bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on induction heating process to join carbon reinforced polyamide (CF-PA6) composite sheets in the presence of metallic interlayer AA 1060 and AISI 1020
Authors: Das Bipul
Published: December 2023

Carbon-fibre-reinforced polymers have been extensively utilized in aviation, automobile and other critical sectors owing to their high strength-to-weight ratio and excellent stiffness. In these industrial usage, the material has to undergo various processes and joining is one of such critical processes. However, the classical joining techniques such as the use of mechanical fasteners and adhesives often result in stress concentration, increased weight, and large processing times unique to each curing cycle. The current research work demonstrates the potential of induction heating for joining carbon-fibre-reinforced polyamide and the influence of the interlayer materials on the joining process. AISI 1020 and AA1060 were used as the interlayer materials for joining the composite material. Numerical investigation of the induction heating was carried out considering the influence of process parameters such as coil current and stand-off distance on magnetic flux density, temperature distribution in the interlayer material. The analysis revealed that stand off distance of 6 mm and coil current 150 A were chosen as optimal process parameters with AISI 1020 as interlayer whereas with AA1060 as interlayer, stand-off distance 2 mm and coil current 200 A were chosen to achieve uniform heating with short processing time.
Novel Standardized Indexes of brainstem auditory evoked po-tentials （BAEPs）for Predicting Hearing Preservation in Vestibular Schwannomas
Authors: Jiao Liwu , Liu Xuyang , Zhu Hongtao , Guo Chao , Wang Junwen , Shu Kai
Published: December 2023

Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 minutes). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post- tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.
“I couldn´t say goodbye”: Thematic analysis of interviews with bereaved relatives who lost their loved ones during the COVID-19 pandemic
Authors: Vlckova Karolina , Polakova Kristyna , Houska Adam , Zindulkova Marketa , Loucka Martin
Published: December 2023

Background
Delivering serious news is usually challenging for healthcare professionals and the pandemic of COVID-19 and related restrictions brought additional challenges in this process. This study aimed to explore the experience of bereaved relatives with receiving serious news from healthcare providers during the pandemic COVID-19.
Methods
This was a qualitative study using deductive thematic analysis of data collected in semi-structured interviews with bereaved relatives. Data were collected from July to August 2022 in person/via phone with bereaved relatives who lost their relatives during the pandemic (from March 2020 to March 2022). Participants were recruited using a convenience sample and snowball method through social media and through one university hospital palliative care unit that invited bereaved relatives of deceased patients treated at the unit to participate in this study.
Results
A total of 22 participants, consisting of 4 men and 18 women, were interviewed for this study. Most of the participants were sons or daughters of individuals who had passed away (5 grandchildren, 14 sons/daughters, 2 spouses, 1 great-niece). Six themes were identified: Tendency to express understanding for difficult conditions of care, Reduced contact with loved ones, Fear of COVID-19, Lack of empathetic communication with staff, Need for emotional support, Need for detailed and honest communication.
Conclusions
Overcoming the challenging circumstances of delivering serious news during a pandemic can be achieved by implementing frequent communication using various communication tools, maintaining empathy and honesty in the communication process, and providing detailed information to relatives despite visiting restrictions.
Hybrid simplicial-randomized approximate stochastic dynamic programming for multireservoir optimization
Authors: Zephyr Luckny , Lamond Bernard F. , Lang Pascal
Published: December 2023

We revisit an approximate stochastic dynamic programming method that we proposed earlier for the optimization of multireservoir problems. The method exploits the convexity properties of the value function to sample the reservoir level space based on the local curvature of the value function, which is estimated by the difference between a lower and an upper bounds (error bound). Unlike the previous approach where the state space was exhaustively partitioned into full dimensional simplices whose vertices formed a discrete grid over which the value function was approximated, here we propose instead a new randomized approach for selecting the grid points from a small number of randomly sampled simplices from which an error bound is estimated. Results of numerical experiments on three literature test problems and simulated midterm reservoir optimization problems illustrate the advantages of the randomized approach which can solve models of higher dimensions than with the exhausitive approach.
A Cross-Sectional Survey on Generation Z Physicians: Professional Value, Educational Expectations, and Work Environment Preferences
Authors: Satoh Kasumi , Mitani Yuki , Ishikane Masahiro , Kamada Shuhei
Published: December 2023

Generation Z (Gen Z) physicians, born between the mid-1990s and the mid-2010s, bring unique professional values and expectations to clinical practice shaped by technological and socioeconomic changes. This study explored these aspects of Gen Z physicians in Japan. A cross-sectional survey focusing on professional values, job-related training, supervisor attitudes, and work environments was conducted among first-year to third-year physicians in Japan. The participants were categorized into Gen Z (≤ 29 years) and non-Gen Z groups. Wilcoxon rank-sum tests identified significant differences between the groups. Of the 429 respondents, 391 were Gen Z members. They value job satisfaction, working for the benefit of others, embracing new challenges, and desire immediate feedback. Notable differences between Gen Z and non-Gen Z members include viewing work primarily as a means of personal life and preferences for teamwork, immediate feedback, proactive communication from supervisors, and chat-based workplace communication. Japanese Gen Z physicians prioritize internal motivation, economic stability, immediate feedback, digital technological integration, and collaborative work environments. These findings necessitate adapted approaches to medical education and workplace settings that align with the distinct outlook of this generation.
Welding of additive manufacturing AlSi10Mg alloys using a laser metal deposition process with different heat input
Authors: Li Jingchuan , Cui Li , Wu Defan , Wang Can , Shi Zhenfu , He Dingyong , Cao Qing
Published: December 2023

Welding of AlSi10Mg alloys fabricated by additive manufacturing (AM) has been recently conducted in response to the demands for joining or repairing the AM parts. However, high susceptibility to porosity occurred in the weld metal (WM) poses a significant challenge for fusion welding of AM AlSi10Mg alloys. The laser metal deposition (LMD) process has emerged as a promising welding solution due to its low dilution rate for reducing the porosity. In this study, LMD welding of AM AlSi10Mg alloys was carried out employing different heat input with five and eight tracks. The study systematically assessed the impact of heat input on porosity, microstructure, microhardness, and tensile properties of the welded joints. As a result, the decrease of heat input from 200 to 65 J/mm results in a substantial reduction in porosity from 7.0% to 2.1%. Additionally, this reduction leads to a 29.4% increase in ultimate tensile strength (UTS) and an 11.7% increase in elongation-to-failure (EI). Notably, the upper region of joints with eight tracks possessing low heat input displays lower porosity and superior mechanical properties than the bottom region with relatively high heat input. Furthermore, the WM with eight tracks exhibits a refinement of α-Al cells and Si-rich eutectic phases, improved connectivity of Si-rich networks, increased solid solution strengthening, compared to the five-track joints with higher heat input. In conclusion, low heat input of the upper region in the LMD welded joints has proven effective in minimizing hydrogen pores, enhancing WM microstructure, and improving the mechanical properties of welded joints.
Long noncoding RNA BANCR promotes lymphangiogenesis and lymph node metastasis of pancreatic carcinoma by regulating VEGF-C/VEGFR-3 signaling pathway
Authors: Hao Shaolong , Li Zeqian , Ji Yu , Sun Hao , Nie Fang , Hu Yang , Zhang Bo , Ji Kailun , Ding Yuchuan , Han Wei
Published: December 2023

Background Long noncoding RNAs ( lncRNAs) have proved to play important roles in the tumorigenesis and development of pancreatic carcinoma (PC). The aim of our study is to investigate the expression of long noncoding BRAF-activated noncoding RNA (BANCR) and its role in PC lymph node metastasis. Methods BANCR expression was detected in PC tissues by using Real-time quantitative PCR (RT-qPCR). The correlation between BANCR expression and lymph node metastasis was analyzed. Immunofluorescence staining was used to determine microlymphatic vessel density (MLVD) of peritumoral tissues. The correlation between MLVD and lymph node metastasis and the association between BANCR expression and MLVD were also analyzed. VEGF-C and VEGFR-3 expressions in PC cells were detected by western blotin vitro, and the regulatory role of BANCR on VEGF-C/VEGFR-3 was identified by cell transfection techniques. The transfected PC cells were co-cultured with human lymphatic endothelial cells (HLECs) and the MLVD was detected by the magnification inverted fluorescence microscope. Results BANCR expression was remarkably increased in PC tissues, especially in the lymph node metastasis group (P < 0.0001). MLVD of the PC tissues in the lymph node metastasis group was significantly higher than the group without lymph node metastasis (P < 0.0001). The BANCR expression level significantly correlated with MLVD (P < 0.05). The result was further verified in PC cell lines. Depletion of BANCR inhibits lymphangiogenesis and down regulates VEGF-C/VEGFR-3 (P < 0.05). However, Overexpression of VEGF-C could counteract the inhibitory effect of siBANCR on lymphangiogenesis. Conclusions BANCR promotes lymphangiogenesis and lymph node metastasis of PC by regulating the VEGF-C /VEGFR-3 signaling pathway.
Study on the weakening law of mechanical properties and damage constitutive model of pre-cracked cyan sandstone after freeze-thaw cycle
Authors: Zhang Chunyang , Li Wanru , Zhao Ercheng , Tan Tao , Ren Qinglin , Huang Shibing
Published: December 2023

Water-bearing fractured rock masses are prone to geological hazards due to freeze-thaw (FT) damage, which brings adverse effects on the stability of rock engineering. In order to study the FT damage characteristics of rocks, the intact and pre-cracked samples of cyan sandstone were taken as the research objects, with pre-crack inclination angles (β) of 0°, 45°, and 90°, respectively. The effects of FT cycle on stress-strain curve, peak strength, apparent stiffness and FT coefficient were investigated by uniaxial compression test after different times of FT damage treatment. Based on macro damage variables, a damage constitutive model of cyan sandstone is proposed by combining strain equivalence hypothesis and Weibull distribution hypothesis. Considering that the strain equivalent hypothesis is difficult to reflect the compaction effect of microfracture, the damage constitutive equation is modified with the ratio of the secant modulus of the actual stress-strain curve to that of the classical Lemaitre damage constitutive curve as the correction coefficient. The application results show that the modified constitutive model can well describe the stress-strain relationship of cyan sandstone before the peak strength, verify the reliability of the model parameters derived from the test data, and the practicability of the damage characterization method and correction coefficient. The results can provide theoretical reference for the study of FT damage of rocks in cold regions.
Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela
Authors: Eligulashvili Anna , Darrell Megan , Gordon Moshe , Jerome William , Fiori Kevin P , Congdon Seth , Duong Tim Q.
Published: December 2023

This study investigated long COVID of patients in the Montefiore Health System COVID-19 (CORE) Clinics in the Bronx with an emphasis on identifying health related social needs (HRSNs). We analyzed a cohort of 643 CORE patients (6/26/2020-2/24/2023) and 52,089 non-CORE COVID-19 patients. Outcomes included symptoms, physical, emotional, and cognitive function test scores obtained at least three months post-infection. Socioeconomic variables included median incomes, insurance status, and HRSNs. The CORE cohort was older age (53.38 ± 14.50 versus 45.91 ± 23.79 years old, p < 0.001), more female (72.47% vs 56.86%, p < 0.001), had higher prevalence of hypertension (45.88% vs 23.28%, p < 0.001), diabetes (22.86% vs 13.83%, p < 0.001), COPD (7.15% vs 2.28%, p < 0.001), asthma (25.51% vs 12.66%, p < 0.001), lower incomes (53.81% vs 43.67%, 1st quintile, p < 0.001), and more unmet social needs (29.81% vs 18.49%, p < 0.001) compared to non-CORE COVID-19 survivors. CORE patients reported a wide range of severe long-COVID symptoms. CORE patients with unmet HRSNs experienced more severe symptoms, worse ESAS-r scores (wellbeing, shortness of breath, anxiety, and depression), PHQ-9 scores (overall: 12.05 ± 7.07 vs 7.71 ± 6.35, p < 0.001), and GAD-7 scores (overall: 9.26 ± 6.63 vs 5.28 ± 5.72, p < 0.001) compared to CORE patients without. Patients with unmet HRSNs experienced worse long-COVID outcomes compared to those without.
Adolescent girls’ explanations of high rates of low mood and anxiety in their population: A co-produced qualitative study
Authors: Demkowicz Ola , Jefferson Rebecca , Nanda Pratyasha , Foulkes Lucy , Lam Jo , Pryjmachuk Steven , Evans Rhiannon , Dubicka Bernadka , Neill Liz , Winter Laura Anne , Nnamani Georgina
Published: December 2023

Background: From early adolescence, girls face greater risk of experiencing low mood and anxiety, with recent evidence that this may be worsening. There is a paucity of mental health research that meaningfully progresses understanding of such disparities, including that engages adolescent girls’ own perspectives, limiting our ability to direct further research and enhance intervention approaches.
Aims: We examined low mood and anxiety from the perspective of adolescent girls, rather than relyingon researcher hypotheses, asking: What do adolescent girls perceive to be causing their population’s high rates of low mood and anxiety?
Methods: We adopted a co-produced qualitative design, guided by ecological systems theory, conducting focus groups in 2022 with 32 adolescent girls aged 16 to 18 years in England, and analysing with reflexive thematic analysis.
Analysis: Participants framed low mood and anxiety among adolescent girls as ‘normal’, and discussed potential explanations including persistent reiteration and expectation of gendered norms, intense educational pressures in ways that can be gendered, difficulties within peer relationships, and comparison and insecurity in social media contexts. Throughout, participants highlighted complexities including individual differences, sociodemographic contexts, and societal contexts.
Conclusions: The study offers a critically important contribution to evidence on gendered inequalities in low mood and anxiety, drawing attention to the interwoven and complex nature of girls’ lives, and holds policy and practical relevance to enhance systems to meet girls’ needs.
Investigating the Physical and Electrical Properties of La 2 O 3 Via Annealing of La(OH) 3
Authors: Ismail Walid , Belal Aya , Abdo Walied , El-Shaer Abdelhamid
Published: December 2023

A simple technique was used to fabricate pure La2O3 nanorods with a hexagonal structure using lanthanum (III) nitrate hexahydrate (La(NO3)3.6H2O) and ammonia (NH4OH). The La2O3 nanoparticles were characterized using XRD, TGA, Raman, SEM, FTIR, PL spectroscopy, and Mott-Schottky. XRD analysis showed the production of La(OH)3 nanorods under appropriate conditions, which were then successfully converted into La2O2CO3 and finally into La2O3 nanorods by annealing. TGA revealed that the total weight loss was caused by water evaporation and the dissolution of the minimal quantity of moisture present in the manufactured La2O3 NPs observed from the environment. The presence of functional groups was verified through FTIR analysis. Additionally, SEM revealed changes in morphology. PL findings displayed three emission peaks at 390, 520, and 698nm due to interband transitions and defects in the samples. Mott–Schottky analysis demonstrated that the flatband potential and acceptor density varied with annealing temperature, ranging from 1 to 1.2 V and 2 × 1018 to 1.4×1019 cm-3, respectively. Furthermore, annealing at 1000°C resulted in the lowest resistance to charge transfer (Rct).
Urban Opening Up,Industrial Agglomeration, and Export Survival of Chinese Enterprises
Authors: Wang Jiayin
Published: December 2023

In this study, which utilizes matched data from 254 cities and micro-enterprises in China, we employ the Kaplan-Meier function and survival analysis model to examine the impact of urban opening up and industrial agglomeration, as well as their interaction, on enterprises’ export survival. The findings indicate that urban opening up enhances the probability and duration of enterprises’ export survival through the mechanisms of competition, learning, and spillover effects. However, these effects display a scale threshold and demonstrate an inverted “U” shaped pattern of agglomeration spillover. By addressing endogeneity concerns through the use of the geographical distance between each prefecture-level city and the nearest port as an instrumental variable for urban opening up, as well as by modifying the measurement techniques of core indicators and the sample selection range, we verify the robustness of the results. Furthermore, our additional analysis reveals that industrial agglomeration improvement has a crowding-out effect on the promoting impact of urban opening up on export survival. In comparison to the central and western regions, urban opening up and industrial agglomeration in the eastern areas exhibit a higher degree of alignment and a relatively smaller crowding-out effect. Moreover, based on the analysis of enterprise ownership differentiation, we observe that foreign-funded enterprises benefit from the combined influence of urban opening up and industrial agglomeration, which consequently enhances their likelihood of export survival. However, the extensive urban opening up diminishes the spillover effect of industrial agglomeration on non-state-owned domestic enterprises. In contrast, state-owned enterprises are not subject to the negative influence from this coupling effect. Mechanism testing confirms the importance of spillover and learning effects as crucial mechanisms through which urban opening up promotes enterprises’ export survival. This article contributes to a comprehensive understanding of the mechanisms underlying urban opening up, industrial agglomeration, and their combined effects on enterprise export survival. It holds significant implications for government policymakers aiming to enhance the quality of external opening and achieve domestic industrial upgrading.
JEL classifications: F061; F11; F14; F16; F41; R12
Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates vascular remodeling in MCT-induced pulmonary arterial hypertension
Authors: Chen Xiaojun , Yu Xing , Lian Guili , Tang Huibin , Yan Yan , Gao Gufeng , Huang Bangbang , Luo Li , Xie Liangdi
Published: December 2023

Background
Pulmonary arterial hypertension (PAH) is a progressive, devastating vascular disease that eventually leads to right heart failure (RHF). Recent studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) are effective in reducing cardiovascular events in patients with HF, but their efficacy in treating PAH remains uncertain. The aim of this study was to investigate the effects of canagliflozin (CANA), an SGLT2i with mild SGLT1 inhibitory effects, on rats with PAH, as well as its direct impact on pulmonary arterial smooth muscle cells (PASMCs).
Methods
PAH was induced in rats by subcutaneous injection of monocrotaline (MCT) (40 mg/kg), followed by 4 weeks of treatment with CANA by gavage (30 mg/kg/day) or saline alone. Echocardiography, hemodynamic measurements, and histological staining were performed to evaluate pulmonary vascular and right ventricular (RV) structure and function. The effect of CANA on cell proliferation was further investigated in PASMCs. Platelet-derived growth factor (PDGF)-BB, AMP kinase (AMPK) inhibitor compound C (CC) and siSGLT1 were utilized to explore the molecular regulation mechanism of CANA.
Results
Pulmonary artery and RV remodeling and dysfunction in PAH were alleviated with CANA, as assessed by echocardiography. Hemodynamic parameters, such as RV systolic pressure, and structural of pulmonary arteriole, including vascular wall thickness and wall area, were reduced by CANA treatment. RV hypertrophy index, cardiomyocyte hypertrophy, and fibrosis were decreased with CANA treatment. In vitro, PASMCs proliferation was inhibited by CANA, regardless of PDGF-BB stimulation. Activation of AMPK was induced by CANA treatment in cultured PASMCs in a time- and concentration-dependent manner. These effects of CANA were attenuated by treatment with CC. Abundant expression of SGLT1 was observed in PASMCs and pulmonary arteries of rats, while SGLT2 expression was undetectable. SGLT1 was increased in response to PDGF-BB stimulation, while PASMCs proliferation was inhibited and beneficial effects of CANA were counteracted by knockdown of SGLT1.
Conclusions
It is demonstrated for the first time that CANA inhibited the proliferation of PASMCs by regulating SGLT1/AMPK signaling and thus exerted an anti-proliferative effect on MCT-induced PAH. Our research revealed a novel mechanism for the beneficial effects of CANA on pulmonary vasculature.
PMNet: A Multi-branch and Multi-scale Semantic Segmentation Approach to Water Extraction from high-resolution remote sensing images with Edge-Cloud Computing
Authors: Zhang Ziwen , Liu Qi , Liu Xiaodong , Zhang Yonghong , Du Zihao , Cao Xuefei
Published: December 2023

In the field of remote sensing image interpretation, automatically extracting water body information from high-resolution images is a key task. However, facing the complex multi-scale features in high-resolution remote sensing images, traditional methods and basic deep convolutional neural networks are difficult to effectively capture the global spatial relationship of the target objects, resulting in incomplete, rough shape and blurred edges of the extracted water body information. Meanwhile, massive image data processing usually leads to computational resource overload and inefficiency. Fortunately, the local data processing capability of edge computing combined with the powerful computational resources of cloud centres can provide timely and efficient computation and storage for high-resolution remote sensing image segmentation. In this regard, this paper proposes PMNet, a lightweight deep learning network for edge-cloud collaboration, which utilises a pipelined multi-step aggregation method to capture image information at different scales and understand the relationships between remote pixels through horizontal and vertical spatial dimensions. Also, it adopts a combination of multiple decoding branches in the decoding stage instead of the traditional single decoding branch. The accuracy of the results is improved while reducing the consumption of system resources. The model obtained F1-score of 90.22 and 88.57 on Landsat-8 and GID remote sensing image datasets with low model complexity, which is better than other semantic segmentation models, highlighting the potential of mobile edge computing in processing massive high-resolution remote sensing image data.
Mesothelin expression correlates with elevated inhibitory immune activity in patients with colorectal cancer
Authors: malla Midhun , Deshkmukh Sachin Kumar , Wu Sharon , Samec Timothy , Olevian Dane , Naili Reima , Bassel El-Rayes , Xiu Joanne , Farrell Alex , Lenz Heinz-Josef , Lou Emil , Goel Sanjay , Spetzler David , Goldberg Richard M. , Hazlehurst Lori
Published: December 2023

The expression of the protein Mesothelin (MSLN) is highly variable in several malignancies including colorectal cancer (CRC) and high levels are associated with aggressive clinicopathological features and worse patient survival. CRC is both a common and deadly cancer; being the third most common in incidence and second most common cause of cancer related death. While systemic therapy remains the primary therapeutic option for most patients with stage IV (metastatic; m) CRC, their disease eventually becomes treatment refractory, and 85% succumb within 5 years. Microsatellite-stable (MSS) CRC tumors, which affect more than 90% of patients with mCRC, are generally refractory to immunotherapeutic interventions. In our current work, we characterize MSLN levels in CRC, specifically correlating expression with clinical outcomes in relevant CRC subtypes and explore how MSLN expression impacts the status of immune activation and suppression in the peritumoral microenvironment. High MSLN expression is highly prevalent in CMS1 and CMS4 CRC subtypes as well as in mCRC tissue and correlates with higher gene mutation rates across the patient cohorts. Further, MSLN-high patients exhibit increased M1/M2 macrophage infiltration, PD-L1 staining, immune-inhibitory gene expression, enrichment in inflammatory, TGF-β, IL6/JAK/STAT3, IL2/STAT5 signaling pathways and mutation in KRAS and FBXW7. Together, these results suggest MSLN protein is a potential target for antigen-specific therapy and supports investigation into its tumorigenic effects to identify possible therapeutic interventions for patients with high MSLN expressing MSS CRC.
Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice
Authors: Nogueira Margareth , Golbert Daiane Ferreira , Menezes Richardson , Almeida Raíssa , Coelho Nicole Galvao , Siroky Andressa , Lima Thiago , Maia Helton , Leao Katarina , Leao Richardson
Published: December 2023

Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are suggested to have plasticity-inducing action. One lesser studied psychedelic, the 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), is suggested to have anxiolytic effects yet a comprehensive mechanism of action is still lacking. Here, we investigated the effects of a single high-dose of the short-acting 5-MeO-DMT on gene expression from microdissected brain regions (anterior cingulate cortex - ACC; basolateral amygdala - BLA; ventral hippocampus CA1 region - vCA1 and dentate gyrus - DG) of naive and stressed mice. Specifically, we compared gene expression of Arc, Zif268, BDNF, CREB, mTORC1, NR2A, TRIP8b and NFkB in mice injected with 5-MeO-DMT or saline at different time points (1 hr, 5 hrs or 5 days prior). 5-MeO-DMT altered mRNA expression of immediate early genes Arc and ZiF268 in the ACC, BLA and vCA1, while only NR2A expression was altered after 5 hrs in the vCA1. We also found a long-term increase in TRIP8b, a gene related to the modulation of neuronal activity, in the vCA1 after 5 days. Behaviorally, 5-MeO-DMT treated mice showed mixed anxiolytic and anxiogenic effects in the elevated plus maze and open field test 24 hr or 5 days after treatment. However, pre-treated mice subjected to acute stress showed both lower corticosterone levels and robust anxiolytic effects of 5-MeO-DMT administration. Together, our findings provide insights into the molecular actions of 5-MeO-DMT in the brain related to anxiolytic effects of behavior.
A saturated 1-system of curves on the surface of genus 3
Authors: Zhai Zhaoshen
Published: December 2023

We construct a saturated system of 33 essential simple closed curves that are pairwise non-homotopic and intersect at most once on the oriented, closed surface of genus 3.
Low-Cost Laser for Affordable Graphene-Induced Microband Sensor Fabrication
Authors: Ribeiro Leonardo M. A. , Feria Deissy J. , Falcoswki Paula C. , Carreño Marcelo N. P. , Pereyra Inés , Bertotti Mauro
Published: December 2023

Graphene microband electrodes were fabricated by direct laser writing on Kapton® polyimide tape utilizing a low-cost, blue laser (500 mW and 405 nm). The structural properties of the graphene were examined by Raman spectroscopy, and key features such as D, G, and 2D bands, and the presence of multilayer structures were revealed. Scanning electron microscopy (SEM) provided insights into the microband morphology, highlighting the 3D (foam-like) nature of the graphene microbands. Electrochemical experiments revealed cyclic voltammetry profiles that demonstrated radial diffusion dominance at low scan rates and Randles–Sevcik behavior at higher scan rates. Reproducibility and repeatability analyses confirmed the stability and consistency of these microband electrodes within individual devices. Scanning electrochemical microscopy (SECM) images revealed the electrochemical reactivity of the microbands. At a relatively low microband separation (200 µm), the produced material can be collected at the adjacent microband, which was confirmed via generator/collector experiments. Theoretical-experimental comparisons regarding the current measured for a single microband were performed, and the obtained results were in good agreement, with deviations attributed to the 3D morphology of the microbands. This research underscores the potential of these cost-effective and reproducible graphene microband electrodes for diverse applications in electrochemical sensing, and we present preliminary results on caffeic acid and paracetamol detection.
Expression and processing of mature human frataxin after gene therapy in mice
Authors: Rojsajjakul Teerapat , Selvan Nithya , De Bishnu , Rosenberg Jonathan B. , Kaminsky Stephen M. , Sondhi Dolan , Janki Peter , Crystal Ronald G. , Mesaros Clementina , Khanna Richie , Blair Ian A.
Published: December 2023

Friedreich’s ataxia is a degenerative and progressive multisystem disorder caused by mutations in the highly conserved frataxin (FXN) gene that results in FXN protein deficiency and mitochondrial dysfunction. While gene therapy approaches are promising, consistent induction of therapeutic FXN protein expression that is sub-toxic has proven challenging, and numerous therapeutic approaches are being tested in animal models. FXN (hFXN in humans, mFXN in mice) is proteolytically modified in mitochondria to produce mature FXN. However, unlike endogenous hFXN, endogenous mFXN is further processed into N-terminally truncated, extra-mitochondrial mFXN forms of unknown function. This study assessed mature exogenous hFXN expression levels in the heart and liver of C57Bl/6 mice 7–10 months after intravenous administration of a recombinant adeno-associated virus encoding hFXN (AAVrh.10hFXN) and examined the potential for hFXN truncation in mice. AAVrh.10hFXN induced dose-dependent expression of hFXN in the heart and liver. Interestingly, hFXN was processed into truncated forms, but found at lower levels than mature hFXN. However, the truncations were at different positions than mFXN. AAVrh.10hFXN induced mature hFXN expression in mouse heart and liver at levels that approximated endogenous mFXN levels. These results demonstrate that AAVrh.10hFXN may induce expression of therapeutic levels of mature hFXN in mice.
Earthquake Risks and Lack of Disaster Management in Afghanistan
Authors: Akhundzadah Noor Ahmad
Published: December 2023

Afghanistan is in a seismically active area and is historically hit by destructive earthquakes. It is located on the edge of the Eurasian tectonic plate, bordered by the northern boundary of the Indian plate, and with the collisional Arabian plate into the South. Afghanistan's Hindukush and Pamir Mountains are the western extension of the Himalayan orogeny uplifted and sheared by Indian and Eurasian plate convergence. These tectonic activities have created several active deep faults across the country and in the Hindukush-Himalayan region, where high-magnitude earthquakes have historically occurred. Earthquakes in Afghanistan are primarily driven by the relative northward movements of the Arabian plate past western Afghanistan and the Indian plate past eastern Afghanistan as both plates subduct under the Eurasian plate. These tectonic movements caused ground shaking from high to moderate and low from the northeast through the country's southwest. On June 22, 2022, the southeastern part of Afghanistan was hit by a destructive Mw6.2 earthquake. The purpose of this study is to develop an ArcGIS Pro database of compiled geologic faults and regions of heightened seismicity for spatial analyses of earthquake disaster severity across Afghanistan. These spatial analyses place better constraints on the placement of active and historic seismicity along mapped and known active faults for progress in earthquake disaster management. Furthermore, we define current hazards associated with building and infrastructural design and competency given the recurrent and eminent seismicity within Afghanistan and describe possible directions and solutions to mitigate the threat to life and property.
Far infrared radiation ameliorates non-alcoholic fatty liver disease in mice by activating AMPK
Authors: xu tianyi , Fu Haijing , zhao wumei , ye chenyan , Shan Shijun
Published: December 2023

Background & Aims:Non-alcoholic fatty liver disease (NAFLD) is a disease that causes an abnormal accumulation of fat in the liver, triggering inflammation and liver damage, the mechanism of which is not fully understood and for which there is a lack of specific drug therapy. Far infrared radiation (FIR) has demonstrated evident therapeutic efficacy across various diseases, and it can be emitted by novel nanomaterial graphene patches through electric heating. This study aimed to investigate the potential protective effects of FIR against NAFLD.
Methods: Mice were fed with MCD diet to mimic NAFLD progression, and the effect of FIR on NAFLD was assessed by histopathology analysis, biochemical analysis, RT-qPCR, and Western blotting analysis. The effect of FIR treatment on lipid deposition in hepatocytes was investigated by cell culture in vitro.
Results: Mice subjected to MCD diet and treated with FIR exhibited reduced hepatic lipid deposition, liver damage and inflammation. The therapeutic effect exerted by FIR in mice is most likely attributed to the enhancement of AMPK phosphorylation. Besides, FIR intervention alleviated lipid accumulation in hepatocytes in vitro.
Conclusion: Our results revealed a promising potential of FIR as a novel therapeutic approach for NAFLD.
Nascent Competition and Killer Acquisitions in Digital Markets: a Decade of Acquisitions by Big Tech
Authors: Lemos Thales de Melo e , Resende Guilherme Mendes
Published: December 2023

Acquisitions in digital markets by dominant companies such as Google, Apple, Facebook, Amazon and Microsoft (GAFAM) raise concerns related to the elimination of potential and nascent competition. While demands for merger control reforms in this segment are proliferating, there are still important controversies and insufficient systemic studies on the matter. Therefore, this study evaluates, based on theoretical and empirical research, the hypothesis that acquisitions of nascent competitors and killer acquisitions are not common enough in digital markets to justify drastic changes in merger control rules. To this end, we more rigorously define important terms, such as killer acquisitions and nascent competitors. Then we investigate and classify all acquisitions made by the GAFAM firms between 2009 and 2018, considering the targets’ ages, their main activities and whether they were shut down after acquisition. The results indicate that most acquisitions did not have a clear horizontal effect, meaning that GAFAM companies often purchase inputs, talents, or complementary products. However, the study identifies and examines in detail possible nascent competitors’ and killer acquisitions. The results indicate that antitrust authorities should be aware of the issue and undertake cautious reforms of merger control rules, balancing competition protection against the risks of unnecessarily harming innovation.JEL:[K21 – Antitrust Law] [L41 – Monopolization • Horizontal Anticompetitive Practices]
Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response
Authors: Smabers Lidwien Paula , Wensink Emerens , Verissimo Carla S. , Koedoot Esmee , Pitsa Katharina-Chara , Huismans Maarten Age , Barón Celia Higuera , Doorn Mayke , Iersel Liselot B. Valkenburg-van , Cirkel Geert Anne , Brousali Anneta , Overmeer René , Koopman Miriam , Braat Manon N. , de Vries Bas Penning , Elias Sjoerd G. , Vries Robert G. , Kranenburg Onno , Boj Sylvia F. , Roodhart Jeanine M.
Published: December 2023

Background The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.Methods We optimized drug screen methods on 5–11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different read-outs and different combination treatment layouts to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient’s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.Results Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0,44-0.95), 0.61 for irinotecan- (n = 10, 95% CI − .03-0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01-0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.005).Conclusions Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.
Clinical analysis of cervical cancer in the second and third trimesters of pregnancy
Authors: Chen Yali , Zou Juan , Han Lin , Wan Qi
Published: December 2023

Background
To explore the clinical and prognostic characteristics of patients with cervical cancer in late pregnancy, and provide guidance for clinical decision-making for both doctors and patients.
Methods
A retrospective analysis was conducted on the clinical data of 13 cases of cervical cancer in late pregnancy treated in our hospital from 2008 to March 2022.
Results
The average age of the patients was 33.54 ± 4.98 years old, with 5 cases diagnosed in late pregnancy and 8 cases in mid-pregnancy. The main clinical manifestation was vaginal bleeding, and cervical biopsy confirmed the diagnoses after the patients sought medical attention. Among them, 9 patients had HPV16 infection. Eight patients underwent chemotherapy during pregnancy, and all patients underwent cesarean section to end the pregnancy. Twelve patients underwent radical surgery during cesarean section, and 1 patient underwent surgical treatment after chemotherapy 6 weeks after cesarean section. Eventually, 11 patients gave birth, while 2 patients gave up on neonatal rescue. Among them 1 patient has developed VIN I, 1 patient is lost to follow-up, and 11 patients have been cured without recurrence.
Conclusion
HPV16 infection before pregnancy is a high-risk factor for cervical cancer during pregnancy, and vaginal bleeding during pregnancy should be taken seriously. The prognosis is good after treatment of cervical cancer in the second and third trimesters of pregnancy.
Comparison between two extraction methods of plant lectins from Ruta graveolens L. and their partial characterization
Authors: Alvarez Amairany Torres , García Laura Flores , Mendoza-V Ernesto , Machuca C.
Published: December 2023

Background:
Ruta graveolens L. is a plant wich has several uses among different communities, such as an anti inflammatory and antitumor, related to the plant lectins available in their different tissues.
Extraction of this molecules is achieved through diverse extraction methods, without knowledge about which one is better to preserve their native structure.
In this study two well- documented methods are compared.
Results:
Lectin-enriched extracts were obtained out of different R. graveolens L. organs, and those were purified trough NaCl salt extraction and Tris-HCl extraction methods. Additionally, several eluents were used in the affinity chromatography method.
Conclussion:
Lectin-like proteins with affinity to several carbohydrates were found. The NaCl extraction method was more efficient at extracting lectin-like proteins than the Tris-HCl method, comparing to the total-protein extract. These results suggest that Tris-HCl buffer is more efficient to extract other proteins.
Co-designing Entrustable Professional Activities in General Practitioner’s Training: a Participatory Research Study
Authors: Andreou Vasiliki , Peters Sanne , Eggermont Jan , Schoenmakers Birgitte
Published: December 2023

Background
In medical education, Entrustable Professional Activities (EPAs) have been gaining momentum for the last decade. Such novel educational interventions necessitate accommodating competing needs, those of curriculum designers, and those of users in practice, in order to be successfully implemented.
Methods
We employed a participatory research design, engaging diverse stakeholders in designing an EPA framework. This iterative approach allowed for continuous refinement of a framework with 62 EPAs. Our approach involved two iterative cycles. In the first cycle, we utilized a modified-Delphi methodology with clinical competence committee (CCC) members, asking them whether each EPA should be included. In the second cycle, we used semi-structured interviews with General Practitioner (GP) trainers and trainees to explore their perceptions about the framework and refine it accordingly.
Results
During the first cycle, 14 CCC members agreed that all the 62 EPAs should be included in the framework. Regarding the formulation of each EPAs, 20 comments were given and 16 adaptations were made to enhance clarity. In the second cycle, the semi-structured interviews with trainers and trainees echoed the same findings, emphasizing the need of the EPA framework for improving workplace-based assessment, and its relevance to real-world clinical scenarios. However, trainees and trainers expressed concerns regarding implementation challenges, such as the large number of EPAs to be assessed, and perception of EPAs as potentially high-stakes.
Conclusion
Accommodating competing stakeholders’ needs during the development process can significantly enhance the EPA implementation process. Recognizing users as experts in their own experiences empower them and enables identification of implementation barriers and potential pitfalls. By embracing a collaborative approach, wherein diverse stakeholders contribute their unique viewpoints, we can only create effective educational interventions to complex assessment challenges.