bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermo-Responsive Polymers Targeting Inflammation in Murine Colitis
Authors: Zhang Sufeng , Jin Amy T. , Tang Wen , Zhang Rachel Y. , Jing Lihong , Zhou Yixuan , Zhang Heng , Lennerz Jochen K. , Korzenik Joshua R. , Langer Robert , Traverso Giovanni
Published: December 2023

Targeting the site of inflammation is an ideal approach for treating inflammatory bowel disease (IBD). Inflammation targeting enables maximal drug-on-target effects while minimizing off-target side effects. Negatively charged drug carriers have been shown to facilitate drug delivery to inflamed colon mucosa after local administration. To modulate the negative charges and integrate responsiveness to stimuli, here we describe thermo-responsive, inflammation-targeting (TRIT) hydrogels based on functionalized poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA). We show that both chemical modification types and polymer molecular weights affect the resultant microgels’ adhesion to the inflamed colon in dextran sulfate sodium (DSS)-induced murine colitisin vivo. Further, we quantified the correlations between microgels’ adhesion and colitis severity for individual mice, demonstrating that the microgels’ adhesion correlated directly with weight loss percentage in DSS-treated mice. By exploiting charge-mediated interaction and thermo-responsiveness, TRIT hydrogels represent a promising strategy to target inflamed colon mucosa as a drug delivery platform for colonic IBD treatment.

Teaser

This study developed thermo-responsive, inflammation-targeting (TRIT) hydrogels that harness charge-mediated interaction and sol-to-gel transition to target inflamed colon mucosa as a new approach for treating inflammatory bowel disease.
Deregulation cascades in carcinogenesis
Authors: Herrero Roberto , Gomez Jean Pierre , Gil Gabriel , Gonzalez Augusto
Published: December 2023

Carcinogenesis is one example of transition between two biological states involving strong gene expression rearrangements [1]. Normal and tumor states are understood as two different states of a Gene Regulatory Network [2]. In terms of the normal state characteristics, the transition may be thought as a deregulation process [3,4,5]. According to a very abstract model for the transition, the available data on cancer risk support the idea of a single big jump in expression space [6], which may be associated to a deregulation cascade. Here, we use the measured frequency distribution of gene deregulations, and concepts from the probabilistic theory of causation [7] in order to infer causal relations between pairs of genes and construct a deregulation causal network [8]. Then, the deregulated genes in each sample are organized according to the network in such a way that they show the deregulation cascade behind the transition from the normal to the tumor state. The explicit analysis for prostate adenocarcinoma is given. In most cases, the cascade happens to be unique and initiated by a single deregulation event. Using results from a companion paper [9], we show that cascades conform classes which may be labeled by the deregulations in a predefined panel of 15 genes. The results of the paper may be checked in experiments with cellular lines or in animal models, and could have an impact on personalized cancer therapy.
Organ specific microenvironmental MR1 expression in cutaneous melanoma
Authors: Gordon Patricia B. , So Woong Young , Azubuike Udochi F , Johnson Bailey , Cicala James , Sturgess Victoria , Wong Claudia , Bishop Kevin , Bresciani Erica , Sood Raman , Ganesan Sundar , Tanner Kandice
Published: December 2023

The microenvironment is an important regulator of intertumoral trafficking and activity of immune cells. Understanding how the immune system can be tailored to maintain anti-tumor killing responses in metastatic disease remains an important goal. Thus, immune mediated eradication of metastasis requires the consideration of organ specific microenvironmental cues. Using a xenograft model of melanoma metastasis in adult zebrafish, we perturbed the dynamic balance between the infiltrating immune cells in the metastatic setting using a suite of different transgenic zebrafish. We employed intravital imaging coupled with metabolism imaging (FLIM) to visualize and map the organ specific metabolism with near simultaneity in multiple metastatic lesions. Of all the MHC complexes examined for brain and skeletal metastases, we determined that there is an organ specific expression ofmhc1uba(human ortholog,MR1) for both the melanoma cells and the resident and infiltrating immune cells. Specifically, immune clusters did not expressmhc1ubain brain metastatic lesions in immune competent fish. Finally, the differential immune response drove organ specific metabolism where tumor glycolysis was increased in brain metastases compared to skeletal and parental lines as measured using fluorescence lifetime imaging microscopy (FLIM). As MR1 belongs to the MHC class I molecules and is a target of immunotherapeutic drugs, we believe that our data presents an opportunity to understand the relationship between organ specific tumor metabolism and drug efficacy in the metastatic setting.
Morphological and yield responses of Cannabis sp. to night-time disruption.
Authors: Gonzalez Vanegas Bryan S. , Sarmiento Felipe S. , Calderon Martinez Camila J. , Osorio Lasso Valentina
Published: December 2023

The production of Cannabis sp. under inductive photoperiods requires investment in lighting infrastructure to delay the inflorescence stage and maintain yield. Previous reports have shown that the interruption of the night phase (Night Break, NB) prevents floral development, however, the effects related to stress response, yield and cannabinoid concentration are unknown for cannabis. The present study sought to study the impact of NB in Cannabis sp. growth, physiology, and yield. Four photoperiod treatments were compared: long day (T1: 18 h light/6 h dark), night break treatments with 12 h light photoperiods supplemented with 1 h light pulse (T2, at ZT+17)) or with four light pulses of 15 minutes each (T3: ZT+15 to ZT+18) and short-day treatment (T4: 12h light /12h dark). The appearance of pistils and reduction of internodes in apical segments were observed after 20 days only in plants subjected to short day (T4), while all four treatments displayed a similar physiological behavior. Regarding yield, plants with supplemental light presented higher biomass accumulation than the short-day treatment. Cannabinoid accumulation profiles showed distinct trends: CBD accumulation showed no differences, while THC accumulation was lower in T3 and T4 compared to T1 and T2. These results suggest that night interruption in non-psychoactive plants is as effective as extending the light phase in preventing inflorescence formation, without generating stress or reductions in yield.
Identification of SLC25A46 interaction interfaces with mitochondrial membrane fusogens Opa1 and Mfn2
Authors: Boopathy Sivakumar , Luce Bridget E. , Lugo Camila Makhlouta , Hakim Pusparanee , McDonald Julie , Kim Ha Lin , Ponce Jackeline , Ueberheide Beatrix M. , Chao Luke H.
Published: December 2023

Mitochondrial fusion requires the sequential merger of four bilayers to two. The outer-membrane solute carrier protein SLC25A46 interacts with both the outer and inner-membrane dynamin family GTPases Mfn1/2 and Opa1. While SLC25A46 levels are known to affect mitochondrial morphology, how SLC25A46 interacts with Mfn1/2 and Opa1 to regulate membrane fusion is not understood. In this study, we use crosslinking mass-spectrometry and AlphaFold 2 modeling to identify interfaces mediating a SLC25A46 interactions with Opa1 and Mfn2. We reveal that the bundle signaling element of Opa1 interacts with SLC25A46, and present evidence of a Mfn2 interaction involving the SLC25A46 cytosolic face. We validate these newly identified interaction interfaces and show that they play a role in mitochondrial network maintenance.
The impact of policy intervention on international wine demand
Authors: Liu Xinyang , Liu Anyu , Jiao Xiaoying , Liu Zhen
Published: December 2023

Purpose

The purpose of the study is to investigate the impact of implementing anti-dumping duties on imported Australian wine to China in the short- and long-run, respectively.

Design/methodology/approach

First, the Difference-in-Differences (DID) method is used in this study to evaluate the short-run causal effect of implementing anti-dumping duties on imported Australian wine to China. Second, a Bayesian ensemble method is used to predict 2023–2025 wine exports from Australia to China. The disparity between the forecasts and counterfactual prediction which assumes no anti-dumping duties represents the accumulated impact of the anti-dumping duties in the long run.

Findings

The anti-dumping duties resulted in a significant decline in red and rose, white and sparkling wine exports to China by 92.59%, 99.06% and 90.06%, respectively, in 2021. In the long run, wine exports to China are projected to continue this downward trend, with an average annual growth rate of −21.92%, −38.90% and −9.54% for the three types of wine, respectively. In contrast, the counterfactual prediction indicates an increase of 3.20%, 20.37% and 4.55% for the respective categories. Consequently, the policy intervention is expected to result in a decrease of 96.11%, 93.15% and 84.11% in red and rose, white and sparkling wine exports to China from 2021 to 2025.

Originality/value

The originality of this study lies in the creation of an economic paradigm for assessing policy impacts within the realm of wine economics. Methodologically, it also represents the pioneering application of the DID and Bayesian ensemble forecasting methods within the field of wine economics.
Effect of the addition of milk fat globule membrane materials to the construction of fat globule interface in infant formula
Authors: Wu Zhengyan , Zheng Shan , Yuan Xianwei , Ji Yanqiao , Li Hongbo , DuoJie RenQing , SuoNan AngDan , Li Hongjuan , Yu Jinghua
Published: December 2023

To investigate whether the addition of milk fat globule membrane (MFGM) materials could improve the fat stability of infant formula and study the mechanism of membrane construction of fat globules, MFGM materials were added to infant formula in raw materials. The results showed that the optimal additional amount of MFGM materials was 0.5% to achieve better fat stability in the infant formula. The concentration of interfacial proteins in the reconstituted milk‐added MFGM materials was higher than in the control sample. Moreover, the laser confocal scanning microscopy image showed that MFGM materials were involved in the membrane construction of fat globules.
Stratigraphy of Late Mid‐Pleistocene in Lithuania: the current status and issues
Authors: Šeirienė Vaida , Bitinas Albertas
Published: December 2023

The principal aim of this paper is to present a critical overview of the stratigraphical subdivision and correlation of the Late Mid‐Pleistocene (LMP) sediments in Lithuania. In recent decades, a number of studies of LMP sediments have been carried out, allowing clarification of the stratigraphical position of individual sedimentary sections. Particular efforts have been made to determine the age of sediments using a variety of absolute age determination methods. However, there are still several outstanding questions. It is still unclear how many warm periods occurred during the Saalian in Lithuania and of what magnitude. The least problematic issue is identification of the Butėnai (Holsteinian) Interglacial as it correlates well biostratigraphically with the contemporaneous sections of adjacent areas. The most controversial unit is the Snaigupėlė Interglacial, the age of which continues to be a subject of debate. Recently, more evidence has emerged that the sediments considered to be of the Snaigupėlė Interglacial are contemporaneous with the Merkinė (Eemian) Interglacial. The chronological placement of these sediments closely hinges on the unresolved stratigraphical classification of the Medininkai deposits (MIS 6 or MIS 8?) and the Žemaitija tills (MIS 8 or MIS 10?). The debate is centred on whether these two tills were formed during two entirely different glaciations or represent different phases of a single major glaciation event. Traditionally, these two tills were attributed to distinct glaciation events separated by the Snaigupėlė Interglacial. However, no sedimentary sections have been discovered that contain both these tills and the interglacial sediments that separate them. Given the similar lithological, geochemical and petrographic composition of the Medininkai and Žemaitija tills some research has supported their possible stadial rank. The clarification of these stratigraphical issues in the future may be facilitated by the application of new proxies and re‐examination of the existing LMP key sections.
Simulator education in Japanese dental education
Authors: Tsuruta Jun
Published: December 2023

Advances in information and communication technology (ICT) and digital technology have contributed greatly to the development of educational methods, and new educational styles have been introduced over the past several years. In recent years, it has become possible to provide more realistic simulator training to prepare for patient care through the development of phantom heads with jaws and artificial teeth that reflect actual anatomical structures and composition. While these phantom head simulator resources are becoming more realistic, the development of digital devices utilizing virtual reality has enabled training that is even more realistic than the jaw models, such as scanning the teeth and transfer this scan into a VR model in the simulator which can be used to practice on prior to treating the patient. There was a basic research report on the development of VR haptics simulators in Japan about 20 years ago, but there have been no reports for some time since then, and there are several reports on VR haptics simulators published after 2018. Even now, in terms of utilization in dental education, it is difficult to say that VR haptics simulator has been widely introduced in Japan. The reasons for this may be related to the evaluation system for clinical dental skills in the Japanese dental education system, as well as issues with budgets and in current condition of dental clinical practice in dental schools. It must be that the VR haptics simulator will be utilized in terms of preparatory training for patient care as clinical dental practice participation is enhanced in the future.
Investigating mother–child inter‐brain synchrony in a naturalistic paradigm: A functional near infrared spectroscopy (fNIRS) hyperscanning study
Authors: Papoutselou Efstratia , Harrison Samantha , Mai Guangting , Buck Bryony , Patil Nikita , Wiggins Ian , Hartley Douglas
Published: December 2023

Successful social interactions between mothers and children are hypothesised to play a significant role in a child's social, cognitive and language development. Earlier research has confirmed, through structured experimental paradigms, that these interactions could be underpinned by coordinated neural activity. Nevertheless, the extent of neural synchrony during real‐life, ecologically valid interactions between mothers and their children remains largely unexplored.

In this study, we investigated mother–child inter‐brain synchrony using a naturalistic free‐play paradigm. We also examined the relationship between neural synchrony, verbal communication patterns and personality traits to further understand the underpinnings of brain synchrony.

Twelve children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother–child dyads were measured bilaterally over frontal and temporal areas using functional Near Infra‐red Spectroscopy (fNIRS) whilst the dyads were asked to play with child‐friendly toys together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded.

Compared to the independent condition, mother–child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo‐parietal junction. There was no significant relationship found between neural synchrony and turn‐taking and between neural synchrony and the personality traits of each member of the dyad.

Overall, we demonstrate the feasibility of measuring inter‐brain synchrony between mothers and children in a naturalistic environment. These findings can inform future study designs to assess inter‐brain synchrony between parents and pre‐lingual children and/or children with communication needs.
Impact of metabolic dysfunction‐associated fatty liver disease on the incidence of Helicobacter pylori‐negative gastric cancer
Authors: Nakane Tomoyuki , Fukunaga Shuhei , Nakano Dan , Tsutsumi Tsubasa , Tanaka Hiroshi , Chou Tomonori , Minami Shinpei , Ohuchi Akihiro , Nagata Tsutomu , Takaki Kota , Takaki Hiroshi , Miyajima Ichiro , Nouno Ryuichi , Yoshinaga Shinobu , Mukasa Michita , Okabe Yoshinobu , Kawaguchi Takumi
Published: December 2023

Aim

The incidence of Helicobacter pylori‐negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction‐associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD.

Methods

This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision‐tree algorithm and random forest analysis.

Results

Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451–16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction‐associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision‐tree analyses. Helicobacter pylori‐negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32).

Conclusions

Metabolic dysfunction‐associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.
Minimum wage and spillover effects in a minimum wage society
Authors: Sefil‐Tansever Sinem , Yılmaz Ensar
Published: December 2023

Minimum wage policies are widely implemented in developing countries, but their consequences remain uncertain. This study empirically investigates the impact of the minimum wage on monthly income inequality and its spillover effects in Turkey between 2004 and 2022, utilizing comprehensive micro data. We aim to shed light on the impact of national minimum wage policies by examining their diverse influences on the wage structure within the country. Our findings reveal that the minimum wage significantly reduces income disparities, particularly among formal workers at the lower and upper end of the wage distribution. While wage gaps below the median wage decline, those above it experience a slower growth rate, ultimately leading to wage convergence. Notably, this effect is more pronounced during macroeconomic instability from 2016 to 2022, compared with the relatively stable period of 2004–15. Moreover, the outcomes differ depending on individual attributes like gender, age, education, and other relevant factors. Furthermore, we observe tentative evidence of a lighthouse effect to some degree: the minimum wage seems to exert an equalizing influence on the wage structure of workers in the informal sector beyond a certain percentile.
Using competition for plasma donor recruitment and retention: An Australian university case study
Authors: Bryant Jack , Woolley Torres , Sen Gupta Tarun , Chell Kathleen
Published: December 2023

Background and Objectives

Using evidence from one Australian university's participation in the Vampire Cup (an 8‐week national inter‐university blood donation competition), this study aimed to (1) understand important motivators and successful promotional strategies driving engagement in the competition, and (2) determine the impact of competition on the recruitment and retention of young adult plasma donors.

Materials and Methods

We used a sequential explanatory mixed‐methods design involving a self‐administered survey (Study 1, n = 64) and four focus groups (Study 2, n = 20) with plasma donors aged 18–29 years who participated in the 2021 Vampire Cup. Also, we used a 12‐month prospective comparative cohort analysis (Study 3) of those who did (n = 224 ‘competition donors’) and did not (n = 448 control group) present to donate for the Vampire Cup.

Results

Competition was a strong motivator, with 76% of survey participants donating to help their university win the Vampire Cup. The survey and focus groups suggested that successful engagement in the competition was due to peer‐led recruitment, leveraging existing rivalries at both the inter‐ and intra‐university level, and using prize draws to create an active online social community promoting blood donation. Competition donors donated plasma significantly more often during the competition but donated at similar rates after the competition, compared to the control group.

Conclusion

Rivalry‐based competition strategies, combined with enthusiastic team leaders and an active social media community, can help to recruit, and retain, young adult plasma donors, and motivate an intermittent boost to donation frequency over a short period each year.
Postactivation Performance Enhancement With Maximal Isometric Contraction on Power-Clean Performance Across Multiple Sets
Authors: Lum Danny , Yang Ong Keng , Haischer Michael H.
Published: December 2023

Purpose: This study investigated the postactivation performance-enhancement effect of maximal voluntary isometric contraction (MVIC) at the starting position on power-clean performance over a series of contrast sets. Methods: Eighteen male (age: 31 [3.7] y, body mass: 76.8 [9.1] kg, height: 175.0 [5.2] cm) and 2 female (age: 27.5 [3.5] y, body mass: 53.3.8 [2.0] kg, height: 158.5 [4.9] cm) resistance-trained individuals performed a contrast postactivation performance-enhancement protocol (isometric contrast training condition [ISO]) consisting of 3 sets of 3 MVICs alternated with 3 power cleans, with an intracontrast rest period of 1 minute. A control protocol consisted of 3 sets of 3 power cleans were performed in a separate session. Barbell velocity during the power clean was measured as an indicator of performance. Results: A significant time effect was observed for both mean velocity (MV; P < .001) and peak velocity (PV; P = .008). Time × group (P = .415–.444) and group (P = .158–.210) effects showed no significant difference for either MV or PV. However, differences in MV and PV between the corresponding sets of ISO and control condition exceeded the minimum worthwhile change, showing a small to moderate effect (MV: d = 0.38–0.50, PV: d = 0.35–0.50) in favor of ISO. There was no significant difference in rating of perceived exertion between conditions (P = .385, d = 0.22). Conclusion: Power-clean performance was potentiated after 1 minute of rest following 3 repetitions of MVIC across 3 sets. Furthermore, the ISO protocol did not result in greater perception of exertion. These results indicate that coaches may incorporate MVICs as the postactivation performance-enhancement stimulus during contrast training involving the power-clean exercise.
DiffuRec: A Diffusion Model for Sequential Recommendation
Authors: Li Zihao , Sun Aixin , Li Chenliang
Published: December 2023

Mainstream solutions to sequential recommendation represent items with fixed vectors. These vectors have limited capability in capturing items’ latent aspects and users’ diverse preferences. As a new generative paradigm,
diffusion models
have achieved excellent performance in areas like computer vision and natural language processing. To our understanding, its unique merit in representation generation well fits the problem setting of sequential recommendation. In this article, we make the very first attempt to adapt the diffusion model to sequential recommendation and propose
DiffuRec
for item representation construction and uncertainty injection. Rather than modeling item representations as fixed vectors, we represent them as distributions in
DiffuRec
, which reflect a user’s multiple interests and an item’s various aspects adaptively. In the diffusion phase,
DiffuRec
corrupts the target item embedding into a Gaussian distribution via noise adding, which is further applied for sequential item distribution representation generation and uncertainty injection. Afterward, the item representation is fed into an approximator for target item representation reconstruction. In the reverse phase, based on a user’s historical interaction behaviors, we reverse a Gaussian noise into the target item representation, then apply a rounding operation for target item prediction. Experiments over four datasets show that
DiffuRec
outperforms strong baselines by a large margin.

1
Application-level Validation of Accelerator Designs Using a Formal Software/Hardware Interface
Authors: Huang Bo-Yuan , Lyubomirsky Steven , Li Yi , He Mike , Smith Gus Henry , Tambe Thierry , Gaonkar Akash , Canumalla Vishal , Cheung Andrew , Wei Gu-Yeon , Gupta Aarti , Tatlock Zachary , Malik Sharad
Published: December 2023

Ideally, accelerator development should be as easy as software development. Several recent design languages/tools are working toward this goal, but actually testing early designs on real applications end-to-end remains prohibitively difficult due to the costs of building specialized compiler and simulator support. We propose a new first-in-class, mostly automated methodology termed “3LA” to enable end-to-end testing of prototype accelerator designs on unmodified source applications. A key contribution of 3LA is the use of a formal software/hardware interface that specifies an accelerator’s operations and their semantics. Specifically, we leverage the Instruction-level Abstraction (ILA) formal specification for accelerators that has been successfully used thus far for accelerator implementation verification. We show how the ILA for accelerators serves as a software/hardware interface, similar to the Instruction Set Architecture for processors, that can be used for automated development of compilers and instruction-level simulators. Another key contribution of this work is to show how ILA-based accelerator semantics enables extending recent work on equality saturation to auto-generate basic compiler support for prototype accelerators in a technique we term “flexible matching.” By combining flexible matching with simulators auto-generated from ILA specifications, our approach enables end-to-end evaluation with modest engineering effort. We detail several case studies of 3LA, which uncovered an unknown flaw in a recently published accelerator and facilitated its fix.
Fine tuning contractility: atrial sarcomere function in health and disease
Authors: Burnham Hope V. , Cizauskas Hannah E. , Barefield David Y.
Published: December 2023

The molecular mechanisms of sarcomere proteins underlie the contractile function of the heart. Although our understanding of the sarcomere has grown tremendously, the focus has been on ventricular sarcomere isoforms due to the critical role of the ventricle in health and disease. However, atrial-specific or -enriched myofilament protein isoforms, as well as isoforms that become expressed in disease, provide insight into ways this complex molecular machine is fine-tuned. Here, we explore how atrial-enriched sarcomere protein composition modulates contractile function to fulfill the physiological requirements of atrial function. We review how atrial dysfunction negatively affects the ventricle and the many cardiovascular diseases that have atrial dysfunction as a comorbidity. We also cover the pathophysiology of mutations in atrial-enriched contractile proteins and how they can cause primary atrial myopathies. Finally, we explore what is known about contractile function in various forms of atrial fibrillation. The differences in atrial function in health and disease underscore the importance of better studying atrial contractility, especially as therapeutics currently in development to modulate cardiac contractility may have different effects on atrial sarcomere function.
Effects of dietary soy content on cerebral artery function and behavior in ovariectomized female mice
Authors: Kehmeier Mackenzie N. , Khurana Aleena , Bedell Bradley R. , Cullen Abigail E. , Cannon Audrey T. , Henson Grant D. , Walker Ashley E.
Published: December 2023

To properly design experiments, we must consider how variables like diet impact our outcomes, particularly the effects of soy on females. We found that cerebral artery vasodilation in response to insulin was impaired in ovariectomized female mice compared with intact shams. However, ovariectomized mice fed a soy diet had a preserved cerebral artery insulin-mediated vasodilation. These results highlight that the effects of diet on vascular function may explain inconsistencies found between studies.
Ghrelin/GHSR Axis Induced M2 Macrophage and Alleviated Intestinal Barrier Dysfunction in a Sepsis Rat Model by Inactivating E2F1/NF-κB Signaling
Authors: Zhu Lei , Dou Zhimin , Wu Wei , Hou Qiliang , Wang Sen , Yuan Ziqian , Li Bin , Liu Jian
Published: December 2023

Sepsis is an inflammatory reaction disorder state that is induced by infection. The activation and regulation of the immune system play an essential role in the development of sepsis. Our previous studies have shown that ghrelin ameliorates intestinal dysfunction in sepsis. Very little is known about the mechanism of ghrelin and its receptor (GHSR) on the intestinal barrier and the immune function of macrophage regulation. Our research is to investigate the regulatory effect and molecular mechanism of the ghrelin/GHSR axis on intestinal dysfunction and macrophage polarization in septic rats. A rat model of sepsis was established by cecal ligation and puncture (CLP) operation. Then, the sepsis rats were treated with a ghrelin receptor agonist (TZP-101) or ghrelin inhibitor (obestatin). The results suggested that TZP-101 further enhanced ghrelin and GHSR expressions in the colon and spleen of septic rats and obestatin showed the opposite results. Ghrelin/GHSR axis ameliorated colonic structural destruction and intestinal epithelial tight junction injury in septic rats. In addition, the ghrelin/GHSR axis promoted M2-type polarization of macrophages, which was characterized by the decreases of IL-1β, IL-6, and TNF-α, as well as the increase of IL-10. Mechanistically, the ghrelin/GHSR axis promoted E2F2 expression and suppressed the activation of the NF-κB signaling pathway in septic rats. Collectively, targeting ghrelin/GHSR during sepsis may represent a novel therapeutic approach for the treatment of intestinal barrier injury.
Switching from Natural Desiccated Thyroid to a Liquid Formulation of Levothyroxine for Hypothyroidism
Authors: Khoshaba Linda , Patarkatsi Laurena
Published: December 2023

Natural desiccated thyroid (NDT) is a treatment option for many patients with hypothyroidism, but some still exhibit symptoms despite achievement of normal levels of thyroid stimulating hormone (TSH). In this retrospective case series, 13 patients with hypothyroid symptoms were switched from NDT to a liquid formulation of levothyroxine (LT4; Tirosint®-SOL). Laboratory values ≥4 weeks following the switch showed a decrease in TSH levels, maintenance of free triiodothyronine (fT3) levels, and significant increases in free thyroxine (fT4) levels. Patients reported good tolerability, and case summaries are presented for four patients. In summary, this small retrospective case series showed that patients who still had hypothyroid symptoms despite use of NDT can respond well to oral LT4 liquid formulation, including patients who are intolerant of gluten and/or lactose or on hormone replacement therapy or iron supplementation.
Investigation of Rock Mechanical Properties under Liquid Nitrogen Environment
Authors: Wang Linchao , Liang Xin , Shi Xuyang , Han Jianyong , Chen Yang , Zhang Wan
Published: December 2023

In order to promote sustainable energy development and reduce the impact of fossil fuels on the environment, it is crucial to strengthen the development and utilization of clean and renewable geothermal energy. Liquid nitrogen fracturing, as an emerging waterless fracturing technology, has outstanding advantages in rock fracturing effect and thermal exchange ability with hot dry rock and is more environmentally friendly. In order to evaluate the influence of liquid nitrogen on the mechanical properties, acoustic emission characteristics, and cross-sectional crack propagation characteristics of granite at different initial temperatures, this paper carried out three-point bending tests and acoustic emission detection on granite treated by high-temperature heating and liquid nitrogen cooling. Finally, based on the cross-sectional scanning test, the expansion characteristics of microcracks in granite were analyzed. The results show that the higher the initial temperature of granite, the stronger the cold impact of liquid nitrogen on granite, and the faster the rock’s mechanical performance declines. The acoustic emission ringing count is closely related to the development of microcracks in granite, and as the initial temperature of granite increases, the more ringing counts there are, indicating that the huge temperature difference induces more microcracks inside the rock. In addition, the cold impact of liquid nitrogen can effectively promote the fracturing of granite. After liquid nitrogen treatment, the fractal dimension of the granite cross-section increases, the shape of the cross-section becomes rough, and many micropores appear. This study can provide a scientific basis for the engineering application of liquid nitrogen fracturing technology.
Twelve-Year Follow-Up of Laser Frenectomy during Early Mixed Dentition
Authors: Awooda Elhadi Mohieldin
Published: December 2023

Median maxillary labial frenum (MMLF) is one of the oral freni, found on the inner side of the centre of the upper lip. Maxillary midline diastema (MMD) is commonly associated with highly attached frenum, and frenectomy during early mixed dentition is controversial. A 6-year-old boy came with a chief complaint of unpleasant spacing between the two upper front teeth. A median maxillary high attached labial frenum with midline spacing of 5 mm was diagnosed. A consensus was made with the child’s father to remove the frenum by laser. Diode laser frenectomy was done, and subsequent follow-up for 12 years revealed no relapse and complete closure of the diastema. Frenectomy during early mixed dentition could be a suitable option for the closure of midline diastema.
Insights from the Analysis of the Sepsis Dataset: Understanding the Immune Dynamics and Molecular Pathways in Sepsis
Authors: Dai Wenyan , Liu Juan , Li Xiaoqiang
Published: December 2023

Sepsis, a critical medical condition instigated by infections, profoundly alters molecular and cellular immune responses. This study focused on the GSE54514 dataset obtained from the GEO database to uncover the complex gene expression patterns and related pathways in sepsis. A total of 42 genes were found to be expressed differently in septic patients compared to those of healthy individuals. The enrichment analyses of pathways revealed the disruption of natural immune pathways such as toll-like receptor signaling, regulation of actin cytoskeleton, and NOD-like receptor signaling. Through ssGSEA analysis, we revealed a strong association between sepsis and immune cell dynamics, finding significant correlations with HLA-related genes and distinct immune cell populations. Furthermore, genes such as CCL5, CD274, CD3E, and CD8A were linked with pathways, notably the “ribosome” pathway, suggesting potential roles in sepsis-related immune responses. The extensive examination provides fresh perspectives on the gene expression and pathway changes in sepsis, laying the groundwork for upcoming therapeutic interventions and a more profound comprehension of this intricate condition.
Mt. Etna Tilt Signals Associated with February 6, 2023, M=7.8 and M=7.5 Turkey Earthquakes
Authors: Privitera Laura , Ferrari Ferruccio , Ferro Angelo , Gambino Salvatore
Published: December 2023

On February 6, 2023, at 01 : 17 UTC, a M=7.8 earthquake struck the southern area of Turkey near Gaziantep town and was followed by a second earthquake of M=7.5 at 10 : 24 UTC with the epicenter in Elbistan city. Both events were associated with the Anatolian Fault System and have claimed over 50,000 victims, as reported by the Disaster and Emergency Management Authority, and caused serious damage in the regions of southern Turkey and northern Syria. Seismic waves related to strong Turkey earthquakes have been recorded both by seismic stations throughout the globe and on other devices such as the ground deformation (GNSS, strainmeters, or tiltmeters) networks. In this paper, we show and analyze the earthquake signals recorded by bore-hole tilt stations that monitor seismic and volcanic activities at Mt. Etna. Tilt stations showed very large variations, despite their distance from the epicenter (approximately 1950 km) with a period between 10 and 25 seconds. We compared tilt and seismic data for a co–located station evidencing a very similar waveform that highlight how tiltmeters respond to translational acceleration rather than ground tilt during a teleseism, suggesting that, for waves with this period, they may behave as horizontal seismometers. By using these signals, we evidence the different behaviors of two of the most used models of tiltmeters on volcanoes (Lily and Pinnacle) and how they are useful for instrument calibration.
Factors Affecting Nurses’ Performance of Noise Management in Adult Intensive Care Units
Authors: Kim Seo Jeong , Min Haeyoung
Published: December 2023

The aim of this study was to identify factors affecting the noise management performance of adult intensive care unit (ICU) nurses in Korea. The ICU environment is exposed to various types of noises due to the use of medical devices for the treatment of critically ill patients. The noise has an adverse effect on nurses’ health and their nursing performance, which might potentially threaten patient safety. A cross-sectional study was conducted with a total of 148 nurses working in adult ICUs from two university hospitals in Korea. Data were collected using self-administered questionnaires, which included various aspects such as noise knowledge, response to noise, patient safety culture, and noise management performance. Multiple regression analysis revealed that teamwork (β = 0.33, p=0.004), patient safety policy, and procedure (β = 0.25, p=0.037), which were subscales of patient safety culture, as well as frequency of noise experience (β = 0.16, p=0.030) were significant factors affecting adult ICU nurses’ performance of noise management. This study provides a significant basis for promoting adult ICU nurses’ performance in noise management. A structured policy and procedure for noise management should be established for reducing noise in adult ICUs. In terms of nursing education, it is necessary to consider and develop team-based training programs to promote noise management performance in the ICU. Nurse managers and nursing organizations should consider how to create conditions in which nurses can recognize the importance of noise reduction and perform well in noise management.
Recursive Delta-Operator-Based Subspace Identification with Fixed Data Size
Authors: Yu Miao , Wang Wanli , Wang Youyi , Liu Liang
Published: December 2023

This paper proposes a recursive delta-operator-based subspace identification method with fixed data size. The majority of existing subspace identification methods are constrained to discrete-time systems because of the disparity in Hankel matrices. Additionally, due to the storage cost, LQ-factorization and singular value decomposition in identification methods are best suited for batch processing rather than online identification. The continuous-time systems are transformed into state space models based on the delta-operator to address these issues. These models approach the original systems when the sampling interval approaches zero. The size of the data matrices is fixed to reduce the computing load. By fading the impact of past data on future data, the amount of data storage can be decreased. The effectiveness of the proposed method is illustrated by the continuous stirred tank reactor system.
Correlation between Physical Activity and Depression in Community-Dwelling Older Adult Palestinians
Authors: Halaweh Hadeel , Al-Khateeb Amal , Rasheed Aya , Tomeze Layth , Sultan Mohammad , Alqaissi Ismail
Published: December 2023

Objective: Investigating the relationship between physical activity (PA) and depressive symptoms is a vital field of research globally. Nonetheless, this association remains unexplored in the context of older Palestinian adults, highlighting the need for additional research on this population. Therefore, this study aimed to examine the association between PA and depressive symptoms among older Palestinian adults. Subjects and Methods: A cross-sectional study was conducted in the West Bank/Palestine with 266 participants. Data were collected using a PA socio-cultural adapted questionnaire (PA-SCAQ), the EuroQuol-5Dimensions-5Levels measure, and the Geriatric depression scale (GDS-15). Independent sample t tests and ANOVA tests were used to investigate mean differences in PA and GDS-15 scores between groups. Furthermore, multiple linear regression analysis was used to examine the relationship between study variables and the impact of the independent variable (PA level) on depressive symptoms. Results: The mean age of the participants was 65.01 ± 8.02 years (range: 55–86), women 51.9%. Lower levels of PA and higher depressive symptoms were recorded among women, participants ≥65 years, and with recorded diagnosed disease (p < 0.05). The regression analysis showed a negative significant correlation between PA and GDS-15 scores (β = −0.235, p < 0.001), when controlling for age (model 2), and for age and sex (model 3), significant associations were recorded, respectively (β = 0.192, p = 0.002), and (β = 0.14, p = 0.015). Conclusion: Participants who recorded higher depressive symptoms had a lower level of PA; regular moderate-intensity aerobic exercises can contribute to prevent depression symptoms in older adults.
Alpha-2-Macroglobulin Is a Novel Anticancer Agent
Authors: Facchiano Francesco , D’Arcangelo Daniela , Facchiano Antonio
Published: December 2023

Introduction: Melanoma is the most aggressive skin cancer, with an increasing occurrence. Despite the recent important improvements due to novel immunotherapy approaches, when late diagnosed, melanoma prognosis is poor due to the metastatic progression and drug-resistance onset. Therefore, there is an urgent need to identify additional therapeutic targets. Melanoma invasive behavior is related to the activity of metalloproteases, able to degrade extracellular matrix leading to tumor dissemination. A recent study suggested that the most potent proteases inhibitor alpha-2-macroglobulin (A2MG) from plasma of hibernating fishes exerts potent antiproliferative effects. Our previous studies showed a significant reduction of A2MG in sera from mice/human melanoma models. Methods: Gene and protein expression studies have been performed by using platforms and databases available online containing expression data from thousands of patients and healthy controls. Results: We carried out an extensive bioinformatics analysis to evaluate the A2MG gene/protein expression on a large cohort of patients affected by many different cancer types, compared to healthy control subjects, and we found a highly significant difference of A2MG expression in 20 out of 31 cancer types (including melanoma) compared to healthy controls. Similar results were also confirmed at the proteomic level using another platform available online. Further, we found that higher A2MG expression is significantly related to overall survival in different cancers including melanoma. Conclusion: Our results strongly suggest A2MG as a novel molecular target in melanoma therapy, as well as in other cancer types.
Genetics of retinitis pigmentosa and other hereditary retinal disorders in Western Switzerland
Authors: Conti Giovanni Marco , Vaclavik Veronika , Rivolta Carlo , Escher Pascal , Schorderet Daniel Francis , Munier Francis L. , Tran Hoai Viet
Published: December 2023

Abstract
Introduction: Mutational screening of inherited retinal disorders is prerequisite for gene targeted therapy. Our aim is to report and analyze the proportions of mutations in inherited retinal disease (IRD) causing genes from a single center in Switzerland in order to describe the distribution of IRDs in Western Switzerland.
Methods: We conducted a retrospective study of patient records. Criteria for inclusion were residence in Western Switzerland for patients and relatives presenting a clinical diagnosis of IRDs and an established molecular diagnosis managed by the genetics service of the Jules-Gonin Eye Hospital (JGEH) of Lausanne between January 2002 and December 2022. We initially investigated the IRD phenotypes in all patients (full cohort) with a clinical diagnosis, then calculated the distribution of IRD gene mutations in the entire cohort (genetically determined cohort). We analyzed a sub-group that comprised pediatric patients (≤ 18 years of age). In addition, we calculated the distribution of gene mutations within the most represented IRDs. Comprehensive gene screening was performed using a combined approach of different generation of DNA microarray analysis, direct sequencing and Sanger sequencing.
Results: The full cohort comprised 899 individuals from 690 families with a clinical diagnosis of IRDs. We identified 400 individuals from 285 families with an elucidated molecular diagnosis (variants in 84 genes) in the genetically determined cohort. The pediatric cohort included 89 individuals from 65 families with an elucidated molecular diagnosis. The molecular diagnosis rate for the genetically determined cohort was 58.2 % (family ratio) and the 5 most frequently implicated genes per family were ABCA4 (11.6 %), USH2A (7.4 %), EYS (6.7 %), PRPH2 (6.3 %) and BEST1 (4.6 %). The pediatric cohort had a family molecular diagnosis rate of 64.4 % and the 5 most common mutated genes per family were RS1 (9.2 %), ABCA4 (7.7 %), CNGB3 (7.7 %), CACNA1F (6.2 %), CEP290 (4.6 %).
Conclusions: This study describes the genetic mutation landscape of IRDs in Western Switzerland in order to quantify their disease burden and contribute to a better orientation of the development of future gene targeted therapies.