bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow Control Device and Liner Floatation: Key Technology Driver in Extreme Extended Reach Shallow Steam Assisted Gravity Drainage Wells
Authors: Izadi H. , Roostaei M. , Mahmoudi M. , Stevenson J. , Tuttle A. , Bustamante G. , Rhein Sh , Sutton C. , Mirzavand R. , Leung J. V. , Fattahpour V.
Published: November 2023

Pursuing more cost-effective well construction and reduced surface footprint has prompted Western Canadian operators to explore extreme extended reach drilling (ERD) wells. However, this endeavor faces a critical challenge: most heavy oil reserves are relatively shallow, resulting in the unwrapped reach ratio (the total horizontal length when projected on the horizontal plane to true vertical depth (TVD)) of more than seven. Therefore, to drill ERD wells, two crucial technical challenges must be tackled: successful liner installation, and efficient steam distribution along these long laterals to enhance production.

This paper delves into the solutions for these challenges and a case study showcasing the recent drilling of a steam-assisted gravity drainage (SAGD) extreme ERD well. While floating liners are a known method for extending well reach, they are uncommon in SAGD wells. However, some companies have started exploring the use of floating liners in SAGD projects due to their potential to greatly expand lateral well length, reducing footprint and increasing the oil recovery from any one well pair. By floating the liner using plugged flow control devices (FCDs), gentler running procedures can be employed to achieve TD without risking the integrity of the liner. Moreover, utilizing FCDs in floating liners improves steam conformance and oil production while reducing the cumulative steam oil ratio (cSOR) during the production phase.

Modeling results can enhance our capabilities in planning shallower SAGD wells with longer productive sections in the future, with (as described herein) horizontal liner lengths of 1700m and true vertical depths of 240m. The modeling results show that floating liners using plugged FCDs reduce torque by an average of 22% and bottom hole torque by 28%, while also decreasing drag by 16% on average, and bottom hole drag by 17%. These findings indicate that floating liners with plugged FCDs offer a promising solution for SAGD and CSS extreme ERD wells limited by liner installation forces. Furthermore, wells with FCDs in uplifted cases displayed a remarkable upswing of 57%, while concurrently, cSOR demonstrated a noteworthy decrease of 18%. Uplifted cases are identified when wells were completed or retrofitted with FCDs and showed increased oil production compared to neighboring wells.

The successful implementation of floating liners with dissolvable or meltable plugs on FCDs enhances confidence in future SAGD extreme ERD wells. The implementation of FCDs in extreme ERD well designs could contribute to reduced greenhouse gas (GHG) emissions, aligning with efforts to combat climate change and minimize environmental impacts. The study's findings elaborated on driving paradigm shifts in the development of heavy oil resources as technology advances, while considering economic factors.
Exosomal circRNAs derived from cancer cells predict the prognosis of hepatocellular carcinoma after surgery: the development and validation of prognostic and recurrent nomograms
Authors: yin kun-li , Sun Tai-wei , Duan Yu-xin , Ye Wen-Tao , Li Ming , Liao Rui
Published: November 2023

Background
Liquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients.
Method
Plasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence.
Result
Among 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.006, HR = 1.96, 95% CI: 1.21–3.18) and RFS (P = 0.024, HR = 1.54, 95% CI: 1.06–2.23). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI: 1.21–3.18), tumor size (HR = 2.11, 95% CI: 1.33–3.32), clinical staging (HR = 2.31, 95% CI: 1.54–3.48), and tumor thrombus (HR = 1.74, 95% CI: 1.12–2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients
Conclusion
Our study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.
Association of intestinal leakage with frailty in patients with age-related diseases
Authors: Qaisar Rizwan , Karim Asima , Muhammad Tahir , Iqbal M. Shahid , Khan Javaidullah , Ahmad Firdos
Published: November 2023

Purpose
Frailty is a geriatric syndrome that precedes disability and is a common finding in patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and Alzheimer’s disease (AD). The contribution of increased intestinal permeability to frailty phenotype in patients with COPD, CHF, and AD is poorly known.
Methods
We conducted a cross-sectional, multicenter study of older men, including controls and patients with COPD, CHF, and AD (n = 37—48/group). We used Fried's cardiovascular health study (CHS) criteria to measure frailty and measured plasma zonulin levels as a biomarker of intestinal permeability. We also measured plasma c-reactive protein (CRP), 8-isoprostanes, and creatine kinase (CK) levels as markers of inflammation, oxidative stress, and muscle damage, respectively.
Results
Frail patients exhibited higher plasma zonulin than pre-frail patients, irrespective of disease type (all p < 0.05). Plasma zonulin exhibited significant positive associations with CHS frailty index, which were strongest in the control group, followed by CHF, COPD, and AD patients, respectively (all p < 0.05). Plasma zonulin demonstrated significantly high areas under the curve in diagnosing frailty in controls and patients with COPD, CHF, and AD (all p < 0.05). In the frail vs. pre-frail comparisons, we also found elevated plasma CK levels in CHF and AD patients, elevated CRP levels in COPD patients, and elevated 8-isoprostanes in AD patients (all p < 0.05).
Conclusion
Together, our data indicate the potential contribution of the disrupted intestinal mucosal barrier and elevated plasma zonulin to frailty phenotype in patients with COPD, CHF, and AD.
Evaluation and Projections of Summer Daily Precipitation over Northeastern China in an Optimal CMIP6 Multi-model Ensemble
Authors: Zi-Liang LI , Xin-Zhe Jiao
Published: November 2023

In the early summer of 2022, the average precipitation in Northeastern China (NEC) was 144.9 mm, which was 62% higher than the normal precipitation (89.5 mm), and was the largest amount of precipitation since historical records began in 1951. Based on the CN05.1 precipitation data, the summer precipitation simulated by the sixth Coupled Model Intercomparison Project (CMIP6) model was evaluated in the NEC region. The model performs well in reproducing the climatological spatial distribution and interannual variability of precipitation. The simulation effect of a multi-model ensemble is better than that of a single model. The top three optimal models (EC-Earth3-Veg, EC-Earth3 and MPI-ESM1-2-LR) can constitute the optimal model ensemble (HMME). Compared with a single model and an ensemble of all 20 models, HMME significantly reduces the wet bias on the southeastern side of the Da Xing-AN Ling Mountains. HMME projects that daily precipitation will show an increasing trend in NEC region from 2015 to 2100. Under the two scenarios of SSP245 and SSP585, the increase rates of precipitation are 0.05mm/10a and 0.15mm/10a respectively. Although precipitation trends varied between scenarios at different times of the year, by the end of the 21st century, precipitation increased significantly across the region, with the largest increase in precipitation located in the southern part of northeastern China.
Getting into a good headspace: A study protocol of an efficacy trial for an eating disorder prevention program in an Australian youth mental health service
Authors: Burton Amy L. , Hatoum Amaani H. , Berry Sophie L. , Hamilton Blake
Published: November 2023

Eating disorders (EDs) are serious, deadly disorders that emerge in adolescence and early adulthood. Further, reported incidences of EDs are increasing worldwide. As such, accessible, affordable, and effective early intervention and prevention efforts are critical. The Body Project is a well-established ED prevention program with demonstrated success at reducing ED symptom severity and the risk of onset of EDs in young females. However, it has not yet been formally evaluated in an Australian population, nor have the benefits of the treatment for young people of all genders been thoroughly investigated. This protocol paper outlines the design for a study which aims to investigate the outcomes and feasibility of the Body Project as a brief ED prevention program within an Australian youth mental health service: headspace Camperdown. This efficacy trial will compare outcomes between a Body Project treatment group and a Treatment-as-usual control group. Primary outcomes include body image concerns, ED symptomatology and general psychological distress, measured pre- and post-treatment, and at one-month follow-up. All young people attending headspace Camperdown for care are eligible for participation in the trial. The Body Project program is comprised of four group-based 1.5-hour sessions run over four consecutive weeks. Overall, a trial of the Body Project as an ED prevention program is warranted to investigate the outcomes of the intervention in this sample and will provide valuable information about the feasibility for widespread implementation of the treatment as part of a stepped-care approach to intervention for EDs at youth mental health service locations across Australia.
Rapid phenotypic differentiation in the iconic Japanese knotweed s.l. invading novel habitats
Authors: Yuan Wei , Pigliucci Massimo , Richards Christina
Published: November 2023

Understanding the mechanisms that underlie plant invasions is critical for management and conservation of biodiversity. At the same time, invasive species also provide a unique opportunity to study rapid adaptation to complex environmental conditions. Using four replicate reciprocal transplant experiments across three habitats, we described patterns of phenotypic response and assessed the degree of local adaptation in knotweed populations. We found plants from beach habitats were generally smaller than plants from marsh and roadside habitats when grown in their home habitat. In the marsh habitat, marsh plants were generally larger than beach plants, but not different from roadside plants. There were no differences among plants grown in the roadside habitat. We found mixed evidence for local adaptation: plants from the marsh habitat had greater biomass in their “home” sites, while plants from beaches and roadsides had greater survival in their “home” sites compared to other plants. In sum, we found phenotypic differentiation and some support for the hypothesis of rapid local adaptation of plants from beach, marsh and roadside habitats. Identifying whether these patterns of differentiation result from genetic or heritable non-genetic mechanisms will require further work.
Dynamics of Explosive Eruptions of Changbaishan Volcano, NE China, since the late Pleistocene from the Composition and Texture of Pumice
Authors: Yu Hongmei , Zhao Bo , Chen Zhengquan , Xu Jiandong
Published: November 2023

The explosive eruptions of Changbaishan volcano in NE China since the late Pleistocene produced large amounts of pyroclastic products, including from the Tianwenfeng (TWF) eruption, the Chifeng stage of the Millennium Eruption (ME-Com), and the Yuanchi stage of the Millennium Eruption (ME-Tr). In this study, we analyzed the differences among these pumices and the magma characteristics reflected in the field stratigraphy, particle size, petrography, and geochemistry. We quantitatively analyzed pumice texture and placed constraints on the eruption dynamics and intensities. For the first time, the ME-Tr pumices are determined to show two colors: earth-yellow and black, which erupted in a pulsing pattern at the first stage of ME-Tr eruption. Both components have trachyte compositions, but the SiO2 contents of the black pumice (59.5–60.6 wt%, ME-Tr-b) are slightly lower than those of the earth-yellow pumice (62.1–63.3 wt%, ME-Tr-a). The black pumice at the Tianwenfeng summit is speculated to be a product of the late ME-Tr eruption (ME-Tr-c). The variety of magma compositions and strata indicates that there may be three main crustal magma batches (ME-Com, ME-Tr-a and ME-Tr-b) of distinct compositions and temperatures were involved during the ME. The vesicle number density of the TWF pumice was the highest, as were the calculated height of the eruption column (23–32 km), and, consequently, the mass eruption rate. The eruption intensity of the ME was high during the ME-Com (24–25 km), and decreased during the ME-Tr (19–23 km). The results of this study improve our understanding of the eruption mechanisms, and the hazard assessments linked to the future Changbaishan eruptions.
Association between employment status and suicidal ideation : Korea national health and nutrition examination survey
Authors: Kim Sun Mi , Oh Jae-won , Son Nak-hoon , Lee San
Published: November 2023

Background: Employment status is a key indicator of socioeconomic status, and unstable employment conditions can cause various social problems. However, research in Asian cultures for the association between employment status and mental health has been limited. This study investigated the association between employment status and suicidal ideation in general population in South Korea.
Methods: Using data from the 2015, 2017, and 2019 Korea National Health and Nutrition Examination Survey (KNHANES), 6,509 participants aged ≥ 20 years were analyzed. Suicidal ideation was characterized by individuals considering suicide seriously within the past year. Covariates were adjusted to account for factors such as sociodemographic, health behavior, and mental health factors. Multivariable logistic regression and subgroup analysis were performed.
Results: In our KNHANES data analysis, unemployed status demonstrated 1.85 times more suicidal ideation than employed (adjusted Odd Ratio (aOR) 1.85, 95% confidence interval (CI) 1.41-2.44, p < .001). Low educational attainment (aOR 2.12, 95% CI 1.51-2.98, p < .001), low income (aOR 1.61, CI 1.22 -2.14, p < .001), presence of stress recognition (aOR 3.06, 95% CI 2.33-4.02, p < .001), and depression (aOR 13.0, 95% CI 10.0-16.9, p < .001) were also associated with suicidal ideation. In subgroup analysis, all covariates, except women and low body mass index, demonstrated combined effects with employment status on suicidal ideation.
Conclusions: This study demonstrated a significant association between employment status and suicidal ideation. Comprehensive supportive measures, including policy interventions and a variety of assistance, are crucial to mitigate the risk of suicidal ideation among the unemployed.
Prebiotic membrane structures mimic the morphology of purported early traces of life on Earth
Authors: Jordan Seán , Zuilen Mark van , Rouillard Joti , Martins Zita , Lane Nick
Published: November 2023

Elucidating the most probable compositions of the first cell membranes prior to the origin of life, within a laboratory setting, requires experiments with organic molecules and chemical conditions representative of those present on the early Earth. As such, the membrane forming molecules used in these experiments are described as ‘prebiotically plausible’, i.e., they could have formed through abiotic reactions and be available for membrane formation prior to the emergence of biology. Similarly, the chemical properties of solutions in which these membranes are formed (e.g., pH, temperature, ionic strength) must represent the early Earth environmental conditions under investigation. Here, using a combined confocal and transmission electron microscopy approach, we show that prebiotically plausible organic molecules, in solutions representative of Hadean submarine alkaline hydrothermal vents, form aggregated structures with substantial morphological diversity. The structures hold the potential for use as traces of prebiotic processes in the ancient rock record. In addition, many of the structures are morphologically similar to those which are presented as early microfossils, thus highlighting the limitations of morphological interpretation in these types of studies. Detailed analyses of abiotic organic structures are essential for our understanding of the earliest living organisms on Earth, as well as for our interpretation of any potential biosignatures recovered in the future from extra-terrestrial bodies.
Physicochemical quality properties of peach (Prunus persica L.) varieties at Holetta, Ethiopia
Authors: Mosie Tajebe , Setu Habtam , Seleshi Getaneh
Published: November 2023

Holetta has different peach fruit varieties that could be used for various purposes. However, their fruit quality characteristics were not fully identified. Studies have indicated that the physicochemical qualities of peach fruits are influenced by a number of factors, with the varietal factor being one of the most important. Limited information regarding the factors that affect these qualities is available in the country, specifically at Holetta. Therefore, this study was initiated to evaluate the physicochemical quality properties of peach fruit varieties. Their physical quality traits such as fruit length, fruit diameter, fruit shape index, and average fruit weight, as well as chemical quality parameters like TSS, specific gravity, TA, ripening index, ascorbic acid content, and pH, were evaluated. The result revealed that both physical and chemical quality parameters were significantly affected by varietal factors. Amongst, Bonny Gold variety had the longest fruit length and Florida down had the largest fruit diameter. As far as average fruit weight is concerned, 88 − 18 W had the heaviest weight with 111.98 g, while Transvalia had the highest TSS and specific gravity. However, the Summersun and 9A-35C varieties recorded the highest TA and ripening index, respectively. Thus, the fruit’s physicochemical quality properties were highly altered with peach varieties.
C-5401331 identified as a novel T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) inhibitor to control acute myeloid leukemia (AML) cell proliferation
Authors: Shahrani Mesfer Al , Gahtani Reem M , Makkawi Mohammed
Published: November 2023

T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a checkpoint protein expressed in exhausted T-cells during cancer scenarios. This exhaustion may end in T-cell effector dysfunction, resulting in suboptimal control of cancers like acute myeloid leukemia (AML). Use of immune checkpoint inhibitors (ICIs) to block checkpoint receptors such as Tim-3 is an emerging, revolutionary concept in the immuno-oncology therapeutic arena; however, ICIs are not effective on myeloid malignancies. Here, a multifaceted approach is utilized to identify novel compounds that target and inhibit Tim-3 with improved efficacy. High-throughput virtual screening of the ChemBridge small molecule library and molecular dynamics simulation yielded a lead molecule C-5401331 predicted to bind with high affinity and inhibit the activity of Tim-3. In vitro evaluations demonstrated the compound to have anti-proliferative effects on Tim-3-positive populations of THP-1 and HC-5401331 AML cells, inducing early and late phase apoptosis. With further development, the lead molecule identified in this work has potential to aid the natural “gatekeeper” functions of the body in immunocompromised AML cancer patients by successfully hampering the binding of Tim-3 to T-cells.
Dietary and potential oat transmission during the Eastern Zhou Guanzhong: evidence from residual starch granules analysis from the Liujiawa site
Authors: CHEN Yutong , Sun Zhanwei , Chong Jianrong , Zhang Zhao , Lam Wengcheong
Published: November 2023

Food plays a significant role in delineating boundaries between ethnic groups, facilitating the exchange of culinary traditions. The article presents the first analysis of starch granule residues found in the Guanzhong basin dating back to the Spring-and-Autumn period. By examining starch granule discovered on the inner surface of pottery excavated at the Liujiawa site, the capital of the Rui State, this study addresses gaps in the understanding of culinary practices during the Eastern Zhou period in the Guanzhong region. Moreover, it provides new insights into potential cultural interactions during this dynamic period. The identification results suggest a significant utilization of Panicoideae, potentially encompassing foxtail millet, broomcorn millet, and Job's tears, alongside oats. Additionally, Triticeae, which includes wheat, barley, and related crops, emerges as a relatively prominent food resource in the region. The presence of oats at the Liujiawa site is suggestive of interactions and cultural exchanges with northern populations, corroborating with other lines of archaeological evidence related to the same vassal state. This research sheds light on the multifaceted interplay of food, culture, and migration during the Spring-and-Autumn period, revealing the complexities of culinary traditions in the region.
Disruption of insulin receptor substrate 2 (Irs2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster
Authors: Hirose Michiko , Inoue Kimiko , Matoba Shogo , Tatebe Takaki , Tokita Syun , Dodo Yukiko , Tomishima Toshiko , Hasegawa Ayumi , Honda Arata , Ozaki Mao , Shinogi Akiko , Yanagisawa Ryoko , Inagaki Nobuya , Tamura Masaru , Ogura Atsuo
Published: November 2023

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin level upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamsters provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.
Monitoring fetal well-being and delivery outcomes in pregnancies complicated by gestational and pregestational diabetes
Authors: Tagliaferri Salvatore , Steyde Giulio , Trinchillo Maria Giuseppina , Campanile Marta , Spairani Edoardo , Maruotti Giuseppe Maria , Magenes Giovanni , Signorini Maria Gabriella
Published: November 2023

Background
diabetes is a very common pregnancy complication. This study aims to compare measurements taken during antenatal monitoring in the third trimester and delivery outcome data in pregnancies complicated by maternal diabetes with respect to healthy controls.
Methods
a prospective observational study included a total of 152 pregnant women. 25 had a diagnosis of pregestational diabetes mellitus (PGDM) and 61 were diagnosed with gestational diabetes mellitus (GDM). The remaining 66 were controls. Data collected antepartum for all pregnancies include ultrasound fetal biometry and amniotic fluid evaluation, Umbilical and Middle Cerebral Artery Pulsatility Index (UA-PI, MCA-PI) and computerized CTG (cCTG) monitoring. The mode of delivery and neonatal data, including umbilical cord gas values, were also obtained. The values collected were compared between groups.
Results
GDM and PGDM groups showed significantly lower values of UA-PI compared to Controls (p < 0.001) and GDMs assumed slightly lower values of MCA-PI compared to Controls (p = 0.028). Some cCTG parameters showed small but significant differences among groups. The analyzed groups presented significant differences in the umbilical artery gas analysis values at birth, which were affected by the mode of delivery. The pH was lower in PGDMs compared to both GDMs (p = 0.0279) and Controls (p < 0.0001), and spontaneous deliveries were associated with lower pH values (p = 0.008). pO2 significantly decreased from Controls to GDMs and PGDMs, respectively (Controls vs GDMs p = 0.0057, Controls vs PGDMs p < 0.001, GDMs vs PGDMs p = 0.0002) while pCO2 followed an opposite trend (Controls vs GDMs p < 0.001, Controls vs PGDMs p < 0.001, GDMs vs PGDMs p = 0.0014). Lactates were higher in PGDMs compared to both other groups (Controls vs PGDMs: p = 0.0128, GDMs vs PGDMs: p = 0.0161) and were higher in vaginal deliveries compared to cesarean sections (p = 0.017).
Conclusions
The results suggest that to date there are no antenatal monitoring methods that can accurately define the true well-being of the fetus in pregnancies complicated by diabetes. In fact, neonatal outcome data show greater differences between groups than those identified antepartum by the analyzed methods. We hypothesize that only a multi-parametric/multimodal approach can help in antepartum management.
Searching for an optimal Preclinical Model for Breast Cancer Research: A Study on the Effects of Diet on Tumor Development in Rats
Authors: Claro Francisco , Angelis Camila , Morare Joseane , Vanzela Emerielle Emerielle , Schiozer Wandir , Velloso Lício , Sarian Luis Otavio
Published: November 2023

Breast cancer research heavily relies on effective preclinical models to accurately study the complex interactions and heterogeneity observed in humans. While in vitro cell lines and athymic mice have been utilized, they have limitations in reflecting the true breast cancer microenvironment and immune response. To bridge this gap, the use of preclinical models developed in immunocompetent hosts is essential for better translation of experimental findings to human breast cancer behavior. This manuscript aims to address the critical lack of data on breast cancer models developed in immunocompetent hosts by presenting a preclinical model that meets specific prerequisites. The proposed model involves inducing luminal breast tumors in rats through a cafeteria diet, which allows for tumor development within a short time frame while maintaining intact host immunity. This model closely simulates the clinical scenario by emulating the microenvironment surrounding luminal tumors, ensuring study reproducibility, and ceasing the effects of the carcinogenic agent on the tumor and other animal tissues upon withdrawal. Additionally, the model allows for a sufficient remaining lifespan of the host post-tumor development to observe tumor evolution over time. The manuscript describes the technical details of the proposed preclinical model and presents experimental results derived from its implementation. By addressing the limitations of previous models, this research enhances our understanding of the breast cancer microenvironment and provides valuable insights into treatment strategies. This model serves as a valuable tool for evaluating the microenvironment, studying risk factors, and assessing treatment outcomes in breast cancer research.
Effects of motor control combined with cervicothoracic spine self-mobilization on chronic non-specific neck pain
Authors: Sun Ximei , Chai Liangwei , Huang Qiuyu , Zhou Hua , Liu Hua
Published: November 2023

To investigate the effects of motor control training and cervicothoracic spine self-mobilization with chronic non-specific neck pain. Thirty participants with chronic non-specific neck pain were randomly divided into motor control, synergistic cervical spine self-mobilization combined with motor control, and synergistic cervicothoracic spine self-mobilization combined with motor control groups. Neck pain, cervical range of motion, neck disability, strength and endurance of deep cervical flexors and quality of life were assessed before and after the 6-week training period. After the intervention, pain, strength and endurance of the deep cervical flexors and neck disability significantly improved in three groups (p < 0.05), cervical extension range of motion and quality of life significantly improved in the two synergistic self-mobilization groups (p < 0.05). Intergroup comparisons showed that the effect size was larger for the two synergistic self-mobilization groups than the motor control group (d = 1.27–1.46) and that the synergistic cervicothoracic self-mobilization had a larger effect size than the other two groups for reducing pain and increasing cervical rotational motion (d = 0.81–1.66) and a moderately larger effect size than the other two groups for dysfunction and quality of life physical function (d = 0.46–1.09). Motor control can enhance strength and endurance of deep cervical flexors, while self-mobilization can improve cervical extension range of motion. Combined with thoracic mobilization, it can further improve lateral flexion and rotation range of motion, thereby reducing pain and dysfunction and improving quality of life.
Developed and characterization of a novel Cd doped CeO2 nanofilm and application of pesticide removed by photodegradation
Authors: Çergel Müge Söyleyici , Demir Ersin , Kurtaran Sema
Published: November 2023

Cadmium (Cd) doped cerium oxide (CeO2) films were prepared by ultrasonic spray pyrolysis (USP) technique. The structural, surface and optical properties of the prepared Cd doped CeO2 films were investigated. All of the films were polycrystalline in exhibiting a cubic fluorite structure. In addition, the optical band gap obtained using the UV data ranged from 3.23 to 3.52 eV. For Cd doped CeO2 films, Raman scattering, in which the multi-peak setting of the first optical longitudinal mode was observed, indicates the Raman shift of the characteristic peak in the ~ 461 cm− 1 range. In addition, the photodegradation capacities of Cd doped CeO2 films were investigated in pesticides removed polluting human and environmental health. As a result, the proposed Cd doped CeO2 thin films show very high photocatalytic activity for the removal of important pollutant as Methyl Orange dyestuff. Consequently, Cd doped CeO2 film could be easily reused for five cycles without significant change in the photocatalytic activity.
DEPTOR levels in patients with mycosis fungoides
Authors: Çerman Aslı Aksu , Bulat Ceylan , Çetinkaya Pınar Özdemir , Kurt Birgül Özkesici , Odabaşı Merve Sena , Altunay İlknur
Published: November 2023

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including cutaneous T cell lymphoma. DEPTOR is an mTOR binding protein and endogenous mTOR inhibitor. However, the significance of DEPTOR in the development of mycosis fungoides (MF) is not known. This study aimed to investigate the possible role of DEPTOR in the pathogenesis of MF. Forty patients with MF and 40 healthy controls were included in the study. Serum fasting DEPTOR levels of the study groups were examined by enzyme-linked immunosorbent assay. The mean serum DEPTOR levels were significantly lower in patients with MF than controls (p<0.05). In conclusion, DEPTOR is possibly a novel tumor suppressor protein in MF. DEPTOR reactivation may be a potential therapeutic approach for patients with MF.
Impact of immunization-preventable infectious diseases on population health using disability-adjusted life years (DALYs) in Spain
Authors: Pérez-Rubio Alberto , Mestre-Ferrandiz Jorge , López-Belmonte Juan Luis , Díaz Ariadna , Lorenzo-Herrero Seila , Crespo Carlos
Published: November 2023

Background
The objective of this study is to estimate the burden of immunization-preventable infectious diseases in Spain using the Burden of Communicable Diseases in Europe (BCoDE) methodology and focusing on the national immunization program and potential new inclusions.
Methods
The BCoDE methodology relies on an incidence and pathogen-based approach to calculate disease burden via disability-adjusted life year (DALY) estimates. It considers short and long-term sequelae associated to an infection via outcome trees. The BCoDE toolkit was used to populate those trees with Spanish-specific incidence estimates, and de novo outcome trees were developed for four infections (herpes zoster, rotavirus, respiratory syncytial virus [RSV], and varicella) not covered by the toolkit. Age/sex specific incidences were estimated based on data from the Spanish Network of Epidemiological Surveillance; hospitalization and mortality rates were collected from the Minimum Basic Data Set. A literature review was performed to design the de novo models and obtain the rest of the parameters. The methodology, assumptions, data inputs and results were validated by a group of experts in epidemiology and disease modelling, immunization and public health policy.
Results
The total burden of disease amounted to 163.56 annual DALYs/100,000 population. Respiratory infections represented around 90% of the total burden. Influenza exhibited the highest burden, with 110.01 DALYs/100,000 population, followed by invasive pneumococcal disease and RSV, with 25.20 and 10.57 DALYs/100,000 population, respectively. Herpes zoster, invasive meningococcal disease, invasive Haemophilus influenza infection and hepatitis B virus infection fell behind in the ranking with less than 10 DALYs/100,000 population each, while the rest of infections had a limited burden (< 1 DALY/100,000 population). A higher burden of disease was observed in the elderly (≥ 60 years) and children < 5 years, with influenza being the main cause. In infants < 1 year, RSV represented the greatest burden.
Conclusions
Aligned with the BCoDE study, the results of this analysis show a persisting high burden of immunization-preventable respiratory infections in Spain and highlight for the first time a high number of DALYs due to RSV. These estimates provide a basis to guide prevention strategies and make public health decisions to prioritize interventions and allocate healthcare resources in Spain.
In Situ Needle Fenestration for Aortic Arch Pathologies During Thoracic Endovascular Aortic Repair
Authors: Li Gang , Li Minghui , Dong Zhiqiang , Gu Jiaxi , Liu Hong , Xu Xinyang , Gu Weidong , Shao Yongfeng , Ni Buqing
Published: November 2023

Background
To evaluate the clinical outcomes and the validity of the in situ needle fenestration (ISNF) technique during thoracic endovascular aortic repair (TEVAR) for patients with aortic arch pathologies.
Methods
In total, 115 patients with aortic arch pathologies treated with ISNF during TEVAR between January 2018 and December 2021 were incorporated. Several clinical variables were recorded, including postoperative mortality, adverse events, aorta-related reintervention, and patient survival rates.
Results
The median age of the patients was 62.0 years, and 10.4% (12/115) were female. The median follow-up time was 31.0 months. A total of 175 supra-arch branches were reconstructed. A single branch was fenestrated in 79 patients, while the left subclavian artery (LSA) and left common carotid artery (LCCA) were fenestrated simultaneously in 12 patients, and all supra-arch branches were fenestrated in 24 patients. The rate of technical success was 100%, 30-day mortality was 2.6% (3/115), overall mortality was 8.7% (10/115), and aortic-related mortality was 2.6% (3/115). Aortic-related reintervention was required in 7.8% (9/115) of patients. Among the major postoperative complications, four patients developed retrograde type A dissection requiring emergent open surgery, three patients had cerebrovascular accidents, two patients suffered paraplegia, and one patient had an endoleak. No occlusions or stenoses of the main or branch aortic stents were observed.
Conclusions
The mid-term results of the ISNF technique during TEVAR for aortic arch pathologies were within the acceptable range; however, further follow-up results are needed and long-term stability and durability needs to be assessed. Related fenestration devices also require further development.
Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line
Authors: Ono Takuya , Noguchi Rei , Osaki Julia , Akiyama Taro , Adachi Yuki , Kojima Naoki , Toda Yu , Fukushima Suguru , Yoshimatsu Yuki , Yoshida Akihiko , Kawai Akira , Kondo Tadashi
Published: November 2023

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.
Predictors of mortality among children at Tertiary Hospital in Tanzania: A cohort study
Authors: Damian Diana K , Furia Francis F , Leyna Germana
Published: November 2023

Background
Tanzania is among the countries in the sub-Saharan Africa with the highest under-five mortality rate. Strategies for reducing under-five mortality require a good knowledge of driving factors, which are largely unknown necessitating this study to be conducted at Muhimbili National Hospital to determine factors associated with under-five mortality.
Method
We conducted a prospective cohort study to determine the predictors of deaths among children aged 1–59 months admitted in the paediatric department wards from October 2017 to April 2018. We recruited children consecutively and followed them up until discharge or death. We calculated the mortality rate as the incidence density rate, and determined causes and predictors of mortality. We analysed data to identify and quantify predictors of deaths, and used Kaplan-Meir and Cox regression analyses to determine predictors of survival. A P-value of < 0.05 was considered statistically significant.
Results
We recruited 925 children aged 1–59 months with a median age of 13 and (IQR) of (6, 26) months, females constituted 40.8% (377/925). The overall mortality rate was 12.2% (95% CI: 10.2%-14.5%). We found septicaemia (27%), malnutrition (12%), congenital heart disease (12%), pneumonia (11%), and HIV (9%) to be leading causes of mortality. More deaths were observed at night, during the first 24 hours of admission, and on weekends. Independent factors for mortality were found to be low wealth quintiles (lowest quintile (AOR = 4.0; 95% CI: 1.19–13.51), second quintile (AOR = 5.2; 95% CI: 1.65–16.69) and middle quintile (AOR = 3.6; 95% CI: 1.14–11.33)), unconsciousness on admission (AOR = 18; 95% CI: 6.70-56.82), inability to feed (AOR = 5.7; 95% CI: 1.97–16.51), lethargy (AOR = 4.9; 95% CI: 2.32–10.40), severe wasting (AOR = 4.5; 95% CI: 2.49–8.10) and respiratory distress (AOR = 2.6; 95% CI: 1.40–4.97)
Conclusion
High mortality rate was noted in this study and low wealth quantile, low parental education, and lack of health insurance were associated with high mortality. Patients had the highest risk of mortality within 24 hours of admission, therefore it is important to raise awareness and improve monitoring of patients, especially within 24 hours of admission.
Combined application of organic material and inorganic compound fertilizer impacting on the structure and function of soil bacterial community
Authors: Yang Kai , Li Yanfeng , Du Yanquan , Wang Mingwei , Zhou Qianshun , Zhang Xixing , Zhu Jianqiang
Published: November 2023

Excessive application of inorganic nitrogen fertilizers leads to soil degradation, while the application of organic materials helps to restore and maintain soil microecological balance. However, different applications of organic materials combined with inorganic fertilizers are possible to produce different influences on soil microbial communities. Therefore, field experiments of five fertilization treatments were carried out, that were: single inorganic compound fertilizer (CK), sheep manure + inorganic compound fertilizer (AF), cassava residue + inorganic compound fertilizer (PF), woody peat + inorganic compound fertilizer (MF), and monosodium glutamate waste slurry + inorganic compound fertilizer (IF). The results revealed that only the MF treatment significantly increased bacterial community richness compared to the CK. The relative abundance of Acidobacteriota was significantly lower in the treatment with combined application of organic materials and chemical fertilizers compared to the sole application of chemical fertilizers. Additionally, the relative abundance of Bacteroidota and Gemmatimonadota was significantly higher in the AF, while the relative abundance of Firmicutes was significantly higher in the IF. Soil organic carbon had the greatest impact on bacterial community structure. The IF significantly enhances soil carbon carbohydrate metabolism, while the AF significantly improves soil amino acid metabolism. The MF treatment had a higher abundance of anaerobic bacteria, while the PF treatment had a higher abundance of biofilm-forming bacteria. The IF treatment had the highest abundance of Gram-positive bacteria. The above results indicated that we can regulate the structure and function of soil bacterial communities, thus providing a favorable condition for crop production.
Selective SERCA2a activator as a candidate for chronic heart failure therapy
Authors: Arici Martina , Hsu Shih-Che , Ferrandi Mara , Barassi Paolo , Ronchi Carlotta , Torre Eleonora , Luraghi Andrea , Chang Gwo-Jyh , Ferrari Patrizia , Bianchi Giuseppe , Peri Francesco , Zaza Antonio , Rocchetti Marcella
Published: November 2023

Background.
The sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) depression substantially contributes to diastolic dysfunction in heart failure (HF), suggesting that SERCA2a stimulation may be a mechanism-based HF therapy. Istaroxime is a drug endowed with both a SERCA2a stimulatory activity and a Na+/K+ pump inhibitory activity for acute HF treatment. Its main metabolite PST3093 shows a more favorable therapeutic profile as compared to the parent drug, but it is still unsuitable for chronic usage. Novel PST3093 derivatives have been recently developed for oral (chronic) HF treatment; compound 8 was selected among them and here characterized.
Methods. Effects of compound 8 were evaluated in a context of SERCA2a depression, by using streptozotocin-treated rats, a well-known model of diastolic dysfunction. The impact of SERCA2a stimulation by compound 8 was assessed at the cellular level ad in vivo, following i.v. infusion (acute effects) or oral administration (chronic effects).
Results. As expected from SERCA2a stimulation, compound 8 induced SR Ca2+ compartmentalization in STZ myocytes. In-vivo echocardiographic analysis during i.v. infusion and after repeated oral administration of compound 8, detected a significant improvement of diastolic function. Moreover, compound 8 did not affect electrical activity of healthy guinea-pig myocytes, in line with the absence of off-target effects. Finally, compound 8 was well tolerated in mice with no evidence of acute toxicity.
Conclusions. The pharmacological evaluation of compound 8 indicates that it may be a safe and selective drug for a mechanism-based treatment of chronic HF by restoring SERCA2a activity.
Distinct serial dependence between small and large numerosity processing
Authors: Huang Yue , Li Haokun , Qiu Shiming , Ding Xianfeng , Li Min , Liu Wangjuan , Fan Zhao , Cheng Xiaorong
Published: November 2023

The serial dependence effect (SDE) is a bias in which the representation of current stimuli is attracted to previous stimuli. Although SDE has been observed in many substrates of visual processing, it remains unsolved whether humans adopt a similar SDE to achieve continuity and stability of numerosity processing in two distinct numerical ranges: subitizing (i.e., small numerosity processing, likely related to early object recognition) and estimation (i.e., large numerosity processing, likely related to ensemble numerosity extraction). Here, we demonstrate that subitizing and estimation are characterized by distinct SDEs, underpinned by different mechanisms: a temporal hysteresis-based perceptual mechanism for subitizing and a combination of perceptual and post-perceptual mechanisms for estimation. Critically, a novel type of SDE characterized by reduced processing precision is found in subitizing only, implying that the continuity and stability of numerical processing can be dissociable in dynamic situations where numerical information is integrated over time. Our findings reveal the multifaceted nature of SDE mechanisms and suggest their engagement with cognitive modules likely subserving different functionalities.