bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Pathologic Downstaging with Induction versus Consolidation Chemotherapy in Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy—A National Cancer Database Analysis
Authors: Fan Austin , Zhao Beiqun , Vu Peter , Abbadessa Benjamin , Lopez Nicole , Eisenstein Samuel , Ramamoorthy Sonia , Liu Shanglei
Published: January 2024

Total neoadjuvant therapy (TNT) is the recommended treatment for locally advanced rectal cancer. The optimal sequence of TNT is debated: induction (chemotherapy first) or consolidation (chemoradiation first)? We aim to evaluate the practice patterns and clinical outcomes of total neoadjuvant therapy with either induction or consolidation regiments in the United States for patients with locally advanced rectal cancer. Methods: This is a retrospective analysis of the National Cancer Database for patients with clinical stage II or stage III rectal cancer, diagnosed between 2006 and 2017, who underwent total neoadjuvant therapy followed by surgery. Results: From 2006 to 2017, we identified 8999 patients and found that the utilization of induction chemotherapy increased from 2.0% to 35.0%. TNT resulted in pathologic downstaging 46.7% of the time and a pathologic complete response 11.6% of the time. Induction chemotherapy lead to higher pathologic downstaging (58% vs. 44.7%, p < 0.001) and pathologic complete responses (16.8% vs. 10.7%, p < 0.001). Similar trends held true in a multivariate analysis and subset analysis of stage II and III disease. Conclusions: These findings suggest that induction chemotherapy may be preferred over consolidation chemotherapy when downstaging prior to oncologic resection is desired. The optimal treatment plan for total neoadjuvant therapy is multi-factorial and requires further elucidation.
Lack of Consensus on the Definition of Aseptic Loosening in Total Ankle Replacement: A Narrative Systematic Review
Authors: Kvarda Peter , Mills Andreea , Shepherd David , Schneider Tim
Published: January 2024

Background: Aseptic loosening is one of the most common modes of failure of total ankle replacement (TAR). However, a precise definition of aseptic loosening is still lacking. This systematic review aimed to identify the variations of applied definitions and offer insights into the lack of consensus. Methods: Human studies reporting aseptic loosening of TAR published in peer-reviewed journals within the last decade were considered. The search strategy involved specific terms in Embase, MEDLINE ALL, and the Cochrane Library. Variations in aseptic loosening definitions were analysed. Results: Of 767 studies, 88 were included in this study. Only nine studies precisely defined aseptic loosening with significant variations. Twenty-two studies referenced the term and fifty-seven reported it as a complication but neither defined nor referenced it. Conclusions: Significant uncertainty exists regarding the universal definition of aseptic loosening of TAR, and many variations occur in terms of the assessment approach and criteria.
Circuit Training Improves the Levels of β-Amyloid and Brain-Derived Neurotrophic Factor Related to Cognitive Impairment Risk Factors in Obese Elderly Korean Women
Authors: Kang Duwang , Koh Suhan , Kim Taekyu , Bressel Eadric , Kim Doyeon
Published: January 2024

Background: The purpose of this study was to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women. Methods: The subjects for the study were aged 65–70 years and were each assigned to a circuit training group (EG, n = 12) or a control group (CG, n = 11). The 60 min combined exercise was performed 3 times per week for 16 weeks. The exercise intensity was progressively increased from a 40% heart rate reserve to a 70% heart rate reserve. The test data were analyzed using a paired t-test, an independent t-test, and a two-way repeated measures ANOVA, and an alpha level of 0.05 was set for all tests of significance. Results: Group-by-time interaction effects were observed for β-amyloid (p < 0.05), brain-derived neurotrophic factor (p < 0.01), and cognitive function (p < 0.05). Within the exercise group, significant differences were found in β-amyloid (p < 0.05), brain-derived neurotrophic factor (p < 0.001), and cognitive function (p < 0.05) when comparing across different time points. Additionally, there were statistically significant differences between groups in post-exercise β-amyloid (p < 0.05), change in β-amyloid (p < 0.05), brain-derived neurotrophic factor (p < 0.01), and cognitive function (p < 0.05). Conclusions: Therefore, it is suggested that the circuit training used in this study could be an effective exercise method for improving the risk factors of cognitive impairment in obese elderly Korean women.
Evaluation of the Efficacy and Safety of Quetiapine in the Treatment of Delirium in Adult ICU Patients: A Retrospective Comparative Study
Authors: Alghadeer Sultan , Almesned Rahaf S. , Alshehri Emad A. , Alwhaibi Abdulrahman
Published: January 2024

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes.
High-Sensitivity Cardiac Troponin T to Exclude Cardiac Involvement in TTR Variant Carriers and ATTRv Amyloidosis Patients
Authors: Tingen Hendrea S. A. , Berends Milou , Tubben Alwin , Bijzet Johan , Houwerzijl Ewout J. , Muntinghe Friso L. H. , Kroesen Bart-Jan , van der Zwaag Paul A. , van der Meer Peter , Slart Riemer H. J. A. , Hazenberg Bouke P. C. , Nienhuis Hans L. A.
Published: January 2024

(1) Background: Individuals carrying a pathogenic transthyretin gene variant (TTRv) are at high risk for developing hereditary transthyretin (ATTRv) amyloidosis and are routinely screened for the development of cardiomyopathy (ATTRv-CM). This study aims to evaluate whether the cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can be used to rule out ATTRv-CM. (2) Methods: In this retrospective case-control study, data from 46 ATTRv-CM patients and 101 TTRv carriers and ATTRv amyloidosis patients without cardiomyopathy were included. Binary logistic regression models were used to assess the ability of NT-proBNP and hs-cTnT to predict the diagnosis of ATTRv-CM. An optimal cutoff for the relevant biomarker(s) was determined based on a sensitivity of ≥99% and the highest possible percentage of additional tests avoided (%ATA) in the index dataset. (3) Results: Hs-cTnT demonstrated the highest predictive capabilities for ATTRv-CM. The addition of NT-proBNP did not improve the predictive model. A hs-cTnT cutoff of <6 ng/L resulted in a 97% sensitivity and a negative predictive value of 95% with a %ATA of 30% in the validation dataset. (4) Conclusion: In conclusion, hs-cTnT is a useful biomarker for excluding cardiac involvement in TTRv carriers and ATTRv amyloidosis patients and it has the potential to prevent unnecessary diagnostic procedures.
Point Projection Mapping System for Tracking, Registering, Labeling, and Validating Optical Tissue Measurements
Authors: Feenstra Lianne , van der Stel Stefan D. , Da Silva Guimaraes Marcos , Dashtbozorg Behdad , Ruers Theo J. M.
Published: January 2024

The validation of newly developed optical tissue-sensing techniques for tumor detection during cancer surgery requires an accurate correlation with the histological results. Additionally, such an accurate correlation facilitates precise data labeling for developing high-performance machine learning tissue-classification models. In this paper, a newly developed Point Projection Mapping system will be introduced, which allows non-destructive tracking of the measurement locations on tissue specimens. Additionally, a framework for accurate registration, validation, and labeling with the histopathology results is proposed and validated on a case study. The proposed framework provides a more-robust and accurate method for the tracking and validation of optical tissue-sensing techniques, which saves time and resources compared to the available conventional techniques.
Predicting Stick-Slips in Sheared Granular Fault Using Machine Learning Optimized Dense Fault Dynamics Data
Authors: Huang Weihan , Gao Ke , Feng Yu
Published: January 2024

Predicting earthquakes through reasonable methods can significantly reduce the damage caused by secondary disasters such as tsunamis. Recently, machine learning (ML) approaches have been employed to predict laboratory earthquakes using stick-slip dynamics data obtained from sheared granular fault experiments. Here, we adopt the combined finite-discrete element method (FDEM) to simulate a two-dimensional sheared granular fault system, from which abundant fault dynamics data (i.e., displacement and velocity) during stick-slip cycles are collected at 2203 “sensor” points densely placed along and inside the gouge. We use the simulated data to train LightGBM (Light Gradient Boosting Machine) models and predict the gouge-plate friction coefficient (an indicator of stick-slips and the friction state of the fault). To optimize the data, we build the importance ranking of input features and select those with top feature importance for prediction. We then use the optimized data and their statistics for training and finally reach a LightGBM model with an acceptable prediction accuracy (R2 = 0.94). The SHAP (SHapley Additive exPlanations) values of input features are also calculated to quantify their contributions to the prediction. We show that when sufficient fault dynamics data are available, LightGBM, together with the SHAP value approach, is capable of accurately predicting the friction state of laboratory faults and can also help pinpoint the most critical input features for laboratory earthquake prediction. This work may shed light on natural earthquake prediction and open new possibilities to explore useful earthquake precursors using artificial intelligence.
Gamma-ray Spectroscopy in Low-Power Nuclear Research Reactors
Authors: Pakari Oskari V. , Lucas Andrew , Darby Flynn B. , Lamirand Vincent P. , Maurer Tessa , Bisbee Matthew G. , Cao Lei R. , Pautz Andreas , Pozzi Sara A.
Published: January 2024

Gamma-ray spectroscopy is an effective technique for radioactive material characterization, routine inventory verification, nuclear safeguards, health physics, and source search scenarios. Gamma-ray spectrometers typically cannot be operated in the immediate vicinity of nuclear reactors due to their high flux fields and their resulting inability to resolve individual pulses. Low-power reactor facilities offer the possibility to study reactor gamma-ray fields, a domain of experiments hitherto poorly explored. In this work, we present gamma-ray spectroscopy experiments performed with various detectors in two reactors: The EPFL zero-power research reactor CROCUS, and the neutron beam facility at the Ohio State University Research Reactor (OSURR). We employed inorganic scintillators (CeBr3), organic scintillators (trans-stilbene and organic glass), and high-purity germanium semiconductors (HPGe) to cover a range of typical—and new—instruments used in gamma-ray spectroscopy. The aim of this study is to provide a guideline for reactor users regarding detector performance, observed responses, and therefore available information in the reactor photon fields up to 2 MeV. The results indicate several future prospects, such as the online (at criticality) monitoring of fission products (like Xe, I, and La), dual-particle sensitive experiments, and code validation opportunities.
Burnup-Dependent Neutron Spectrum Behaviour of a Pressurised Water Reactor Fuel Assembly
Authors: Mweetwa Bright Madinka , Margulis Marat
Published: January 2024

Understanding the behaviour of a neutron spectrum with burnup is important for describing various phenomena associated with reactor operation. The quest to understand the neutron spectrum comes with a lot of questions. One question that is usually asked by students is: Does the neutron spectrum harden or soften with burnup? Most textbooks used by students do not provide a definite answer to this question. This paper seeks to answer this question using a 3D model of a standard 17 × 17 pressurised water reactor fuel assembly. Two cases were studied using the Serpent Monte Carlo code: the first considered the fuel assembly with constant boron concentration (traditionally found in many published papers), and the second considered boron iteration (where the boron concentration was reduced with burnup). Neutron spectra for the two cases at beginning of life and end of life were compared for spectral shifts. In addition, thermal spectral indices were used to assess spectrum hardening or softening with burnup. Spectral shifts to lower energies were observed in the thermal region of the neutron spectrum, whereas the fast region experienced no spectral shift. There was an increase in thermal spectral indices indicating that the spectrum became soft with burnup.
Fungal Endophytes as Mitigators against Biotic and Abiotic Stresses in Crop Plants
Authors: Gowtham H. G. , Hema P. , Murali Mahadevamurthy , Shilpa N. , Nataraj K. , Basavaraj G. L. , Singh Sudarshana Brijesh , Aiyaz Mohammed , Udayashankar A. C. , Amruthesh Kestur Nagaraj
Published: January 2024

The escalating global food demand driven by a gradually expanding human population necessitates strategies to improve agricultural productivity favorably and mitigate crop yield loss caused by various stressors (biotic and abiotic). Biotic stresses are caused by phytopathogens, pests, and nematodes, along with abiotic stresses like salt, heat, drought, and heavy metals, which pose serious risks to food security and agricultural productivity. Presently, the traditional methods relying on synthetic chemicals have led to ecological damage through unintended impacts on non-target organisms and the emergence of microbes that are resistant to them. Therefore, addressing these challenges is essential for economic, environmental, and public health concerns. The present review supports sustainable alternatives, emphasizing the possible application of fungal endophytes as innovative and eco-friendly tools in plant stress management. Fungal endophytes demonstrate capabilities for managing plants against biotic and abiotic stresses via the direct or indirect enhancement of plants’ innate immunity. Moreover, they contribute to elevated photosynthesis rates, stimulate plant growth, facilitate nutrient mineralization, and produce bioactive compounds, hormones, and enzymes, ultimately improving overall productivity and plant stress resistance. In conclusion, harnessing the potentiality of fungal endophytes represents a promising approach toward the sustainability of agricultural practices, offering effective alternative solutions to reduce reliance on chemical treatments and address the challenges posed by biotic and abiotic stresses. This approach ensures long-term food security and promotes environmental health and economic viability in agriculture.
Prognostic Value of Lymph Node Ratio in Patients with Uterine Carcinosarcoma
Authors: Bharathan Rasiah , Polterauer Stephan , Lopez-Sanclemente Martha C. , Trukhan Hanna , Pletnev Andrei , Heredia Angel G. , Gil Maria M. , Bakinovskaya Irina , Dalamanava Alena , Romeo Margarita , Rovski Dzmitry , Baquedano Laura , Chiva Luis , Schwameis Richard , Zapardiel Ignacio ,   on behalf of SARCUT Study Group
Published: January 2024

Uterine carcinosarcoma is a rare high-grade endometrial cancer. Controversy has surrounded a number of aspects in the diagnosis and management of this unique clinicopathological entity, including the efficacy of adjuvant therapy, which has been questioned. An unusual surgico-pathological parameter with prognostic significance in a number of tumour sites is the lymph node ratio (LNR). The availability of data in this respect has been scarce in the literature. The primary aim of this collaborative study was to evaluate the prognostic value of LNR in patients with uterine carcinosarcoma. LNR is a recognized lymph node metric used to stratify prognosis in a variety of malignancies. In this European multinational retrospective study, 93 women with uterine carcinosarcoma were included in the final analysis. We used t-tests and ANOVA for comparison between quantitative variables between the groups, and chi-square tests for qualitative variables. A multivariate analysis using Cox regression analysis was performed to determine potential prognostic factors, including the LNR. Patients were grouped with respect to LNR in terms of 0%, 20% > 0% and >20%. The analysis revealed LNR to be a significant predictor of progression-free survival (HR 1.69, CI (1.12–2.55), p = 0.012) and overall survival (HR 1.71, CI (1.07–2.7), p = 0.024). However, LNR did not remain a significant prognostic factor on multivariate analysis. Due to limitations of the retrospective study, a prospective large multinational study, which takes into effect the most recent changes to clinical practice, is warranted to elucidate the value of the pathophysiological metrics of the lymphatic system associated with prognosis.
Accuracy Comparison between Five Machine Learning Algorithms for Financial Risk Evaluation
Authors: Dong Haokun , Liu Rui , Tham Allan W.
Published: January 2024

An accurate prediction of loan default is crucial in credit risk evaluation. A slight deviation from true accuracy can often cause financial losses to lending institutes. This study describes the non-parametric approach that compares five different machine learning classifiers combined with a focus on sufficiently large datasets. It presents the findings on various standard performance measures such as accuracy, precision, recall and F1 scores in addition to Receiver Operating Curve-Area Under Curve (ROC-AUC). In this study, various data pre-processing techniques including normalization and standardization, imputation of missing values and the handling of imbalanced data using SMOTE will be discussed and implemented. Also, the study examines the use of hyper-parameters in various classifiers. During the model construction phase, various pipelines feed data to the five machine learning classifiers, and the performance results obtained from the five machine learning classifiers are based on sampling with SMOTE or hyper-parameters versus without SMOTE and hyper-parameters. Each classifier is compared to another in terms of accuracy during training and prediction phase based on out-of-sample data. The 2 data sets used for this experiment contain 1000 and 30,000 observations, respectively, of which the training/testing ratio is 80:20. The comparative results show that random forest outperforms the other four classifiers both in training and actual prediction.
Land Management Drifted: Land Use Scenario Modeling of Trancura River Basin, Araucanía, Chile
Authors: Díaz-Jara Alejandro , Manuschevich Daniela , Grau Aarón , Zambrano-Bigiarini Mauricio
Published: January 2024

Modeling land use scenarios is critical to understand the socio-environmental impacts of current decisions and to explore future configurations for management. The management of regulations and permits by central and local governments plays an important role in shaping land use, with different complexities arising from site-specific socioeconomic dynamics. In Chile, the complexity is even more evident due to insufficient binding land regulations, fragmented government procedures, and the primacy of cities over rural areas. Yet land use must be managed to support sustainable development. This research integrates several state management dynamics into scenario modeling to support decision making at the basin scale through 2050. We employed a mixed qualitative-quantitative approach using interviews with state officials and local stakeholders as the basis for the Conversion of Land Use and its Effects (CLUE) model, which resulted in three scenarios with spatially explicit maps. Key findings indicate that opportunities for developing normative planning tools are limited, leaving state management without clear direction. However, current management practices can address problematic activities such as second-home projects and industrial monocultures while promoting small-scale agriculture. Scenario modeling is useful for understanding how the specifics that arise from the scalar dynamics of state management affect land use change and how existing management resources can be leveraged to achieve positive outcomes for both the ecosystem and society.
Assessing Trends in Tree Cover, Wildfire and Population Growth in Zimbabwe since 2000
Authors: Underwood Emma C. , Hollander Allan D. , Hahn Beth A.
Published: January 2024

Zimbabwe’s woodland and forests have experienced substantial change over the last two decades. In this study, our objective was to assess national-scale spatio-temporal changes in tree loss, wildfire, and population growth since 2000 using global data. Our results showed rates of tree loss were highest in the urbanized Harare and Bulawayo provinces between 2000–2004, followed by Masvingo and Manicaland provinces. We found agricultural versus non-agricultural land type classes had higher tree loss, with the highest rates in small resettlement farms (‘A1’ farms, averaging 5 ha in size) between 2000–2008. The findings from our analysis of wildfire showed burning peaked in 2010, impacting 12% of the country. In the peak fire years of 2008–2012, 30% of A2 self-contained resettlement farms (‘A2’ farms, averaging 318 ha in size) burned, along with 19% of A1 resettlement farms. Analysis of global population data showed increases across all provinces, particularly in large-scale commercial farming areas, with gradual increases seen in A1 and A2 farms. Understanding the trends over two decades and the patterns in three key pressures—tree loss, population change, and fire—provides an important contribution to help guide regional assistance efforts in Zimbabwe.
Mitochondria in Alzheimer’s Disease Pathogenesis
Authors: Reiss Allison B. , Gulkarov Shelly , Jacob Benna , Srivastava Ankita , Pinkhasov Aaron , Gomolin Irving H. , Stecker Mark M. , Wisniewski Thomas , De Leon Joshua
Published: January 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment.
Use of Ultrasound to Verify the Impact of Telemedicine Myofunctional Therapy on Sleep Apnea Syndrome: Study Protocol Proposal
Authors: Rodriguez Alcala Cristina , Rodriguez Alcala Laura , Ignacio Garcia Jose Maria , Plaza Guillermo , Baptista Peter , Lujan Guillermina , Mazzei Paula , Ibañez-Rodriguez Juan Antonio , O’Connor-Reina Carlos
Published: January 2024

The anatomy of the upper airways influences the risk of obstructive sleep apnea (OSA). The size of soft tissue structures, such as the tongue, soft palate, and lateral walls of the pharynx, contributes to the pathogenesis of OSA. New lines of treatment for sleep apnea, such as myofunctional therapy (MT), aim to strengthen the oropharyngeal musculature to improve the defining parameters of apnea. The present protocol uses ultrasound imaging to measure the size of the lingual musculature non-invasively and cost-effectively and evaluates the changes in its morphology. Eligible patients include those with OSA who have undergone submental cervical ultrasound and drug-induced sleep endoscopy before starting MT with the AirwayGym app. Follow-up evaluations are conducted at 3 months after beginning treatment. Patients diagnosed with OSA via questionnaires and polysomnography or respiratory polygraphy are evaluated anatomically and functionally using the Iowa Oral Performance Instrument, a tongue digital spoon, somnoscopy, and submental cervical ultrasound to assess their responses to the AirwayGym app. The lingual thickness (mm) and volume (cm3) and the distance between both lingual arteries (mm) are measured. The AirwayGym app helps users and therapists monitor the patient performance of MT. Incorporating submental ultrasound can be a useful non-invasive tool to evaluate OSA and MT.
Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis
Authors: Prikhodko Veronika A. , Matuzok Tatyana M. , Karev Vadim E. , Karavaeva Anna V. , Spasenkova Olga M. , Kirillova Nadezhda V. , Ivkin Dmitry Yu. , Okovityi Sergey V.
Published: January 2024

Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.
Local (Co)homology and Čech (Co)complexes with Respect to a Pair of Ideals
Authors: Zhang Pinger
Published: January 2024

Let I and J be two ideals of a commutative ring R. We introduce the concepts of the Cˇech complex and Cˇech cocomplex with respect to (I,J) and investigate their homological properties. In addition, we show that local cohomology and local homology with respect to (I,J) are expressed by the above complexes. Moreover, we provide a proof for the Matlis–Greenless–May equivalence with respect to (I,J), which is an equivalence between the category of derived (I,J)-torsion complexes and the category of derived (I,J)-completion complexes. As an application, we use local cohomology and the Cˇech complex with respect to (I,J) to prove Grothendieck’s local duality theorem for unbounded complexes.
Decoding of Z2S Linear Generalized Kerdock Codes
Authors: Minja Aleksandar , Šenk Vojin
Published: January 2024

Many families of binary nonlinear codes (e.g., Kerdock, Goethals, Delsarte–Goethals, Preparata) can be very simply constructed from linear codes over the Z4 ring (ring of integers modulo 4), by applying the Gray map to the quaternary symbols. Generalized Kerdock codes represent an extension of classical Kerdock codes to the Z2S ring. In this paper, we develop two novel soft-input decoders, designed to exploit the unique structure of these codes. We introduce a novel soft-input ML decoding algorithm and a soft-input soft-output MAP decoding algorithm of generalized Kerdock codes, with a complexity of O(NSlog2N), where N is the length of the Z2S code, that is, the number of Z2S symbols in a codeword. Simulations show that our novel decoders outperform the classical lifting decoder in terms of error rate by some 5 dB.
Cooling Efficiency of Sleeveless 3D-Printed Surgical Guides with Different Cylinder Designs
Authors: Ali Aisha , Brintouch Ido , Romanos Georgios , Delgado-Ruiz Rafael
Published: January 2024

Background and Objectives: Surgical guides might impede the flow of coolant to the implant drills during the preparation of the implant bed, potentially contributing to increased temperatures during bone drilling. The objective of this experimental study was to assess the cooling efficiency of various guiding cylinder designs for sleeveless surgical guides used in guided surgery. Materials and Methods: In this experimental study, surgical guides with three different guiding cylinder designs were printed. One group had solid cylinders (control) and two test groups (cylinders with pores and cylinders with windows). Forty customized polyurethane blocks with type III bone characteristics were fitted into the guide and fixed in a vise, and implant bed preparations were completed using a simplified drilling protocol with and without irrigation. An infrared thermographic camera was used to record the temperature changes during drilling at the coronal, middle, and apical areas. ANOVA test and Games-Howell post hoc test were used to determine significant thermal differences among groups. Results: A significant thermal increase was observed at the coronal area in the group without irrigation (39.69 ± 8.82) (p < 0.05). The lowest thermal increase was recorded at the surgical guides with windows (21.451 ± 0.703 °C) compared to solid (25.005 ± 0.586 °C) and porous surgical guides (25.630 ± 1.004) (p < 0.05). In the middle and apical areas, there were no differences between solid and porous cylinders (p > 0.05). Conclusions: 3D-printed sleeveless surgical guides with window openings at the guiding cylinders reduce the temperature elevation at the cortical bone in guided implant surgery.
The Arthroscopic Biceps Rerouting Technique Shows Better Early Clinical Outcomes within 1 Year Than Partial Repair in Large to Massive Rotator Cuff Tears
Authors: Park Hyung-Seok , Ham Kwon-Hyoung , Kim Yang-Soo
Published: January 2024

Background and Objectives: The arthroscopic biceps rerouting (BR) technique was introduced as a novel technique for large-to-massive rotator cuff tears (LMRCTs). This method can restore shoulder stability, and its biomechanical effect was verified in a cadaver experiment. Recent reports have shown favorable clinical outcomes. This study aimed to compare the clinical outcomes of partial repair with those of the BR technique in LMRCTs. Materials and Methods: We included 72 patients who had undergone LMRCTs. Arthroscopic partial repair was performed in 31 patients (group I), while repair with the BR technique was performed in 41 patients (group II). Functional and imaging outcomes were evaluated and compared using a visual analog scale for pain, range of motion (ROM), American Shoulder and Elbow Surgeons (ASES) score, Constant score, and Korean Shoulder Score (KSS) before the surgery and at 3, 6, and 12 months after the surgery and at the last follow-up. Tendon integrity was investigated using magnetic resonance in all the patients at 12 months postoperative. Results: The mean follow-up period was 22.11 ± 10.47 months (range, 12–53 months). Forward flexion (p = 0.02) and external rotation at the side (p = 0.04) were significantly higher in group II than in group I on postoperative day (POD) 12 months. For internal rotation, group II showed significant improvement compared to group I on POD 3 months (p = 0.002) and at 6 months postoperative (p = 0.01). On POD 12 months, the ASES (p = 0.047) and KSS (p = 0.048) were better in group II. Significant improvements in pain and clinical scores were observed in both groups at the last follow-up. However, the two groups had no significant differences in pain, clinical scores, or ROM at the last follow-up. Retear of the repaired tendon was observed in nine patients in group I (29.03%) and eight in group II (19.51%, p = 0.35). Conclusions: Partial repair and repair using the BR technique effectively improved clinical and radiologic outcomes. The BR technique revealed early recovery of ROM and better clinical results than partial repair at one year postoperative. This could be a useful method in treating LMRCTs.
Cytomegalovirus Pneumonia in a Patient with Down Syndrome
Authors: Perrotta Francesco , Piscopiello Donato , Rizzo Daniela , Iosa Gaetano , Garzya Giorgio , Calò Piero , Gemma Daniele
Published: January 2024

Down syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and they represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, when causing interstitial pneumonia, associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient with DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation, and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.
The Current State of Extracellular Matrix Therapy for Ischemic Heart Disease
Authors: Hamsho Khaled , Broadwin Mark , Stone Christopher R. , Sellke Frank W. , Abid M. Ruhul
Published: January 2024

The extracellular matrix (ECM) is a three-dimensional, acellular network of diverse structural and nonstructural proteins embedded within a gel-like ground substance composed of glycosaminoglycans and proteoglycans. The ECM serves numerous roles that vary according to the tissue in which it is situated. In the myocardium, the ECM acts as a collagen-based scaffold that mediates the transmission of contractile signals, provides means for paracrine signaling, and maintains nutritional and immunologic homeostasis. Given this spectrum, it is unsurprising that both the composition and role of the ECM has been found to be modulated in the context of cardiac pathology. Myocardial infarction (MI) provides a familiar example of this; the ECM changes in a way that is characteristic of the progressive phases of post-infarction healing. In recent years, this involvement in infarct pathophysiology has prompted a search for therapeutic targets: if ECM components facilitate healing, then their manipulation may accelerate recovery, or even reverse pre-existing damage. This possibility has been the subject of numerous efforts involving the integration of ECM-based therapies, either derived directly from biologic sources or bioengineered sources, into models of myocardial disease. In this paper, we provide a thorough review of the published literature on the use of the ECM as a novel therapy for ischemic heart disease, with a focus on biologically derived models, of both the whole ECM and the components thereof.
Effect of Interface Wettability on Additively Manufactured Metal Matrix Composites: A Case Study of 316L-Y2O3 Oxide Dispersion-Strengthened Steel
Authors: Zhai Wengang , Zhou Wei , Nai Sharon Mui Ling
Published: January 2024

Laser powder bed fusion (LPBF) is a fusion-based additive manufacturing process. It has the advantage of allowing the manufacturing of metal matrix composites. This advantage arises from its small melting zone and rapid cooling rate, which minimize the risk of reinforcement segregation. In this work, 0.3 wt% and 1.0 wt% Y2O3 nanoparticles were added to 316L to fabricate oxide dispersion-strengthened (ODS) steels using the LPBF process. Notably, Y2O3 agglomerates were identified in the LPBF-fabricated 316L ODS steels, without inducing grain refinement, while the impact on tensile strength of Y2O3 addition proved negligible. Tensile elongation was decreased due to the poor bonding of the Y2O3 agglomerations to the matrix. The crucial role of the wettability of the reinforcement and the matrix in facilitating grain refinement and strength enhancement is discussed. The poor wettability of the Y2O3 particles and 316L emerged as the primary cause for Y2O3 agglomeration. This finding highlights the importance of addressing wettability issues to optimize the manufacturing process and enhance the overall performance of LPBF-fabricated metal matrix composites.
A Comprehensive Comparison between Primary Liver Cancer and Liver Metastases through scRNA-Seq Data Analysis
Authors: Hao Shuang , Chen Liqun , Du Wenhui , Sun Huiyan
Published: January 2024

Metastasis is one of the leading causes of cancer-related deaths. A comprehensive comparison of the differences between primary and metastatic cancers within the same organ can aid in understanding the growth mechanisms of cancer cells at metastatic sites, thereby helping to develop more effective targeted treatment strategies. Primary liver cancer is one of the most common types of cancer, and the liver is also one of the main metastatic sites. In this paper, we utilize single-cell RNA-Seq data to compare primary liver cancer and colorectal liver metastases from multiple perspectives, including cell types and proportions, activity of various cell types, cell–cell communication, mRNA expression differences within the same types of cells, key factors associated with cell proliferation, etc. Our analysis results show the following: (i) Compared to primary tissue, metastatic tissue contains more cytotoxic T cells and exhausted T cells, and it retains some specific characteristics of the primary site. (ii) Cells of the same type exhibit functional differences between primary and metastatic cancers, with metastatic cancer cells showing lower metabolism levels and immune cells exhibiting stronger immune activity. (iii) Interactions between monocytes and hepato-associated cells are strong in primary cancer, while depleted T cells frequently communicate with hepatocytes in metastatic cancer. (iv) Proliferation-related genes in primary and metastatic cancers are mainly involved in cell energy supply and basic metabolism activity, respectively.
Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity
Authors: Cao Zhi , Chen Hongyu , Zhou Chenli , Gong Ming , Li Yan , Shao Youran , Wu Yingying , Bao Dapeng
Published: January 2024

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.
Advancing Glucose Conjugated Gibberellins Discovery: A Structure–Oriented Screening and Identification Method for Unraveling Gibberellin Metabolites in Plants
Authors: Zeng Chen , Cai Wen-Jing , Jiang Liu-Cheng , Ye Tiantian , Feng Yu-Qi
Published: January 2024

Gibberellins (GAs) play a pivotal role in modulating plant growth and development. Glucose–conjugated gibberellins (Glc–GAs), a prevalent conjugated form of GAs, regulate intracellular GA levels by the coupling and decoupling of glucose groups. However, the diversity of Glc–GAs identified within individual species remains limited, hinting at a multitude of yet undiscovered gibberellin metabolites. This lacuna poses considerable impediments to research efforts dedicated to comprehensively delineating the GA metabolic pathway. In this study, we developed a structure–oriented screening and identification method for Glc–GAs in plant species by employing LC–MS/MS coupled with chemical derivatization. Through the application of chemical derivatization technique, carboxyl groups on Glc–GAs were labeled which effectively enhanced the sensitivity and selectivity of mass spectrometry detection for these compounds. Concurrently, the integration of mass spectrometry fragmentation and chromatographic retention behavior facilitated the efficient screening and identification of potential Glc–GAs. With this strategy, we screened and identified 12 potential Glc–GAs from six plant species. These findings expand the Glc–GA diversity in plants and contribute to understanding GA metabolic pathways.
Endothelial Mechanistic Target of Rapamycin Activation with Different Strains of R. rickettsii: Possible Role in Rickettsial Pathogenesis
Authors: Sahni Abha , Alsing Jessica , Narra Hema P. , Montini Michelle , Zafar Yasim , Sahni Sanjeev K.
Published: January 2024

Rickettsia rickettsii is an obligate intracellular pathogen that primarily targets endothelial cells (ECs), leading to vascular inflammation and dysfunction. Mechanistic target of rapamycin (mTOR) regulates several cellular processes that directly affect host immune responses to bacterial pathogens. Here, we infected ECs with two R. rickettsii strains, avirulent (Iowa) and highly virulent Sheila Smith (SS) to identify differences in the kinetics and/or intensity of mTOR activation to establish a correlation between mTOR response and bacterial virulence. Endothelial mTOR activation with the highly virulent SS strain was significantly higher than with the avirulent Iowa strain. Similarly, there was increased LC3-II lipidation with the virulent SS strain compared with the avirulent Iowa strain of R. rickettsii. mTOR inhibitors rapamycin and Torin2 significantly increased bacterial growth and replication in the ECs, as evidenced by a more than six-fold increase in rickettsia copy numbers at 48 h post-infection. Further, the knockdown of mTOR with Raptor and Rictor siRNA resulted in a higher rickettsial copy number and the altered expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6, and IL-8. These results are the first to reveal that endothelial mTOR activation and the early induction of autophagy might be governed by bacterial virulence and have established the mTOR pathway as an important regulator of endothelial inflammation, host immunity, and microbial replication.
Cu and Au Mineralization of the Tolparovo Ore Occurrence: Evidence for the Formation of Redbed Copper Occurrences in Neoproterozoic Deposits of the Southern Urals
Authors: Michurin Sergey Vasilievich , Kazbulatova Gulfiya Mavletovna
Published: January 2024

The mineralization and geochemical features of the Tolparovo ore occurrence are studied to reveal the contribution of diagenetic and epigenetic processes in the formation of copper mineralization in redbed deposits. The methods of electron microscopy, ICP MS, X-ray fluorescence, X-ray phase, atomic absorption, thermogravimetric analyses, and C and O isotopic composition were used. The ore is confined to the fault zone and feathering dolomite–calcite veins, having formed at temperatures of ~330–200 °C and pressures of 0.8–0.2 kbar. Similar to other copper redbed occurrences of the Bashkirian uplift, the Tolparovo copper ore occurrence is confined to basal Neoproterozoic deposits. Siliciclastic and carbonate deposits of this level were accumulated at low paleoequator latitudes in arid climates of continental and coastal–marine environments close to evaporite ones. Rocks of this stratigraphic interval demonstrate increased background concentrations of copper (~2–5 times exceeding the clark), which explains the stratification of redbed copper ore occurrences, indicating a predominantly sedimentary copper source. However, most of the redbed copper ore occurrences of the Bashkirian uplift are located in tectonic zones and are associated with the dikes of the Inzer gabbrodolerite complex. This connects the generation of ore occurrences with the formation of the Southern Urals Arsha Large Igneous Province (707–732 Ma) and the activity of postmagmatic fluids. Magmatic processes were presumably activated due to the collapse of the Rodinia supercontinent. It is shown that copper mineralization in stratiform deposits may result from a joint manifestation of dia- and epigenesis processes.