bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysarthria Subgroups in Talkers with Huntington’s Disease: Comparison of Two Data-Driven Classification Approaches
Authors: Kim Daniel , Diehl Sarah , de Riesthal Michael , Tjaden Kris , Wilson Stephen M. , Claassen Daniel O. , Mefferd Antje S.
Published: April 2022

Although researchers have recognized the need to better account for the heterogeneous perceptual speech characteristics among talkers with the same disease, guidance on how to best establish such dysarthria subgroups is currently lacking. Therefore, we compared subgroup decisions of two data-driven approaches based on a cohort of talkers with Huntington’s disease (HD): (1) a statistical clustering approach (STATCLUSTER) based on perceptual speech characteristic profiles and (2) an auditory free classification approach (FREECLASS) based on listeners’ similarity judgments. We determined the amount of overlap across the two subgrouping decisions and the perceptual speech characteristics driving the subgrouping decisions of each approach. The same speech samples produced by 48 talkers with HD were used for both grouping approaches. The STATCLUSTER approach had been conducted previously. The FREECLASS approach was conducted in the present study. Both approaches yielded four dysarthria subgroups, which overlapped between 50% to 78%. In both grouping approaches, overall bizarreness and speech rate characteristics accounted for the grouping decisions. In addition, voice abnormalities contributed to the grouping decisions in the FREECLASS approach. These findings suggest that apart from overall bizarreness ratings, indexing dysarthria severity, speech rate and voice characteristics may be important features to establish dysarthria subgroups in HD.
The Detection of Face-like Stimuli at the Edge of the Infant Visual Field
Authors: Capparini Chiara , To Michelle P. S. , Reid Vincent M.
Published: April 2022

Human infants are highly sensitive to social information in their visual world. In laboratory settings, researchers have mainly studied the development of social information processing using faces presented on standard computer displays, in paradigms exploring face-to-face, direct eye contact social interactions. This is a simplification of a richer visual environment in which social information derives from the wider visual field and detection involves navigating the world with eyes, head and body movements. The present study measured 9-month-old infants’ sensitivities to face-like configurations across mid-peripheral visual areas using a detection task. Upright and inverted face-like stimuli appeared at one of three eccentricities (50°, 55° or 60°) in the left and right hemifields. Detection rates at different eccentricities were measured from video recordings. Results indicated that infant performance was heterogeneous and dropped beyond 55°, with a marginal advantage for targets appearing in the left hemifield. Infants’ orienting behaviour was not influenced by the orientation of the target stimulus. These findings are key to understanding how face stimuli are perceived outside foveal regions and are informative for the design of infant paradigms involving stimulus presentation across a wider field of view, in more naturalistic visual environments.
Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice
Authors: Shuvaev Anton N. , Belozor Olga S. , Mozhei Oleg I. , Mileiko Aleksandra G. , Mosina Ludmila D. , Laletina Irina V. , Mikhailov Ilia G. , Fritsler Yana V. , Shuvaev Andrey N. , Teschemacher Anja G. , Kasparov Sergey
Published: April 2022

Memantine is an FDA approved drug for the treatment of Alzheimer’s disease. It reduces neurodegeneration in the hippocampus and cerebral cortex through the inhibition of extrasynaptic NMDA receptors in patients and mouse models. Potentially, it could prevent neurodegeneration in other brain areas and caused by other diseases. We previously used memantine to prevent functional damage and to retain morphology of cerebellar neurons and Bergmann glia in an optogenetic mouse model of spinocerebellar ataxia type-1 (SCA1). However, before suggesting wider use of memantine in clinics, its side effects must be carefully evaluated. Blockers of NMDA receptors are controversial in terms of their effects on anxiety. Here, we investigated the effects of chronic application of memantine over 9 weeks to CD1 mice and examined rotarod performance and anxiety-related behaviors. Memantine-treated mice exhibited an inability to adapt to anxiety-causing conditions which strongly affected their rotarod performance. A tail suspension test revealed increased signs of behavioral despair. These data provide further insights into the potential deleterious effects of memantine which may result from the lack of adaptation to novel, stressful conditions. This effect of memantine may affect the results of tests used to assess motor performance and should be considered during clinical trials of memantine in patients.
First Report of Tumor Treating Fields (TTFields) Therapy for Glioblastoma in Comorbidity with Multiple Sclerosis
Authors: Kassubek Rebecca , Mathieu René
Published: April 2022

Tumor Treating Fields (TTFields) therapy is FDA approved and has the CE mark for treatment of newly diagnosed and recurrent glioblastoma. To our knowledge, to date TTFields therapy remains unstudied in glioblastoma patients with multiple sclerosis (MS) as a comorbidity. Here, we present a patient who was diagnosed with MS at the age of 34. Treatment included several corticoid pulse treatments and therapies with interferon beta-1a and sphingosine-1-phosphate receptor modulator fingolimod. At the age of 52 the patient was diagnosed with glioblastoma, after experiencing worsening headaches which could not be attributed to the MS condition. After subtotal resection and concomitant radiochemotherapy, the patient received temozolomide in combination with TTFields therapy. For two years, the tumor condition remained stable while the patient showed high adherence to TTFields therapy with low-grade skin reactions being the only therapy-related adverse events. After two years, the tumor recurred. The patient underwent re-resection and radiotherapy and restarted TTFields therapy together with chemotherapy and is currently still on this therapy regime. Although having not been studied systematically, the case presented here demonstrates that TTFields therapy may be considered for newly diagnosed and recurrent glioblastoma patients with previously diagnosed multiple sclerosis.
Modified FOLFIRINOX as a Second-Line Treatment for Patients with Gemcitabine-Failed Advanced Biliary Tract Cancer: A Prospective Multicenter Phase II Study
Authors: Lee Yong-Pyo , Oh Sung Yong , Kim Kwang Min , Go Se-Il , Kim Jung Hoon , Huh Seok Jae , Kang Jung Hun , Ji Jun Ho
Published: April 2022

Background: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. Methods: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. Results: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6–4.0 months) and 6.2 months (95% CI: 5.0–7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. Conclusions: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.
Pre-Clinical Study Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Neuroblastoma
Authors: Bownes Laura , Marayati Raoud , Quinn Colin , Beierle Andee , Hutchins Sara , Julson Janet , Erwin Michael , Stewart Jerry , Mroczek-Musulman Elizabeth , Ohlmeyer Michael , Aye Jamie , Yoon Karina , Beierle Elizabeth
Published: April 2022

Background: Protein phosphatase 2A (PP2A) functions as an inhibitor of cancer cell proliferation, and its tumor suppressor function is attenuated in many cancers. Previous studies utilized FTY720, an immunomodulating compound known to activate PP2A, and demonstrated a decrease in the malignant phenotype in neuroblastoma. We wished to investigate the effects of two novel PP2A activators, ATUX-792 (792) and DBK-1154 (1154). Methods: Long-term passage neuroblastoma cell lines and human neuroblastoma patient-derived xenograft (PDX) cells were used. Cells were treated with 792 or 1154, and viability, proliferation, and motility were examined. The effect on tumor growth was investigated using a murine flank tumor model. Results: Treatment with 792 or 1154 resulted in PP2A activation, decreased cell survival, proliferation, and motility in neuroblastoma cells. Immunoblotting revealed a decrease in MYCN protein expression with increasing concentrations of 792 and 1154. Treatment with 792 led to tumor necrosis and decreased tumor growth in vivo. Conclusions: PP2A activation with 792 or 1154 decreased survival, proliferation, and motility of neuroblastoma in vitro and tumor growth in vivo. Both compounds resulted in decreased expression of the oncogenic protein MYCN. These findings indicate a potential therapeutic role for these novel PP2A activators in neuroblastoma.
Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer
Authors: Nasser Nicola J.
Published: April 2022

Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which locally advanced prostate cancer could be cured while patients maintain potency.
The Landscape of lncRNAs in Multiple Myeloma: Implications in the “Hallmarks of Cancer”, Clinical Perspectives and Therapeutic Opportunities
Authors: Saltarella Ilaria , Apollonio Benedetta , Lamanuzzi Aurelia , Desantis Vanessa , Mariggiò Maria Addolorata , Desaphy Jean-François , Vacca Angelo , Frassanito Maria Antonia
Published: April 2022

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as “hallmarks of cancer” that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncRNAs in MM suggests their potential use as clinical biomarkers for diagnosis, patient stratification, and clinical management. Moreover, they represent ideal candidates for therapeutic targeting.
Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions
Authors: Żak Klaudia , Zaremba Bartłomiej , Rajtak Alicja , Kotarski Jan , Amant Frédéric , Bobiński Marcin
Published: April 2022

The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing available parameters and to combine them with imaging methods with the aim of ULMs and ULM preoperative differentiation ULMs and ULM. Moreover, it has been observed that the technology, meaning machine learning models and artificial intelligence (AI), is entering the world of medicine, including gynecology. Therefore, we can predict the diagnosis not only through symptoms, laboratory tests or imaging methods, but also, we can base it on AI. What is the best option to differentiate ULM and ULMS preoperatively? In our review, we focus on the possible methods to diagnose uterine lesions effectively, including clinical signs and symptoms, laboratory tests, imaging methods, molecular aspects, available scales, and AI. In addition, considering costs and availability, we list the most promising methods to be implemented and investigated on a larger scale.
Hashimoto’s Thyroiditis Does Not Influence the Malignancy Risk in Nodules of Category III in the Bethesda System
Authors: Słowińska-Klencka Dorota , Popowicz Bożena , Klencki Mariusz
Published: April 2022

The aim of this study was to evaluate the risk of malignancy (RoM) in category III thyroid nodules of the Bethesda system in patients with and without Hashimoto thyroiditis (HT) and to analyze whether obtaining category III with a repeat FNA (rFNA) increases RoM. The study included 563 HT and 1250 non-HT patients; rFNA was performed in 349 and 575 patients, and surgical treatment in 160 and 390, respectively. There was no difference in RoM between HT and non-HT patients in the whole examined population (lower limit of RoM), nor in operated patients (upper limit of RoM), HT: 5.0–17.5%, non-HT: 4.7–15.1%. RoM in patients with AUS nodules (with nuclear atypia) was similar in both groups (HT: 21.7–40.0%, non-HT: 16.9–41.4%), as it was in patients with FLUS nodules (with architectural atypia) (HT: 3.5–13.3%, non-HT: 4.0–13.0%). In patients from both groups together, with category III diagnosed twice and AUS identified at least once, RoM was 16.7–50.0% and it was higher than that in patients with FLUS nodule diagnosed twice: 3.2–13.0% (p < 0.005). Concluding, RoM in category III nodules is not affected by the presence of HT. Subcategorization of category III nodules (FLUS vs. AUS) may provide guidance toward further follow-up or surgery in both groups.
Predictors for the Recurrence of Clinically Uterine-Confined Endometrial Cancer and the Role of Cytokeratin Immunohistochemistry Stain in the Era of Sentinel Lymph Node Mapping
Authors: Ting Wan-Hua , Hsieh Shu-Wei , Chen Hui-Hua , Wei Ming-Chow , Lin Ho-Hsiung , Hsiao Sheng-Mou
Published: April 2022

Background: The primary objective of this study was to elucidate the predictors for cancer recurrence in women with clinically uterine-confined endometrial cancer in the era of sentinel lymph node (SLN) mapping. Methods: All consecutive women with clinically determined uterine-confined endometrial cancer who had lymph node assessment by either SLN mapping or traditional pelvic lymphadenectomy were reviewed. Results: Women in the SLN mapping group had lower total dissected pelvic nodes, lower incidence of para-aortic lymph node dissection, less intraoperative blood loss and lower complication rates, but a longer operation time compared to the traditional lymphadenectomy group. Para-aortic lymph node metastasis (hazard ratio = 7.60, p = 0.03) was the sole independent predictor for recurrence-free survival. In addition, the utilization of cytokeratin immunohistochemistry stain detected more lymph node metastases (adjusted odds ratio = 3.04, p = 0.03). Recurrence-free survival did not differ between SLN mapping and traditional lymphadenectomy groups (p = 0.24). Conclusions: Para-aortic lymph node metastasis is an important predictor of cancer recurrence. Women with negative hematoxylin and eosin stain should undergo cytokeratin immunohistochemistry stain to increase the detection rate of positive lymph node metastasis. Besides, the probabilities of recurrence seem to be similar between SLN mapping and traditional lymphadenectomy groups in women with clinically uterine-confined endometrial cancer.
The Autophagy Process in Cervical Carcinogenesis: Role of Non-Coding-RNAs, Molecular Mechanisms, and Therapeutic Targets
Authors: Lagunas-Martínez Alfredo , Madrid-Marina Vicente , Gómez-Cerón Claudia , Deas Jessica , Peralta-Zaragoza Oscar
Published: April 2022

Autophagy is a highly conserved multistep lysosomal degradation process in which cellular components are localized to autophagosomes, which subsequently fuse with lysosomes to degrade the sequestered contents. Autophagy serves to maintain cellular homeostasis. There is a close relationship between autophagy and tumor progression, which provides opportunities for the development of anticancer therapeutics that target the autophagy pathway. In this review, we analyze the effects of human papillomavirus (HPV) E5, E6, and E7 oncoproteins on autophagy processes in cervical cancer development. Inhibition of the expression or the activity of E5, E6, and E7 can induce autophagy in cells expressing HPV oncogenes. Thus, E5, E6, and E7 oncoproteins target autophagy during HPV-associated carcinogenesis. Furthermore, noncoding RNA (ncRNA) expression profiling in cervical cancer has allowed the identification of autophagy-related ncRNAs associated with HPV. Autophagy-related genes are essential drivers of autophagy and are regulated by ncRNAs. We review the existing evidence regarding the role of autophagy-related proteins, the function of HPV E5, E6, and E7 oncoproteins, and the effects of noncoding RNA on autophagy regulation in the setting of cervical carcinogenesis. By characterizing the mechanisms behind the dysregulation of these critical factors and their impact on host cell autophagy, we advance understanding of the relationship between autophagy and progression from HPV infection to cervical cancer, and highlight pathways that can be targeted in preventive and therapeutic strategies against cervical cancer.
Human iPSC-Derived Renal Cells Change Their Immunogenic Properties during Maturation: Implications for Regenerative Therapies
Authors: Rossbach Bella , Hariharan Krithika , Mah Nancy , Oh Su-Jun , Volk Hans-Dieter , Reinke Petra , Kurtz Andreas
Published: April 2022

The success of human induced pluripotent stem cell (hiPSC)-based therapy critically depends on understanding and controlling the immunological effects of the hiPSC-derived transplant. While hiPSC-derived cells used for cell therapy are often immature with post-grafting maturation, immunological properties may change, with adverse effects on graft tolerance and control. In the present study, the allogeneic and autologous cellular immunity of hiPSC-derived progenitor and terminally differentiated cells were investigated in vitro. In contrast to allogeneic primary cells, hiPSC-derived early renal progenitors and mature renal epithelial cells are both tolerated not only by autologous but also by allogeneic T cells. These immune-privileged properties result from active immunomodulation and low immune visibility, which decrease during the process of cell maturation. However, autologous and allogeneic natural killer (NK) cell responses are not suppressed by hiPSC-derived renal cells and effectively change NK cell activation status. These findings clearly show a dynamic stage-specific dependency of autologous and allogeneic T and NK cell responses, with consequences for effective cell therapies. The study suggests that hiPSC-derived early progenitors may provide advantageous immune-suppressive properties when applied in cell therapy. The data furthermore indicate a need to suppress NK cell activation in allogeneic as well as autologous settings.
Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice
Authors: Tarban Nastaran , Halász Hajnalka , Gogolák Péter , Garabuczi Éva , Moise Alexander R. , Palczewski Krzysztof , Sarang Zsolt , Szondy Zsuzsa
Published: April 2022

Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth. Therefore, improper efferocytosis results in impaired muscle repair. Retinol saturase (RetSat) initiates the formation of various dihydroretinoids, a group of vitamin A derivatives that regulate transcription by activating retinoid receptors. Previous studies from our laboratory have shown that RetSat-null macrophages produce less milk fat globule-epidermal growth factor-factor-8 (MFG-E8), lack neuropeptide Y expression, and are characterized by impaired efferocytosis. Here, we investigated skeletal muscle repair in the tibialis anterior muscle of RetSat-null mice following cardiotoxin injury. Our data presented here demonstrate that, unexpectedly, several cell types participating in skeletal muscle regeneration compensate for the impaired macrophage functions, resulting in normal muscle repair in the RetSat-null mice.
Systems Challenges in Accessing Medicines among Children under Thailand’s Universal Health Coverage: A Qualitative Study of a Provincial Public Hospital Network
Authors: Daojorn Rangsan , Suwannaprom Puckwipa , Suttajit Siritree , Kanjanarat Penkarn , Tiengket Prangtong , Lallemant Marc
Published: April 2022

Lack of access to child-appropriate medicines results in off-label use. This study aimed to explore medicine management for paediatric patients and to highlight the challenges of the healthcare system under the universal health coverage of Thailand. Semi-structured interviews were conducted with 35 healthcare practitioners working in the public hospital network of Chiang Mai province from February to September 2020. Participants were asked about their experiences in managing the medicine supply for children. Findings revealed that paediatric patients had limited access to age-appropriate medicines. Children’s medicines are rarely selected for inclusion into hospital formularies because of constraining regulations and limited budgets. Additionally, child-appropriate formulations are unavailable on the market. Pharmaceutical compounding is unavoidable. Prepared products are provided weekly or monthly because of product stability concerns. Often, tablets are dispensed, and caregivers are instructed to cut up a tablet and disperse it in syrup in order to obtain a smaller dose in a dosage form appropriate for children to use at home. Without systematic support, access to safe and quality medicines for children is limited.
Thriving despite Parental Physical Abuse in Adolescence: A Two-Wave Latent Transition Analysis on Hedonic and Eudaimonic Violence-Resilience Outcome Indicators
Authors: Kassis Wassilis , Aksoy Dilan , Favre Céline Anne , Janousch Clarissa , Artz Sibylle Talmon-Gros
Published: April 2022

Internationally, about 25% of all children experience physical abuse by their parents. Despite the numerous odds against them, about 30% of adolescents who have experienced even the most serious forms of physical abuse by their parents escape the vicious family violence cycle. In this study, we analyzed longitudinally the data from a sample of N = 1767 seventh-grade high school students in Switzerland on physical abuse by their parents. We did this by conducting an online questionnaire twice within the school year. We found that in our sample, about 30% of the participating adolescents’ parents had physically abused them. We considered violence resilience a multi-systemic construct that included the absence of psychopathology on one hand and both forms of well-being (psychological and subjective) on the other. Our latent construct included both feeling good (hedonic indicators, such as high levels of self-esteem and low levels of depression/anxiety and dissociation) and doing well (eudaimonic indicators, such as high levels of self-determination and self-efficacy as well as low levels of aggression toward peers). By applying a person-oriented analytical approach via latent transition analysis with a sub-sample of students who experienced physical abuse (nw2 = 523), we identified and compared longitudinally four distinct violence-resilience patterns and their respective trajectories. By applying to the field of resilience, one of the most compelling insights of well-being research (Deci & Ryan, 2001), we identified violence resilience as a complex, multidimensional latent construct that concerns hedonic and eudaimonic well-being and is not solely based on terms of psychopathology.
Managing Care during the COVID-19 Pandemic: The Point of View and Fears of Pediatric Cancer Patients’ Families
Authors: Nigro Olga , Sironi Giovanna , Ferrari Andrea , Tinè Gabriele , Infante Gabriele , Barretta Francesco , Silva Matteo , Clerici Carlo Alfredo , Chiaravalli Stefano , Schiavello Elisabetta , Biassoni Veronica , Podda Marta , Meazza Cristina , Spreafico Filippo , Casanova Michela , Terenziani Monica , Luksch Roberto , Massimino Maura
Published: April 2022

(1) Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Unit. We investigated how the families perceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan in order to explore how the pandemic had affected the experience of patients who had been or were being treated at our hospital, as well as their families. These questionnaires were administered to three groups of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as important, and it was reported that 77.5% of parents judged social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents’ opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topics of relationships in the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients’ parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, all parents indicated strong degrees of satisfaction with the care received and the organizational arrangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.
Joint Attention and Its Relationship with Autism Risk Markers at 18 Months of Age
Authors: Montagut-Asunción Maite , Crespo-Martín Sarah , Pastor-Cerezuela Gemma , D’Ocon-Giménez Ana
Published: April 2022

(1) Joint attention is the ability to coordinate attention to share a point of reference with another person. It has an early onset and is a clear indicator of understanding the representations of others, and it is essential in the development of symbolic thought and the acquisition of language. Deficiencies in this prelinguistic early communication skill are strong markers of the risk of autism spectrum disorder (ASD); (2) this longitudinal study aimed to evaluate joint attention skills in a group of 32 infants at two developmental moments (8 and 12 months) in order to explore whether their performance on this skill was related to the presence of early signs of ASD at 18 months. Logistic multiple regressions were carried out for the data analysis; (3) results of the analysis showed that the variables of initiating joint attention at 8 months and responding to joint attention at 12 months were linked to the risk of ASD at 18 months of age; (4) in conclusion, early joint attention skills had a pivotal role in defining early manifestations of ASD.
Microstructure and Electric Properties of Bi2O3-Doped (K0.5Na0.5)NbO3 Lead-Free Ceramics
Authors: Li Jiaqi , Wang Junjun , Wu Fengmin , Ma Hui , Ma Tianyi , Tian Yu , Liu Danqing , Yang Bin
Published: April 2022

In this paper, Bi2O3-doped (K0.5Na0.5)NbO3 (x = 0.1, 0.2, 0.3, 0.4) lead-free ceramics are prepared by a conventional solid-state reaction and analyzed by studying the structure, ferroelectric, and piezoelectric properties. It is found that the doping of Bi2O3 increases the proportion of the trigonal phase in KNN ceramics, thus enabling the construction of KNN ceramics with an orthogonal–trigonal phase boundary at room temperature. At the same time, doping with Bi2O3 can reduce the grain size and improve grain size uniformity of the ceramics. The KNN-0.1%Bi2O3 ceramic has the best piezoelectric properties in all composition; the results are as follows: d33 = 121pC/N, kp = 0.474, kt = 0.306.
Development of an Interactive AI System for the Optimal Timing Prediction of Successful Weaning from Mechanical Ventilation for Patients in Respiratory Care Centers
Authors: Liao Kuang-Ming , Ko Shian-Chin , Liu Chung-Feng , Cheng Kuo-Chen , Chen Chin-Ming , Sung Mei-I , Hsing Shu-Chen , Chen Chia-Jung
Published: April 2022

Successful weaning from prolonged mechanical ventilation (MV) is an important issue in respiratory care centers (RCCs). Delayed or premature extubation increases both the risk of adverse outcomes and healthcare costs. However, the accurate evaluation of the timing of successful weaning from MV is very challenging in RCCs. This study aims to utilize artificial intelligence algorithms to build predictive models for the successful timing of the weaning of patients from MV in RCCs and to implement a dashboard with the best model in RCC settings. A total of 670 intubated patients in the RCC in Chi Mei Medical Center were included in the study. Twenty-six feature variables were selected to build the predictive models with artificial intelligence (AI)/machine-learning (ML) algorithms. An interactive dashboard with the best model was developed and deployed. A preliminary impact analysis was then conducted. Our results showed that all seven predictive models had a high area under the receiver operating characteristic curve (AUC), which ranged from 0.792 to 0.868. The preliminary impact analysis revealed that the mean number of ventilator days required for the successful weaning of the patients was reduced by 0.5 after AI intervention. The development of an AI prediction dashboard is a promising method to assist in the prediction of the optimal timing of weaning from MV in RCC settings. However, a systematic prospective study of AI intervention is still needed.
Prognostic Factors for Recurrence in Pituitary Adenomas: Recent Progress and Future Directions
Authors: Lu Liang , Wan Xueyan , Xu Yu , Chen Juan , Shu Kai , Lei Ting
Published: April 2022

Pituitary adenomas (PAs) are benign lesions; nonetheless, some PAs exhibit aggressive behaviors, which lead to recurrence. The impact of pituitary dysfunction, invasion-related risks, and other complications considerably affect the quality of life of patients with recurrent PAs. Reliable prognostic factors are needed for recurrent PAs but require confirmation. This review summarizes research progress on two aspects—namely, the clinical and biological factors (biomarkers) for recurrent PAs. Postoperative residue, age, immunohistological subtypes, invasion, tumor size, hormone levels, and postoperative radiotherapy can predict the risk of recurrence in patients with PAs. Additionally, biomarkers such as Ki-67, p53, cadherin, pituitary tumor transforming gene, matrix metalloproteinase-9, epidermal growth factor receptor, fascin actin-bundling protein 1, cyclooxygenase-2, and some miRNAs and lncRNAs may be utilized as valuable tools for predicting PA recurrence. As no single marker can independently predict PA recurrence, we introduce an array of comprehensive models and grading methods, including multiple prognostic factors, to predict the prognosis of PAs, which have shown good effectiveness and would be beneficial for predicting PA recurrence.
Cell-Free DNA Fragmentomics in Liquid Biopsy
Authors: Ding Spencer C. , Lo Y.M. Dennis
Published: April 2022

Cell-free DNA (cfDNA) in bodily fluids has rapidly transformed the development of noninvasive prenatal testing, cancer liquid biopsy, and transplantation monitoring. Plasma cfDNA consists of a mixture of molecules originating from various bodily tissues. The study of the fragmentation patterns of cfDNA, also referred to as ‘fragmentomics’, is now an actively pursued area of biomarker research. Clues that cfDNA fragmentation patterns might carry information concerning the tissue of origin of cfDNA molecules have come from works demonstrating that circulating fetal, tumor-derived, and transplanted liver-derived cfDNA molecules have a shorter size distribution than the background mainly of hematopoietic origin. More recently, an improved understanding of cfDNA fragmentation has provided many emerging fragmentomic markers, including fragment sizes, preferred ends, end motifs, single-stranded jagged ends, and nucleosomal footprints. The intrinsic biological link between activities of various DNA nucleases and characteristic fragmentations has been demonstrated. In this review, we focus on the biological properties of cell-free DNA unveiled recently and their potential clinical applications.
The Stockholm Study: Over 30 years’ Observation of the Effect of Oral Infections on Systemic Health
Authors: Meurman Jukka H. , Söder Birgitta
Published: April 2022

The Stockholm Studies are a series of investigations started in 1985 and still ongoing. Out of 105,798 inhabitants, aged 30 and 40 years and living in the greater Stockholm area in Sweden, 3273 subjects were randomly selected. Of them, 1676 were clinically examined focusing on oral health. The subjects were then followed up using national population and health registers in order to study associations between oral health parameters and systemic health outcomes and finally death. The 35 years of observation provides unique possibilities to analyze, for example, how periodontitis links to a number of systemic health issues. The results have consequently provided numerous new associations and confirmed earlier observations on how poor oral health is associated with heart diseases and cancer.
Disaster Region Coverage Using Drones: Maximum Area Coverage and Minimum Resource Utilisation
Authors: Munawar Hafiz Suliman , Hammad Ahmed W.A. , Waller S. Travis
Published: April 2022

The purpose of this study is to develop a design for maximum area drone coverage in a post-disaster flood situation. When it comes to covering a disaster-region for monitoring and detection of the extent of damage and losses, a suitable and technically balanced approach is vital to achieving the best solution while covering the maximum affected area. Therefore, a mathematical optimisation model is proposed to effectively capture maximum images of the impacted region. The particle swarm optimisation (PSO) algorithm is used to solve the optimisation problem. Modern relief missions heavily rely on drones, specifically in the case of flooding, to capture the damage due to the disaster and to create roadmaps to help impacted people. This system has convincing results for inertia, exploration, exploitation, velocity, and determining the height of the drones to enhance the response to a disaster. The proposed approach indicates that when maintaining the flight height of the drone above 120 m, the coverage can be enhanced by approximately 34% compared with a flight height of 100 m.
A Conversation with Søren Johansen
Authors: Mosconi Rocco , Paruolo Paolo
Published: April 2022

This article was prepared for the Special Issue “Celebrated Econometricians: Katarina Juselius and Søren Johansen” of Econometrics. It is based on material recorded on 30 October 2018 in Copenhagen. It explores Søren Johansen’s research, and discusses inter alia the following issues: estimation and inference for nonstationary time series of the I(1), I(2) and fractional cointegration types; survival analysis; statistical modelling; likelihood; econometric methodology; the teaching and practice of Statistics and Econometrics.
Fostering Teamwork through Design Thinking: Evidence from a Multi-Actor Perspective
Authors: Guaman-Quintanilla Sharon , Everaert Patricia , Chiluiza Katherine , Valcke Martin
Published: April 2022

This study examines the effects of a design thinking intervention on first-year students’ teamwork skills from a multi-actor perspective. A design thinking course was evaluated throughout a semester. Six-hundred-and-forty university students participated, guided by twenty-six facilitators. The students received in-class training and worked in multi-disciplinary teams to develop a solution for a real-life problem. In this quasi-experimental study, data were collected twice: in the middle (t1), and at the end (t2) of the course. Each time, students were rated by their teammates, themselves, and the course facilitator, using a rubric to map teamwork skills. The results show a significant improvement in teamwork skills, as consistently observed in the three ratings. The results also show a significant effect of sex on the improvement over time. Female students showed more considerable progress than male students. This study addresses researchers’ demands regarding the lack of robust evidence to assess the impact of design thinking in higher education settings. Furthermore, building on the data from a large sample size and an intervention designed in a replicable way, this study contributes to the available empirical evidence that helps one to adopt and implement design thinking in universities to develop essential skills, such as teamwork.
Modelling of the Electrically Excited Synchronous Machine with the Rotary Transformer Design Influence
Authors: Manko Roman , Vukotić Mario , Makuc Danilo , Vončina Danijel , Miljavec Damijan , Čorović Selma
Published: April 2022

An electrically excited synchronous machine (EESM) is a promising alternative to the permanent magnets synchronous machines being used in the automotive industry. However, the main disadvantage of the EESM with the conventional excitation system with brushes is the presence of slip rings on the shaft, which need regular maintenance. A promising alternative to the conventional excitation system of the EESM is a wireless power transfer (WPT) system. In this paper, we focused on WPT excitation system based on the rotary transformers. First, the model of the EESM in the d-q reference frame with vector control system has been built (based on the parameters of the real machine) and analyzed using MATLAB/Simulink software. Second, the influence of the rotary transformer design parameters on the dynamic performance of the EESM has been investigated. Finally, different topologies of the rotary transformers found in the literature have been analyzed, modeled and compared using an analytical and numerical approach. Based on the obtained results, the most suitable electrical parameters (i.e., geometry parameters, supply frequency, magnetizing and leakage inductance, winding resistance and efficiency) of the rotary transformer have been identified and implemented into the d-q model of EESM.
Thermal Stratification and Temperature Variation in Horizontal Electric Water Heaters: A Characterisation Platform
Authors: van Schalkwyk Pieter D. , Engelbrecht Jacobus A. A. , Booysen Marthinus J.
Published: April 2022

Electric water heaters, which have the capacity to act as thermal energy storage, are well suited to demand management strategies in smart grid applications. However, finding the balance between managing power load, reducing thermal energy losses, user’s convenience, and bacterial growth control, requires accurate modelling of the internal thermal dynamics of the tank, including stratification. As a black box, this unknown is dependent on a multitude of environmental factors (e.g., ambient temperature and inlet temperature), water draw patterns, scheduling, set temperatures and orientation of the vessel. The latter affects the stratification and temperature variation inside the tank, and therefore has a direct bearing on the balancing act of demand management. Although this has been assessed inside vertically oriented tanks, what happens inside the horizontal variety—ubiquitous in developing countries—is currently left to the guesswork. In this paper, we present the development of an embedded hardware and software platform with which the temperature variations inside a horizontal water heater can be characterised under numerous environmental and usage conditions. The importance of doing so is highlighted by the preliminary results, which clearly show the expected substantial temperature variation along the vertical axis, but also show interesting phenomena along the longitudinal and transverse axes, for both static (no water draw) and dynamic (with water draw) conditions. We conclude by highlighting potential for further research.
State of Charge Centralized Estimation of Road Condition Information Based on Fuzzy Sunday Algorithm
Authors: Hu Jingwei , Lin Bing , Wang Mingfen , Zhang Jie , Zhang Wenliang , Lu Yu
Published: April 2022

Accurate estimation of the state of charge (SOC) is critical for battery management systems. A backpropagation neural network (BPNN) based on a modified fuzzy Sunday algorithm is proposed to improve the accuracy of SOC predictions of lithium-ion batteries (LIBs). The road condition information relating to the data is obtained using the fuzzy Sunday algorithm, and the acquired feature information is used to estimate SOC using BPNN based on the Levenberg–Marquardt (L–M) training process. The change from exact character matching to fuzzy number matching is an improvement to the Sunday algorithm. The quantification of the road condition is innovatively integrated into the neural network. At present, this kind of feature is new to the estimation process, and our experiment proved that the effect is good. To quickly estimate the SOC under different driving conditions, the same network was used to predict the data of different road conditions. In addition, a strategy is proposed for SOC estimation under unknown road conditions, which improves the estimation accuracy. Studies have shown that the model used in the experiment is more accurate than other machine learning models. This model assures prediction accuracy, reliability, and timeliness.
Cyclodextrin-Based Nanosponges and Proteins
Authors: Lucia Appleton Silvia , Khazaei Monfared Yousef , Vidal-Sánchez Francisco José , Caldera Fabrizio , Cavalli Roberta , Trotta Francesco , Matencio Adrián
Published: April 2022

Cyclodextrin-based nanosponges (CD-NSs) have gained importance in drug delivery in the last years due to their easy synthesis and versatility. However, their use as carriers for the delivery of macromolecules such as proteins is less known and sometimes difficult to consider. In this entry, the authors summarize and highlight the multiple possibilities of CD-NSs to deliver active proteins, improving their activity or stability. Starting with a brief description of CD-NSs and their characteristics, the entry will be focused on several proteins, such as (1) Lipase, (2) Insulin and (3) Nisin, for chemical or pharmaceutical applications. The revised results demonstrated that CD-NSs can generate different and interesting applications with proteins. These results could be added to their uses with small drugs, being an interesting alternative for protein delivery and applicability.
Genetics of Thyroid Disorders
Authors: Gavryutina Irina , Fordjour Lawrence , Chin Vivian L.
Published: April 2022

Thyroid diseases in children and adolescents include acquired or congenital conditions, including genetic disorders either isolated or part of a syndrome. Briefly, we will review the physiology and pathophysiology of the thyroid gland and its disorders. The aim of this chapter is to describe genetic abnormalities of the thyroid gland.
Assessment of Different Measurement Methods/Techniques in Predicting Modulus of Elasticity of Plantation Eucalyptus nitens Timber for Structural Purposes
Authors: Ettelaei Azin , Taoum Assaad , Nolan Gregory
Published: April 2022

The mechanical properties of plantation Eucalyptus Nitens timber are currently assessed by applying visual stress grading (VSG) designed for the sawn timber from the mature plantation and do not represent the actual characteristics of the resource. However, the well-known limitation of VSG application for this resource led to the discovery of other methods to grade the timber to its relevant structural grade. There is potential for hardwood plantations in Australia to supply wood to the timber industry and be used in structural applications. However, it is necessary to employ criteria to evaluate the structural properties of this resource before it could be satisfactorily used for structural purposes. This research aimed to assess the use of non-destructive technique (NDT) through acoustic wave velocity (AWV), machine stress grading (MSG), and multiple linear regression (MLR) model to predict the modulus of elasticity (MOE) as a grade-determining factor. The results showed that there was a strong correlation (R2 = 0.88) between the dynamic MOE (MOEdyn) and static MOE (MOEs) of the boards, proving the NDT as a reliable method for the MOE estimations of E. nitens timber. The results from the MLR model also showed that the density and AWV are effective parameters and their combination can be practical to estimate the MOE. There was a high correlation between the MOE obtained from MSG and MOE obtained from four-point bending, demonstrating that the MSG method through the flat-wise bending can be a suitable method for fast grading. The results also indicated that the measured MOE in the edgewise direction correlates with both the flatwise and longitudinal directions. The results also showed that the E. nitens timber resource has the potential to be used in structural applications with a wide range of MOE from 7 GPa to 21 GPa.