bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of switch therapy to tenofovir versus entecavir maintenance on recurrence of hepatocellular carcinoma after surgery (SWITE): study protocol for a randomized controlled trial
Authors: Peng Wei , Yi Mengshi , Qi Xin , Qi Weili , Li Chuan , Wen Tianfu 
Published: December 2023

Abstract
Background
Antiviral therapy has been reported to be associated with lower recurrence rate of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV) infection. While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were both recommended as first-line therapies for HBV patients, recent retrospective studies proposed a lower incidence rate of HCC occurrence or recurrence in those receiving TDF compared ETV. However, the survival benefits of switching to TDF therapy after prolonged ETV treatment before surgery remain uncertain. We delineate the rationale and design of SWITE, a randomized, open-label, phase III trial contrasting TDF switch therapy versus ETV maintenance in HBV-related HCC patients.

Methods and analysis
This is a prospective, randomized, controlled, single-center study with two parallel groups of patients with HBV-related HCC who have received long-term ETV therapy before surgery. West China Hospital will enroll 238 patients, randomized in a 1:1 ratio to TDF switch therapy or ETV maintenance after surgery. The primary endpoint of this study is 3-year recurrence free survival (RFS), with the secondary endpoint being 3-year overall survival (OS) after curative surgery of HCC. Safety events will be diligently recorded.

Ethics and dissemination
The study protocol aligns with the ethical guidelines of the 1975 Declaration of Helsinki. It was approved by ethics committee of West China Hospital (approval number: 2022-074) and was registered with chictr.org.cn (chiCTR2200057867). Informed consent will be obtained from all participants. The results of this trial will be published in peer-reviewed journals and presentations at national and international conferences relevant to this topic.

Trial registration
chiCTR2200057867. Date of registration is March 20 2022.
Efficacy of an oral formulation of afoxolaner and milbemycin oxime against Tunga penetrans in naturally infected dogs
Authors: dos Santos Katharine Costa , Tielemans Eric , Cutolo Andre Antonio , Guedes Paula Elisa Brandão , Harvey Tatiani Vitor , de Carvalho Teixeira Jamille Bispo , Vitor Rebeca Costa , da Paixão Sevá Anaiá , de Melo Navarro Adan William , Lima Ana Carolina Ribeiro , Botteon Karin Denise , Bittar Thammy Vieira , Albuquerque George Rêgo , de Almeida Borges Fernando , Beugnet Frederic , Carlos Renata Santiago Alberto 
Published: December 2023

Abstract
Background
The sand flea Tunga penetrans is one of the agents of tungiasis, an important parasitic skin disease affecting humans and several mammalian species. Tungiasis is mainly observed in disadvantaged rural and peripheral urban communities in Latin America and sub-Saharan Africa. The dog is a major reservoir of Tunga fleas. Hematophagous adult female Tunga spp. embed and grow in their host’s epidermis and cause cutaneous inflammatory disorders. NexGard Spectra® is an orally administered endectocide for dogs, a co-formulation of the isoxazoline afoxolaner and the macrocyclic lactone milbemycin oxime. The objective of this study was to assess the efficacy of this product against canine tungiasis.

Methods
A blinded, negative-controlled field trial was conducted in a Brazilian community known to be highly endemic for tungiasis. Sixty-six dogs naturally infected with live T. penetrans were randomly allocated to a treated group (44 dogs) and an untreated control group (22 dogs). In a first phase, dogs from the treated group were treated on days 0, 30, and 60. Efficacy was evaluated on the basis of the macroscopic parasitic skin lesions (Fortaleza classification) on days 7, 14, 21, 30, 45, 60, 75, and 90. In a second phase, to evaluate natural reinfections, all dogs were treated on day 90 and evaluated every 2 weeks thereafter until at least 30% of dogs were infected with live sand fleas.

Results
During the first phase, efficacy (reduction in live sand fleas) of 92.4% was demonstrated on day 7. From day 14 until day 90, the efficacy of NexGard Spectra® was 100%. In the second phase, all dogs were free of live T. penetrans from 15 until 45 days after the day 90 treatment; 60 days post-treatment, 11% of dogs were reinfected, and 75 days post-treatment, 40% of dogs were reinfected.

Conclusions
NexGard Spectra® was demonstrated to be highly effective against canine tungiasis. In addition to an obvious beneficial effect on the health and welfare of the treated dog, the use of this product may have a one-health benefit on human cases by controlling the main reservoir of sand fleas.

Graphical Abstract
Predictors for CD4 cell count and hemoglobin level with survival time to default for HIV positive adults under ART treatment at University of Gondar Comprehensive and Specialized Hospital, Ethiopia
Authors: Muhie Nurye Seid , Tegegne Awoke Seyoum 
Published: December 2023

Abstract
Background
HIV/AIDS is the most known powerful risk factor for morbidity and mortality in the world. The greatest biological markers in HIV patients are CD4 cell count and hemoglobin level, as they are independent predictors of survival of HIV patients. The objective of this study was to investigate the common socio-demographic, clinical, and behavioral Predictor’s affecting the CD4 cell count, and hemoglobin level with survival time to default from ART treatment among HIV positive adults under ART treatment at university of Gondar comprehensive and specialized hospital, North-west Ethiopia.

Method
This study was conducted at University of Gondar comprehensive specialized hospital by using a retrospective cohort follow up study design. The source of data in this study was secondary data obtained from patients chart. Bayesian joint models were employed to get wide-ranging information about HIV/AIDS progression.

Result
From a total of 403 HIV positive adults, about 44.2% were defaulted from therapy and the rest were actively followed ART treatment. The estimate of the association parameter for the current true value of CD4 cell count ($${\alpha }_{1}$$

α
1

), and hemoglobin level ($${\alpha }_{2}$$

α
2

), trend of CD4 cell count ($${\alpha }_{2}$$

α
2

) and hemoglobin level ($${b}_{2}$$

b
2

) is positive. Positive values indicating that the higher CD4 cell count and hemoglobin level is related with the higher time of defaulting from ART. Predictor’s hematocrit, weight, platelet cell count, lymphocyte count, sex, adherence, and WHO clinical stage were joint determinate risk factors affecting CD4 cell count, hemoglobin level and time to default at 5% level of significance.

Conclusion
Current study results revealed that hematocrit, weight, BMI, platelet cell count, lymphocyte count, sex (female), and good treatment adherence were significantly associated with higher CD4 cell count, hemoglobin level and time to default while having advanced WHO clinical stage-IV had significantly decreased CD4 cell, hemoglobin level, and time to default from treatment. Patients with HIV should be given special attention based on these important factors to improve their health and prolong their lives.
Clinico-biological-radiomics (CBR) based machine learning for improving the diagnostic accuracy of FDG-PET false-positive lymph nodes in lung cancer
Authors: Ren Caiyue , Zhang Fuquan , Zhang Jiangang , Song Shaoli , Sun Yun , Cheng Jingyi 
Published: December 2023

Abstract
Background
The main problem of positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging is the high false positive rate (FPR). Thus, we aimed to explore a clinico-biological-radiomics (CBR) model via machine learning (ML) to reduce FPR and improve the accuracy for predicting the hypermetabolic mediastinal–hilar LNs status in lung cancer than conventional PET/CT.

Methods
A total of 260 lung cancer patients with hypermetabolic mediastinal–hilar LNs (SUVmax ≥ 2.5) were retrospectively reviewed. Patients were treated with surgery with systematic LN resection and pathologically divided into the LN negative (LN-) and positive (LN +) groups, and randomly assigned into the training (n = 182) and test (n = 78) sets. Preoperative CBR dataset containing 1738 multi-scale features was constructed for all patients. Prediction models for hypermetabolic LNs status were developed using the features selected by the supervised ML algorithms, and evaluated using the classical diagnostic indicators. Then, a nomogram was developed based on the model with the highest area under the curve (AUC) and the lowest FPR, and validated by the calibration plots.

Results
In total, 109 LN− and 151 LN + patients were enrolled in this study. 6 independent prediction models were developed to differentiate LN− from LN + patients using the selected features from clinico-biological-image dataset, radiomics dataset, and their combined CBR dataset, respectively. The DeLong test showed that the CBR Model containing all-scale features held the highest predictive efficiency and the lowest FPR among all of established models (p < 0.05) in both the training and test sets (AUCs of 0.90 and 0.89, FPRs of 12.82% and 6.45%, respectively) (p < 0.05). The quantitative nomogram based on CBR Model was validated to have a good consistency with actual observations.

Conclusion
This study presents an integrated CBR nomogram that can further reduce the FPR and improve the accuracy of hypermetabolic mediastinal–hilar LNs evaluation than conventional PET/CT in lung cancer, thereby greatly reducing the risk of overestimation and assisting for precision treatment.
Efficacy of pharmacotherapies for bulimia nervosa: a systematic review and meta-analysis
Authors: Yu Sijie , Zhang Yuhan , Shen Chongkai , Shao Fei 
Published: December 2023

Abstract
Objective
The main purpose was to evaluate the efficacy and tolerability of different medications used to treat bulimia nervosa (BN).

Methods
Randomized controlled trials (RCTs) were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2022. Primary outcomes were changes in the frequency of binge eating episodes and vomiting episodes from baseline to endpoint. Secondary outcomes were differences in the improvement of scores in depressive symptoms, tolerability (dropout due to adverse events) and weight change.

Results
The literature search ultimately included 11 drugs, 33 studies and 6 types of drugs, 8 trials with TCAs (imipramine, desipramine), 14 with SSRIs (fluoxetine, citalopram and fluvoxamine), 6 with MAOIs (phenelzine, moclobemide and brofaromine), 3 with antiepileptic drugs (topiramate), 1 with mood stabilizers (lithium), and 1 with amphetamine-type appetite suppressant (fenfluramine). The reduction in binge eating episodes was more likely due to these drugs than the placebo, and the SMD was -0.4 (95% CI -0.61 ~ -0.19); the changes in the frequency of vomiting episodes (SMD = -0.16, 95% CI -0.3 ~ -0.03); weight (WMD = -3.05, 95% CI -5.97 ~ -0.13); and depressive symptoms (SMD = -0.32, 95% CI -0.51 ~ -0.13). However, no significant difference was found in dropout due to adverse events (RR = 1.66, 95% CI 1.14 ~ 2.41).

Conclusions
This meta-analysis indicates that most pharmacotherapies decreased the frequency of binge-eating and vomiting episodes, body weight, and depressive symptoms in BN patients, but the efficacy was not significant. In each drug the efficacy is different, treating different aspects, different symptoms to improve the clinical performance of bulimia nervosa.
Advances towards the use of gastrointestinal tumor patient-derived organoids as a therapeutic decision-making tool
Authors: Obreque Javiera , Vergara-Gómez Luis , Venegas Nicolás , Weber Helga , Owen Gareth I. , Pérez-Moreno Pablo , Leal Pamela , Roa Juan Carlos , Bizama Carolina 
Published: December 2023

AbstractIn December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.
Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation
Authors: Dai Bing , Liu Si , Shen Wenxin , Chen Li , Zhou Qianlan , Han Lina , Zhang Qinzhen , Shan Lishen 
Published: December 2023

Abstract
Background
Asthma is a heterogenous disease that characterized by airway remodeling. SYVN1 (Synoviolin 1) acts as an E3 ligase to mediate the suppression of endoplasmic reticulum (ER) stress through ubiquitination and degradation. However, the role of SYVN1 in the pathogenesis of asthma is unclear.

Results
In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma. An increase in SYVN1 expression was observed in the lungs of mice after OVA induction. Overexpression of SYVN1 attenuated airway inflammation, goblet cell hyperplasia and collagen deposition induced by OVA. The increased ER stress-related proteins and altered epithelial-mesenchymal transition (EMT) markers were also inhibited by SYVN1 in vivo. Next, TGF-β1-induced bronchial epithelial cells (BEAS-2B) were used to induce EMT process in vitro. Results showed that TGF-β1 stimulation downregulated the expression of SYVN1, and SYVN1 overexpression prevented ER stress response and EMT process in TGF-β1-induced cells. In addition, we identified that SYVN1 bound to SIRT2 and promoted its ubiquitination and degradation. SIRT2 overexpression abrogated the protection of SYVN1 on ER stress and EMT in vitro.

Conclusions
These data suggest that SYVN1 suppresses ER stress through the ubiquitination and degradation of SIRT2 to block EMT process, thereby protecting against airway remodeling in asthma.
Simulation-based development: shaping clinical procedures for extra-uterine life support technology
Authors: van Haren J. S. , van der Hout-van der Jagt M. B. , Meijer N. , Monincx M. , Delbressine F. L. M. , Griffith X. L. G. , Oei S. G. 
Published: December 2023

Abstract
Background
Research into Artificial Placenta and Artificial Womb (APAW) technology for extremely premature infants (born < 28 weeks of gestation) is currently being conducted in animal studies and shows promising results. Because of the unprecedented nature of a potential treatment and the high-risk and low incidence of occurrence, translation to the human condition is a complex task. Consequently, the obstetric procedure, the act of transferring the infant from the pregnant woman to the APAW system, has not yet been established for human patients. The use of simulation-based user-centered development allows for a safe environment in which protocols and devices can be conceptualized and tested. Our aim is to use participatory design principles in a simulation context, to gain and integrate the user perspectives in the early design phase of a protocol for this novel procedure.

Methods
Simulation protocols and prototypes were developed using an iterative participatory design approach; usability testing, including general and task-specific feedback, was obtained from participants with clinical expertise from a range of disciplines. The procedure made use of fetal and maternal manikins and included animations and protocol task cards.

Results
Physical simulation with the active participation of clinicians led to the diffusion of tacit knowledge and an iteratively formed shared understanding of the requirements and values that needed to be implemented in the procedure. At each sequel, participant input was translated into simulation protocols and design adjustments.

Conclusion
This work demonstrates that simulation-based participatory design can aid in shaping the future of clinical procedure and product development and rehearsing future implementation with healthcare professionals.
Market integration and asymmetric price transmission in selected domestic markets for major staple foods in Uganda
Authors: Waiswa Denis , Yavuz Fahri 
Published: December 2023

AbstractIn this study, we examined the price transmission dynamics and market integration among domestic markets for Uganda’s major staple foods (matoke, maize, and beans) utilizing the Granger causality analysis, bounds test, Wald test for long- and short-run asymmetry, and the nonlinear ARDL model. Among the key findings, the causal order between wholesale and retail commodity prices flows unidirectionally forward from the wholesale to the retail level across all markets. Wholesale and retail prices for Uganda’s staple foods are interlinked in all markets, and spatially separated markets are also well integrated. The Wald test revealed asymmetric price transmission (APT) in speed alone for the pairs wholesale and retail prices of matoke in Kampala, and wholesale prices of matoke in Mbarara with Kampala retail prices, both APT in magnitude and APT in speed for the pairs wholesale and retail prices of beans in Kampala, wholesale and retail prices of maize in Masindi, and wholesale prices of beans in Masindi with wholesale and retail prices in Kampala. We also found that in the long run, retail prices respond more strongly to wholesale price increases than decreases, an implication of positive APT in the marketing supply chain of Uganda’s major staples. This may be linked to information asymmetry between traders and consumers, traders’ adjustment costs, production levels, inventory management, and the market power of retailers. We thus concluded that final consumers are more likely to experience an increase rather than a decrease in the prices of staples at the retail level, while retailers are more likely to benefit from price decreases at the wholesale level.
Inorganic Metal Oxides and Multi-Component Nanocomposites Based Photocatalysts for the Superior Degradation of Pollutants from Water
Authors: Kokila Selvasubramanian , Nesaraj Arputharaj Samson 
Published: December 2023

Water is a primary and essential source of every living organism and it is a most precious gift of Mother Nature which helps every living creature to survive. However, this water is highly polluted now-a-days by various unethical activities by human beings. Many industrial units like textile mills, pharmaceutical units, mines, paper mills, dyeing units, sugar industries, leather purifying units, electroplating plants, fine chemical units, oil refineries, etc. produce huge amount waste products in the form of toxic chemicals and pollutants every day and enter the water bodies without proper treatment. Various techniques are available to purify the polluted water by eliminating the toxicity of pollutants; some of them are reverse osmosis, electrode ionization, ion exchange, submicron filtrations, etc. Among all these water treatment procedures, photocatalysis is found to be most versatile, low cost and environmentally benign technique. In this review, a prime focus is given on the performance of different photocatalysts based on ZnO, CuO, NiO, SnO2, MgO, multicomponent metal oxides and composites in degrading and removing unwanted impurities present in polluted water. The importance of using metal oxide based photocatalyts in treating the polluted water is also discussed.
Geometrical Optimization and Natural Bond Orbital Analysis of Relevant Structures in the Diastereoselective Cuprate Conjugate Addition Reaction of α,β-Unsaturated Lactams using Density Functional Theory
Authors: Arisha Anan 
Published: December 2023

In this study, density functional theory calculations at the wB97XD/Def2TZVPP level were performed to analyze the mechanism underlying the cuprate conjugate addition reaction of α,β-unsaturated lactams. The calculation results were well-aligned with those obtained experimentally–the keto-aminal and aldo-aminal, i.e. 2 and 1a, yield the syn- and anti-products, respectively. The diastereoselectivity reversal originates from the small differences in the structure of the reactants. The pyramidalization and C7N3C2 angle between the aminal carbon, nitrogen and carbonyl carbon are large in 2. The dihedral angle of the aminal oxygen, aminal carbon, nitrogen and carbonyl carbon, O8C7N3C2, is closer to 180º in 2 than in 1a. The NBO analysis revealed string interactions between the lone pair of N3 and carbonyl π*(O1–C2) bond. These results validate the assumption—the planarity around nitrogen in molecule 2 increases the nucleophilicity of the carbonyl oxygen, thereby driving the reaction between molecule 2 and trimethylsilyl chloride (TMSCl), which yields a siloxyiminium cation 5b and this 5b propels the syn addition of dimethylcuprate, leading to the formation of complex 7. The π(C5–C6) (HOMO) and π*(C2–N3) (LUMO) interactions in the siloxyiminium cation explain the increased C5–C6 double bond electrophilicity. The aldo-aminal 1a directly reacts with dimethylcuprate under steric control and yields the anti complex 6a, whose π character is stronger than that of the syn complex 7 and this weak π characteristics of 7 increases its stability to compensate for the trimethylsilyl disturbance. The bicyclic α,β-unsaturated lactam 8 does not contain aminal oxygen and thus remains unreactive during the cuprate conjugate addition reaction. Moreover, its pyramidalization is higher than that of the keto-aminal 2 and its dihedral angle of C8C7N3C2 is closer to 180º. Finally, a thermodynamic anti product is obtained, which is more stable than the syn- product because of less torsional strain.
The effect of weathering on drillability of dolomites
Authors: Bilen Candan , Sakız Utku 
Published: December 2023

Abstract
In this study, an aggregate quarry was investigated in order to understand the impact of weathering phenomenon on the drillability of dolomite stones, respectively. Samples were collected from the study area and analyzed in terms of physicomechanical tests (specific gravity, dry unit weight, uniaxial compressive strength, point load index (Is50), and Brazillian tensile strength). The drillability of the rocks was investigated using the drilling rate index method. Based on the analysis results, significant relationships were obtained between physicomechanical properties and drillability of dolomites at different weathering grades. Initial evaluations can be interpreted as an increase in the weathering degree would result in an increase in drillability. This understanding of weathering's impact on drillability is actually the main purpose of this study. This article could be a tool as regards initial evaluations of the drillability of dolomites combined with the weathering mechanism, since successful evaluations and meaningful relations were achieved.