodologies espoused by Anderson and Kitcher implicitly appeal to the substantive principle of “moral universalism.” This sets up the positive project of the paper: an attempt to vindicate moral universalism with a pragmatic genealogy. Using resources from cultural evolutionary theory and the history of ideas we argue that the universalistic norms widely committed to in many societies today have the function of maintaining cooperation in large anonymous groups. Furthermore, while universalistic norms play this instrumental role, their functional benefits are best secured when people following such norms do so for intrinsic rather than instrumental reasons. Finally, having elaborated our pragmatic genealogy, we close by considering how this genealogy should affect our commitment to moral universalism and how it can complement the methods of Anderson and Kitcher.
EU constitutional dismantling through strategic informalisation: Soft readmission governance as concerted dis‐integration
Authors: Moreno‐Lax Violeta
Published: June 2024

This contribution takes issue with what I have called the ‘constitutional dismantling’ of external migration policy through the tactical informalisation of readmission cooperation. It maps out the strategic use of soft law mediating the tacit approval or active involvement of the main EU actors. The strategy is supposed to enhance policy outcomes but is at the expense of foundational principles. The principles of conferral, institutional balance, and sincere/loyal cooperation impose key constraints on EU/Member State action that the choice for soft law ignores. My main contention is that this is not an unintended consequence, but a deliberate or, at least, tolerated result, amounting to a form of ‘concerted dis‐integration’ pursued by the very actors supposed to guard the EU integration project in line with Treaty provisions. The approach denotes the instrumentalisation of legal mechanisms for the advancement of policy objectives, embracing a regulation‐without‐legitimation paradigm that unravels the EU’s constitutional framework.
Exploring the capacities of ChatGPT: A comprehensive evaluation of its accuracy and repeatability in addressing helicobacter pylori‐related queries
Authors: Lai Yongkang , Liao Foqiang , Zhao Jiulong , Zhu Chunping , Hu Yi , Li Zhaoshen
Published: June 2024

Background

Educational initiatives on Helicobacter pylori (H. pylori) constitute a highly effective approach for preventing its infection and establishing standardized protocols for its eradication. ChatGPT, a large language model, is a potentially patient‐friendly online tool capable of providing health‐related knowledge. This study aims to assess the accuracy and repeatability of ChatGPT in responding to questions related to H. pylori.

Materials and Methods

Twenty‐one common questions about H. pylori were collected and categorized into four domains: basic knowledge, diagnosis, treatment, and prevention. ChatGPT was utilized to individually answer the aforementioned 21 questions. Its responses were independently assessed by two experts on H. pylori. Questions with divergent ratings were resolved by a third reviewer. Cohen's kappa coefficient was calculated to assess the consistency between the scores of the two reviewers.

Results

The responses of ChatGPT on H. pylori‐related questions were generally satisfactory, with 61.9% marked as “completely correct” and 33.33% as “correct but inadequate.” The repeatability of the responses of ChatGPT to H. pylori‐related questions was 95.23%. Among the responses, those related to prevention (comprehensive: 75%) had the best response, followed by those on treatment (comprehensive: 66.7%), basic knowledge (comprehensive: 60%), and diagnosis (comprehensive: 50%). In the “treatment” domain, 16.6% of the ChatGPT responses were categorized as “mixed with correct or incorrect/outdated data.” However, ChatGPT still lacks relevant knowledge regarding H. pylori resistance and the use of sensitive antibiotics.

Conclusions

ChatGPT can provide correct answers to the majority of H. pylori‐related queries. It exhibited good reproducibility and delivered responses that were easily comprehensible to patients. Further enhancement of real‐time information updates and correction of inaccurate information will make ChatGPT an essential auxiliary tool for providing accurate H. pylori‐related health information to patients.
Enhanced properties of multi‐element soluted (Nb0.8Ti0.05Zr0.05Mo0.05M0.05)4AlC3 (M = Hf, Ta) ceramics
Authors: Soomro Sumair Ahmed , Jahanger Muhammad Irfan , Khan Maaz Ullah , Zhou Yanchun , Fu Shuai , Wan Detian , Bao Yiwang , Feng Qingguo , Hu Chunfeng
Published: June 2024

Recently multielements solid solution has shown significant improvement to the mechanical properties of parent MAX phases. Therefore, in this work, five elements with different radii were incorporated to check the effect on properties of MAX phases. (Nb0.8Ti0.05Zr0.05Mo0.05Hf0.05)4AlC3 (MAXHf) and (Nb0.8Ti0.05Zr0.05Mo0.05Ta0.05)4AlC3 (MAXTa) ceramics were successfully synthesized using the spark plasma sintering technique. The microstructure and elemental map analysis results further confirmed that the five transition metals were successfully solid soluted at the M‐sites of the hexagonal M4AlC3 unit cell. The mean elemental compositions for M‐site elements were achieved as Nb0.85Ti0.052Zr0.035Mo0.027Hf0.036 and Nb0.847Ti0.051Zr0.043Mo0.025Ta0.033 for MAXHf and MAXTa ceramics, respectively. The electrical and thermal conductivities of multielement solid solution MAX phases were decreased compared to pure Nb4AlC3. However, Mechanical properties were significantly increased with the solid solution of five transition metals. The fracture toughness, flexural strength, compressive strength and Vickers hardness (10 N) of MAXHf and MAXTa ceramics were achieved as 8.87 MPa m1/2, 448 MPa, 867 MPa, 6.5 GPa and 10.36 MPa m1/2, 557 MPa, 1039 MPa, 8.2 GPa, respectively. The enhanced mechanical properties suggest the effectiveness of the solid solution strengthening effect and provide new opportunities to further tailor the mechanical properties of the MAX phase ceramics.
Utilisation of Lactococcus lactis subsp. lactis (PY91K) and Lactiplantibacillus plantarum (Y48) to control Clostridium sporogenes during Turkish white cheese production and storage
Authors: Demirbaş Fatma Nur , Arıcı Muhammet , Dertli Enes
Published: June 2024

This study investigated the inhibition of Clostridium species, isolated from cheeses with late‐blowing defects, by lactic acid bacteria (LAB). Four batches of Turkish white cheeses were produced; control cheese, cheese sample containing Lactococcus lactis subsp. lactis (PY91K) and Lactiplantibacillus plantarum (Y48) as protective cultures (LAB), a cheese sample containing the protective culture and inoculated with Clostridium sporogenes spores (CL‐LAB) and finally a cheese sample containing only Cl. sporogenes spores (CL). White cheese's microbiological and physicochemical properties were also determined throughout the 90‐day storage period at 4 °C. Approximately 1 log reduction in Cl. sporogenes (ZMP‐1‐4) spores was observed in the LAB co‐inoculated Turkish white cheese samples.
Effect of air‐abrasion pretreatment with three desensitizing agents on efficacy of in‐office tooth bleaching
Authors: Memis Ioannis , Dionysopoulos Dimitrios , Papadopoulos Constantinos , Mourouzis Petros , Davidopoulou Sotiria , Tolidis Kosmas
Published: June 2024

Objective

To evaluate the influence of air‐abrasion of enamel with three different desensitizing powders on the whitening effect of a bleaching gel containing 40% H2O2, which was used for in‐office tooth bleaching.

Materials and Methods

Forty human incisors, extracted and prepared, were acquired for this study and subsequently randomized into four groups (n = 10). The control group specimens underwent no pretreatment prior to the bleaching procedure, whereas the remaining three groups underwent air abrasion using distinct desensitizing powders; (a) Sylc, which contains bioglass 45S5; (b) BioMinF, which contains calcium phospho‐fluoro‐silicate glass; and (c) MI Pearls, which contains nano‐hydroxyapatite, 1 h preceding the Opalescence Boost PF 40% bleaching procedure. Color measurements were conducted using a double‐beam UV–Vis spectrophotometer at four distinct time points (prior to bleaching, 24 h, 15 days, and 30 days post‐bleaching).

Results

Tooth color change outcomes revealed that there were no statistically significant results with respect to the interaction of the two criteria (treatments and time) (p = 0.990). Additionally, there were no statistically significant results with respect to the main effects of treatments (p = 0.385), while there were statistically significant effects with respect to the time criterion (p = 0.013).

Conclusions

The use of the tested desensitizing powders prior the bleaching procedure did not affect the tooth color change induced by the tested bleaching agent.

Clinical Significance

Tooth color change and whiteness are not affected by air‐abrasion desensitizing treatments when applied prior to in‐office bleaching procedures.
Incidence and risk factors of post‐operative delirium in glioma patients: A prospective cohort study in general wards
Authors: Yuan Caiyun , Cheng Ziying , Liu Yapeng , You Yuan , Wang Linlin , Li Deling , Zhong Liyun
Published: June 2024

Aims

Glioma patients are at high risk for postoperative delirium (POD), yet studies focusing on this population in general neurosurgical ward settings are limited. This paper investigates the incidence of POD and related risk factors in glioma patients hospitalized in general wards.

Design

Prospective observational study.

Methods

This prospective study included 133 adult glioma patients hospitalized in the general neurosurgery ward. In addition to collecting routine perioperative general clinical data, patients' psychological status was assessed preoperatively using the Hospital Anxiety and Depression Scale (HADS). POD was assessed within 3 days postoperatively using the Confusion of Consciousness Assessment method, twice daily. The incidence of POD was calculated, and risk factors were identified using logistic regression analysis.

Results

The incidence of POD in glioma patients admitted to the general ward was 31.6% (40/133). Multivariate regression revealed advanced age (age > 50 years), frontal lobe tumour, presence of preoperative anxiety or depression, retention of a luminal drain, postoperative pain, indwelling catheter these six factors were independent risk factors for the development of delirium in patients after surgery.

Conclusion

In general ward settings, supratentorial glioma patients exhibit a high risk of POD. Critical risk factors include preoperative psychological conditions, as well as postoperative pain, drainage and catheterization. Rigorous preoperative evaluations, effective pain management strategies and the integration of humanistic care principles are essential in mitigating the risk of POD for glioma patients.

Relevance to Clinical Practice

In general ward settings, this study reveals the high occurrence of POD in glioma patients and identifies preoperative psychological states, age, tumour location and several postoperative factors as significant risk factors for POD, which provides a framework for targeted interventions. By integrating these insights into clinical practice, healthcare teams can better identify glioma patients at risk for POD and implement preventive measures, thereby enhancing recovery and overall care quality for glioma patients in general neurosurgical wards.

Reporting Method

This study adheres to the STROBE guidelines, ensuring a transparent and comprehensive reporting of the observational research methodology and results.

Patient or Public Contribution

Patients involvement was limited to the provision of data through their participation in the study's assessments and the collection of clinical information. The study did not involve a direct patient or public contribution in the design, conduct, analysis, or interpretation of the data, nor in the preparation of the manuscript.
REM sleep and neurodegeneration
Authors: Pérez‐Carbonell Laura , Iranzo Alex
Published: June 2024

Several brainstem, subcortical and cortical areas are involved in the generation of rapid eye movement (REM) sleep. The alteration of these structures as a result of a neurodegenerative process may therefore lead to REM sleep anomalies. REM sleep behaviour disorder is associated with nightmares, dream‐enacting behaviours and increased electromyographic activity in REM sleep. Its isolated form is a harbinger of synucleinopathies such as Parkinson's disease or dementia with Lewy bodies, and neuroprotective interventions are advocated. This link might also be present in patients taking antidepressants, with post‐traumatic stress disorder, or with a history of repeated traumatic head injury. REM sleep likely contributes to normal memory processes. Its alteration has also been proposed to be part of the neuropathological changes occurring in Alzheimer's disease.
Habenular volume changes after venlafaxine treatment in patients with major depression
Authors: Etienne Josselin , Boutigny Alexandre , David Denis J , Deflesselle Eric , Gressier Florence , Becquemont Laurent , Corruble Emmanuelle , Colle Romain
Published: June 2024

Background

Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement.

Methods

Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant‐free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment.

Results

A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness.

Conclusion

Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.
A molecular phylogeny of scuttle flies (Diptera: Phoridae) unveils extensive concordance but intriguing divergences from morphological results
Authors: Li Xuankun , Hash John M. , Hartop Emily , Yang Ding , Smith Paul T. , Brown Brian V.
Published: June 2024

We present the most comprehensive molecular phylogeny of scuttle flies (Diptera: Phoridae) to date based on seven genetic loci—four protein‐coding genes: arginine kinase (AK), carbamoylphosphate synthase 2 domain of CAD (rudimentary; CAD2), cytochrome oxidase I (CO1), NADH1 dehydrogenase (ND1) and three ribosomal DNAs: 12S, 18S and 28S. Our analyses include 122 species including nine outgroup taxa and 113 phorids (representing 61 genera). Phylogenetic relationships based on the approximately 5.3 kb of sequence data were inferred by maximum likelihood and Bayesian methods. Results are broadly congruent with recent morphological phylogenies of the group, with some significant exceptions. Our data support the monophyletic Sciadocerinae as sister to the remainder of the family. However, we found Ctenopleuriphora Liu to be sister to Phorinae with low support, and subfamilies Chonocephalinae and Termitoxeniinae are placed deep within Phorinae, and their monophyly is not consistently recovered. Our dating analyses indicate a lower Cretaceous origin of Phoridae at 120.8 Ma (125.4–111.2 Ma).
Electrochemotherapy in dogs and cats–A review
Authors: Ramos Sofia Chichorro , Dias‐Pereira Patrícia , Luís Ana Lúcia , MacFarlane Michael , Santos Andreia Alexandra
Published: June 2024

Electrochemotherapy (ECT) is a treatment modality that combines the electroporation of cell membranes with chemotherapy to facilitate the transport of non‐permeant molecules into cells. Several canine and feline studies have shown promising results, suggesting that ECT can be a valid adjuvant or alternative treatment option for some tumours. The objective of this paper is to provide a bibliographic review of the principles and applications of ECT in veterinary medicine and to compare to its use in human medicine.
Selection of Beam, Plate, and Shell Theories Using an Axiomatic/Asymptotic Method and Neural Networks
Authors: Petrolo Marco , Iannotti Pierluigi , Pagani Alfonso , Carrera Erasmo
Published: June 2024

Using 1D and 2D theories for structural problems remains desirable to reduce computational costs. Beam (1D), plate, and shell (2D) elements require fewer degrees of freedom than 3D ones as their aspect ratio constraints are less demanding. The accuracy of 1D and 2D theories depends on the assumptions retained to build the primary unknown fields, e.g., the classical models for composites are the Classical Lamination Theory (CLT) and the First-Order Shear Deformation Theory (FSDT) do not consider transverse stretching. Over the last decades, many refined 1D and 2D models have been developed to overcome the limitations of classical theories and reduce the accuracy gap with 3D elements. The present work presents the latest developments concerning the synergistic use of the Carrera Unified Formulation (CUF), the Axiomatic/Asymptotic Method (AAM), and Neural Networks (NN) to develop 1D and 2D models. CUF generates any-order theory’s governing equations and finite element (FE). AAM evaluates the influence of each generalized unknown variable on the solution to retain only those variables influencing the solution, reducing the number of degrees of freedom. NNs are used to explore the multitude of combinations of generalized variables and problem parameters, e.g., geometry, boundary conditions, material systems, and obtain the best theories for given input parameters. For the first time, this paper extends the approach to beam models for dynamic and static analyses. Various cross-section geometries are considered, and natural frequencies, modal shapes, and stress fields are evaluated. A displacement-based formulation is adopted in which the three displacement components are expanded over the cross-section using polynomials and CUF. AAM is then used to generate reduced models as accurate as 3D elements, and such models are then used to train NN. Trained NN accepts as input parameters, e.g., cross-section geometry or elastic properties, and provides the structural theory to use to fulfill the 3D accuracy requirement.
Progressive Damage Analysis of Curved Composite Laminates Incorporating Effects of Manufacturing Using a Semi-Discrete Damage Model
Authors: Meka Sai Krishna , Enos Ryan , Roach James , Zhang Dianyun
Published: June 2024

This study underscores the remarkable strength-to-weight advantage offered by curved composite laminates in comparison to conventional materials like metal, preserving or even surpassing strength levels. To comprehensively assess the strength characteristics of such laminates, the research delves into the primary failure modes governing their out-of-plane strength, predominantly matrix failure and delamination. It is essential to consider the impact of manufacturing processes, which introduce residual stresses and spring-in phenomena.

To address these complexities, a finite element simulation is employed, integrating manufacturing effects and adopting a semi-discrete damage model. Within this model, matrix failure within the plies is delineated using a smeared crack approach, whereby crack directionality aligns passively with fiber orientation within each ply. Furthermore, the smeared crack approach is extended to model damage occurring at ply interfaces.

This comprehensive investigation is done for the layup sequence: [45°/0°/−45°/90°]3S - symmetric and balanced laminate. Experimental validation is achieved through a 4-point bending test by adhering close to ASTM D6415 standards, gauging the curved beam strength/inter-laminar strength of fiber-reinforced polymer matrix composites. The utilization of DIC images aids in the systematic observation and comprehension of failure modes across various scenarios.
Novel Polyetheretherketone/Polytetrafluoroethylene Composites Reinforced With Titanium Silicon Carbide for Conveyor Chute
Authors: Ahmed Nihal , Okolie Nzubechukwu , Ghosh Sujan
Published: June 2024

The e-commerce industry has witnessed unprecedented growth in recent years, accelerated by the global pandemic and changing consumer behaviors. This demand has placed great strain on traditional conveyor chute materials, causing high friction and wear, leading to high maintenance costs and reduced operational efficiency. In this research, Polyetheretherketone (PEEK) + Polytetrafluoroethylene (PTFE) + MAX phases (Ti3SiC2) nanocomposite materials were tested for conveyor chute applications. The composite was fabricated by mixing the powder in a specific weight ratio, pressing them in a die, and finally sintering the pressed disc at 300°C. Tribological tests were performed in linear reciprocating motion using a Cr-Steel counterface. The nanocomposite materials show a COF of 0.06, lower than the PEEK and PTFE materials. More importantly, when tested under the same condition, the PTFE+PEEK+MAX phases composite showed a one-degree lower wear rate than the PEEK and PTFE materials. The microscope image shows that the physical presence of MAX phases helps the composites to attain better compaction, higher hardness, and better load-carrying capacity. The materials’ better compression and enhanced hardness help improve the composite’s tribological properties. Moreover, the better compaction of the PTFE+PEEK+MAX composite increases the water contact angle of these materials compared to the PTFE and PEEK materials. This novel composite can be an excellent replacement for the current materials used for conveyor chute applications.
Fatigue Delamination Damage Sensing and Self-Healing in Thermoset Composites Using Thermoplastic Healants
Authors: Vishe Nilesh J. , Aditya Sankha S. , Mulani Sameer B. , Roy Samit
Published: June 2024

In this study, fatigue testing under mode-I loading and damage (delamination) detection tests were carried out on double cantilever beam (DCB) specimens, and subsequent healing of the delamination was investigated. Due to the susceptibility of laminated composites to delamination, fatigue delamination is one of the critical damage modes in laminated composites and can lead to catastrophic failure if it is allowed to proceed unchecked. Hence, it is necessary to investigate and quantify the delamination crack growth behavior due to fatigue loading and to accurately predict the size of the delamination crack and then to heal it in situ in a repeatable manner. A DCB specimen with an array of 8 MFCs was used to detect damage with the actuation signal as anti-symmetric Lamb wave excitation. The signal difference coefficient (SDC) was used as a delamination detection metric and calculated for different actuator and sensor location combinations.
Same Game, Many Cultures: A Multicultural Reflection on a Trainee’s Intervention Work With a Professional Esports Team
Authors: Agrawal Anjali , Gupta Sahen , Swettenham Laura
Published: June 2024

This applied case study aims to explore the experience and multicultural reflections of a trainee sport and exercise psychologist working with a professional, multicultural esports team. We showcase the context of the case with a League of Legends team, consisting of five players, along with the intervention conducted. The case is supplemented by critical reflections on practice in a multicultural context from learning logs and applied practice notes with the T-R-E-E-S model for multicultural practice in sport psychology. This study delves into several critical aspects, namely: (a) recognizing multicultural elements, (b) customizing interventions to the dynamic esports environment, (c) scrutinizing how language and culture impact team cohesion, and (d) considering individual boundaries in personal-disclosure interventions. Finally, as one of the first case studies to reflect on multicultural practice in esports, we provide key recommendations and implications to promote multicultural work in research and applied practice in esports.
In vivo editing of lung stem cells for durable gene correction in mice
Authors: Sun Yehui , Chatterjee Sumanta , Lian Xizhen , Traylor Zachary , Sattiraju Sandhya R. , Xiao Yufen , Dilliard Sean A. , Sung Yun-Chieh , Kim Minjeong , Lee Sang M. , Moore Stephen , Wang Xu , Zhang Di , Wu Shiying , Basak Pratima , Wang Jialu , Liu Jing , Mann Rachel J. , LePage David F. , Jiang Weihong , Abid Shadaan , Hennig Mirko , Martinez Anna , Wustman Brandon A. , Lockhart David J. , Jain Raksha , Conlon Ronald A. , Drumm Mitchell L. , Hodges Craig A. , Siegwart Daniel J.
Published: June 2024

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)–sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.
A CRISPR-Cas-associated transposon system for genome editing in
Burkholderia cepacia
complex species
Authors: Yap Zhong Ling , Rahman A. S. M. Zisanur , Hogan Andrew M. , Levin David B. , Cardona Silvia T.
Published: June 2024

Genome editing in non-model bacteria is important to understand gene-to-function links that may differ from those of model microorganisms. Although species of the
Burkholderia cepacia
complex (Bcc) have great biotechnological capacities, the limited genetic tools available to understand and mitigate their pathogenic potential hamper their utilization in industrial applications. To broaden the genetic tools available for Bcc species, we developed RhaCAST, a targeted DNA insertion platform based on a CRISPR-associated transposase driven by a rhamnose-inducible promoter. We demonstrated the utility of the system for targeted insertional mutagenesis in the Bcc strains
B. cenocepacia
K56-2 and
Burkholderia multivorans
ATCC17616. We showed that the RhaCAST system can be used for loss- and gain-of-function applications. Importantly, the selection marker could be excised and reused to allow iterative genetic manipulation. The RhaCAST system is faster, easier, and more adaptable than previous insertional mutagenesis tools available for Bcc species and may be used to disrupt pathogenicity elements and insert relevant genetic modules, enabling Bcc biotechnological applications.

IMPORTANCE

Species of the
Burkholderia cepacia
complex (Bcc) have great biotechnological potential but are also opportunistic pathogens. Genetic manipulation of Bcc species is necessary to understand gene-to-function links. However, limited genetic tools are available to manipulate Bcc, hindering our understanding of their pathogenic traits and their potential in biotechnological applications. We developed a genetic tool based on CRISPR-associated transposase to increase the genetic tools available for Bcc species. The genetic tool we developed in this study can be used for loss and gain of function in Bcc species. The significance of our work is in expanding currently available tools to manipulate Bcc.
A riboswitch-controlled TerC family transporter Alx tunes intracellular manganese concentration in
Escherichia coli
at alkaline pH
Authors: Sharma Ravish , Mishanina Tatiana V.
Published: June 2024

Cells use transition metal ions as structural components of biomolecules and cofactors in enzymatic reactions, making transition metal ions integral cellular components. Organisms optimize metal ion concentration to meet cellular needs by regulating the expression of proteins that import and export that metal ion, often in a metal ion concentration-dependent manner. One such regulation mechanism is via riboswitches, which are 5′-untranslated regions of an mRNA that undergo conformational changes to promote or inhibit the expression of the downstream gene, commonly in response to a ligand. The
yybP-ykoY
family of bacterial riboswitches shares a conserved aptamer domain that binds manganese ions (Mn
2+
). In
Escherichia coli
, the
yybP-ykoY
riboswitch precedes and regulates the expression of two different genes:
mntP
, which based on genetic evidence encodes an Mn
2+
exporter, and
alx
, which encodes a putative metal ion transporter whose cognate ligand is currently in question. The expression of
alx
is upregulated by both elevated concentrations of Mn
2+
and alkaline pH. With metal ion measurements and gene expression studies, we demonstrate that the alkalinization of media increases the cytoplasmic manganese pool, which, in turn, enhances
alx
expression. The Alx-mediated Mn
2+
export prevents the toxic buildup of the cellular manganese, with the export activity maximal at alkaline pH. We pinpoint a set of acidic residues in the predicted transmembrane segments of Alx that play a critical role in Mn
2+
export. We propose that Alx-mediated Mn
2+
export serves as a primary protective mechanism that fine tunes the cytoplasmic manganese content, especially during alkaline stress.

IMPORTANCE

Bacteria use clever ways to tune gene expression upon encountering certain environmental stresses, such as alkaline pH in parts of the human gut and high concentration of a transition metal ion manganese. One way by which bacteria regulate the expression of their genes is through the 5′-untranslated regions of messenger RNA called riboswitches that bind ligands to turn expression of genes on/off. In this work, we have investigated the roles and regulation of
alx
 and 
mntP
, the two genes in 
Escherichia coli
 regulated by the
yybP-ykoY
  riboswitches, in alkaline pH and high concentration of Mn
2+
. This work highlights the intricate ways through which bacteria adapt to their surroundings, utilizing riboregulatory mechanisms to maintain Mn
2+
levels amidst varying environmental factors.
Flying microbes—survival in the extreme conditions of the stratosphere during a stratospheric balloon flight experiment
Authors: Heitkämper Tim , Roth Raphael , Harteneck Stephan , Berger Felix , Salam Sonya , Fey-Du Chunyu , Flöck Christopher , Tschierske Niclas , Vonderbank Vincent , Martin Alexander , Erren Sebastian , Zimmermann Joel , Lutz Mike , Kujala Katharina
Published: June 2024

Earth’s stratosphere is characterized by hypobaric conditions, low temperatures, and high intensities of ultraviolet (UV) and cosmic radiation as well as low water and nutrient availability. While it is not considered a permanent habitat for microorganisms, they can be transported to the stratosphere by storms, volcanic action, or human activity. The impact of those extreme conditions on microorganisms and their survival were tested by sending a sample gondola to the stratosphere. The sample gondola was built to allow exposure of
Bacillus subtilis
endospores at different angles to the sun. It moreover had holders for three environmental samples to test the effect of stratospheric conditions on complex microbial communities. The gondola attached to a stratospheric balloon was launched near Kiruna, Sweden, ascended to ~25 km, and drifted eastward for ~200 km. Samples were exposed to pressures as low as 2 kPa and temperatures as low as −50°C as well as high UV radiation. Survival rates of
B. subtilis
were determined by comparing the numbers of colony-forming units (CFUs) for the different exposure angles. Survival was negatively correlated with exposure angle, indicating the significant impact of UV radiation. The effect of stratospheric conditions on environmental samples was assessed by comparing most probable numbers, microbial community composition, and substrate-use profiles to controls that had stayed on the ground. Cultivation was possible from all samples with survival rates of at least 1%, and differences in community composition were observed. Survival of environmental microorganisms might have been supported by the sample matrix, which provided protection from radiation and desiccation.

IMPORTANCE

Earth's stratosphere is a hostile environment that has challenged microbial survival. We set out to test the effect of stratosphere exposure on survival of single species (
Bacillus subtilis
) and complex microbial communities from soils and sediment.
B. subtilis
survival was strongly impacted by sun exposure, i.e., ultraviolet (UV) radiation, with only 1% survival at full sun exposure. Complex microbial communities had high survival rates, and the soil or sediment matrix may have provided protection against radiation and desiccation, supporting the survival of environmental microorganisms.
Generation of Archean TTGs via sluggish subduction
Authors: Foley Bradford J.
Published: June 2024

The trondhjemite-tonalite-granodiorite (TTG) suite of rocks prominent in Earth’s Archean continents is thought to form by melting of hydrated basalt, but the specific tectonic settings of formation are unclear. Models for TTG genesis range from melting of downgoing mafic crust during subduction into a hotter mantle to melting at the base of a thick crustal plateau; while neither uniquely defines a global tectonic regime, the former is consistent with mobile lid tectonics and the latter a stagnant lid. One major problem for a subduction model is slabs sinking too quickly and steeply in a hotter mantle to melt downgoing crust. I show, however, that grain size reduction in the lithosphere leads to relatively strong plate boundaries on the early Earth, which slow slab sinking. During this “sluggish subduction,” sinking plates can heat up enough to melt when the mantle temperature is ≳1600 °C. Crustal melting via sluggish subduction can thus explain TTG formation during the Archean due to elevated mantle temperatures and the paucity of TTG production since due to mantle cooling.
Cardiac troponin concentrations following exercise and the association with cardiovascular disease and outcomes: rationale and design of the prospective TREAT cohort study
Authors: Janssen Sylvan L J E , Lamers Sacha K , Vroemen Wim H M , Denessen Ellen J S , Berge Kristian , Bekers Otto , Hopman Maria T E , Brink Monique , Habets Jesse , Nijveldt Robin , Van Everdingen Wouter M , Aengevaeren Vincent L , Mingels Alma M A , Eijsvogels Thijs M H
Published: June 2024

Exercise can produce transient elevations of cardiac troponin (cTn) concentrations, which may resemble the cTn release profile of myocardial infarction. Consequently, clinical interpretation of postexercise cTn elevations (ie, values above the 99th percentile upper reference limit) remains challenging and may cause clinical confusion. Therefore, insight into the physiological versus pathological nature of postexercise cTn concentrations is warranted. We aim to (1) establish resting and postexercise reference values for recreational athletes engaged in walking, cycling or running exercise; (2) compare the prevalence of (sub)clinical coronary artery disease in athletes with high versus low postexercise cTn concentrations and (3) determine the association between postexercise cTn concentrations and the incidence of major adverse cardiovascular events (MACE) and mortality during long-term follow-up. For this purpose, the prospective TRoponin concentrations following Exercise and the Association with cardiovascular ouTcomes (TREAT) observational cohort study was designed to recruit 1500 recreational athletes aged ≥40 to <70 years who will participate in Dutch walking, cycling and running events. Baseline and postexercise high-sensitivity cTnT and cTnI concentrations will be determined. The prevalence and magnitude of coronary atherosclerosis on computed tomography (eg, coronary artery calcium score, plaque type, stenosis degree and CT-derived fractional flow reserve) will be compared between n=100 athletes with high postexercise cTn concentrations vs n=50 age-matched, sex-matched and sport type-matched athletes with low postexercise cTn concentrations. The incidence of MACE and mortality will be assessed in the entire cohort up to 20 years follow-up. The TREAT study will advance our understanding of the clinical significance of exercise-induced cTn elevations in middle-aged and older recreational athletes.

Trial registration numberNCT06295081.