bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide population genetics and molecular surveillance of insecticide resistance in Anopheles stephensi mosquitoes from Ethiopia
Authors: Acford-Palmer Holly , Tadesse Fitsum , Manko Emilia , Phelan Jody , Higgins Matthew , Osborne Ashley , Kristan Mojca , Walker Thomas , Bousema Teun , Messenger Louisa , Clark Taane , Campino Susana
Published: April 2024

Since the detection of the Asian mosquito Anopheles stephensi in Dijbouti in 2012, it has spread throughout the Horn of Africa. This invasive vector has continued moving across the continent and is a threat to malaria control programs. Vector control methods including insecticide-treated nets and indoor residual spraying, have substantially reduced the malaria burden. However, the increasing prevalence of mosquitos resistant to insecticides, including An. stephensi populations, threaten reductions made so far. Here, we generate whole genome sequencing data for An. stephensi sourced from an Ethiopian town (n=27) and compare South Asian populations (n=45; India and Pakistan), assessing genomic diversity, population structure, and uncovering insecticide resistance mutations.
Population structure analysis using genome-wide single nucleotide polymorphisms (n=15,533,476), revealed Ethiopian isolates clustering as a distinct ancestral group, separate to South Asian isolates. Three insecticide resistance-associated SNPs (gaba gene: A296S and V327I; vgscL1014F) were detected. Evidence of ongoing selection was found in several loci, including genes previously associated with neonicotinoids, ivermectin, DDT, and pyrethroid resistance.
This study represents the first genome-wide population genetics study of invasive An. stephensi, revealing genomic differences from South Asian populations, which can be used for future assessments of vector population dispersal and detection of insecticide resistance mechanisms.
The plasma metabolome of systemic juvenile idiopathic arthritis is different to non-JIA controls and partially explained by chronic inflammation
Authors: kwon jooa , Neeland Melanie R , Ellis Justine A , Munro Jane , Saffery Richard , Novakovic Boris , Mansell Toby
Published: April 2024

Background: Diagnosis of juvenile idiopathic arthritis (JIA) is challenging due to shared clinical features between subtypes and with other inflammatory conditions. A molecular signature may therefore be useful for subtype classification in JIA, and targeted plasma metabolomics profiling has the potential to provide such a signature.
The study aimed to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls, and to determine the extent to which these differences are due to chronic inflammation measured by glycoprotein acetyls (GlycA).
Methods: Nuclear magnetic resonance (NMR) metabolomics of plasma of 73 children with JIA and 18 age- and sex- matched controls was assessed cross-sectionally. Associations between 71 metabolomic biomarkers and JIA, four JIA subtypes, and inflammation (measured by GlycA) were assessed using multivariable linear regression models.
Results: Three biomarkers were different between the control and JIA group, with acetate reduced in JIA (mean difference -0.98 standard deviations, [95% confidence interval -1.49, -0.47], Padj =0.015), while docosahexaenoic acid (DHA) (1.01 [0.47, 1.55], Padj =0.015) and GlycA (0.91, [0.36, 1.46], Padj =0.041) were elevated in JIA. Subtype analysis revealed that systemic JIA (sJIA) samples accounted for these changes, with no significant metabolic differences identified in oligoarticular and polyarticular (rheumatoid factor positive and rheumatoid factor negative) JIA relative to controls. A total of 24 of 71 biomarkers were significantly different (Padj <0.05) in systemic JIA compared to controls, including acetate, DHA and GlycA. Of the 24 biomarkers, only 6 were significantly associated with levels of the inflammatory marker GlycA.
Conclusion: The variation of plasma NMR metabolome of systemic JIA is the most pronounced relative to non-JIA controls and other JIA subtypes, which show limited evidence of metabolomic disruption. Only a small number of metabolomic profile differences in sJIA were associated with levels of GlycA, indicating a complex relationship between JIA, metabolic disruption, and chronic inflammation.
Global Water Basins under Combined Climate Mitigation, Adaptation, and Sustainable Development Targets
Authors: Awais Muhammad , Vinca Adriano , Byers Edward , Andrijevic Marina , Harmsen Mathijs , Niazi Hassan , Tagomori Isabela Schmidt , Rowe Andrew , McPherson Madeleine , Krey Volker , Riahi Keywan
Published: April 2024

Water systems are crucial for sustainable development and energy-water-land system-wide climate mitigation and adaptation to changing climate. We explore the dynamic interplay between climate change adaptation, mitigation, and sustainable development within these systems. We demonstrate, how strategic investments in a “Resilience scenario” – climate mitigation and Sustainable Development Goals (SDGs) combined, leads to approximately 20% reduction in water stress for vulnerable populations promoting sustainable water and energy systems. Despite the Resilience scenario targets, about one-third of global population (2.8 billion people) is expected to face adaptation barriers by mid-century, hindered by inadequate governance capacity. We demonstrate that investments in SDGs, combined with climate mitigation strategies, are more beneficial for the water sector than pursuing SDGs alone. Our findings suggest a necessary convergence of sustainable development, climate resilience, and human welfare to create a climate-resilient sustainable future, marking a significant step forward in facilitating integrated environmental policy and decision-making.
Targeting Metabolic Vulnerability by Combining NAMPT Inhibitors and Disulfiram for Treatment of Recurrent Ovarian Cancer
Authors: Lipkowitz Stanley , Kudo Kei , Crooks Daniel , Greer Yoshimi , Yang Ye , Brender Jeffrey , Yoshida Teruhiko , Harrington Brittney , Kamdar Rahul , Korrapati Soumya , Shibuya Yusuke , Henegar Leah , Kopp Jeffrey , Fujii Takeo , Annunziata Christina
Published: April 2024

Ovarian cancer (OV) has the highest mortality rate among gynecological cancers. As the OV progresses, tumor cells spread outside the ovaries to the peritoneal and abdominal cavities, forming cell clusters that float in the ascitic fluid caused by peritonitis carcinomatosa, leading to further dissemination and metastasis. These cell clusters are enriched with cancer stem cells (CSCs) which are responsible for treatment resistance, recurrence, and metastasis. Therefore, targeting CSCs is a potentially effective approach for treating OV. However, understanding how CSCs acquire treatment resistance and identifying targets against CSCs remains challenging. In this study, we demonstrate that 3D-spheroids of OV cell lines exhibit higher stemness than conventional adherent cells. Metabolomics profiling studies have revealed that 3D-spheroids maintain a high-energy state through increased glucose utilization in the citric acid cycle (TCA), efficient nucleotide phosphorylation, and elevated phosphocreatine as an energy buffer. We also found that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ production, is highly expressed and is a potential therapeutic target against CSCs, while also serving as a prognostic indicator in OV. Moreover, we identified a previously unrecognized anti-tumor mechanism whereby disulfiram, an aldehyde dehydrogenase (ALDH) inhibitor, synergistically inhibited mitochondrial function when combined with NAMPT inhibitors. Finally, the combination of a NAMPT inhibitor and disulfiram showed significant anti-tumor effects and extended survival in an animal model. Our findings demonstrate the potential of spheroids as a preclinical model for targeting OV CSCs and also indicate that the combination of NAMPT inhibitors and disulfiram is a promising therapeutic strategy to overcome recurrent OV.
Low Density Phases of TiO2 by Cluster Self-Assembly
Authors: Ayuela Andrés , Aguilera-Granja Faustino
Published: April 2024

The interest in titanium dioxide (TiO2) phases is growing due to the number of applications in cosmetics, food industry andphotocatalysis, an increase that is driven by its exceptional properties when engineered at the nanoscale like in the form ofnanoparticles. Our goal is to discovered previously unknown low-density phases of TiO2, with potential for applications invarious fields. We then use well-known TiO2 clusters as fundamental building blocks to be self-assembled into unique structuresto study their distinct characteristics. Density functional calculations are emplyed to relax the structures and identify the moststable TiO2 structures within an energy range of 0.1 eV per atom from the rutile and anatase phases, which are confirmed,validating our methodology. Going beyond conventional phases, we found two-dimensional TiO2 structures, previously exploredin separate studies, and showing typical structures of transition metal dichalcogenide layers, that forge a bridge betweendifferent TiO2 structures. It is noteworthy that our investigation uncovered an entirely novel class of TiO2 structures featuringhexagonal cages like beehive channels, opening novel phases with huge potential. These discovered low-density phases areinteresting, particularly the hexagonal cage structures with remarkable large gaps, because they introduce other dimensions foruncharted applications in the ever-growing TiO2 landscape.
c-Myc inhibition and p21 modulation contribute to unsymmetrical bisacridines-induced apoptosis and senescence in pancreatic cancer cells
Authors: Kurdyn Agnieszka , Pawłowska Monika , Paluszkiewicz Ewa , Cichorek Mirosława , Augustin Ewa
Published: April 2024

Pancreatic cancer (PC) is one of the most aggressive cancers and is the seventh cause of cancer deaths worldwide. Mutations in the KRAS, CDKN2A, TP53, SMAD4/DPC4, and MYC are major genetic alterations associated with cell cycle deregulation, apoptosis inhibition, invasion, metastasis, and poor treatment outcomes in PC. The standard therapy for PC is gemcitabine, nab-paclitaxel, and FOLFIRINOX, however, they have poor survival rates. Therefore, optimizing therapy for patients with PC is a tremendous challenge. Unsymmetrical bisacridines (UAs), synthesized by our group, are new promising compounds that exhibited high cytotoxicity and antitumor activity against several solid tumors, including pancreatic cancer. Accordingly, here we investigated their cellular mechanism of action, with a particular focus on the proteins frequently mutated in PC. We showed that apoptosis was the main triggered mechanism of death and the induction of SMAD4 protein can facilitate this process. c-Myc, which is one of the molecular targets for UAs can ease the induction of cell death in the p53-independent manner. Moreover, UAs can also induce accelerated senescence through the upregulation of p21. What is remarkable, senescent cells after prolonged exposition to UAs can die by apoptosis. Thus, UAs exhibit desirable features of promising candidates for future pancreatic cancer therapies.
An Environmental Scan and Qualitative Inquiry of Cancer Patient Navigation Services in North Carolina
Authors: Fathi Leila , Umble Karl , Waters Austin R. , Kent Erin E.
Published: April 2024

Background and Objectives: Patient navigation services reduce barriers to accessing cancer care and lead to improved outcomes for patients. North Carolina (NC) has thousands of cancer patients seeking cancer care services each year. We sought to complete a digital environmental scan and qualitative inquiry of cancer patient navigation services throughout the state to better inform patients, hospitals administrators, and state officials about the current state of patient navigation programs for cancer patients throughout NC.
Methods: For seven cancer hospitals in NC, two steps were used: an environmental scan of publicly available information on the hospitals’ websites about navigation services, and key informant interviews with navigation staff at each site.
Results: The website scans revealed information about navigation services was incomplete. Each hospital had a page dedicated to cancer navigation, but many did not outline the specific services available to patients. Interviews revealed that navigation services are available to cancer patients across diagnoses, although only a subset of patients receive services. Cancer navigators reported that their work includes care coordination, patient advocacy, emotional support, and addressing non-medical barriers to health care access (transportation, finances, childcare, etc.). Each navigation service had a unique configuration and referral pattern.
Conclusions: Cancer hospitals throughout NC are working to address barriers to care commonly faced by patients, with some programs offering more robust services compared to others. Hospitals would benefit from updating their websites at regular intervals to fully report the services available to patients through their programs, including direct and clear patient navigation contact methods.
Diffusion in Biological Media: A Comprehensive Numerical-Analytical Study via Surface Analysis and Diffusivities Calculation
Authors: Pacheco Juan Ignacio González , Maldonado Mariela
Published: April 2024

This study examines the diffusion of substances through biological porous materials (analytically and numerically) via diffusion coefficients calculation and surface analysis. The research proposes a sweetening Bing-type cherries (Prunus avium) process using a combination of sucrose and xylitol and a staining technique utilising erythrosine and red gardenia at varying concentrations (119, 238 and 357 ppm) and temperatures (40, 50 and 60°C). Given the fruit's epidermis resistance, the effective diffusivities of skin were inferior to those in flesh. Temperature and concentration synergise in enhancing diffusion coefficients and dye penetration within the food matrix (357 ppm and 60°C). Red gardenia displayed significant temperature-dependent variation (p = 0.019), whereas erythrosine dye remained stable by temperature changes (p>0.05). Gardenia's effective diffusivities in cherry flesh and skin, at 357 ppm and 60°C, 2.43E-08 and 4.12E-09 m2/s, respectively, significantly differed from those obtained at lower temperatures and concentrations. The results emphasise the importance of considering temperature-concentration effects on mass transfer calculations for food colouring processes.
Analysis of the Therapeutic Efficacy of Arthroscopic Repair of the Subscapularis Tendon Combined with Coracoplasty
Authors: Zheng Hanlin , Liu Yulong , Tu Bizhi , Chen Guang , Ning Rende
Published: April 2024

Objective: The purpose of this study was to analyze the outcomes of arthroscopic subscapularis tendon repair combined with coracoplasty in the treatment.
Methods: The study included 80 patients (46 males, 34 females; age range 33 to 73 years old), they underwent arthroscopic repair for subscapularis tear (typeⅠ，typeⅡ and type Ⅲ) presenting with symptoms of anterior shoulder pain and tenderness. Subcoracoid impingement was defined as a coracohumeral distance of less than 6 mm on the preoperative magnetic resonance image, and the follow-up was at least two years. Patients included two groups: Group A underwent coracoplasty, while Group B did not. The postoperative functional results of the two groups were compared and analyzed. The prognosis of patients was evaluated preoperatively and postoperatively by the University of California Los Angeles (UCLA) shoulder score，American Shoulder and Elbow Surgeons（ASES) shoulder score and Visual Analog Scale（VAS）pain score.
Results: Postoperative observations revealed successful primary wound healing among all patients, without any systemic or localized shoulder joint infections or brachial plexus nerve injuries. Both groups exhibited a notable enhancement in overall functional outcomes following surgical intervention. At the 24-month postoperative follow-up, all assessed parameters in both groups showed substantial improvement compared to the preoperative values (P<0.05). The functional scores demonstrated a noteworthy increase in both groups after surgery compared to the preoperative values (p<0.01). When comparing two groups, the p-values for all indicators, except for the forward flexion range of motion, were less than 0.01. The statistical results indicated that patients in Group A had better recovery outcomes than those in Group B, except for forward flexion range of motion.
Conclusion: The findings suggested that subcoracoid impingement syndrome could potentially serve as a significant precursor to subscapularis tendon injuries.It is worth noting that the combined approach of subscapularis tendon repair and coracoplasty demonstrated superior therapeutic efficacy compared to isolated subscapularis tendon repair, when subscapularis tendon injuries were associated with subcoracoid impingement.
Hyperoxaemia in Acute Trauma is Common and Associated with a Longer Hospital Stay – a Multicentre Retrospective Cohort Study
Authors: Iten Manuela , Pietsch Urs , Knapp Juergen , Jakob Dominik , Kummrey Gerd , Maschmann Christian , Steinmetz Jacob , Arleth Tobias , Mueller Martin , Hautz Wolf
Published: April 2024

Background: Trauma poses a significant global health challenge. Despite advancements in the management of severely injured patients, (poly)trauma continues to be a primary contributor to morbidity and mortality worldwide. In the context of trauma resuscitation, supplemental oxygen is commonly administered generously as suggested by guidelines. Yet, it remains uncertain whether the trauma population might derive advantages from a more conservative approach to supplemental oxygen.
Methods: In this retrospective cohort study from two Swiss trauma centers, severely injured adult (>16 years) trauma patients with an Injury Severity Score (ISS) ≥16 were divided into four groups according to the first blood gas analysis taken: hypoxaemia (PaO2 <80mmHg), normoxaemia (PaO2 80-120mmHg), which served as reference, moderate hyperoxaemia (PaO2 >120-300mmHg) and severe hyperoxaemia (PaO2 >300mmHg). The primary outcome was 28-day mortality. Length of hospital stay (LOS) and length of intensive care unit stay (LOS-ICU) were analyzed as secondary outcomes.
Results: Of 1,189 trauma patients, 41.3% had hyperoxaemia (18.8% with severe hyperoxaemia) and 19.3% had hypoxaemia. No difference was found for 28-day mortality (hypoxaemia: 15.7%, normoxaemia: 14.1%, hyperoxaemia: 13.8%, severe hyperoxaemia: 16.0%, p = 0.846). Patients with severe hyperoxaemia had a significant prolonged LOS (median 12.5 [IQR 7-18.5] days vs. 10 [7-17], p = 0.040) and extended LOS-ICU (3.8 [1.8-9] vs. 2 [1-5] days, p=0.149) compared to normoxaemic patients. In multivariable analysis, oxygen group was not associated with the primary ouerstcome 28-day mortality or LOS-ICU. Severe hyperoxaemia patients had a tendency towards longer hospital stay (adjusted coefficient 2.23 days [95% CI: -0.32; 4.79], p=0.087).
Conclusion: Hyperoxaemia was not associated with an increased 28-day mortality when compared to normoxaemia. However, both moderate and severe hyperoxaemia is frequently observed in trauma patients, and the presence of severe hyperoxaemia showed a tendency with extended hospital stay compared to normoxaemia patients. Robust randomized controlled trials are imperative to thoroughly evaluate the potential correlation between hyperoxaemia and outcomes in trauma patients.
Trial Registration: Retrospectively registered
Interventions can improve patient experienced quality of care in transitions between healthcare settings: A scoping review.
Authors: Hindsbak Natasia , Morsø Lars , Hvidtjørn Dorte , Walløe Sisse
Published: April 2024

Transitions in healthcare settings can be a challenge for patients and they express a need for guidance and support to cope with these transitions. The aim of this scoping review was to investigate if interventions can improve patients’ experiences when transitioning between healthcare settings. This review was conducted following the Johanna Briggs Institute’s methods and reported according to the PRISMA-ScR Checklist. Included articles were published and peer-reviewed, and reported qualitative and quantitative findings on patient experiences with interventions when transitioning between healthcare settings. The search was conducted in December 2021 in Medline Ovid, Embase Ovid, and Cinahl and 19 studies were included. Factors extracted from the studies were: author(s), year of publication, country of origin, study design, theoretical methods, population description, intervention, phenomena of interest(s), and key findings. There has been an increase in published studies on the subject in the last few years, and most of the included studies originated from Western countries. Most studies were quantitative, primarily RCTs, and the theoretical methods were thus mainly statistical analysis. The study populations were found to be heterogeneous. The interventions were categorized: care coordinator, program, integrated care, coaching, discharge care plan, and miscellaneous interventions. Overall interventions were found to improve the patient experience. Re-centralization of healthcare has increased the number of transitions, and patients express that the coordination of healthcare transitions can be improved. This review’s findings should be used alongside other research on interventions’ effect on factors like hospital readmissions and mortality to determine the optimal intervention to implement.
Development of a tool outline measurement system by using vision-based algorithms
Authors: Kim Sumin , Jung Minsu , Park Jong-kyu
Published: April 2024

Current domestic reground tool measurement methods either rely on the operator's experience or involve analyzing signals from multiple sensors to determine the tool condition. Despite the availability of numerous measurement techniques, accurately determining the condition of reground tools' condition remains challenging due to the varying time, equipment requirements, and the inherent difficulty in analyzing complex signals. Consequently, collecting comprehensive tool data becomes imperative. This study introduces a novel approach by developing a method for measuring the outer edge of tools, enabling precise condition assessment through a vision-based measurement system. This system not only aims to mitigate the errors commonly associated with manual measurements in the manufacturing sector but also seeks to enhance the process analysis efficiency. By doing so, it aims to significantly decrease the rejection rates of tool measurements and streamline the analysis process, potentially extending tool life and improving performance management. This method promises to contribute to more sustainable manufacturing practices by optimizing tool usage and reducing waste.
Immune cells and blood lipids mediation: a Mendelian randomization study on metabolic dysfunction-associated fatty liver disease
Authors: Shen Qi-En , Liu Zhening , Huang Hangkai , Liang Yujie , Chen Minjie , Xu Chengfu
Published: April 2024

Background: The current understanding of the relationship between immune cells and metabolic dysfunction-associated fatty liver disease (MAFLD) is limited. The purpose of this study was to examine the causal role played by immune cells in MAFLD.
Methods:
To investigate the causal association between immune cells and MAFLD, two-sample Mendelian randomization (MR) studies were conducted. Summary statistics were obtained from genome-wide association studies (GWASs) of 731 immune traits (4 types and 7 panels) and from the two largest meta-GWASs of MAFLD. Thorough reverse and sensitivity analyses were utilized to validate the strength of the findings. Mediation MR analyses were performed to investigate the potential mediating effects of various MAFLD risk factors, such as blood lipids, on the relationship between immune traits and MAFLD.
Results:
We found that genetically predicted higher CD25 expression on IgD- CD38dim B cells (OR = 0.93, 95% CI = 0.88–0.99) was associated with a lower risk of developing MAFLD. The proportion of genetically predicted CD25 on IgD- CD38dim B cells mediated by high-density lipoprotein cholesterol (HDL-C) was 2.21% and that on Apolipoprotein A1 is 1.91%. During the reverse analysis of the significant impact of NAFLD on immunophenotype, the leukocyte AC TBNK (OR = 1.66, 95% CI = 1.22 ~ 2.27) was identified.
Conclusion: Our study provides genetic evidence regarding the role of CD25 on IgD- CD38dim B cells in MAFLD mediated by blood lipids and supports a causal association between various immune cells and MAFLD.
Menstrual Practice Needs among College going Women in Coimbatore district, India: An analytical cross-sectional study
Authors: Ramya V , Kumar Mohan , Jeevithan S , Seetharaman N , Mahanshetty Sushmitha , Dhandapani Srihari , Aparnavi P , Durairaj T , Ramesh M
Published: April 2024

Background: In India, twenty-five percent of women who menstruate are unable to utilize sanitary methods, and even among those who have access, there are multiple obstacles to achieving proper menstrual hygiene management. The consequences of inadequate menstrual health affect a girl's school participation and extend to her empowerment, overall well-being, and even survival.
Objectives: To estimate the prevalence of unmet menstrual practice needs and its determinants among college going women in Coimbatore district, India.
Methodology: A questionnaire based analytical cross-sectional study was conducted among 3144 college going women from October 2022 to January 2023. Menstrual Practice Needs Scale (MPNS-36) was used to collect data regarding the unmet needs and their mean scores were compared across socio-demographic variables, menstrual knowledge, and the choice of hygiene material.
Results: The mean (SD) age of the study population was 19.3 (1.8) years. The prevalence of unmet menstrual practice needs was 62.8% with a mean (SD) MPNS score of 1.8 (0.4). The total MPNS score was low for those currently residing in rural or having a rural hometown. The unmet need was better for those residing in-campus of the educational institute and having educated parents. The socioeconomic class and presence of a personal income also influenced the total MPNS scores significantly (p<0.05). Menstrual talks with friends before puberty and with friends and family after puberty improved the MPNS scores. Regarding menstrual hygiene methods, modern menstrual methods (MMM), disposable and bio-degradable materials had a lower unmet need. Marital status, freedom to manage expenses, pre-pubertal menstrual talks with family, and total number of family members did not influence the scores of MPNS. Multivariate regression analysis showed that maternal education, menstrual talks with family after puberty, and type of menstrual hygiene method including its disposability were independent predictors of total MPNS scores.
Conclusion: Addressing unmet menstrual practice needs among college-going women in Coimbatore district necessitates a multifaceted approach encompassing education, access to affordable and sustainable menstrual products, and destigmatization efforts.
Oxford-Palestine (OxPal) partnership: evaluation of an online medical research fellowship aiming to build local research capacity
Authors: Saini Kirandeep , Jurdon Rebecca , Conway-Jones Rebecca , Penfold Rose , Alser Osaid
Published: April 2024

Background
Innovative methods of delivering medical education across borders have the potential to further the development of healthcare capacity in austere environments. Medical students and doctors in the occupied Palestinian territory (oPt) face barriers to their education; whilst geographical, technological, and financial obstacles have limited the ability of institutions in high-income countries to share effective educational resources. We aimed to investigate the effectiveness of an international partnership in meeting the expressed educational needs of Palestinian medical students and doctors, through a locally tailored research training online course.
Methods
A needs assessment was used to guide the design, format, topic and content of an interactive lecture course. It was delivered to medical students in the oPt by clinicians & scientists from the U.K. and U.S.A. through an online lecture platform. The programme was evaluated through questionnaires and focus groups.
Results
We found students’ greatest expressed need was for supplementary teaching on medical research. Students perceived interactive online distance-teaching, delivered by utilising excess tutor capacity at educational-resource rich institutions, as equal (22%, n = 20) or superior (76%, n=71) to local in-person alternatives.
Conclusions
We demonstrate a low-cost, replicable method of supplementing medical education, generating engagement and building healthcare research capacity in an austere environment. Other institutions can rapidly deploy this model to upscale outreach efforts and improve global medical education.
A diagnostic model for hydraulic fracture in naturally fractured reservoir utilising water-hammer signal
Authors: Deng Shijie , Yi Liangping , Li Xiaogang , Yang Zhaozhong , Zhang Nanqiao
Published: April 2024

Diagnostic technique for hydraulic fracture based on the water-hammer pressure have been gradually highlighted owing to their cost effectiveness and simplicity. The present diagnostic models overlook the effects of fluid leak-off and natural fracture, and it is limited in naturally fractured reservoir. In this study, the location and number of hydraulic fractures are first obtained through the enhancement and cepstrum processing of a water-hammer signal. Subsequently, the water-hammer pressure within the wellbore is calculated by solving the continuity and momentum equations for the fluid. Wellbore and hydraulic fractures are considered as a hydraulic system. To estimate the fracture dimension, flow boundary conditions are imposed to the fluid leak-off, interactions between natural and hydraulic fractures, and multifracture stress shadows. Based on the results, (1) the fracturing shut-in method can be appropriately adjusted to avoid large pressure pulsations, which damage well integrity, and to obtain a clear water-hammer signal for fracture diagnosis. (2) As the perforation cluster spacing increases, the fractures on both sides first decrease and then increase, whereas the centre fracture increases consistently. (3) Natural fractures reduce the hydraulic fracture dimensions but facilitate the creation of complex fracture networks; however, this complexity cannot be increased indefinitely. (4) The minimum horizontal stress decreases the fracture dimension and a greater difference in the horizontal stress renders it easier for hydraulic fractures to cross natural fractures to create larger dimensions. (5) The field study demonstrates the practicality of our model, and optimisation measures can be recommended based on the diagnostic results.
First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma: a real-world study
Authors: Lin Yan-Song , Li Shuo , Yang Xia , Guo Rong-Ping , Huang Yu-Hua , Bai Kun-Hao , Weng Jun , Yun Jing-Ping
Published: April 2024

Purpose
Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC.
Methods
Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups.
Results
The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS and OS compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3–4 adverse events (AEs) compared with others.
Conclusion
In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.
Research on Sub-Pixel Accuracy Flange Disk Dimension Measurement Based on Machine Vision
Authors: Guo Jun , Yang Yang , Chen Yuxin
Published: April 2024

Addressing the inefficiencies and inaccuracies inherent in manual measurements of flange disk dimensions, we propose a machine vision-based method for sub-pixel measurement, alongside a dedicated visual measurement system. This system utilizes a CCD camera, calibrated via PyCharm software, to capture images of the flange disk. These images undergo preprocessing—conversion to grayscale, filtering, noise reduction, and binary segmentation—to delineate the flange disk area for further analysis. For edge detection, an improved Canny adaptive threshold selection algorithm is employed. Additionally, we introduce a new edge judgment criterion based on the Zernike algorithm, which, in conjunction with the advanced Canny operator for initial positioning, allows our refined Zernike matrix algorithm to accurately identify the flange disk edge with sub-pixel precision. The least squares fitting algorithm is then applied to determine the flange disk's outer and inner diameters accurately. A comparative analysis of experimental results demonstrates that our enhanced algorithm significantly reduces relative errors compared to both its predecessor and manual measurements. Importantly, the measurements obtained with the improved algorithm closely match manual measurements and are markedly more accurate than those achieved with the traditional Zernike matrix algorithm. This level of precision ensures that our measurement method meets the high accuracy requirements of industrial parts manufacturing.
Assessing reliability and validity of the Chi nese version of the Depression Change Exp ectancy Scale and its application in college students
Authors: Li Shuoshuo , Zhou Zhongtao , Cai Fulin , Cheng Ling , Du Weina , Bai Huaiyu , Li Qingyang , Wang Wenjuan , Zhang Jing
Published: April 2024

Background With mental health issues getting worse, depression plays an essential role in the development of individuals. There are few measurements of depression change expectancy for college students. This study examines the applicability of the Depression Change Expectancy Scale for Adults to a sample of Chinese college students. It provides a measurement tool for depression change expectancy among Chinese college students.
Methods According to the Brislin translation model, the first draft was translated and translated into the scale. The Chinese version of the scale was formed through expert localization debugging and pre-investigation. Using the convenience sampling method, 1138 students were surveyed in several medical schools in Anhui province from September to December 2023, and 481 students with depressive symptoms or tendencies were screened out for the reliability and validity analysis of the change in depression expectation scale.
Results: The scale has a good single-factor structure (CMIN/DF = 2.604, CFI = 0.973, TLI = 0.970, GFI = 0.912, NFI = 0.958, RMSEA = 0.058). The content validity (S-CVI) is 0.898, and each item's content validity (I-CVI) is 0.830 ~ 1.000. The coherence within The reliability analysis scale's Cronbach's coefficient is 0.910, and each dimension is 0.888–0.980. the test-retest reliability is 0.985, and each dimension's test-retest reliability is 0.982–0.985.
Conclusion According to this study, the Chinese version of the DCES has excellent validity and reliability. It may be used as a tool for evaluation to determine how patients' depression is changing over time.
Castor oil based biolubricant: optimization of the synthesis process and investigating its effects on two-stroke engine parameters
Authors: Soufi Masoud Dehghani , Sabzimaleki Mohammadreza , Khashehchi Morteza , Ghobadian Barat , Rahmanivahid Pooyan , Heidari Milad
Published: April 2024

Biolubricants are new generation of lubricants, which are vegetable based, renewable and eco-friendly. In this study, trimethylolpropane ester (biolubricant) was synthesized from castor oil methyl ester through transesterification reaction. The reaction was optimized using response surface methodology (RSM) and the optimal parameters were obtained for maximizing the reaction yield. In continuation, the physicochemical specifications of the purified product was measured and met the requirements of ISO-VG lubricant standard. The castor oil based biolubricant then was mixed with gasoline with 1:10 volumetric ratio and was used in a 200 cc two stroke petrol engine to investigate its effects on the performance and exhaust emissions of the engine. The optimal conditions for biolubricant synthesis reaction were obtained as the methyl ester to TMP molar ratio of 4.78:1, reaction temperature of 139.9°C, and the catalyst (potassium carbonate) concentration of 1.4%. In this optimum condition, the reaction yield was obtained as 96.13%. The engine tests results showed that the engine power and torque increases by 2.89% and 1.97%, respectively using castor oil based biolubricant compared with SAE10 oil. Moreover, the brake specific fuel consumption (BSFC) of the engine fuelled with biolubricant had a 4.6% decrease compared to the commercial two-stroke engine oil. It was also found that the produced castor biolubricant can significantly decrease the carbon monoxide and unburned hydrocarbons emissions of the engine by nearly 153% and 59%, respectively in comparison with SAE10 oil.
Experimental Methods for Establishing and Maintaining Canine Bladder Cancer Organoids
Authors: Elbadawy Mohamed , Zdyrski Christopher , Wickham Hannah , Saba Corey F , Thenuwara Savantha , Mosichuk Alison , Sahoo Dipak Kumar , Mochel Jonathan P. , Allenspach Karin
Published: April 2024

Dogs share many anatomical and physiological characteristics with humans and, in certain instances, represent a more reliable research model than rodents for some diseases, including several types of human cancer. Advances in adult stem cell research have accelerated the development of 3D organoid cultures in non-model animals, such as dogs. These advancements have the potential to significantly impact disease modeling, biomarker discovery, and drug development for both human and canine diseases, including bladder cancer (BC). In this Chapter, we present a standardized protocol for generating BC organoids from canines. The chapter describes the detailed methodology for establishing canine BC organoids from urine or tissue-derived stem cells. Additionally, it highlights the potential of these organoids to recapitulate the expression of key markers from their original tissues and their utility in various biomedical applications such as drug screening, gene mutation analysis, and toxicology. Finally, we discuss potential future research directions for canine BC organoids in translational research.
A Case Series of Patients with Altered Gut Anatomy Treated for Biliary Disease with Percutaneous Transhepatic Cholangioscopy with Lithotripsy
Authors: Chaudhary Ammad Javaid , Faisal Muhammad Salman , Ashraf Taha , Dang Duyen , Elatrache Mazen , Pompa Robert , Watson Andrew , Piraka Cyrus , Zuchelli Tobias , Singla Sumit
Published: April 2024

Background and Aims: Treating obstructive bile duct pathologies in individuals with altered bowel anatomy is challenging, since the physiological context may render endoscopic retrograde cholangiopancreatography (ERCP) difficult or unfeasible. Percutaneous transhepatic cholangiography (PTC) with drain placement can provide adequate drainage in this patient group, but it has limited therapeutic options.
Methods: In this case series, we present 14 patients with altered bowel anatomy who underwent PTC drain placement followed by percutaneous cholangioscopy (PC) between January 2015 and May 2022 at a single institution.
Results: Of the 14 patients, most common indication for PTC was choledocholithiasis in 13 (92.9%) patients and 8 (57.1%) of these patients exhibited cholangitis on initial presentation. The mean age was 66.4 years, and most were female (64.3%). All patients had altered anatomy, with Roux-en-Y gastric bypass being the most common (71.4%). There were 3 patients who had previous unsuccessful attempts at ERCP. Pre-procedural laboratory tests indicated elevated mean liver enzyme levels, and all cases of choledocholithiasis were successfully treated (92.9%). No complications were reported in any patients after a mean follow-up period of more than 2 years.
Conclusions Cholangioscopy and lithotripsy via the PTC route may be a viable therapeutic option, with a high success rate and low risks, when ERCP is challenging or impossible due to patient’s altered gut anatomy.
Approximate KNN Query Processing of Multiple Data Sources Based on Data Source Selection
Authors: Zhang Yu , Song Xin , Wei Yonggang
Published: April 2024

A KNN query aims to identify the K closest neighbors or tuples from a dataset based on a specified distance metric. This paper delves into the realm of approximate KNN query processing, focusing on the meticulous selection of multiple data sources characterized by diverse dimensions. We provide a framework for processing approximate KNN queries over multiple data sources, proposing algorithms to construct a UBR-Tree and a Centroid Base for selecting related data sources and retrieving KNN tuples. We enhance and apply an index structure to quickly retrieve related data sources and KNN tuples for a query. For a KNN query Q, the query processing consists of the following steps: (1) Estimate a search distance using the index structure. (2) Use the search distance to select relevant data sources from the Centroid Base, sorting them according to their representative tuple. (3) Employ a heap structure to merge the local KNN tuples obtained from the related data sources to form global KNN tuples for Q. Additionally, update the index structure when processing the query. Extensive experiments over low-dimensional and high-dimensional datasets demonstrate the performances of our proposed approaches.
RETRACTED: Nanocomputing ALU: Harnessing Quantum-inspired Principles for Enhanced Processing
Authors: Krishna Yellapragada Charan
Published: April 2024

The authors have requested that this preprint be removed from Research Square.
Time-series of Landsat-based spectral indices for continental Europe for 2000--2022 to support soil health monitoring
Authors: Tian Xuemeng , Hengl Tom , Consoli Davide , Schneider Florian , Parente Leandro , Şahin Murat , Minařík Robert , Ho Yu-Feng
Published: April 2024

As the importance of soil health in supporting European ecosystems and agriculture becomes increasingly critical, effective monitoring is essential for its protection and restoration. This paper describes production and quality assessment of a data cube (17TB in size) derived from Landsat Analysis Ready Data version 2 (ARD V2) dataset and tailored for soil health monitoring, featuring multiple spectral indices, long time span, high resolution, and analysis readiness. The focus was on indices of importance for monitoring soil health: Normalized Difference Vegetation Index (NDVI), Soil Adjusted Vegetation Index (SAVI), Fraction of Absorbed Photosynthetically Active Radiation (FAPAR), Normalized Difference Snow Index (NDSI), Normalized Difference Water Index (NDWI), Normalized Difference Tillage Index (NDTI), minimum Normalized Difference Tillage Index (minNDTI), Bare Soil Fraction (BSF), Number of Seasons (NOS) and Crop Duration Ratio (CDR). The data set is available with a resolution of 30~m, with bimonthly (i.e. one image available per two months), annual, and long-term analysis throughout continental Europe, including Ukraine, the UK, and Turkey, covering 2000 to 2022. The results of the quality assessment, including both visual examination and plausibility check with ground survey data, show that these indices can effectively capture environmental processes and offer insight into soil health through aspects such as vegetation, crop status, tillage practices, and soil exposure directly or serve as covariates in digital soil mapping. In particular, the BSF shows a strong negative correlation of -0.73 with crop coverage data from 2006 to 2017, suggesting an effective detection of soil exposure. The minNDTI shows a moderate positive correlation of 0.57 with the Eurostat tillage practices survey data, indicating that it provides valuable information on tillage intensity, although not definitively. This data set is analysis-ready and cloud-optimized, making it suitable for applications in soil property mapping and the development of comprehensive soil health assessment approaches throughout Europe.
Exact instanton transseries for quantum mechanics
Authors: van Spaendonck Alexander , Vonk Marcel
Published: April 2024

We calculate the instanton corrections to energy spectra of one-dimensional quantum mechanical oscillators to all orders and unify them in a closed form transseries description. Using alien calculus, we clarify the resurgent structure of these transseries and demonstrate two approaches in which the Stokes constants can be derived. As a result, we formulate a minimal one-parameter transseries for the natural nonperturbative extension to the perturbative energy, which captures the Stokes phenomenon in a single stroke. We derive these results in three models: quantum oscillators with cubic, symmetric double well and cosine potentials. In the latter two examples, we find that the resulting full transseries for the energy has a more convoluted structure that we can factorise in terms of a minimal and a median transseries. For the cosine potential we briefly discuss this more complicated transseries structure in conjunction with topology and the concept of the resurgence triangle.
Discounted Mean-Field Game model of a dense static crowd with variable information crossed by an intruder
Authors: Butano Matteo , Appert-Rolland Cécile , Ullmo Denis
Published: April 2024

It was demonstrated in [Bonnemain et al., Phys. Rev. E 107, 024612 (2023)] that the anticipation pattern displayed by a dense crowd crossed by an intruder can be successfully described by a minimal Mean-Field Games model. However, experiments show that changes in the pedestrian knowledge significantly modify the dynamics of the crowd. Here, we show that the addition of a single parameter, the discount factor \gammaγ, which gives a lower weight to events distant in time, is sufficient to observe the whole variety of behaviors observed in the experiments. We present a comparison between the discounted MFG and the experimental data, also providing new analytic results and insight about how the introduction of \gammaγ modifies the model.