bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetabular Revision with McMinn Cup: Development and Application of a Patient-Specific Targeting Device
Authors: Csernátony Zoltán , Manó Sándor , Szabó Dániel , Soósné Horváth Hajnalka , Kovács Ágnes Éva , Csámer Loránd
Published: September 2023

Background: Surgeries of severe periacetabular bone defects (Paprosky ≥ 2B) are a major challenge in current practice. Although solutions are available for this serious clinical problem, they all have their disadvantages as well as their advantages. An alternative method of reconstructing such extensive defects was the use of a cup with a stem to solve these revision situations. As the instrumentation offered is typically designed for scenarios where a significant bone defect is not present, our unique technique has been developed for implantation in cases where reference points are missing. Our hypothesis was that a targeting device designed based on the CT scan of a patient’s pelvis could facilitate the safe insertion of the guiding wire. Methods: Briefly, our surgical solution consists of a two-step operation. If periacetabular bone loss was found to be more significant during revision surgery, all implants were removed, and two titanium marker screws in the anterior iliac crest were percutaneously inserted. Next, by applying the metal artifact removal (MAR) algorithm, a CT scan of the pelvis was performed. Based on that, the dimensions and positioning of the cup to be inserted were determined, and a patient-specific 3D printed targeting device made of biocompatible material was created to safely insert the guidewire, which is essential to the implantation process. Results: In this study, medical, engineering, and technical tasks related to the design, the surgical technique, and experiences from 17 surgical cases between February 2018 and July 2021 are reported. There were no surgical complications in any cases. The implant had to be removed due to septic reasons (independently from the technique) in a single case, consistent with the septic statistics for this type of surgery. There was not any perforation of the linea terminalis of the pelvis due to the guiding method. The wound healing of patients was uneventful, and the implant was fixed securely. Following rehabilitation, the joints were able to bear weight again. After one to four years of follow-up, the patient satisfaction level was high, and the gait function of the patients improved a lot in all cases. Conclusions: Our results show that CT-based virtual surgical planning and, based on it, the use of a patient-specific 3D printed aiming device is a reliable method for major hip surgeries with significant bone loss. This technique has also made it possible to perform these operations with minimal X-ray exposure.
ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis
Authors: Membrive-Jiménez Cristina , Vieira-Maroun Sayleth , Márquez-Pete Noelia , Cura Yasmin , Pérez-Ramírez Cristina , Tercedor-Sánchez Jesús , Jiménez-Morales Alberto , Ramírez-Tortosa María del Carmen
Published: September 2023

Background: Methotrexate (MTX) is one of the most extensively used drugs in the treatment of moderate-to-severe psoriasis (PS). However, it frequently must be suspended owing to the toxicity in certain patients. Objective: To evaluate the influence of ABCC1, ABCG2, and FOXP3 in the development of MTX toxicity in PS. Methods: Retrospective cohort study with 101 patients. Five single-nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction with TaqMan probes. Results: Patients carrying ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.04; 95% CI = 1.48–46.78; p = 0.015); FOXP3 rs376154-GT and GG genotypes (GT vs. TT/GG: OR = 3.86; 95% CI = 1.17–13.92; p = 0.031) and ABCG2 rs13120400-T allele (T vs. CC: OR = 8.33; 95% CI = 1.24–164.79; p = 0.059) showed a higher risk of developing more than one adverse effect. The toxicity analysis by subtypes showed that the ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.10; 95% CI = 1.69–46.63; p = 0.011) and FOXP3 rs376154-GT genotype (OR = 4.11; 95% CI = 1.22–15.30; p = 0.027) were associated with the appearance of asthenia. No association of the other ABCC1 polymorphisms (rs35592 and rs246240) with MTX toxicity was found. Conclusion: ABCC1, ABCG2, and FOXP3 polymorphisms can be considered to be risk biomarkers of toxicities in PS patients treated with MTX.
Research on Self-Stiffness Adjustment of Growth-Controllable Continuum Robot (GCCR) Based on Elastic Force Transmission
Authors: Wang Mingyuan , Yuan Jianjun , Bao Sheng , Du Liang , Ma Shugen
Published: September 2023

Continuum robots have good adaptability in unstructured and complex environments. However, affected by their inherent nature of flexibility and slender structure, there are challenges in high-precision motion and load. Thus, stiffness adjustment for continuum robots has consistently attracted the attention of researchers. In this paper, a stiffness adjustment mechanism (SAM) is proposed and built in a growth-controllable continuum robot (GCCR) to improve the motion accuracy in variable scale motion. The self-stiffness adjustment is realized by antagonism through cable force transmission during the length change of the continuum robot. With a simple structure, the mechanism has a scarce impact on the weight and mass distribution of the robot and required no independent actuators for stiffness adjustment. Following this, a static model considering gravity and end load is established. The presented theoretical static model is applicable to predict the shape deformations of robots under different loads. The experimental validations showed that the maximum error ratio is within 5.65%. The stiffness of the robot can be enhanced by nearly 79.6%.
Adaptive PI Controller Based on a Reinforcement Learning Algorithm for Speed Control of a DC Motor
Authors: Alejandro-Sanjines Ulbio , Maisincho-Jivaja Anthony , Asanza Victor , Lorente-Leyva Leandro L. , Peluffo-Ordóñez Diego H.
Published: September 2023

Automated industrial processes require a controller to obtain an output signal similar to the reference indicated by the user. There are controllers such as PIDs, which are efficient if the system does not change its initial conditions. However, if this is not the case, the controller must be retuned, affecting production times. In this work, an adaptive PID controller is developed for a DC motor speed plant using an artificial intelligence algorithm based on reinforcement learning. This algorithm uses an actor–critic agent, where its objective is to optimize the actor’s policy and train a critic for rewards. This will generate the appropriate gains without the need to know the system. The Deep Deterministic Policy Gradient with Twin Delayed (DDPG TD3) was used, with a network composed of 300 neurons for the agent’s learning. Finally, the performance of the obtained controller is compared with a classical control one using a cost function.
Establishment and Validation of an Integrated Microfluidic Step Emulsification Chip Supporting Droplet Digital Nucleic Acid Analysis
Authors: Luo Gangyin , Zhang Ying , Wang Shun , Lv Xinbei , Yang Tianhang , Wang Jinxian
Published: September 2023

Uniform and stable droplet generation is critical for accurate and efficient digital nucleic acid analysis (dNAA). In this study, an integrated microfluidic step emulsification device with wide-range droplet generation capability, small device dimensions, convenient fabrication strategy, low contamination and high robustness was developed. A tree-shaped droplet generation nozzle distribution design was proposed to increase the uniformity of droplet generation by equating flow rates, and the flow field in the design was numerically simulated. Theoretical analysis and comparative experiments on droplet size were performed regarding the influences of nozzle dimensions and surface properties. With incubation and hydrophobic reagent treatment, droplets as small as 73.1 μm were generated with multiplex nozzles of 18 μm (h) × 80 μm (w). The droplets were then collected into a standard PCR tube and an on-chip monolayer droplet collection chamber, without manual transfer and sample contamination. The oil-to-sample volume ratio in the PCR tube was recorded during collection. In the end, the droplets generated and collected using the microfluidic device proved to be stable and uniform for nucleic acid amplification and detection. This study provides reliable characteristic information for the design and fabrication of a micro-droplet generation device, and represents a promising approach for the realization of a three-in-one dNAA device under a step emulsification method.
Unraveling the Possibilities: Recent Progress in DNA Biosensing
Authors: Yu Meng , He Tingli , Wang Qianqian , Cui Cheng
Published: September 2023

Due to the advantages of its numerous modification sites, predictable structure, high thermal stability, and excellent biocompatibility, DNA is the ideal choice as a key component of biosensors. DNA biosensors offer significant advantages over existing bioanalytical techniques, addressing limitations in sensitivity, selectivity, and limit of detection. Consequently, they have attracted significant attention from researchers worldwide. Here, we exemplify four foundational categories of functional nucleic acids: aptamers, DNAzymes, i-motifs, and G-quadruplexes, from the perspective of the structure-driven functionality in constructing DNA biosensors. Furthermore, we provide a concise overview of the design and detection mechanisms employed in these DNA biosensors. Noteworthy advantages of DNA as a sensor component, including its programmable structure, reaction predictility, exceptional specificity, excellent sensitivity, and thermal stability, are highlighted. These characteristics contribute to the efficacy and reliability of DNA biosensors. Despite their great potential, challenges remain for the successful application of DNA biosensors, spanning storage and detection conditions, as well as associated costs. To overcome these limitations, we propose potential strategies that can be implemented to solve these issues. By offering these insights, we aim to inspire subsequent researchers in related fields.
Genetically Encoded Fluorescent Probe for Detection of Heme-Induced Conformational Changes in Cytochrome c
Authors: Genceroglu Mehmet Yunus , Cavdar Cansu , Manioglu Selen , Bayraktar Halil
Published: September 2023

Cytochrome c (Cytc) is a key redox protein for energy metabolism and apoptosis in cells. The activation of Cytc is composed of several steps, including its transfer to the mitochondrial membrane, binding to cytochrome c heme lyase (CCHL) and covalent attachment to heme. The spectroscopic methods are often applied to study the structural changes of Cytc. However, they require the isolation of Cytc from cells and have limited availability under physiological conditions. Despite recent studies to elucidate the tightly regulated folding mechanism of Cytc, the role of these events and their association with different conformational states remain elusive. Here, we provide a genetically encoded fluorescence method that allows monitoring of the conformational changes of Cytc upon binding to heme and CCHL. Cerulean and Venus fluorescent proteins attached at the N and C terminals of Cytc can be used to determine its unfolded, intermediate, and native states by measuring FRET amplitude. We found that the noncovalent interaction of heme in the absence of CCHL induced a shift in the FRET signal, indicating the formation of a partially folded state. The higher concentration of heme and coexpression of CCHL gave rise to the recovery of Cytc native structure. We also found that Cytc was weakly associated with CCHL in the absence of heme. As a result, a FRET-based fluorescence approach was demonstrated to elucidate the mechanism of heme-induced Cytc conformational changes with spatiotemporal resolution and can be applied to study its interaction with small molecules and other protein partners in living cells.
A Dynamic Probabilistic Model for Heterogeneous Data Fusion: A Pilot Case Study from Computer-Aided Detection of Depression
Authors: Vitale Federica , Carbonaro Bruno , Esposito Anna
Published: September 2023

The present paper, in the framework of a search for a computer-aided method to detect depression, deals with experimental data of various types, with their correlation, and with the way relevant information about depression delivered by different sets of data can be fused to build a unique body of knowledge about individuals’ mental states facilitating the diagnosis and its accuracy. To this aim, it suggests the use of a recently introduced «limiting form» of the kinetic-theoretic language, at present widely used to describe complex systems of objects of the most diverse nature. In this connection, the paper mainly aims to show how a wide range of experimental procedures can be described as examples of this «limiting case» and possibly rendered by this description more effective as methods of prediction from experience. In particular, the paper contains a simple, preliminary application of the method to the detection of depression, to show how the consideration of statistical parameters connected with the analysis of speech can modify, at least in a stochastic sense, each diagnosis of depression delivered by the Beck Depression Inventory (BDI-II).
Adapting to Altered Sensory Input: Effects of Induced Paresthesia on Goal-Directed Movement Planning and Execution
Authors: Mortaza Niyousha , Passmore Steven R. , Glazebrook Cheryl M.
Published: September 2023

The current study investigated how temporarily induced paresthesia in the moving limb affects the performance of a goal-directed target aiming task. Three-dimensional displacement data of 14 neurotypical participants were recorded while they pointed to a target on a computer monitor in four conditions: (i) paresthesia-full-vision; (ii) paresthesia-without-target vision; (iii) no-paresthesia-full-vision; (iv) no paresthesia-without-target vision. The four conditions were blocked and counterbalanced such that participants performed the paresthesia and no-paresthesia conditions on two separate days. To assess how aiming performance changed in the presence of paresthesia, we compared early versus late performance (first and last 20% of trials). We found that endpoint accuracy and movement speed were reduced in the presence of paresthesia, but only without target vision. With repetition, participants adjusted their movement performance strategy, such that with induced paresthesia, they used a movement strategy that included more pre-planned movements that depended less on online control.
Association between Daytime Sleepiness, Fatigue and Autonomic Responses during Head-Up Tilt Test in Multiple Sclerosis Patients
Authors: Zawadka-Kunikowska Monika , Rzepiński Łukasz , Cieślicka Mirosława , Klawe Jacek J. , Tafil-Klawe Małgorzata
Published: September 2023

We aimed to assess dynamic changes in hemodynamic and autonomic function in response to the head-up tilt test (HUTT) in patients with multiple sclerosis (MS) compared to healthy controls (HCs) and evaluate its relationship with the patients’ reported daytime sleepiness and fatigue symptoms. A total of 58 MS patients and 30 HCs were included in the analysis. Fatigue and sleepiness were evaluated using the Chalder Fatigue Scale (CFQ) and the Epworth Sleepiness Scale (ESS), respectively. Hemodynamic response, baroreflex sensitivity, heart rate variability, and systolic and diastolic blood pressure (BP) variability (SBPV, DBPV) parameters were calculated at rest, and in response to the HUTT. The MS patients displayed attenuated BP responses coupled with a more pronounced decrease in cardiac index as well as a reduced increase in the low frequency (LFnu) of DBPV (p = 0.021) and the sympathovagal ratio (p = 0.031) in the latter-phase orthostatic challenge compared to HCs. In MS patients, the ESS score showed no correlation with CFQ or clinical disease outcomes, but exhibited a moderate correlation with LFnu of BPVrest. Fatigue and disease variants predicted blood pressure response to HUTT. These findings underscore the importance of subjective daytime sleepiness and fatigue symptoms and their role in blood pressure regulation in MS patients.
Does Decreased Vitamin D Level Trigger Bipolar Manic Attacks?
Authors: İmre Okan , Karaağaç Mustafa , Caglayan Cuneyt
Published: September 2023

Background: Bipolar disorder is a chronic psychiatric disorder with depression and manic episodes. It is one of the leading causes of disease-related disability worldwide. Despite the presence of various alternative drug options for bipolar disorder, some patients do not adequately benefit from the treatment. Therefore, possible underlying mechanisms need to be clarified. Recently, studies on the relationship between bipolar disorder and vitamin D (Vit D) have attracted attention. Although many studies have found an association between depression and Vit D deficiency, little is known about the relationship between manic episodes and Vit D. The aim of this study was to compare Vit D and related metabolites of bipolar manic episodes prior to treatment, bipolar remission after treatment, and healthy control groups. Methods: This case–control study consisted of 34 bipolar manic episode patients and 34 healthy controls. Disease activity was evaluated with the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Firstly, serum 25-hydroxy vitamin D (25-OHD), calcium (Ca) and phosphorus (P) levels of patients in the bipolar manic episode were measured and compared with healthy control. Secondly, serum 25-OHD, Ca and P levels in the euthymic periods of the same patients were measured and compared with healthy control. Results: Bipolar manic episode Vit D levels were lower when compared to healthy controls; while there was no difference in terms of Ca and P levels. There was no significant difference between the bipolar euthymic period patients and the healthy control group in terms of 25-OHD, Ca and P levels. Conclusion: Our results demonstrated low serum Vit D concentrations in the acute manic episode of bipolar disorder. Decreased Vit D level may play a role in the onset of the manic episode, or malnutrition and insufficient sunlight during the manic episode may have caused Vit D deficiency. Future studies are needed to exclude potential confounding factors and to compare all mood episodes.
Follow-Up after Curative Surgical Treatment of Soft-Tissue Sarcoma for Early Detection of Recurrence: Which Patients Have More or Fewer Visits than Advised in Guidelines?
Authors: Kruiswijk Anouk A. , Kuhrij Laurien S. , Dorleijn Desiree M. J. , van de Sande Michiel A. J. , van Bodegom-Vos Leti , Marang-van de Mheen Perla J.
Published: September 2023

Introduction: Follow-up (FU) in soft-tissue sarcoma (STS) patients is designed for early detection of disease recurrence. Current guidelines are not evidenced-based and not tailored to patient or tumor characteristics, so they remain debated, particularly given concerns about cost, radiation frequency, and over-testing. This study assesses the extent to which STS patients received guideline-concordant FU and to characterize which type of patients received more or fewer visits than advised. Methods: All STS patients surgically treated at the Leiden University Medical Center between 2000–2020 were included. For each patient, along with individual characteristics, all radiological examinations from FU start up to 5 years were included and compared to guidelines. Recurrence was defined as local/regional recurrence or metastasis. Results: A total of 394 patients was included, of whom 250 patients had a high-grade tumor (63.5%). Only 24% of patients received the advised three FU visits in the first year. More FU visits were observed in younger patients and those diagnosed with a high-grade tumor. Among patients with a recurrence, 10% received fewer visits than advised, while 28% of patients without a recurrence received more visits than advised. Conclusions: A minority of STS patients received guideline-concordant FU visits, suggesting that clinicians seem to incorporate recurrence risk in decisions on FU frequency.
Deep Learning and Registration-Based Mapping for Analyzing the Distribution of Nodal Metastases in Head and Neck Cancer Cohorts: Informing Optimal Radiotherapy Target Volume Design
Authors: Weissmann Thomas , Mansoorian Sina , May Matthias Stefan , Lettmaier Sebastian , Höfler Daniel , Deloch Lisa , Speer Stefan , Balk Matthias , Frey Benjamin , Gaipl Udo S. , Bert Christoph , Distel Luitpold Valentin , Walter Franziska , Belka Claus , Semrau Sabine , Iro Heinrich , Fietkau Rainer , Huang Yixing , Putz Florian
Published: September 2023

We introduce a deep-learning- and a registration-based method for automatically analyzing the spatial distribution of nodal metastases (LNs) in head and neck (H/N) cancer cohorts to inform radiotherapy (RT) target volume design. The two methods are evaluated in a cohort of 193 H/N patients/planning CTs with a total of 449 LNs. In the deep learning method, a previously developed nnU-Net 3D/2D ensemble model is used to autosegment 20 H/N levels, with each LN subsequently being algorithmically assigned to the closest-level autosegmentation. In the nonrigid-registration-based mapping method, LNs are mapped into a calculated template CT representing the cohort-average patient anatomy, and kernel density estimation is employed to estimate the underlying average 3D-LN probability distribution allowing for analysis and visualization without prespecified level definitions. Multireader assessment by three radio-oncologists with majority voting was used to evaluate the deep learning method and obtain the ground-truth distribution. For the mapping technique, the proportion of LNs predicted by the 3D probability distribution for each level was calculated and compared to the deep learning and ground-truth distributions. As determined by a multireader review with majority voting, the deep learning method correctly categorized all 449 LNs to their respective levels. Level 2 showed the highest LN involvement (59.0%). The level involvement predicted by the mapping technique was consistent with the ground-truth distribution (p for difference 0.915). Application of the proposed methods to multicenter cohorts with selected H/N tumor subtypes for informing optimal RT target volume design is promising.
Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study
Authors: Fracchiolla Nicola Stefano , Sciumè Mariarita , Papayannidis Cristina , Vitale Antonella , Chiaretti Sabina , Annunziata Mario , Giglio Fabio , Salutari Prassede , Forghieri Fabio , Lazzarotto Davide , Lunghi Monia , Imovilli Annalisa , Scappini Barbara , Bonifacio Massimiliano , Dargenio Michelina , Gurrieri Carmela , Todisco Elisabetta , Defina Marzia , Del Principe Maria Ilaria , Zappasodi Patrizia , Cerrano Marco , Santoro Lidia , Tagliaferri Elena , Barozzi Enrico , De Roberto Pasquale , Canzi Marta , Buzzatti Elisa , Sartor Chiara , Passamonti Francesco , Foà Robin , Curti Antonio
Published: September 2023

Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: In the Blina/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD−); after InO, a CR was achieved in 47 patients (82%, 34 MRD−). In the InO/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD−); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD−). Twenty-six patients proceeded to allo-HSCT. In the Blina/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD− vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD− vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR. Conclusion: In our series of R/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT.
Single-Step IGHV Next-Generation Sequencing Detects Clonality and Somatic Hypermutation in Lymphoid Malignancies: A Phase III Diagnostic Accuracy Study
Authors: Gazzola Anna , Navari Mohsen , Mannu Claudia , Donelli Riccardo , Etebari Maryam , Piccaluga Pier Paolo
Published: September 2023

Background: Multiplex PCR based on consensus primers followed by capillary electrophoresis and Sanger sequencing are considered as the gold standard method for the evaluation of clonality and somatic hypermutation in lymphoid malignancies. As an alternative, the next-generation sequencing (NGS) of immune receptor genes has recently been proposed as a solution, due to being highly effective and sensitive. Here, we designed a phase III diagnostic accuracy study intended to compare the current gold standard methods versus the first commercially available NGS approaches for testing immunoglobulin heavy chain gene rearrangements. Methods: We assessed IGH rearrangements in 68 samples by means of both the NGS approach (LymphoTrack® IGH assay, and LymphoTrack® IGH somatic hypermutation assay, run on Illumina MiSeq) and capillary electrophoresis/Sanger sequencing to assess clonality and somatic hypermutations (SHM). Results: In comparison to the routine capillary-based analysis, the NGS clonality assay had an overall diagnostic accuracy of 96% (63/66 cases). Other studied criteria included sensitivity (95%), specificity (100%), positive predictive value (100%) and negative predictive value (75%). In discrepant cases, the NGS results were confirmed by a different set of primers that provided coverage of the IGH leader sequence. Furthermore, there was excellent agreement of the SHM determination with both the LymphoTrack® FR1 and leader assays when compared to the Sanger sequencing analysis (84%), with NGS able to assess the SHM rate even in cases where the conventional approach failed. Conclusion: Overall, conventional Sanger sequencing and next-generation-sequencing-based clonality and somatic hypermutation analyses gave comparable results. For future use in a routine diagnostic workflow, NGS-based approaches should be evaluated prospectively and an analysis of cost-effectiveness should be performed.
Reducing Chemotherapy Waiting Times in the Ambulatory Setting of a Tertiary Cancer Centre Using a Design Thinking Approach
Authors: Jen Wei-Ying , Chan Zhi Yao , Lee Yee Mei , Ng Noel , Tan Belinda , Teo Constance , Wong Yuet Peng , Chee Cheng Ean , Chee Yen-Lin
Published: September 2023

Introduction: Chemotherapy is complex. We hypothesized that a design thinking approach could redesign preparatory processes and reduce wait times. Methods: A multidisciplinary process mapping exercise was undertaken to understand the current processes, followed by proposing and testing solutions. Proposals were selected based on desirability and feasibility. These focused on starting the morning treatments on time and scheduling pre-made regimens in these slots. The primary outcome measure was the time from the appointment to starting treatment. Treatments in the post-intervention study group were compared against a historical control group. Results: The median time to start morning treatment decreased by 46%, from 83 min (with an interquartile range 50–127) in the control group to 45 min (with an interquartile range of 24–81 min) in the study group (p < 0.001). This translated into an overall improvement for the day, with the median time to start treatment decreasing from 77 min (with an interquartile range of 40–120 min) to 47 min (with an interquartile range of 20–79 min) (p < 0.001). Pre-makes increased by 258%, from 908 (28.5%) to 2340 (71.7%) regimens (p < 0.001). The number of patients starting treatment within an hour of their appointment increased from 1688 (32.8%) to 3355 (62.3%, p < 0.001). Conclusion: We have shown that a data-driven, design thinking approach can improve waiting times. This can be adapted to improve other processes in an empathetic, sustainable manner.
Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure
Authors: Gruol Donna L. , Calderon Delilah , Huitron-Resendiz Salvador , Cates-Gatto Chelsea , Roberts Amanda J.
Published: September 2023

Alcohol consumption activates the neuroimmune system of the brain, a system in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels of neuroimmune factors, which are important signaling factors and regulators of brain function. Alcohol activation of the neuroimmune system is known to dysregulate the production of neuroimmune factors, such as the cytokine IL-6, thereby changing the neuroimmune status of the brain, which could impact the actions of alcohol. The consequences of neuroimmune–alcohol interactions are not fully known. In the current studies we investigated this issue in transgenic (TG) mice with altered neuroimmune status relative to IL-6. The TG mice express elevated levels of astrocyte-produced IL-6, a condition known to occur with alcohol exposure. Standard behavioral tests of alcohol drinking and negative affect/emotionality were carried out in homozygous and heterozygous TG mice and control mice to assess the impact of neuroimmune status on the actions of chronic intermittent alcohol (ethanol) (CIE) exposure on these behaviors. The expressions of signal transduction and synaptic proteins were also assessed by Western blot to identify the impact of alcohol–neuroimmune interactions on brain neurochemistry. The results from these studies show that neuroimmune status with respect to IL-6 significantly impacts the effects of alcohol on multiple levels.
What Mothers Know about Newborn Bloodspot Screening and the Sources They Use to Acquire This Knowledge: A Pilot Study in Flanders
Authors: di Gangi Caroline , Hermans Maren , Rayyan Maissa , Eyskens François , Allegaert Karel
Published: September 2023

To learn what mothers know about newborn bloodspot screening (NBS), the procedure, and the sources used, a pilot study was performed. An online questionnaire was developed, with the first part focused on characteristics and the NBS procedure, and the second on knowledge, information sources, and health care providers (HCPs). This questionnaire was accessible until 200 answers were received. The characteristics of respondents were representative for the population. Mothers gave verbal consent in 69.5% of cases, 12.5% did not, and 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, five multiple-choice questions on sources, and assessments (5-point Likert scores) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory was poorly known, and post-analysis sample handling procedures were poorly understood. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was provided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 for clarity, timing appropriateness, sufficiency, and usefulness. The knowledge level and consent practices were reasonably good. Key HCP were midwives and nurses, the leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.
The Influence of Chitosan on Water Absorption and Solubility of Calcium Phosphate Cement
Authors: Lacan Ioana , Moldovan Mărioara , Ardelean Ioan
Published: September 2023

Calcium phosphate cements are widely used biomaterials for bone regeneration due to their biological properties, such as biocompatibility, biodegradability, and bioactivity. The presence of chitosan in cement composition influences the resorption rate of the material and its mechanical properties. In the present work, the water absorption and solubility of a tricalcium phosphate bone cement, prepared with and without chitosan addition, was comparatively evaluated. The absorption and solubility properties were monitored for 21 days by immersing the samples in water at room temperature and then weighing them. A morphological analysis of the samples was carried out via scanning electron microscopy (SEM). The absorption dynamics and pore evolution were investigated with low-field nuclear magnetic resonance (NMR) relaxometry. It was demonstrated that the presence of chitosan accelerates the hardening dynamics, reduces water absorption, and influences the solubility and degradation behavior of the cement. It was also observed that, independent of the presence of chitosan, the polymerization process is not completed even after one hour, which influences the solubility process. It was also shown that the presence of chitosan reduces the amount of microcracks and improves the functional properties of the hardened cement.
Tribological Examination of Anodized Al-356 for Automotive Use
Authors: Musza Alexandra , Windisch Márk , Török Mátyás , Molnár Tamás , Kovács Sándor , Sátán-Papp Szonja , Szegedi Krisztián , Ugi Dávid , Chinh Nguyen Quang , Vida Ádám
Published: September 2023

The A356 alloy is commonly used in the foundry industry to produce high-stressed automotive components, such as motor frames and cylinder heads. The aim of this work was to investigate how the mechanical and tribological properties of this alloy can be improved by applying an anodizing process. The properties of the oxide layer formed by anodizing using oxalic acid at low temperatures were characterized by different analytical and tribological methods. The combination of tribological methods with standard measurement techniques—such as hardness measurement, layer thickness measurement, as well as the analysis of the morphological characteristics—was used to track the layer evolution during wear developments.
Nucleation and Growth Kinetics of Sodium Chloride Crystallization from Water and Deuterium Oxide
Authors: Flannigan James M. , MacIver Daniel , Jolliffe Hikaru , Haw Mark D. , Sefcik Jan
Published: September 2023

Despite the ubiquity of the crystallization of sodium chloride (NaCl) throughout history, few detailed, well-controlled quantitative studies of the kinetics of NaCl crystallization have been published. Taking advantage of recent advances in technology such as image analysis for crystallite counting and ‘high-throughput’ techniques for characterizing the highly stochastic nucleation process, we report on a detailed examination of the primary and secondary nucleation kinetics of NaCl, crystallized from solution, in water (H2O) and in the isotopologue D2O. We show that crystallization conditions, especially sample agitation, have a very significant effect on crystallization kinetics. We also critically evaluate the workflow employed and the associated nucleation/growth models used to interpret its results, comparing outcomes from NaCl with those from organic crystal systems with which the workflow was originally developed and demonstrated. For primary nucleation, some key assumptions of the workflow and data interpretation are called into question for the NaCl system. Even so, it can still provide direct measurements of secondary nucleation and crystal growth from crystal counting and sizing, providing valuable characterization under consistent controlled conditions to enhance and ‘bring up to date’ the literature on the crystallization of this ubiquitous system.
Photonic Crystal Waveguides Composed of Hyperbolic Metamaterials for High-FOM Nano-Sensing
Authors: Zheng Yaoxian , Khan Fahim , Asrafali Barkathulla , Wang Qiong
Published: September 2023

This study introduces an innovative integration of hyperbolic metamaterials (HMMs) and photonic crystals (PtCs), each possessing unique dispersion properties that effectively manipulate the propagation of light. We present a PtC waveguide consisting of arrays of HMM nanorods, denoted as HMM PtCs. This waveguide configuration enables the realization of a high figure of merit (FOM) nano-sensor. HMMs and PtCs share the same underlying physics. HMMs can generate surface plasmonics, while PtCs offer a bandgap for the waveguide. This configuration presents a novel sensing solution that directly couples surface plasmonics and waveguide modes. By modifying the refractive indices of the surrounding materials, the PtC waveguide exhibits alterations in absorption and transmission, allowing for the detection of temperature, pressure, and material variations. The refractive indices of the surrounding materials can be adjusted based on the sensor’s intended application. For instance, when the sensor is utilized for temperature sensing, thermal infrared materials can serve as the surrounding medium. As the temperature rises, the refractive index of the surrounding material changes accordingly, impacting the waveguide modes and thereby altering absorption and transmission. We utilized the finite element method to conduct numerical simulations in order to assess the absorption and transmission characteristics of the proposed system. Given that this approach involves a full electromagnetic calculation based on Maxwell’s equations, it closely approximates real-world scenarios. The employed numerical method demonstrates the remarkable performance of this proposed system, achieving a sensitivity of 324.16 nm/RIU (refractive index unit) and an impressive FOM of 469.58 RIU−1. These results signify a substantial improvement over surface plasmonic sensors, which typically exhibit limited FOMs. The direct coupling between surface plasmonics and waveguide modes provides a distinct advantage, allowing the proposed sensor to deliver a superior performance. As a consequence, the HMM PtC waveguide sensor emerges as an exceptionally appealing option for photonic sensing applications. The complexity of the proposed system presents a fabrication challenge. Nevertheless, as fabrication technology continues to advance, we anticipate that this issue can be effectively resolved. The proposed HMM PtC waveguide holds vast potential across diverse fields, including biology, medicine, and clinics, representing an exciting advancement for both industry and scientific research.
D,L-Citrullinato-bipyridine Copper Complex: Experimental and Theoretical Characterization
Authors: Ramírez-Contreras Diego , García-García Amalia , Mendoza Angel , Serrano-de la Rosa Laura E. , Sánchez-Gaytán Brenda L. , Melendez Francisco J. , Castro María Eugenia , González-Vergara Enrique
Published: September 2023

Citrulline is a non-protein amino acid that acts as a metabolic intermediate in the urea cycle and arginine synthesis. It is present in some foods, although its name derives from watermelon (Citrullus vulgaris), from which it was first identified. Under normal conditions, Citrulline exists as a zwitterion in aqueous solutions since its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, Citrulline possesses in the aliphatic chain a terminal ureide group, which could also coordinate. Although Citrulline is comparable to other classical amino acids, its coordination chemistry has yet to be explored. Only two metal complexes have been reported, and the copper complex is a polymeric and insoluble material. As part of our search for active Casiopeina® analogs, we created a more soluble complex by combining 2,2′-Bipyridine into a new mixed material, resulting in the mononuclear complex [Cu(Bipy)(Citr)(H2O)(NO3)]·H2O. Single-crystal X-ray diffraction, spectroscopic methods (FT-IR, UV-Vis, Raman), and mass spectrometry characterized the material. Interestingly, both isomers of Citrulline, R(D), and S(L) are present in the same crystal. In addition, the molecular structure and electronic properties of the complex were calculated using density functional theory (DFT). Non-covalent interactions were characterized using the atoms-in-molecules (AIM) approach and Hirshfeld surface (HS) analysis. This ternary complex containing Citrulline and 2,2′-Bipyridine will be used for docking calculations and preliminary biological studies using calf thymus DNA (CT-DNA) and plasmid pUC19 as a first approximation to cytotoxic activity against cancer cell lines.
Post-Operative Care of the Cancer Patient: Emphasis on Functional Recovery, Rapid Rescue, and Survivorship
Authors: Morrison-Jones Victoria , West Malcolm
Published: September 2023

A cancer diagnosis and its subsequent treatments are life-changing events, impacting the patient and their family. Treatment options available for cancer care are developing at pace, with more patients now able to achieve a cancer cure. This is achieved through the development of novel cancer treatments, surgery, and modern imaging, but also as a result of better understanding treatment/surgical trauma, rescue after complications, perioperative care, and innovative interventions like pre-habilitation, enhanced recovery, and enhanced post-operative care. With more patients living with and beyond cancer, the role of survivorship and quality of life after cancer treatment is gaining importance. The impact cancer treatments can have on patients vary, and the "scars" treatments leave are not always visible. To adequately support patients through their cancer journeys, we need to look past the short-term interactions they have with medical professionals and encourage them to consider their lives after cancer, which often is not a reflection of life before a cancer diagnosis.
Active Coral Restoration to Preserve the Biodiversity of a Highly Impacted Reef in the Maldives
Authors: Pancrazi Irene , Feairheller Kayla , Ahmed Hassan , di Napoli Carolina , Montefalcone Monica
Published: September 2023

Maldivian coral reefs have been experiencing significant degradation due to a combination of global climate change and local anthropogenic pressures. To enforce the conservation of coral reefs worldwide, coral restoration is becoming a popular tool to restore ecosystems actively. In the Maldives, restoration interventions are performed only around touristic islands, where there are economic resources available to support these projects. Unfortunately, on local islands, coral restoration does not benefit from the same support and is rarely boosted. A challenging coral restoration experiment has been performed, for the first time, on a local island of the Maldives affected by intense human pressures that caused the degradation of its reefs. A total of 242 coral fragments were collected from impacted colonies and transferred to the coral nursery of the island. Survival and growth rates of the fragments were monitored for 12 months. After one year, a survival rate of 70% was recorded. Although this rate might appear lower when compared to other restoration experiences, it is very promising considering the origin of the fragments and the poor quality of the environment where they have been transplanted. Some potential threats to the success of this restoration have also been identified, i.e., water temperature anomaly, diseases, and parasites, the latter being the leading causes of coral mortality. The procedure presented here is less expensive compared to the typical relocation of entire coral colonies from donor-healthy reefs to degraded reefs, thus providing an opportunity and a viable option for local islands to restore their reefs and preserve local biodiversity.
Hypecoum spp.—Chemistry and Biological Activity of Alkaloids
Authors: Kostova Nadezhda , Doncheva Tsvetelina
Published: September 2023

Genus Hypecoum Tourn. ex L. belongs to the poppy family Papaveraceae and comprises about 19 species occurring in Europe, Northern Africa and Asia. Hypecoum species have been widely used in traditional medicine as antipyretic, analgesic and anti-inflammatory remedies. Their effects are associated with the biologically and pharmacologically active isoquinoline alkaloids in them, such as protopines, protoberberines, benzophenanthridines, aporphines, simple isoquinolines, secoberbines, spirobenzylisoquinolines and others. In this study, we aimed to review and organize information on ethnomedicinal, phytochemical, chemotaxonomical and pharmacological studies of alkaloids and extracts obtained from Hypecoum plants, and to suggest opportunities for further research.
Modified Vaginal Mesh Procedure with DynaMesh®-PR4 for the Treatment of Anterior/Apical Vaginal Prolapse
Authors: Lin Chia-Ju , Liu Chih-Ku , Hsieh Hsiao-Yun , Chen Ming-Jer , Tsai Ching-Pei
Published: September 2023

(1) Background: Treating female pelvic organ prolapse (POP) is challenging. Surgical meshes have been used in transvaginal surgeries since the 1990s, but complications such as mesh exposure and infection have been reported. Polyvinylidene fluoride (PVDF) mesh, known for its stability and non-reactive properties, has shown promise in urogynecological surgeries. (2) Methods: A retrospective analysis was conducted on 27 patients who underwent a modified PVDF vaginal mesh repair procedure using DynaMesh®-PR4 and combined trans-obturator and sacrospinous fixation techniques. Additional surgeries were performed as needed. (3) Results: The mean operation time was 56.7 min, and the mean blood loss was 66.7 mL. The average hospitalization period was 4.2 days with Foley catheter removal after 2 days. Patients experienced lower pain scores from the day of the operation to the following day. Postoperative follow-up revealed that 85.2% of patients achieved anatomic success, with 14.8% experiencing recurrent stage II cystocele. No recurrence of apical prolapse was observed. Complications were rare, with one case (3.7%) of asymptomatic mesh protrusion. (4) Conclusions: The modified vaginal mesh procedure using DynaMesh®-PR4 showed favorable outcomes with a short operation time, low recurrence rate, rare complications, and improved functional outcomes. This surgical option could be considered for anterior and apical pelvic organ prolapse in women.