bluuebunny/crossref_metadata_2025 huggingface dataset:
All-in-One Digital Microfluidics System for Molecular Diagnosis with Loop-Mediated Isothermal Amplification
Authors: Hu Siyi , Jie Yuhan , Jin Kai , Zhang Yifan , Guo Tianjie , Huang Qi , Mei Qian , Ma Fuqiang , Ma Hanbin
Published: May 2022

In this study, an “all-in-one” digital microfluidics (DMF) system was developed for automatic and rapid molecular diagnosis and integrated with magnetic bead-based nucleic acid extraction, loop-mediated isothermal amplification (LAMP), and real-time optical signal monitoring. First, we performed on- and off-chip comparison experiments for the magnetic bead nucleic acid extraction module and LAMP amplification function. The extraction efficiency for the on-chip test was comparable to that of conventional off-chip methods. The processing time for the automatic on-chip workflow was only 23 min, which was less than that of the conventional methods of 28 min 45 s. Meanwhile, the number of samples used in on-chip experiments was significantly smaller than that used in off-chip experiments; only 5 µL of E. coli samples was required for nucleic acid extraction, and 1 µL of the nucleic acid template was needed for the amplification reaction. In addition, we selected SARS-CoV-2 nucleic acid reference materials for the nucleic acid detection experiment, demonstrating a limit of detection of 10 copies/µL. The proposed “all-in-one” DMF system provides an on-site “sample to answer” time of approximately 60 min, which can be a powerful tool for point-of-care molecular diagnostics.
Specific and Sensitive Detection of Tartrazine on the Electrochemical Interface of a Molecularly Imprinted Polydopamine-Coated PtCo Nanoalloy on Graphene Oxide
Authors: Cheng Shuwen , Tang Danyao , Zhang Yi , Xu Libin , Liu Kunping , Huang Kejing , Yin Zhengzhi
Published: May 2022

A novel electrochemical sensor designed to recognize and detect tartrazine (TZ) was constructed based on a molecularly imprinted polydopamine (MIPDA)-coated nanocomposite of platinum cobalt (PtCo) nanoalloy-functionalized graphene oxide (GO). The nanocomposites were characterized and the TZ electrochemical detection performance of the sensor and various reference electrodes was investigated. Interestingly, the synergistic effect of the strong electrocatalytic activity of the PtCo nanoalloy-decorated GO and the high TZ recognition ability of the imprinted cavities of the MIPDA coating resulted in a large and specific response to TZ. Under the optimized conditions, the sensor displayed linear response ranges of 0.003–0.180 and 0.180–3.950 µM, and its detection limit was 1.1 nM (S/N = 3). The electrochemical sensor displayed high anti-interference ability, good stability, and adequate reproducibility, and was successfully used to detect TZ in spiked food samples. Comparison of important indexes of this sensor with those of previous electrochemical sensors for TZ revealed that this sensor showed improved performance. This surface-imprinted sensor provides an ultrasensitive, highly specific, effective, and low-cost method for TZ determination in foodstuffs.
Positive Psychology in Therapeutic Songwriting for People Living with Late-Life Depression—An Intervention Protocol
Authors: Eickholt Jasmin , Baker Felicity A. , Clark Imogen N.
Published: May 2022

(1) Background: An increasing number of people are living with late-life depression, yet non-pharmacological treatments to help manage symptoms are limited. Two interventions, positive psychology and music therapeutic songwriting, have independently led to decreased depressive symptoms and an improved wellbeing in older people over 65 years old. (2) Methods: This article describes the development of a therapeutic songwriting program for people living with late-life depression. Knowledge from positive psychology and therapeutic songwriting was combined to maximize the potential benefits. (3) Results: The intervention program has ten weekly 45 min sessions that incorporate elements from positive psychology into therapeutic songwriting. Using a three-song approach encompassing ongoing musical practices, different positive psychology interventions were incorporated to support the experiences associated with a flourishing life. The intervention protocol for older people presented here is distinct from previous deficit-orientated approaches in that it shifts the focus to positive experiences, resources, and the individual’s ability to decrease their own depressive symptoms and improve their wellbeing. (4) Discussion: This protocol presenting a therapeutic songwriting program meets the need to develop new non-pharmacological treatment options. However, further studies are needed to examine the feasibility and impact of the intervention program on late-life depression and wellbeing in older people.
A Depression Prediction Algorithm Based on Spatiotemporal Feature of EEG Signal
Authors: Liu Wei , Jia Kebin , Wang Zhuozheng , Ma Zhuo
Published: May 2022

Depression has gradually become the most common mental disorder in the world. The accuracy of its diagnosis may be affected by many factors, while the primary diagnosis seems to be difficult to define. Finding a way to identify depression by satisfying both objective and effective conditions is an urgent issue. In this paper, a strategy for predicting depression based on spatiotemporal features is proposed, and is expected to be used in the auxiliary diagnosis of depression. Firstly, electroencephalogram (EEG) signals were denoised through the filter to obtain the power spectra of the three corresponding frequency ranges, Theta, Alpha and Beta. Using orthogonal projection, the spatial positions of the electrodes were mapped to the brainpower spectrum, thereby obtaining three brain maps with spatial information. Then, the three brain maps were superimposed on a new brain map with frequency domain and spatial characteristics. A Convolutional Neural Network (CNN) and Gated Recurrent Unit (GRU) were applied to extract the sequential feature. The proposed strategy was validated with a public EEG dataset, achieving an accuracy of 89.63% and an accuracy of 88.56% with the private dataset. The network had less complexity with only six layers. The results show that our strategy is credible, less complex and useful in predicting depression using EEG signals.
Preconditioned MSCs Alleviate Cerebral Ischemia-Reperfusion Injury in Rats by Improving the Neurological Function and the Inhibition of Apoptosis
Authors: Zheng Jin , Mao Xueyu , Wang Delong , Xia Shiliang
Published: May 2022

Mesenchymal stem cells (MSCs) have great application prospects in the treatment of ischemic injury. However, their long-time cultivation before transplantation and poor survival after transplantation greatly limit the therapeutic effect and applications. This study aimed to investigate whether MSCs under the ischemic microenvironment could improve their survival and better alleviate cerebral ischemic injury. Firstly, we used ischemic brain tissue to culture MSCs and evaluated the functional changes of MSCs. Then a middle cerebral artery occlusion (MCAO) model was induced in rats, and the pretreated MSCs were injected via the tail vein. The adhesive removal test, rotarod test, modified neurological severity score, and pathological analyses were applied to assess the rats’ neurological function. Then the expression of neuron and apoptosis related markers was detected. The results indicated that ischemic brain tissue pretreated MSCs promoted the proliferation and the release of the growth factors of MSCs. Meanwhile, in MCAO model rats, transplantation of pretreated MSCs enhanced the neurogenesis, attenuated behavioral changes, reduced infarct size, and inhibited apoptosis. The expression of B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), NF-L, and NeuN were increased, while BCL2-Associated X (Bax) and Caspase-3 decreased. Our results suggest that MSCs pretreatment with stroke brain tissue could be an effective strategy in treating cerebral ischemic injury.
The Effects of Working Memory Capacity in Metaphor and Metonymy Comprehension in Mandarin–English Bilinguals’ Minds: An fMRI Study
Authors: Yin Chia-Hsin , Yang Fan-Pei Gloria
Published: May 2022

This study investigated the role of working memory capacity (WMC) in metaphoric and metonymic processing in Mandarin–English bilinguals’ minds. It also explored the neural correlations between metaphor and metonymy computations. We adopted an event-related functional magnetic resonance imaging (fMRI) design, which consisted of 21 English dialogic sets of stimuli and 5 conditions: systematic literal, circumstantial literal, metaphor, systematic metonymy, and circumstantial metonymy, all contextualized in daily conversations. Similar fronto-temporal networks were found for the figurative language processing patterns: the superior temporal gyrus (STG) for metaphorical comprehension, and the inferior parietal junction (IPJ) for metonymic processing. Consistent brain regions have been identified in previous studies in the homologue right hemisphere of better WMC bilinguals. The degree to which bilateral strategies that bilinguals with better WMC or larger vocabulary size resort to is differently modulated by subtypes of metonymies. In particular, when processing circumstantial metonymy, the cuneus (where putamen is contained) is activated as higher-span bilinguals filter out irrelevant information, resorting to inhibitory control use. Cingulate gyrus activation has also been revealed in better WMC bilinguals, reflecting their mental flexibility to adopt the subjective perspective of critical figurative items with self-control. It is hoped that this research provides a better understanding of Mandarin–English bilinguals’ English metaphoric and metonymic processing in Taiwan.
Conceptual Framework for Building Permit Process Modeling: Lessons Learned from a Comparison between Germany and the United States regarding the As-Is Building Permit Processes
Authors: Fauth Judith , Soibelman Lucio
Published: May 2022

Without a building permit, a construction project cannot be legally implemented. For this, the building project must undergo a review process by the competent authority. As the number of building projects to be inspected increases, building authorities are faced with ever greater challenges, due to the lack of adequate personnel to manage the inefficient, labor extensive, and lengthy building permit process. In-depth scientific studies of the existing building permit processes are missing so far. This paper introduces a proposed framework that aims to investigate and compare the building permit processes in Germany and in the United States of America (USA). Among other things, the processes are studied for both by-right and non-by-right cases. In doing so, the data are based on a collected empirical study in the form of qualitative expert interviews. The findings of the comparison provide a detailed description and illustration of the current building permit processes, as well as the lessons learned from both countries.
AlphaTruss: Monte Carlo Tree Search for Optimal Truss Layout Design
Authors: Luo Ruifeng , Wang Yifan , Xiao Weifang , Zhao Xianzhong
Published: May 2022

Truss layout optimization under complex constraints has been a hot and challenging problem for decades that aims to find the optimal node locations, connection topology between nodes, and cross-sectional areas of connecting bars. Monte Carlo Tree Search (MCTS) is a reinforcement learning search technique that is competent to solve decision-making problems. Inspired by the success of AlphaGo using MCTS, the truss layout problem is formulated as a Markov Decision Process (MDP) model, and a 2-stage MCTS-based algorithm, AlphaTruss, is proposed for generating optimal truss layout considering topology, geometry, and bar size. In this MDP model, three sequential action sets of adding nodes, adding bars, and selecting sectional areas greatly expand the solution space and the reward function gives feedback to actions according to both geometric stability and structural simulation. To find the optimal sequential actions, AlphaTruss solves the MDP model and gives the best decision in each design step by searching and learning through MCTS. Compared with existing results from the literature, AlphaTruss exhibits better performance in finding the truss layout with the minimum weight under stress, displacement, and buckling constraints, which verifies the validity and efficiency of the established algorithm.
Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines
Authors: Khetan Riya , Dharmayanti Cintya , Gillam Todd A. , Kübler Eric , Klingler-Hoffmann Manuela , Ricciardelli Carmela , Oehler Martin K. , Blencowe Anton , Garg Sanjay , Albrecht Hugo
Published: May 2022

The five-year survival rate for women with ovarian cancer is very poor despite radical cytoreductive surgery and chemotherapy. Although most patients initially respond to platinum-based chemotherapy, the majority experience recurrence and ultimately develop chemoresistance, resulting in fatal outcomes. The current administration of cytotoxic compounds is hampered by dose-limiting severe adverse effects. There is an unmet clinical need for targeted drug delivery systems that transport chemotherapeutics selectively to tumor cells while minimizing off-target toxicity. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer. This review summarizes the progress in engineered nanoparticle research for drug delivery for ovarian cancer and discusses the potential use of GPCRs as molecular entry points to deliver anti-cancer compounds into ovarian cancer cells. A newly emerging treatment paradigm could be the personalized design of nanomedicines on a case-by-case basis.
Lightweight Deep Learning Model for Assessment of Substitution Voicing and Speech after Laryngeal Carcinoma Surgery
Authors: Maskeliūnas Rytis , Kulikajevas Audrius , Damaševičius Robertas , Pribuišis Kipras , Ulozaitė-Stanienė Nora , Uloza Virgilijus
Published: May 2022

Laryngeal carcinoma is the most common malignant tumor of the upper respiratory tract. Total laryngectomy provides complete and permanent detachment of the upper and lower airways that causes the loss of voice, leading to a patient’s inability to verbally communicate in the postoperative period. This paper aims to exploit modern areas of deep learning research to objectively classify, extract and measure the substitution voicing after laryngeal oncosurgery from the audio signal. We propose using well-known convolutional neural networks (CNNs) applied for image classification for the analysis of voice audio signal. Our approach takes an input of Mel-frequency spectrogram (MFCC) as an input of deep neural network architecture. A database of digital speech recordings of 367 male subjects (279 normal speech samples and 88 pathological speech samples) was used. Our approach has shown the best true-positive rate of any of the compared state-of-the-art approaches, achieving an overall accuracy of 89.47%.
Radiological Underestimation of Tumor Size as a Relevant Risk Factor for Positive Margin Rate in Breast-Conserving Therapy of Pure Ductal Carcinoma In Situ (DCIS)
Authors: Schultek Gesche , Gerber Bernd , Reimer Toralf , Stubert Johannes , Hartmann Steffi , Martin Annett , Stachs Angrit
Published: May 2022

Background: Radiological underestimation of the actual tumor size is a relevant problem in reaching negative margins in ductal carcinoma in situ (DCIS) associated with microcalcifications in breast-conserving therapy (BCT). The aim of this study is to evaluate whether the radiological underestimation of tumor size has an influence on the histopathological margin status. Methods: Patients who underwent BCT with preoperatively diagnosed pure DCIS were included (pooled analysis of two trials). Multiple factors were analysed regarding radiological underestimation ≥10 mm. Radiological underestimation was defined as mammographic minus histological tumor size in mm. Results: Positive margins occurred in 75 of 189 patients. Radiological underestimation ≥10 mm was an independent influencing factor (OR 5.80; 95%CI 2.55–13.17; p < 0.001). A radiological underestimation was seen in 70 patients. The following parameters were statistically significant associated with underestimation: pleomorphic microcalcifications (OR 3.77; 95%CI 1.27–11.18), clustered distribution patterns (OR 4.26; 95%CI 2.25–8.07), and mammographic tumor sizes ≤20 mm (OR 7.47; 95%CI 3.49–15.99). Only a mammographic tumor size ≤20 mm was an independent risk factor (OR 6.49; 95%CI 2.30–18.26; p < 0.001). Grading, estrogen receptor status, and comedo necrosis did not influence the size estimation. Conclusion: Radiological underestimation is an independent risk factor for positive margins in BCT of DCIS associated with microcalcifications predominantly occurring in mammographic small tumors.
A Multidisciplinary Approach for the Personalised Non-Operative Management of Elderly and Frail Rectal Cancer Patients Unable to Undergo TME Surgery
Authors: Ketelaers Stijn H. J. , Jacobs Anne , Verrijssen An-Sofie E. , Cnossen Jeltsje S. , van Hellemond Irene E. G. , Creemers Geert-Jan M. , Schreuder Ramon-Michel , Scholten Harm J. , Tolenaar Jip L. , Bloemen Johanne G. , Rutten Harm J. T. , Burger Jacobus W. A.
Published: May 2022

Despite it being the optimal curative approach, elderly and frail rectal cancer patients may not be able to undergo a total mesorectal excision. Frequently, no treatment is offered at all and the natural course of the disease is allowed to unfold. These patients are at risk for developing debilitating symptoms that impair quality of life and require palliative treatment. Recent advancements in non-operative treatment modalities have enhanced the toolbox of alternative treatment strategies in patients unable to undergo surgery. Therefore, a proposed strategy is to aim for the maximal non-operative treatment, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The complexity of treating elderly and frail patients requires a patient-centred approach to personalise treatment. The main challenge is to optimise the balance between local control of disease, patient preferences, and the burden of treatment. A comprehensive geriatric assessment is a crucial element within the multidisciplinary dialogue. Since limited knowledge is available on the optimal non-operative treatment strategy, these patients should be treated by dedicated multidisciplinary rectal cancer experts with special interest in the elderly and frail. The aim of this narrative review was to discuss a multidisciplinary patient-centred treatment approach and provide a practical suggestion of a successfully implemented clinical care pathway.
Metastasis-Directed Radiation Therapy with Consolidative Intent for Oligometastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis
Authors: Longo Nicola , Celentano Giuseppe , Napolitano Luigi , La Rocca Roberto , Capece Marco , Califano Gianluigi , Collà Ruvolo Claudia , Mangiapia Francesco , Fusco Ferdinando , Morra Simone , Turco Carmine , Di Bello Francesco , Fusco Giovanni Maria , Cirillo Luigi , Cacciapuoti Crescenzo , Spirito Lorenzo , Calogero Armando , Sica Antonello , Sagnelli Caterina , Creta Massimiliano
Published: May 2022

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n = 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.
Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy
Authors: Morote Juan , Borque-Fernando Angel , Triquell Marina , Celma Anna , Regis Lucas , Mast Richard , de Torres Inés M. , Semidey María E. , Abascal José M. , Servian Pol , Santamaría Anna , Planas Jacques , Esteban Luis M. , Trilla Enrique
Published: May 2022

This study is a head-to-head comparison between mPSAD and MRI-PMbdex. The MRI-PMbdex was created from 2432 men with suspected PCa; this cohort comprised the development and external validation cohorts of the Barcelona MRI predictive model. Pre-biopsy 3-Tesla multiparametric MRI (mpMRI) and 2 to 4-core transrectal ultrasound (TRUS)-guided biopsies for suspicious lesions and/or 12-core TRUS systematic biopsies were scheduled. Clinically significant PCa (csPCa), defined as Gleason-based Grade Group 2 or higher, was detected in 934 men (38.4%). The area under the curve was 0.893 (95% confidence interval [CI]: 0.880–0.906) for MRI-PMbdex and 0.764 (95% CI: 0.774–0.783) for mPSAD, with p < 0.001. MRI-PMbdex showed net benefit over biopsy in all men when the probability of csPCa was greater than 2%, while mPSAD did the same when the probability of csPCa was greater than 18%. Thresholds of 13.5% for MRI-PMbdex and 0.628 ng/mL2 for mPSAD had 95% sensitivity for csPCa and presented 51.1% specificity for MRI-PMbdex and 19.6% specificity for mPSAD, with p < 0.001. MRI-PMbdex exhibited net benefit over mPSAD in men with prostate imaging report and data system (PI-RADS) <4, while neither exhibited any benefit in men with PI-RADS 5. Hence, we can conclude that MRI-PMbdex is more accurate than mPSAD for the proper selection of candidates for prostate biopsy among men with suspected PCa, with the exception of men with a PI-RAD S 5 score, for whom neither tool exhibited clinical guidance to determine the need for biopsy.
Influences of Long-Term Exercise and High-Fat Diet on Age-Related Telomere Shortening in Rats
Authors: Semeraro Maria Donatella , Almer Gunter , Renner Wilfried , Gruber Hans-Jürgen , Herrmann Markus
Published: May 2022

(1) Obesity and exercise are believed to modify age-related telomere shortening by regulating telomerase and shelterins. Existing studies are inconsistent and limited to peripheral blood mononuclear cells (PBMCs) and selected solid tissues. (2) Female Sprague Dawley (SD) rats received either standard diet (ND) or high-fat diet (HFD). For 10 months, half of the animals from both diet groups performed 30 min running at 30 cm/s on five consecutive days followed by two days of rest (exeND, exeHFD). The remaining animals served as sedentary controls (coND, coHFD). Relative telomere length (RTL) and mRNA expression of telomerase (TERT) and the shelterins TERF-1 and TERF-2 were mapped in PBMCs and nine solid tissues. (3) At study end, coND and coHFD animals showed comparable RTL in most tissues with no systematic differences in TERT, TERF-1 and TERF-2 expression. Only visceral fat of coHFD animals showed reduced RTL and lower expression of TERT, TERF-1 and TERF-2. Exercise had heterogeneous effects on RTL in exeND and exeHFD animals with longer telomeres in aorta and large intestine, but shorter telomeres in PBMCs and liver. Telomere-regulating genes showed inconsistent expression patterns. (4) In conclusion, regular exercise or HFD cannot systematically modify RTL by regulating the expression of telomerase and shelterins.
Inflammation and Wasting of Skeletal Muscles in Kras-p53-Mutant Mice with Intraepithelial Neoplasia and Pancreatic Cancer—When Does Cachexia Start?
Authors: Hildebrandt Wulf , Keck Jan , Schmich Simon , Bonaterra Gabriel A. , Wilhelm Beate , Schwarzbach Hans , Eva Anna , Bertoune Mirjam , Slater Emily P. , Fendrich Volker , Kinscherf Ralf
Published: May 2022

Skeletal muscle wasting critically impairs the survival and quality of life in patients with pancreatic ductal adenocarcinoma (PDAC). To identify the local factors initiating muscle wasting, we studied inflammation, fiber cross-sectional area (CSA), composition, amino acid metabolism and capillarization, as well as the integrity of neuromuscular junctions (NMJ, pre-/postsynaptic co-staining) and mitochondria (electron microscopy) in the hindlimb muscle of LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre mice with intraepithelial-neoplasia (PanIN) 1-3 and PDAC, compared to wild-type mice (WT). Significant decreases in fiber CSA occurred with PDAC but not with PanIN 1-3, compared to WT: These were found in the gastrocnemius (type 2x: −20.0%) and soleus (type 2a: −21.0%, type 1: −14.2%) muscle with accentuation in the male soleus (type 2a: −24.8%, type 1: −17.4%) and female gastrocnemius muscle (−29.6%). Significantly higher densities of endomysial CD68+ and cyclooxygenase-2+ (COX2+) cells were detected in mice with PDAC, compared to WT mice. Surprisingly, CD68+ and COX2+ cell densities were also higher in mice with PanIN 1-3 in both muscles. Significant positive correlations existed between muscular and hepatic CD68+ or COX2+ cell densities. Moreover, in the gastrocnemius muscle, suppressor-of-cytokine-3 (SOCS3) expressions was upregulated >2.7-fold with PanIN 1A-3 and PDAC. The intracellular pools of proteinogenic amino acids and glutathione significantly increased with PanIN 1A-3 compared to WT. Capillarization, NMJ, and mitochondrial ultrastructure remained unchanged with PanIN or PDAC. In conclusion, the onset of fiber atrophy coincides with the manifestation of PDAC and high-grade local (and hepatic) inflammatory infiltration without compromised microcirculation, innervation or mitochondria. Surprisingly, muscular and hepatic inflammation, SOCS3 upregulation and (proteolytic) increases in free amino acids and glutathione were already detectable in mice with precancerous PanINs. Studies of initial local triggers and defense mechanisms regarding cachexia are warranted for targeted anti-inflammatory prevention.
Biomarkers of Favorable vs. Unfavorable Responses in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy
Authors: Lee Hsin-Hua , Chen Chien-Hung , Huang Yu-Hsiang , Chiang Cheng-Han , Huang Ming-Yii
Published: May 2022

Colorectal cancer is the second leading cause of cancer death globally. The gold standard for locally advanced rectal cancer (LARC) nowadays is preoperative concurrent chemoradiation (CCRT). Approximately three quarters of LARC patients do not achieve pathological complete response and hence suffer from relapse, metastases and inevitable death. The exploration of trustworthy and timely biomarkers for CCRT response is urgently called for. This review focused upon a broad spectrum of biomarkers, including circulating tumor cells, DNA, RNA, oncogenes, tumor suppressor genes, epigenetics, impaired DNA mismatch repair, patient-derived xenografts, in vitro tumor organoids, immunity and microbiomes. Utilizing proper biomarkers can assist in categorizing appropriate patients by the most efficient treatment modality with the best outcome and accompanied by minimal side effects. The purpose of this review is to inspect and analyze accessible data in order to fully realize the promise of precision oncology for rectal cancer patients.
Cytoskeleton Dependent Mobility Dynamics of FcγRIIA Facilitates Platelet Haptotaxis and Capture of Opsonized Bacteria
Authors: Palankar Raghavendra , Sachs Laura , Wesche Jan , Greinacher Andreas
Published: May 2022

Platelet adhesion and spreading at the sites of vascular injury is vital to hemostasis. As an integral part of the innate immune system, platelets interact with opsonized bacterial pathogens through FcγRIIA and contribute to host defense. As mechanoscavangers, platelets actively migrate and capture bacteria via cytoskeleton-rich, dynamic structures, such as filopodia and lamellipodia. However, the role of human platelet FcγRIIA in cytoskeleton-dependent interaction with opsonized bacteria is not well understood. To decipher this, we used a reductionist approach with well-defined micropatterns functionalized with immunoglobulins mimicking immune complexes at planar interfaces and bacteriamimetic microbeads. By specifically blocking of FcγRIIA and selective disruption of the platelet cytoskeleton, we show that both functional FcγRIIA and cytoskeleton are necessary for human platelet adhesion and haptotaxis. The direct link between FcγRIIA and the cytoskeleton is further explored by single-particle tracking. We then demonstrate the relevance of cytoskeleton-dependent differential mobilities of FcγRIIA on bacteria opsonized with the chemokine platelet factor 4 (PF4) and patient-derived anti-PF4/polyanion IgG. Our data suggest that efficient capture of opsonized bacteria during host-defense is governed by mobility dynamics of FcγRIIA on filopodia and lamellipodia, and the cytoskeleton plays an essential role in platelet morphodynamics at biological interfaces that display immune complexes.
Spectroscopic Recognition of Metal Ions and Non-Linear Optical (NLO) Properties of Some Fluorinated Poly(1,3,4-Oxadiazole-Ether)s
Authors: Homocianu Mihaela , Airinei Anton , Ipate Alina Mirela , Hamciuc Corneliu
Published: May 2022

In this paper, we examined the sensing ability of some fluorinated 1,3,4-oxadiazole-containing assemblies toward various metal ions and their nonlinear optical (NLO) properties. The changes in the spectral characteristics of these compounds in the existence of Mg2+, Mn2+, Ni2+, Cd2+, Zn2+, Co2+, Cu2+, Hg2+, Sn2+, and Ag+ metal ions were performed, and they were found to be selective and more sensitive toward the addition of Ag+, Co2+, and Cu2+ ions (new bands appeared). Instead, spectral changes in the presence of Mg2+, Mn2+, Ni2+, Cd2+, Zn2+, Hg2+, and Sn2+ were not significant, so we did not evaluate the corresponding binding parameters. Therefore, all of these compounds were found to be selective and sensitive to Ag+, Co2+, and Cu2+ ions. Furthermore, the first-order polarizability (αCT), the first-order hyperpolarizability (βCT), and the second-order hyperpolarizability (γCT) were evaluated using the solvatochromic approach, and the intramolecular charge transfer (ICT) characteristics were investigated using a generalized Mulliken–Hush (GMH) analysis.
Usage Patterns and Self-Esteem of Female Consumers of Antiaging Cosmetic Products
Authors: Evangelista Marta , Mota Sandra , Almeida Isabel Filipa , Pereira M. Graça
Published: May 2022

Aging is an irreversible process of the human body, resulting from a progressive decrease in the biological functions of the organs, including the skin. This study analyzed the relationship between usage patterns of different types of anti-aging cosmetic products, sociodemographic variables, appearance schemes, psychological morbidity, perfectionism, and aging perception of aging with self-esteem. This cross-sectional study included a sample of 260 women, aged between 25 and 64 years, who are users of anti-aging cosmetics and/or aesthetic treatments. Participants were assessed on psychological morbidity (Hospital Anxiety and Depression Scale), appearance schemes (Appearance Schemas Inventory—Revised), perfectionism (Frost Multidimensional Perfectionism Scale), aging perceptions (Brief Aging Perceptions Questionnaire), and self-esteem (Rosenberg Self-Esteem Scale). The use of facial-firming cosmetics positively correlated with self-esteem. The results of regression analysis revealed that psychological morbidity and perfectionism contribute negatively to self-esteem, while marital status, professional status, and aging perceptions (positive consequences) contribute positively. According to the results, intervention programs to promote women’s self-esteem should focus on the reduction in psychological morbidity and the promotion of adaptive patterns of perfectionism and address aging perceptions. Longitudinal studies might help explain the complex relationship between the use of anti-aging cosmetic products and psychological variables, particularly self-esteem in women.
Two New Species of Dacrymyces (Dacrymycetales, Basidiomycota) from Southwestern China
Authors: Lian Ya-Ping , Tohtirjap Ablat , Wu Fang
Published: May 2022

Two new species of Dacrymyces, D. cerebriformis and D. sinostenosporus, are presented from southwestern China, based on morphological characteristics and phylogenetic analyses. Dacrymyces cerebriformis is characterized by obviously cerebriform basidiomata when mature, hyphae without clamp connections, and hyaline, thin-walled, allantoid, 0–7-septate basidiospores (18.4–23.1 × 5.5–7.7 μm). Dacrymyces sinostenosporus is characterized by discoid and applanate basidiomata when mature, hyphae without clamp connections, and hyaline, thin-walled, cylindrical to allantoid, 0–7-septate basidiospores (18.0–23.5 × 6.3–8.0 μm). Dacrymyces cerebriformis can be distinguished from D. sinostenosporus by the narrower thin- or thick-walled terminal cells in the marginal hyphae of the sterile surface (1.7–3.5 μm vs. 3.5–6.0 μm in diameter) and thinner basidiospores (Q = 3.14–3.28 vs. Q = 2.63–2.77). A phylogenetic analysis of Dacrymyces is performed by using a dataset composed of concatenated internal transcribed spacer regions (ITS) and a large subunit (nrLSU) of ribosomal DNA gene, and two new species nested in two distinct lineages with robust support. A full description and illustrations of the two new species are provided here.
Comprehensive Landscape of STEAP Family Members Expression in Human Cancers: Unraveling the Potential Usefulness in Clinical Practice Using Integrated Bioinformatics Analysis
Authors: Rocha Sandra M. , Socorro Sílvia , Passarinha Luís A. , Maia Cláudio J.
Published: May 2022

The human Six-Transmembrane Epithelial Antigen of the Prostate (STEAP) family comprises STEAP1-4. Several studies have pointed out STEAP proteins as putative biomarkers, as well as therapeutic targets in several types of human cancers, particularly in prostate cancer. However, the relationships and significance of the expression pattern of STEAP1-4 in cancer cases are barely known. Herein, the Oncomine database and cBioPortal platform were selected to predict the differential expression levels of STEAP members and clinical prognosis. The most common expression pattern observed was the combination of the over- and underexpression of distinct STEAP genes, but cervical and gastric cancer and lymphoma showed overexpression of all STEAP genes. It was also found that STEAP genes’ expression levels were already deregulated in benign lesions. Regarding the prognostic value, it was found that STEAP1 (prostate), STEAP2 (brain and central nervous system), STEAP3 (kidney, leukemia and testicular) and STEAP4 (bladder, cervical, gastric) overexpression correlate with lower patient survival rate. However, in prostate cancer, overexpression of the STEAP4 gene was correlated with a higher survival rate. Overall, this study first showed that the expression levels of STEAP genes are highly variable in human cancers, which may be related to different patients’ outcomes.
Zika Virus Envelope Protein Domain III Produced in K. phaffii Has the Potential for Diagnostic Applications
Authors: Prates John Willians Oliveira , Xisto Mariana Fonseca , Rodrigues João Vitor da Silva , Colombari João Pedro Cruz , Meira Júlia Maria Alves , Dias Roberto Sousa , Silva Cynthia Canedo da , de Paula e Sérgio Oliveira
Published: May 2022

Zika virus (ZIKV) represents a global human health threat and it is related to severe diseases such as congenital Zika syndrome (CZS) and Guillain-Barré syndrome (GBS). There is no vaccine available nor specific antiviral treatment, so developing sensitive, specific, and low-cost diagnostic tests is necessary. Thus, the objective of this work was to produce the Zika virus envelope protein domain III (ZIKV-EDIII) in Komagataella phaffii KM71H and evaluate its potential for diagnostic applications. After the K. phaffii had been transformed with the pPICZαA-ZIKV-EDIII vector, an SDS-PAGE and Western Blot were performed to characterize the recombinant protein and an ELISA to evaluate the antigenic potential. The results show that ZIKV-EDIII was produced in the expected size, with a good purity grade and yield of 2.58 mg/L. The receiver operating characteristic (ROC) curve showed 90% sensitivity and 87.5% specificity for IgM, and 93.33% sensitivity and 82.76% specificity for IgG. The ZIKV-EDIII protein was efficiently produced in K. phaffi, and it has the potential for diagnostic applications.
Novel Markers in Diabetic Kidney Disease—Current State and Perspectives
Authors: Piwkowska Agnieszka , Zdrojewski Łukasz , Heleniak Zbigniew , Dębska-Ślizień Alicja
Published: May 2022

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Along with the increasing prevalence of diabetes, DKD is expected to affect a higher number of patients. Despite the major progress in the therapy of DKD and diabetes mellitus (DM), the classic clinical diagnostic tools in DKD remain insufficient, delaying proper diagnosis and therapeutic interventions. We put forward a thesis that there is a need for novel markers that will be early, specific, and non-invasively obtained. The ongoing investigations uncover new molecules that may potentially become new markers of DKD—among those are: soluble α-Klotho and proteases (ADAM10, ADAM17, cathepsin, dipeptidyl peptidase 4, caspase, thrombin, and circulating microRNAs). This review summarizes the current clinical state-of-the-art in the diagnosis of DKD and a selection of potential novel markers, based on up-to-date literature.
Field Evaluation of a Hemozoin-Based Malaria Diagnostic Device in Puerto Lempira, Honduras
Authors: Fontecha Gustavo , Escobar Denis , Ortiz Bryan , Pinto Alejandra , Serrano Delmy , Valdivia Hugo O.
Published: May 2022

The diagnosis of malaria in Honduras is based mainly on microscopic observation of the parasite in thick smears or the detection of parasite antigens through rapid diagnostic tests when microscopy is not available. The specific treatment of the disease depends exclusively on the positive result of one of these tests. Given the low sensitivity of conventional methods, new diagnostic approaches are needed. This study evaluates the in-field performance of a device (Gazelle™) based on the detection of hemozoin. This was a double-blind study evaluating symptomatic individuals with suspected malaria in the department of Gracias a Dios, Honduras, using blood samples collected from 2021 to 2022. The diagnostic performance of Gazelle™ was compared with microscopy and nested 18ssr PCR as references. The sensitivity and specificity of Gazelle™ were 59.7% and 98.6%, respectively, while microscopy had a sensitivity of 64.9% and a specificity of 100%. The kappa index between microscopy and Gazelle™ was 0.9216 using microscopy as a reference. Both methods show similar effectiveness and predictive values. No statistical differences were observed between the results of the Gazelle™ compared to light microscopy (p = 0.6831). The turnaround time was shorter for Gazelle™ than for microscopy, but the cost per sample was slightly higher for Gazelle™. Gazelle™ showed more false-negative cases when infections were caused by Plasmodium falciparum compared to P. vivax. Conclusions: The sensitivity and specificity of Gazelle™ are comparable to microscopy. The simplicity and ease of use of the Gazelle™, the ability to run on batteries, and the immediacy of its results make it a valuable tool for malaria detection in the field. However, further development is required to differentiate Plasmodium species, especially in those regions requiring differentiated treatment.
Outcome Analysis of the Use of Cerament® in Patients with Chronic Osteomyelitis and Corticomedullary Defects
Authors: Niemann Marcel , Graef Frank , Ahmad Sufian S. , Braun Karl F. , Stöckle Ulrich , Trampuz Andrej , Meller Sebastian
Published: May 2022

Background: Chronic osteomyelitis (OM) is a progressive but mostly low-grade infection of the bones. The management of this disease is highly challenging for physicians. Despite systematic treatment approaches, recurrence rates are high. Further, functional and patient-reported outcome data are lacking, especially after osseous defects are filled with bioresorbable antibiotic carriers. Objective: To assess functional and patient-reported outcome measures (PROM) following the administration of Cerament® G or V due to corticomedullary defects in chronic OM. Methods: We conducted a retrospective study from 2015 to 2020, including all patients who received Cerament® for the aforementioned reason. Patients were diagnosed and treated in accordance with globally valid recommendations, and corticomedullary defects were filled with Cerament® G or V, depending on the expected germ spectrum. Patients were systematically followed up, and outcome measures were collected during outpatient clinic visits. Results: Twenty patients with Cierny and Mader type III OM were included in this study and followed up for 20.2 ± 17.2 months (95%CI 12.1–28.3). Ten of these patients needed at least one revision (2.0 ± 1.3 revisions per patient (95%CI 1.1–2.9) during the study period due to OM persistence or local wound complications. There were no statistically significant differences in functional scores or PROMs between groups. Conclusion: The use of Cerament® G and V in chronic OM patients with corticomedullary defects appears to have good functional outcomes and satisfactory PROMs. However, the observed rate of local wound complications and the OM persistence rate may be higher when compared to previously published data.
Data-Driven Decision Support for Adult Autism Diagnosis Using Machine Learning
Authors: Batsakis Sotirios , Adamou Marios , Tachmazidis Ilias , Jones Sarah , Titarenko Sofya , Antoniou Grigoris , Kehagias Thanasis
Published: May 2022

Adult referrals to specialist autism spectrum disorder diagnostic services have increased in recent years, placing strain on existing services and illustrating the need for the development of a reliable screening tool, in order to identify and prioritize patients most likely to receive an ASD diagnosis. In this work a detailed overview of existing approaches is presented and a data driven analysis using machine learning is applied on a dataset of adult autism cases consisting of 192 cases. Our results show initial promise, achieving total positive rate (i.e., correctly classified instances to all instances ratio) up to 88.5%, but also point to limitations of currently available data, opening up avenues for further research. The main direction of this research is the development of a novel autism screening tool for adults (ASTA) also introduced in this work and preliminary results indicate the ASTA is suitable for use as a screening tool for adult populations in clinical settings.
Entrepreneurship Education: A Systematic Literature Review and Identification of an Existing Gap in the Field
Authors: Banha Francisco , Coelho Luís Serra , Flores Adão
Published: May 2022

Having identified the need to conduct research on the intersection between entrepreneurship education (EE) and public policies, we carried out a systematic literature review on decision-making processes regarding the implementation of education for entrepreneurship programs in schools and the introduction of this topic in the policy-making process. This SLR followed every process inherent to its well-established protocol. The research undertaken confirmed that the understanding of decision processes associated with the implementation of EE programs is not only a “missing link” in the discussions about the way in which countries manage situations related to EE, but also a gap in academic knowledge. Indeed, the SLR process included only nine articles in the final review (obtained through a methodology based on an algorithm)—which is a clear sign that further scientific research around this specific topic is needed. The articles included in the final review suggest that: (i) entrepreneurship is fundamental to the progress and evolution of countries and their regions, (ii) there is evidence that EE is central to a more entrepreneurial youth, and (iii) the successful implementation of recommendations from regulatory institutions is based on political commitment and implementation capacities.
Hydrodynamic and Energy Transport Model-Based Hot-Carrier Effect in GaAs pin Solar Cell
Authors: Sogabe Tomah , Shiba Kodai , Sakamoto Katsuyoshi
Published: May 2022

The hot-carrier effect and hot-carrier dynamics in GaAs solar cell device performance were investigated. Hot-carrier solar cells based on the conventional operation principle were simulated based on the detailed balance thermodynamic model and the hydrodynamic energy transportation model. A quasi-equivalence between these two models was demonstrated for the first time. In the simulation, a specially designed GaAs solar cell was used, and an increase in the open-circuit voltage was observed by increasing the hot-carrier energy relaxation time. A detailed analysis was presented regarding the spatial distribution of hot-carrier temperature and its interplay with the electric field and three hot-carrier recombination processes: Auger, Shockley–Read–Hall, and radiative recombinations.
Ternary Neural Networks Based on on/off Memristors: Set-Up and Training
Authors: Morell Antoni , Machado Elvis Díaz , Miranda Enrique , Boquet Guillem , Vicario Jose Lopez
Published: May 2022

Neuromorphic systems based on hardware neural networks (HNNs) are expected to be an energy and time-efficient computing architecture for solving complex tasks. In this paper, we consider the implementation of deep neural networks (DNNs) using crossbar arrays of memristors. More specifically, we considered the case where such devices can be configured in just two states: the low-resistance state (LRS) and the high-resistance state (HRS). HNNs suffer from several non-idealities that need to be solved when mapping our software-based models. A clear example in memristor-based neural networks is conductance variability, which is inherent to resistive switching devices, so achieving good performance in an HNN largely depends on the development of reliable weight storage or, alternatively, mitigation techniques against weight uncertainty. In this manuscript, we provide guidelines for a system-level designer where we take into account several issues related to the set-up of the HNN, such as what the appropriate conductance value in the LRS is or the adaptive conversion of current outputs at one stage to input voltages for the next stage. A second contribution is the training of the system, which is performed via offline learning, and considering the hardware imperfections, which in this case are conductance fluctuations. Finally, the resulting inference system is tested in two well-known databases from MNIST, showing that is competitive in terms of classification performance against the software-based counterpart. Additional advice and insights on system tuning and expected performance are given throughout the paper.