bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic model of minute virus of mice elution behavior in anion exchange chromatography purification
Authors: Kitamura Ryunosuke , Enghauser Lena , Miyamoto Riku , Ichikawa Takahiro , Aiso Takaki , Masuda Yumiko , Kajihara Daisuke , Kakihara Hirofumi , Nonaka Koichi
Published: October 2024

This study aimed to propose a methodology for developing a mechanistic model for viral clearance of the minute virus of mice (MVM) on flow‐through anion exchange (AEX) chromatography. Protein surface analysis was applied to investigate the possibility of molecular interaction between the recombinant biotherapeutic and MVM. The protein product‐free Tris buffers were spiked with MVM, and the MVM elution profile from AEX chromatography was quantitatively analyzed using quantitative polymerase chain reaction (qPCR) for pooled fractions. GoSilico™ Chromatography Modeling Software was applied to develop the mechanistic models for MVM species. For evaluating the visual fit of the developed model, the R2 of intact MVM virions and uncoated capsids between the simulated and measured amount in each fraction are 0.880 and 0.948, respectively. Response surface plots of logarithmic reduction values (LRV) against pH and conductivity in loaded sample were generated to show the range for suitable loaded sample conditions for achieving a good LRV. To evaluate the applicability of the developed MVM elution model to a recombinant biotherapeutic, two demonstrations of AEX chromatography purification were performed with a loaded sample of a model monoclonal antibody. The peaks of the MVM species in the elution step of both runs were accurately simulated by the developed model. In addition, to assess the possibility of molecular interaction between the virus and the target protein significantly affecting the MVM elution behavior, the antibody's surface was evaluated in terms of hydrophobicity/hydrophilicity using surface analysis.
Development and validation of a hierarchical approach for lymphoma classification using immunohistochemical markers
Authors: Xu Jiming , Shi Yunfei , Cui Mengxuan , Wang Yao , Fan Wenhui , Yun Jingping , Li Linfeng , Cai Muyan
Published: October 2024

Background

Accurate lymphoma classification is critical for effective treatment and immunohistochemistry is a cost‐effective and time‐saving approach. Although several machine learning algorithms showed effective results, they focused on a specific task of classification but not the whole classification workflow, thus impractical to be applied in clinical settings. Thus, we aim to develop an effective and economic machine learning‐assisted system that can streamline the lymphoma differential diagnostic workflow using EBER in situ hybridization and immunohistochemical markers.

Methods

We included pathological reports diagnosed as lymphomas from two cancer centers (Sun Yat‐sen University Cancer Center and Peking University Cancer Hospital & Institute). We proposed a hierarchical approach that mimicked the human diagnostic process and employed simplified panels of markers to perform a series of interpretable classification. The diagnostic accuracy for lymphoma pathological subtypes and the markers saving ratio were investigated in both temporal independent population and external medical center.

Results

A total of 14,927 patients and corresponding immunohistochemical results from two cancer centers were included. The proposed system had high discriminative ability for differentiating lymphoma pathological subtypes (measured by mean AUC in three validation cohorts, non‐Hodgkin and Hodgkin lymphoma: 0.959; non‐Hodgkin subtypes: 0.983; B‐lymphoma subtypes: 0.868; T‐lymphoma subtypes: 0.962; DLBCL subtypes: 0.957). In addition, the system's well selected characteristics can contribute to the development of agreement on panels of markers for differential diagnosis and help minimize cost of immunohistochemical marker techniques (measured by marker saving ratio compared to real clinical settings, internal primary‐stage cohort: 16.45% saved, p < 0.001; internal later‐stage cohort: 21.73% saved, p < 0.001; external cohort: 3.67% saved, p < 0.001).

Conclusions

Machine learning‐based hierarchical system using EBER in situ hybridization and IHC markers was developed, which could streamline the workflow by sequentially determining each lymphoma pathological subtype. The proposed system proved to be effective and cost‐saving in independent and external validation, thus could be adopted affordably in future clinical practice.
Predicting Disease Progression in Inoperable Localized NSCLC Patients Using ctDNA Machine Learning Model
Authors: Wu Yuqi , Li Canjun , Yang Yin , Zhang Tao , Wang Jianyang , Tang Wanxiangfu , Li Ningyou , Bao Hua , Wang Xin , Bi Nan
Published: October 2024

Introduction

There is an urgent clinical need to accurately predict the risk for disease progression in post‐treatment NSCLC patients, yet current ctDNA mutation profiling approaches are limited by low sensitivity. We represent a non‐invasive liquid biopsy assay utilizing cfDNA neomer profiling for predicting disease progression in 44 inoperable localized NSCLC patients.

Methods

A total of 97 plasma samples were collected at various time points during or post‐treatments (TP1: 39, TP2: 33, TP3: 25). cfDNA neomer profiling, generated based on target sequencing data, was used to fit survival support vector machine models for each time point. Leave‐one‐out cross‐validation (LOOCV) was performed to evaluate the models' predictive performances.

Results

Our cfDNA neomer profiling assay showed excellent performance in detecting patients with a high risk for disease progression. At TP1, the high‐risk patients detected by our model showed an increased risk of 3.62 times (hazard ratio [HR] = 3.62, p = 0.0026) for disease progression, compared to 3.91 times (HR = 3.91, p = 0.0022) and 4.00 times (HR = 4.00, p = 0.019) for TP2 and TP3. These neomer profiling determined HRs were higher than the ctDNA mutation‐based results (HR = 2.08, p = 0.074; HR = 1.49, p = 0.61) at TP1 and TP3. At TP1, the predictive model reached 40% sensitivity at 92.9% specificity, outperforming the mutation‐based method (40% sensitivity at 78.6% specificity), while the combination results reached a higher sensitivity (60%). Finally, the longitudinal analysis showed that the combination of neomer and ctDNA mutation‐based results could predict disease progression with an excellent sensitivity of 88.9% at 80% specificity.

Conclusion

In conclusion, we developed a cfDNA neomer profiling assay for predicting disease progression in inoperable NSCLC patients. This assay showed increased predicting power during and post‐treatment compared to the ctDNA mutation‐based method, thus illustrating a great clinical potential to guide treatment decisions in inoperable NSCLC patients.

Trial Registration

ClinicalTrials.gov: NCT04014465
Understanding Short and Long Mobilities Together: Place Attachment and Community Dynamics in Mouraria, Lisbon
Authors: Alba Maria , Batel Susana
Published: October 2024

The increase in mobilities over the last decades has facilitated the circulation of people, with short‐ and long‐term mobility practices often intertwining in the same destinations. Alongside migration processes of long‐term mobility to search for better living conditions, short mobility processes, such as touristification, started to significantly shape some cities and their communities in Southern Europe. This study examines place attachments, community and cultural dynamics of ‘migrant’ and ‘local’ residents of Mouraria, a historic and multicultural neighbourhood in Lisbon, and the consequences of touristification on those. Through walking interviews with ‘local’ residents and long‐term ‘migrants’ (n = 20), we concluded that most of the interviewed ‘migrants’ presented a traditional‐active place attachment associated both with proximity to their culture of origin and practices envisioning the well‐being of the neighbourhood's community. Additionally, we found that the essentialisation of Mouraria's community life (‘bairrismo’) was endorsed mainly by ‘local’ residents and associated with a conditional acceptance of new residents, while touristification tended to highlight structural social injustices for both ‘local’ and ‘migrant’ residents. We discuss how the community dynamics created between these different mobility processes contribute to generate multicultural and community practices in both groups of residents.
Analysis of Chemical Composition, Antioxidant Capacity, Acute Toxicity, and Antinociceptive Properties of Aqueous Extract of Origanum Majorana L.
Authors: El Amiri My Ahmed , Kabdy Hamid , Aitbaba Abdelfatah , Laadraoui Jawad , Aboufatima Rachida , El Yazouli Loubna , Abdelmounaim Baslam , Moubtakir Soad , Garzoli Stefania , Abderrahman Chait
Published: October 2024

Pharmacological evaluation showed that AEOM significantly reduced pain in an animal model, suggesting potential analgesic properties. Acute toxicity studies indicated no adverse effects on kidney and liver function or blood parameters at doses up to 800 mg/kg. The analgesic effect is likely mediated by flavonoids in the extract, which may inhibit pain pathways. These findings suggest that O. majorana has promising therapeutic applications, particularly as a natural analgesic agent.
Detection Strategies for Sialic Acid and Sialoglycoconjugates
Authors: Hunter Carmanah D. , Cairo Christopher W.
Published: October 2024

Glycoconjugates are a vast class of biomolecules implicated in biological processes important for human health and disease. The structural complexity of glycoconjugates remains a challenge to deciphering their precise biological roles and for their development as biomarkers and therapeutics. Human glycoconjugates on the outside of the cell are modified with sialic (neuraminic) acid residues at their termini. The enzymes that install sialic acids are sialyltransferases (SiaTs), a family of 20 different isoenzymes. The removal and degradation of sialic acids is mediated by neuraminidase (NEU; sialidase) enzymes, of which there are four isoenzymes. In this review, we discuss chemical and biochemical approaches for the detection and analysis of sialoglycoconjugate (SGC) structures and their enzymatic products. The most common methods include affinity probes and synthetic substrates. Fluorogenic and radiolabelled substrates are also important tools for many applications, including screening for enzyme inhibitors. Strategies that give insight into the native substrate‐specificity of enzymes that regulate SGCs (SiaT & NEU) are necessary to improve our understanding of the role of sialic acid metabolism in health and disease.
Structure and Dynamics in Solid Electrolyte Composites of the Organic Ionic Plastic Crystal HMGFSI and Lithium Sulphonamide Functional Acrylate Polymer Nanoparticles
Authors: García Yady , Porcarelli Luca , Kang Colin , Zhu Haijin , Mecerreyes David , Forsyth Maria , O'Dell Luke A.
Published: October 2024

Solid electrolyte composites between organic ionic plastic crystals (OIPCs) and polymers can potentially show enhanced mechanical properties and ion conduction. These properties can be determined by the formation of interfacial regions which affect the structure, thermal properties, and ion transport of the composite material. Here we studied the properties of composites between the OIPC hexamethylguanidinium bis(fluorosulfonyl)imide (HMGFSI) and acrylate polymer nanoparticles functionalised with lithium, using various techniques including solid‐state NMR spectroscopy. An enhancement in ionic conductivity of three orders of magnitude as well as increased lithium and OIPC cation and anion dynamics were observed in the composite as prepared with 40 v% of polymer nanoparticles with respect to the pure OIPC at 50 °C. This was attributed to the increased overall structural disorder as a result of the formation of disordered interfacial regions, which were evidenced by solid‐state NMR spectroscopy. In addition, the importance of the thermal history of these composites is highlighted, with differences in the conductivity and ion dynamics observed after melting and recrystallizing the OIPC component, leading to less disordered interfacial regions. This study enriches our fundamental understanding of the formation of interfacial regions in OIPC composites and their effect on the bulk properties of the electrolyte.
Facile Synthesis Route for Bulk Production of Complex Fullerene‐Like MoS2 Nanostructures With Enhanced Tribological Properties
Authors: Drnovšek Aljaž , Vengust Damjan , Šumandl Patrik , Korbar Domen , Mrzel Aleš , Vilfan Mojca
Published: October 2024

Molybdenum‐based nanoparticles are often used as oil additives to enhance a material's tribological performance. Here, we present a highly efficient synthetic route for the bulk production of two types of MoS2 nanostructures: multi‐wall nanotubes and fullerene‐like nanostructures. The presented two‐step synthesis involves the transformation of ammonium heptamolybdate tetrahydrate and aniline into precursor nanowires, which are later transformed into MoS2 through heating in a H2S, H2, and argon atmosphere to approximately 800 °C. Depending on the heating rate, we successfully grew MoS2 layered compounds in various shapes and sizes. The resulting structures and compositions were characterised by X‐ray powder diffraction, Raman spectroscopy, energy‐dispersive X‐ray spectroscopy, and electron microscopy. To assess the application potential of these MoS2 compounds, they were dispersed in polyalphaolefin (PAO 6) oil. Improved tribological properties were observed compared to typically used transition metal dichalcogenides.
The TELCoMB Protocol for High‐Sensitivity Detection of ARG‐MGE Colocalizations in Complex Microbial Communities
Authors: Bravo Jonathan E. , Slizovskiy Ilya , Bonin Nathalie , Oliva Marco , Noyes Noelle , Boucher Christina
Published: October 2024

Understanding the genetic basis of antimicrobial resistance is crucial for developing effective mitigation strategies. One necessary step is to identify the antimicrobial resistance genes (ARGs) within a microbial population, referred to as the resistome, as well as the mobile genetic elements (MGEs) harboring ARGs. Although shotgun metagenomics has been successful in detecting ARGs and MGEs within a microbiome, it is limited by low sensitivity. Enrichment using cRNA biotinylated probes has been applied to address this limitation, enhancing the detection of rare ARGs and MGEs, especially when combined with long‐read sequencing. Here, we present the TELCoMB protocol, a Snakemake workflow that elucidates resistome and mobilome composition and diversity and uncovers ARG‐MGE colocalizations. The protocol supports both short‐ and long‐read sequencing and does not require enrichment, making it versatile for various genomic data types. TELCoMB generates publication‐ready figures and CSV files for comprehensive analysis, improving our understanding of antimicrobial resistance mechanisms and spread. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Installing TELCOMB Locally

Alternate Protocol: Installing TELCOMB on a SLURM Cluster

Basic Protocol 2: Data Preprocessing

Basic Protocol 3: Calculation of Resistome Distribution and Composition

Basic Protocol 4: Identification of ARG‐MGE Colocalizations
Win‐Win Strategies Enable Efficient Anode‐Less Zinc‐Ion Hybrid Supercapacitors
Authors: Hung Tai‐Feng , Amirtha Rene Mary , Yang Chun‐Chen
Published: October 2024

Boosting the energy and power densities of electrochemical energy storage (EES) devices to broaden their practicality is of great significance and emergently desirable. Recently, the EES cells with an anode‐free concept have been announced to realize those targets. Herein, 20 μm of a zincophilic layer prepared by blending ZIF‐8 and sodium alginate (SA) is uniformly coated on Cu foil (Z8‐SA@Cu) as an alternative anode for anode‐less zinc‐ion hybrid supercapacitors (ALZHSCs). Contributing by the distinctive features evidenced by electrochemical measurements and post‐mortem analyses: (1) less nucleation barrier and overpotential, (2) limited zincate formation, (3) improved Zn2+ flux and (4) efficient Zn plating/stripping, the as‐prepared Z8‐SA@Cu is rationally considered to be a promising anode for ALZHSCs. Encouragingly, the assembled ALZHSC device not only delivers an impressive rate capability (40 mAh/g at 1 mA/cm2 and 34 mAh/g at 10 mA/cm2) but also achieves the excellent cycling stability (capacity retention: 88 % after 12,000 cycles at 5 mA). Most importantly, the ALZHSC device also reveals significant increases in gravimetric energy density and high‐power ability as compared to the traditional ZHSCs.
Effect‐Directed Synthesis of a Dithioacetal Tyrosinase Inhibitor
Authors: Escalante Andrea M. , Riera Micaela B. , Salazar Mario O. , Furlan Ricardo L. E.
Published: October 2024

Traditional methods for discovering bioactive compounds can be time‐consuming and resource‐intensive, often requiring extensive synthesis and evaluation. To address these challenges, this study combines TLC‐based assays with dithioacetal mixture‐library preparation, enabling rapid and effective bioactivity screening. Tyrosinase, an enzyme crucial for melanin production and fruit browning, serves as a significant therapeutic target in this context. Despite the substantial potential of sulfur‐containing compounds in medicinal chemistry, the use of dithioacetals in drug discovery remains limited. In this study, two small libraries of dithioacetals, comprising more than 150 compounds, were prepared as mixture‐libraries and screened on TLC by directly measuring tyrosinase activity on the plate surface. This approach facilitated the efficient preparation and identification of a potent, simple, and readily accessible dithioacetal inhibitor of tyrosinase, with the entire process being conducted on a low milligram scale.
Health Profile Transitions and the Association With Cognitive Impairment in Older Nursing Home Residents With Suicidal Ideation
Authors: Yuan Yiyang , Barooah Adrita , Lapane Kate L. , Mack Deborah , Rothschild Anthony J. , Ulbricht Christine M.
Published: October 2024

Objectives

In older U.S. nursing home residents with suicidal ideation (SI), limited studies have longitudinally investigated their health changes as related to cognitive function. This study aimed to identify the health profiles and the transitions between profiles at admission and 90‐days and examine the associations with cognitive impairment.

Methods

Using Minimum Data Set 3.0 (2011–15), we identified 10,079 older residents without severe cognitive impairment who reported SI on Patient Health Questionnaire‐9. Health profile indicators included at‐admission and 90‐day post‐admission depressive symptoms, frailty, and pain frequency and intensity. Using latent transition analysis, we identified distinct health profiles, examined the transitions between profiles over time, and estimated their associations with cognitive impairment.

Results

One third of residents continued to report SI at 90 days. The five health profiles identified at admission were distinctive with varying levels of frailty, depressive symptoms, and pain, from the most severe Profile 1 characterized by frailty, all depressive symptoms, and horrible or frequent pain, to the least severe Profile 5 characterized by pre‐frailty, depressed mood, and no pain. The 90‐day profiles were mostly consistent. Most residents remained in a similar profile over time. Relative to residents with intact cognition/mild cognitive impairment, those with moderate impairment were less likely to belong to profiles characterized by more depressive symptoms and pain.

Conclusions

Residents with SI had heterogeneous health profiles, which varied by cognitive impairment levels, but showed minimal changes despite being in a medically supervised setting. Findings highlighted the critical need for adequate recognition and management of SI in nursing homes.
A meta‐analysis of letter–sound integration: Assimilation and accommodation in the superior temporal gyrus
Authors: Gao Danqi , Liang Xitong , Ting Qi , Nichols Emily Sophia , Bai Zilin , Xu Chaoying , Cai Mingnan , Liu Li
Published: October 2024

Despite being a relatively new cultural phenomenon, the ability to perform letter–sound integration is readily acquired even though it has not had time to evolve in the brain. Leading theories of how the brain accommodates literacy acquisition include the neural recycling hypothesis and the assimilation–accommodation hypothesis. The neural recycling hypothesis proposes that a new cultural skill is developed by “invading” preexisting neural structures to support a similar cognitive function, while the assimilation–accommodation hypothesis holds that a new cognitive skill relies on direct invocation of preexisting systems (assimilation) and adds brain areas based on task requirements (accommodation). Both theories agree that letter–sound integration may be achieved by reusing pre‐existing functionally similar neural bases, but differ in their proposals of how this occurs. We examined the evidence for each hypothesis by systematically comparing the similarities and differences between letter–sound integration and two other types of preexisting and functionally similar audiovisual (AV) processes, namely object–sound and speech–sound integration, by performing an activation likelihood estimation (ALE) meta‐analysis. All three types of AV integration recruited the left posterior superior temporal gyrus (STG), while speech–sound integration additionally activated the bilateral middle STG and letter–sound integration directly invoked the AV areas involved in speech–sound integration. These findings suggest that letter–sound integration may reuse the STG for speech–sound and object–sound integration through an assimilation–accommodation mechanism.
Cancers attributable to diet in Italy
Authors: Turati Federica , Alicandro Gianfranco , Collatuzzo Giulia , Pelucchi Claudio , Malvezzi Matteo , Parazzini Fabio , Negri Eva , Boffetta Paolo , La Vecchia Carlo , Di Maso Matteo
Published: October 2024

Cancer burden can be reduced by controlling modifiable risk factors, including diet. We provided an evidence‐based assessment of cancer cases and deaths attributable to diet in Italy in 2020. We considered dietary factor‐cancer type pairs for which the World Cancer Research Fund/American Institute for Cancer Research – Continuous Update Project reported either ‘convincing’ or ‘probable’ evidence of causal association. Relative risks were retrieved from recent meta‐analyses and dietary intakes (around 2005) from a national food consumption survey. Sex‐specific population attributable fractions (PAFs) were computed by comparing the distribution of dietary intakes in the Italian population against counterfactual scenarios based on dietary recommendations. Using data from national cancer and mortality registries in 2020, we estimated the number of attributable cancer cases and deaths, assuming ~15‐year lag period. Unhealthy diet accounted for 6.3% (95% CI: 2.5%–9.9%) of all cancer cases in men and 4.5% (95% CI: 1.7%–7.4%) in women. PAFs of colorectal cancer were 10.5% and 7.0% for any intake of processed meat, 3.3% and 2.0% for high red meat, 4.8% and 4.3% for low dairy products, and 7.9% and 9.0% for low fiber intakes in men and women, respectively. PAFs for low intake of non‐starchy vegetables and fruit ranged from 0.8% to 16.5% in men and 0.6%–17.8% in women for cancers of the aerodigestive tract. The estimated cancer burden associated with unfavorable dietary habits in Italy is considerable, but appears lower than for other high‐income countries, reflecting the typically Mediterranean diet.
Severe hyponatremia in obstetrics: Presentations and outcome. Retrospective cohort over 10 years
Authors: Elbarbary Nouran , Datta Tamal , Viswanatha Radhika , Johnstone Helen , Shehata Hassan , Ganapathy Ramesh
Published: October 2024

Hyponatremia in labor and the postpartum period is generally underreported. In this study we aimed to identify attributable causes of severe hyponatremia in an obstetric population and define maternal outcomes. This was a retrospective cohort study, in a single center over a period of 10 years. The study setting was an NHS maternity trust serving a multi‐ethnic population in southwest London. The hospital cared for 53 649 pregnant women in the study period. All patients with severe hyponatremia in labor and immediate postpartum period from January 2011 until December 2020 were identified from the laboratory database. Individual case notes were analyzed for fluid use, use and duration of oxytocin, medical conditions, and delivery details. Severe peripartum hyponatremia was identified in 77 patients. A total of 28% of those analyzed required ITU admission for electrolyte correction, of whom 6% presented with severe neurologic symptoms, making symptoms a poor marker of severity (P = 0.051). The main association was to oxytocin and intravenous fluid infusions (80% and 86%, respectively), only one‐third of patients had pre‐eclampsia. Other associated medical conditions did not appear to have a significant influence on disease course nor prognosis (P = 0.359). Hyponatremia during labor can have detrimental effect on maternal outcomes. Lower threshold for testing and diligent maintenance of fluid balance charts during labor can help with primary prevention.
Cervical ripening with a double balloon device for 6 h in patients with a long cervix: Secondary analysis of a randomized controlled trial
Authors: Sammour Rami , Dikopoltsev Elena , Sagi Shlomi , Vitner Dana , Bleicher Inna
Published: October 2024

Objective

To examine whether cervical ripening with a double balloon device for 6 h is as effective as 12 h in patients with a cervical length ≥ 30 mm measured on transvaginal ultrasound before induction of labor, and to determine whether patients with a long cervix need to have the balloon placed for a longer time.

Methods

This is a secondary analysis of data from a randomized controlled trial that compared maternal and neonatal outcomes between women undergoing cervical ripening with a double balloon device for 6 h (study group) versus 12 h (control group). In this secondary analysis, we included only patients who had cervical length ≥ 30 mm measured on transvaginal ultrasound on admission. Our primary outcome was a Bishop score change after removal of the device. Secondary outcomes included insertion to delivery interval, mode of delivery, and oxytocin infusion duration.

Results

Sixty‐seven women met the inclusion criteria and were included in the analysis: 33 in the 6‐h group and 34 in the 12‐h group. Maternal characteristics were similar between both groups. Bishop score difference between the preinsertion and the postremoval scores were similar in the two groups (2.67 ± 1.8 vs. 2.53 ± 1.69, P = 0.76), while insertion to delivery time was 10 h shorter in the 6‐h group (20.95 vs. 31.21, P = 0.02; mean difference, −10.26 [95% CI, −19.0 to −1.51]). The other secondary outcomes remained similar in both groups.

Conclusion

In women undergoing induction of labor who have a cervical length ≥ 30 mm measured on admission transvaginal ultrasound, removing a double balloon device after 6 h achieved similar Bishop score changes as removal after 12 h, but significantly reduced the time to delivery.

Registration at Clinical Trials

https://classic.clinicaltrials.gov/ct2/show/NCT03045939.
Latent profiles of home behaviour problems in Trinidad and Tobago
Authors: Gerstner Clara‐Christina E. , McDermott Paul A. , Weiss Emily M. , Rovine Michael J. , Worrell Frank C. , Hall Tracey E.
Published: October 2024

Caregivers who interact with children at home can provide a critical, complementary perspective on a child's behaviour functioning. This research used a parent‐administered measure of problem behaviours to study perceptions of child behaviours across home situations. We applied latent profile analysis to identify subgroups of children with common behavioural tendencies in a nationally representative sample (N = 709) of 4‐ to 13‐year‐old children in Trinidad and Tobago. This study (a) identified latent profiles of children's over‐ and underactive behaviour problems in varied home settings and (b) examined how profile membership predicted academic skills and teacher‐observed problem behaviours. The best‐fitting four‐profile model included one profile of adjusted behaviours (56%), one of the elevated attention‐seeking behaviours (21%), a profile featuring withdrawn and disengaged behaviours (15%) and a relatively rare profile emphasising aggressive behaviours (8%). Children classified in the last profile displayed the poorest academic outcomes and the highest levels of teacher‐observed behaviour problems.
Research and scholarly methods: Research collaboration
Authors: Smith Susan E. , Bland Christopher M. , Branan Trisha N. , Sikora Andrea , Hawkins William Anthony
Published: October 2024

The pursuit of research and scholarly productivity is critical for clinician scientists, yet achieving impactful outcomes often necessitates collaboration within a well‐structured team. This review explores the foundational elements of team building that support sustained research productivity among health care professionals and academicians. Drawing on principles from team science, the importance of establishing a shared vision and mission, fostering authentic relationships, and creating an efficient infrastructure to enhance and sustain collaborative efforts is discussed. The four stages of team development—forming, storming, norming, and performing—are examined to provide insights into the dynamic nature of teamwork. Emphasizing the need for intentional practices, we highlight methods for identifying and integrating team members, managing conflicts, and leveraging diverse skill sets to achieve collective goals. Best practices for sustaining research teams, including the implementation of SMART (Specific, Measurable, Assignable, Realistic, Time‐related) goals, regular retreats, and strategic alignment of activities to maximize output are also discussed. Two collaborative teams are used as exemplars to illustrate the successful application of these principles, resulting in significant scholarly output. By understanding and applying the concepts of team building, clinician scientists can enhance their research output, contribute to the advancement of health care, and achieve a fulfilling and sustainable career.
Ti3C2Tx‐UHMWPE Nanocomposites—Towards an Enhanced Wear‐Resistance of Biomedical Implants
Authors: Rothammer Benedict , Feile Klara , Werner Siegfried , Frank Rainer , Bartz Marcel , Wartzack Sandro , Schubert Dirk W. , Drummer Dietmar , Detsch Rainer , Wang Bo , Rosenkranz Andreas , Marian Max
Published: October 2024

There is an urgent need to enhance the mechanical and biotribological performance of polymeric materials utilized in biomedical devices such as load‐bearing artificial joints, notably ultrahigh molecular weight polyethylene (UHMWPE). While two‐dimensional (2D) materials like graphene, graphene oxide (GO), reduced GO, or hexagonal boron nitride (h‐BN) have shown promise as reinforcement phases in polymer matrix composites (PMCs), the potential of MXenes, known for their chemical inertness, mechanical robustness, and wear‐resistance, remains largely unexplored in biotribology. This study aims to address this gap by fabricating Ti3C2T
x
‐UHMWPE nanocomposites using compression molding. Primary objectives include enhancements in mechanical properties, biocompatibility, and biotribological performance, particularly in terms of friction and wear resistance in cobalt chromium alloy pin‐on‐UHMWPE disk experiments lubricated by artificial synovial fluid. Thereby, no substantial changes in the indentation hardness or the elastic modulus are observed, while the analysis of the resulting wettability and surface tension as well as indirect and direct in vitro evaluation do not point towards cytotoxicity. Most importantly, Ti3C2T
x
‐reinforced PMCs substantially reduce friction and wear by up to 19% and 44%, respectively, which was attributed to the formation of an easy‐to‐shear transfer film.
An Optimized CRISPR/Cas12a Assay to Facilitate the BRAF V600E Mutation Detection
Authors: Etemadzadeh Azadeh , Salehipour Pouya , Motlagh Fatemeh Movahedi , Khalifeh Masoomeh , Asadbeigi Adnan , Tabrizi Mina , Shirkouhi Reza , Modarressi Mohammad Hossein
Published: October 2024

Background

Accurate detection of the BRAF V600E (1799T > A) mutation status can significantly contribute to selecting an optimal therapeutic strategy for diverse cancer types. CRISPR‐based diagnostic platforms exhibit simple programming, cost‐effectiveness, high sensitivity, and high specificity in detecting target sequences. The goal of this study is to develop a simple BRAF V600E mutation detection method.

Methods

We combined the CRISPR/Cas12a system with recombinase polymerase amplification (RPA). Subsequently, several parameters related to CRISPR/Cas12a reaction efficiency were evaluated. Then, we conducted a comparative analysis of three distinct approaches toward identifying BRAF V600E mutations in the clinical samples.

Results

Our data suggest that CRISPR/Cas detection is considerably responsive to variations in buffer conditions. Magnesium acetate (MgOAc) demonstrated superior performance compared to all other examined additive salts. It was observed using 150 nM guide RNA (gRNA) in an optimized reaction buffer containing 14 mM MgOAc, coupled with a reduction in the volumes of PCR and RPA products to 1 μL and 3 μL, respectively, resulted in an enhanced sensitivity. Detection time was decreased to 75 min with a 2% limit of detection (LOD), as evidenced by the results obtained from the blue light illuminator. The CRISPR/Cas12a assay confirmed the real‐time PCR results in 31 of 32 clinical samples to identify the BRAF V600E mutation status, while Sanger sequencing detected BRAF V600E mutations with lower sensitivity.

Conclusion

We propose a potential diagnostic approach that is facile, fast, and affordable with high fidelity. This method can detect BRAF V600E mutation with a 2% LOD without the need for a thermocycler.
MR Elastography for Classification of Focal Liver Lesions Using Viscoelastic Parameters: A Pilot Study Based on Intrinsic and Extrinsic Activations
Authors: Baradaran Najar Amirhosein , Gilbert Guillaume , Karam Elige , Volniansky Anton , Fohlen Audrey , Barat Maxime , Montagnon Emmanuel , Castel Hélène , Giard Jeanne‐Marie , Nguyen Bich N. , Cloutier Guy , Tang An , Van Houten Elijah
Published: October 2024

Background

Intrinsic activation MR elastography (iMRE) uses cardiovascular pulsations to assess tissue viscoelastic properties. Applying it to focal liver lesions extends its capabilities.

Purpose

To assess the viscoelastic parameters of focal liver lesions measured by iMRE and compare its diagnostic performance with extrinsic MRE (eMRE) for differentiating malignant and benign lesions.

Study type

Prospective.

Population

A total of 55 participants underwent MRI with research MRE sequences; 32 participants with 17 malignant and 15 benign lesions underwent both iMRE and eMRE.

Field Strength/Sequence

iMRE at ~1 Hz heart rate used a 3 T scanner with a modified four‐dimensional (4D)‐quantitative flow gradient‐echo phase contrast and low‐velocity encoding cardiac‐triggered technique. eMRE employed a gradient‐echo sequence at 30, 40, and 60 Hz.

Assessment

Liver displacements were measured using 4D‐phase contrast and reconstructed via a nonlinear inversion algorithm to determine shear stiffness (SS) and damping ratio (DR). iMRE parameters were normalized to the corresponding values from the spleen. Lesions were manually segmented, and image quality was reviewed.

Statistical Tests

Kruskal–Wallis, Mann–Whitney, Dunn's test, and areas under receiver operating characteristic curves (AUC) were assessed.

Results

SS was significantly higher in malignant than benign lesions with iMRE at 1 Hz (3.69 ± 1.31 vs. 1.63 ± 0.45) and eMRE at 30 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), 40 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), and 60 Hz (7.32 ± 2.87 vs. 2.48 ± 1.12 kPa). DR was also significantly higher in malignant than benign lesions at 40 Hz (0.36 ± 0.11 vs. 0.21 ± 0.01) and 60 Hz (0.89 ± 0.86 vs. 0.22 ± 0.09). The AUC were 0.86 for iMRE SS, 0.87–0.98 for eMRE SS, 0.47 for iMRE DR, and 0.62–0.86 for eMRE DR.

Data Conclusion

Cardiac‐activated iMRE can characterize liver lesions and differentiate malignant from benign lesions through normalized SS maps.

Level of Evidence

2

Technical Efficacy

Stage 2
An ultrastructure analysis of the developing human anterior cruciate ligament tibial enthesis
Authors: Hidalgo Perea Sofia , Uppstrom Tyler J. , Lin Kenneth M. , Klinger Craig E. , Bromage Timothy G. , Shea Kevin G. , Green Daniel W. , Rodeo Scott A.
Published: October 2024

This study aimed to investigate the ultrastructural anatomy of the developing ACL tibial enthesis. We hypothesized that enthesis architecture would progressively mature and remodel, eventually resembling that of the adult by the early postnatal stage. Five fresh‐frozen human pediatric cadaveric knees aged 1–36 months underwent anatomical dissection to harvest the ACL insertion and underlying tibial chondroepiphysis. The samples were prepared for scanning electron microscopy (SEM) to examine the ultrastructural anatomy of the enthesis and underwent histological staining for circular polarized light (CPL) and light microscopy imaging. SEM analysis of the 1‐ and 8‐month‐old samples revealed a shallow interdigitation between the dense fibrous (ligamentous) tissue and unmineralized chondrogenic tissues, with a minimal transition zone. By 11‐month, a more complex transition zone was present. By age 19‐ and 36‐month‐old, a progressively more complex and defined fibrocartilage zone was observed. CPL analysis revealed distinct collagen fiber continuity, alignment, and organization changes over time. By 19 and 36 months, the samples exhibited complex fiber arrangements and a progression toward uniform fiber orientation. Similarly, histological analysis demonstrated progressive remodeling of the enthesis with increasing age. Our results suggest that the ACL enthesis of the developing knee begins to mimic that of an adult as early as 19 months of age, as a more complex transition between ligamentous and chondro‐epiphyseal tissue can be appreciated. We hypothesize that the observed changes are likely due to mechanical loading of the enthesis with the onset of weightbearing. Future investigations of ACL reconstruction and repair will benefit from improved understanding of the chondro‐epiphyseal/ACL regions.
Morbidity and Mortality Following Surgery for Pancreatic Cancer in Low‐ and Middle‐Income Countries: A Systematic Review and Meta‐Analysis
Authors: Khan Mustafa Ali , Sherwani Maryam , Ahmed Kaleem S. , Ali Mubeen , Kumar Priya Ashok , Tariq Javeria , Christensen Leslie , Bogale Netsanet , Schwartz Patrick B. , Zafar Syed Nabeel
Published: October 2024

Background and Objectives

Measuring postoperative outcomes after complex cancer operations such as pancreatectomy is vital to improve cancer surgery in low‐ and middle‐income countries (LMICs); however, such data is often limited. This study aimed to review existing research and obtain baseline estimates for postoperative mortality and morbidity after pancreatic cancer surgery in LMICs.

Methods

PubMed, Embase, Web of Science Core Collection, and Global Index Medicus were systematically searched for original articles published between January 2005 and May 2022. LMICs based studies reporting postoperative mortality, morbidity, and/or length of stay of patients with primary pancreatic tumors undergoing pancreaticoduodenectomy and/or distal pancreatectomy were included.

Results

Of 18 344 unique titles and abstracts retrieved, 114 studies met the inclusion criteria. Of these, 51 “good” quality studies comprising 7528 patients were included in the meta‐analyses. Pooled estimates for pancreatic fistula were 16.6% (95% CI 14.0–19.7, p < 0.001); 16.0% (95% CI 11.1–22.5, p < 0.001) for Clavien‐Dindo grade 3 and 4 complications; 13.4% (95% CI 9.8–17.9, p < 0.001) for wound infection; and 4.4% (95% CI 3.3–5.7, p < 0.001) for postoperative mortality.

Conclusion

This is the first systematic review and meta‐analysis examining surgical complications after pancreatic surgery in LMICs. We highlight a lack of data and the need to further evaluate surgical outcomes in LMICs.
Evaluation of a novel robotic testing method for stability and kinematics of total knee arthroplasty
Authors: Holthof Sander R. , Rock Mick , van Arkel Richard , Brivio Angela , Barrett David , Amis Andrew A.
Published: October 2024

Purpose

This work developed a novel preclinical test of total knee replacements (TKRs) in order to explain TKR instability linked to patient dissatisfaction. It was hypothesized that stability tests on the isolated moving prostheses would provide novel comparative data on the stability and kinematics among TKR designs.

Methods

Three TKR designs, DePuy Synthes Attune MS, Stryker Triathlon and Zimmer Biomet Persona MC, were assessed using a robotic arm while flexing–extending 0–140°. Tests imposed 710 N body weight combined with three tibial loads: no anterior–posterior (AP) force, 90 N anterior or 90 N posterior force. Other load effects were minimized and the kinematics was recorded. Each implant was tested six times to investigate the repeatability of the method. Data were analysed using statistical parametric mapping with one‐way analysis of variance (ANOVA). If significance was found (p < 0.05), post hoc t tests with Bonferroni correction were used to contrast groups.

Results

Significant differences were found throughout flexion–extension. Femoral rollback, AP stability, coupled internal–external rotation and AP position (roll‐back) were all influenced by implant design. AP stability of the TKRs reduced with flexion reaching Attune 15 mm, Persona 13 mm and Triathlon 21 mm at 140° flexion. Tractive rolling significantly affected kinematics in the less congruent Triathlon design, with 6 mm different paths between flexion and extension motion (p < 0.05 across 5–100°). Paradoxical anterior femoral sliding in early flexion (0–40°) occurred in Persona and Triathlon designs.

Conclusions

The novel testing technique provides, for the first time, comparative data on the inherent stability and kinematics of the TKR implants themselves across the arc of flexion–extension, independent of variables including soft tissue behaviour and surgical technique. The data show how much each prosthesis can contribute to the stability and motion of the implanted knee. Similar data from a wider range of designs will enable more informed decisions regarding implant design choice, aiming to reduce the prevalence of TKR instability in patients.

Level of Evidence

Controlled laboratory study.
An Injectable IPN Nanocomposite Hydrogel Embedding Nano Silica for Tissue Engineering Application
Authors: Kakapour Ali , Nouri Khorasani Saied , Khalili Shahla , Hafezi Mahshid , Sattari‐Najafabadi Mehdi , Najarzadegan Mahsa , Saleki Samin , Bagheri‐Khoulenjani Shadab
Published: October 2024

Gelatin methacrylate (GM) and sodium alginate (SA) are two biomaterials that have been widely employed in tissue engineering, particularly in 3D bioprinting. However, they have some drawbacks including undesirable physico‐mechanical properties and printability, hindering their application. This work developed an interpenetrating polymeric network (IPN) of GM and SA reinforced with silica nanoparticles (SNPs) to deal with hydrogels’ drawbacks. Besides, for cross‐linking, visible light is used as an alternative to UV light to prevent disruptions in cellular metabolism and immune system reactions. Four GM/SA/SNP hydrogels different in SNPs concentration (0, 0.5, 1, and 2 w/w%) are studied. The performance of the hydrogels is evaluated in terms of physico‐mechanical properties (viscoelasticity, compressive modulus, degradation, and swelling), rheological properties, and biological properties (fibroblast cell growth and adhesion, and MTT assay). The results demonstrated that the GM/SA/SNP hydrogel with 1% SNPs provided desirable physical (645% swelling and 59.3% degradation), mechanical strength (270 kPa), rheological (tan δ of almost 0.14), and biological performances (≈98% viability after 3 days) while maintaining appropriate printability. The findings suggest that the GM/SA/SNP hydrogel holds great potential for applications in soft tissue regeneration.
Flat top coverage pattern maintaining via boundary subarray elements thinning
Authors: Abdulqader Ahmed Jameel , Mohammed Jafar Ramadhan , Ali Y. E. Mohammed
Published: October 2024

This paper aims to study the effect of eliminating some elements from the original planar array (OPA) to generate a useful flat‐top coverage pattern (FTCP) using a genetic algorithm. The study involves dividing the fully planar array (i.e., OPA) into two regions with an unequal number of elements. The first region includes the elements located in the core (center) of the array, and the remaining elements are the second region, and their location is within the boundary (side) of the array. Only the elements of the first region are included in the optimization process, while the elements of the second region are eliminated in the form of a specific geometric composition without affecting the FTCP generation. Comparing the OPA that N×M elements with the first region (active subarray) elements, it is noted that the number of elements has been reduced from N×M to (N − 2x) × (M − 2y) to reduce the complexity of the system as much as possible without affecting the performance in general. Different boundary subarray shapes are presented in this paper with different numbers of elements. The obtained results showed the effectiveness of the proposed method in generating FTCP close to its counterpart in the OPA.
David Garbers' Contributions to Chemotaxis Signaling in Sperm
Authors: Kaupp U. B. , Kendall Olivia
Published: October 2024

This review focuses on the contribution of the late David Garbers to chemotaxis of sperm, in particular from sea urchin. We will describe his discovery of chemotactic peptides and their cognate receptors, his discovery of a sperm‐specific, unique Na+/H+ exchanger that represents a chimera between a solute carrier (SLC) and an ion channel. Finally, we will discuss his contributions to the understanding of cAMP signaling in sperm via soluble adenylyl cyclase (sAC) and its control by Ca2+ ions.