bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogenic KRAS-induces necroptotic priming of pancreatic neoplasia
Authors: Tishina Sofya , Dahlhaus Alina , Androulidaki Ariadne , Kotliar Michael , Mulalic Lejla , Rakhsh-Khorshid Hassan , Hocher Florian , Stroh Jenny , Beck Julia , Manik Marta , Williams Riley , Gülcüler Gülce , Abdallah Ali , Bebber Christina , Reese Moritz , Lim Jonathan , Trauzold Anna , Quaas Alexander , Brägelmann Johannes , Beleggia Filippo , Pasparakis Manolis , Liccardi Gianmaria , Balachandran Siddharth , Astsaturov Igor , Von Karstedt Silvia
Published: July 2023

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality. PDAC expresses high levels of caspase 8, a central enzyme controlling various types of regulated cell death. Here, using genetically engineered mouse models we find that oncogenic KRAS-driven neoplastic transformation induces a transcriptional state of necroptotic priming, but necroptosis itself is counter selected against through co-upregulation of caspase 8. Mechanistically, expression of the driver oncogene KRAS induced a STING-dependent type I interferon (IFN) response resulting in upregulation of the necroptosis pathway leading to necroptotic priming. High caspase 8 expression in precursor lesions was a result of co-selection to prevent necroptosis. Hence, genetic or pharmacological targeting of caspase 8 was therapeutically highly efficacious in models of genetically engineered PDAC in vivo. These results identify type I IFN-induced necroptotic priming as synthetic lethality of KRAS-driven PDAC and show that targeting it has therapeutic benefit in this incurable malignancy.
The Growth Hormone Deficiency (GHD) Reversal Trial: Effect on final height of discontinuation versus continuation of growth hormone treatment in pubertal children with isolated GHD – A non-inferiority randomised controlled trial (RCT).
Authors: Brettell Elizabeth , Högler Wolfgang , Woolley Rebecca , Cummins Carole , Mathers Jonathan , Oppong Raymond , Roy Laura , Khan Adam , Hunt Charmaine , Dattani Mehul
Published: July 2023

The GHD Reversal trial is a non-inferiority RCT (ISRCTN12552768) funded by the NIHR HTA Programme (NIHR127468)
Background: Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64-82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved.
Methods/Design: Evidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH <6.7mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This Phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (1° outcome; inferiority margin 0.55 SD), Target Height (TH) minus near FH , HRQoL, bone health index and lipid profiles (2° outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario.
Discussion: If this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8-4.6 Million (€2.05-5.24 Million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects.
Oscillatory dynamics of the mammalian circadian clock induced by the core delayed negative feedback loop
Authors: Wang Conghua , Liu Haihong , Zhang Yuan
Published: July 2023

The mammalian circadian clock plays a crucial role in regulating the 24-hour physiological and behavioral processes. This work presents an improved model for the mammalian circadian clock by integrating physiologically plausible modifications into the Kim-Forger model, and investigates the oscillatory dynamics of the mammalian circadian clock induced by the core delayed negative feedback loop using bifurcation theory. The modifications involve introducing time delays in PER protein transcription, translation, and translocation, replacing the first-order law for PER degradation rate with the Michaelis-Menten law, and revising the transcription rate of $Per$ genes. The modified model accurately captures circadian oscillations and overcomes the unrealistic constraints of the Kim-Forger model. In addition, by utilizing the time delay as a control parameter, the theoretical results reveal that the delay induces a supercritical Hopf bifurcation, leading to the emergence of circadian oscillations with enhanced robustness, longer periods, increased amplitudes, and phase delays. Finally, numerical simulations are presented to assess the efficacy of the modified model and to validate the theoretical analysis.
Comparison of corticocancellous bone graft from the anterolateral metaphysis of the distal radius versus iliac crest for the treatment of unstable scaphoid nonunion with humpback deformity
Authors: Shin Sung-Chul , Kang Ho-Jung , Kim Nah-Yon , Lee Shin-Woo , Kim Ji-Sup
Published: July 2023

Background
Corticocancellous bone grafting from the iliac crest is acceptable treatment for unstable scaphoid nonunion with a viable proximal pole. However, harvesting graft from the iliac crest is associated with donor site morbidity and the requirement of general anesthesia. Thus, bone grafting from the anterolateral metaphysis of the distal radius (DR) can be a treatment option. However, no study has compared the clinical effect between the two grafting techniques.
Methods
From 2010 to 2016, patients with unstable scaphoid nonunion with humpback deformity underwent corticocancellous bone grafting from the anterolateral metaphysis of the DR (group DR) or iliac crest (group IC). Humpback deformity was determined by evaluating the scapholunate angle (SLA) ≥ 60°, intrascaphoid angle (ISA) ≥ 45°, and radiolunate angle (RLA) ≥ 15° from preoperative radiographs and computed tomography scans. The SLA, ISA, and RLA served to gauge carpal alignment. The operative time, grip strength, active range of motion (ROM), Mayo wrist score (MWS), and Disabilities of Arm, Shoulder, and Hand (DASH) score were assessed postoperatively.
Results
Thirty-eight patients qualified for the study (group DR, 15; group IC, 23). Union rates did not differ by patient subset (group DR, 100%; group IC, 95.7%; P = .827), and grip strength, ROM, MWS, and DASH score were similar between groups at the last follow-up. The operative time (minutes) was significantly shorter in group DR (median, 98; quartiles, 80, 114) than in group IC (median, 125; quartiles, 105, 150, P < .001). The ISA, RLA, and SLA improved postoperatively in both groups (P < 0.001). The degree of restoring carpal alignment, as evaluated by SLA, showed superior correction capability in group DR (median, 25.3% quartiles, 21.1, 35.3, P < 0.05). Donor site complications were not significantly different between the groups.
Conclusions
Corticocancellous bone graft from the anterolateral metaphysis of the DR for unstable scaphoid nonunion is associated with a shorter operation time and comparable results with that from the iliac crest in regard to union, restoration of carpal alignment, and wrist function.
Level of Evidence: Level III
Risk Stratification Tool for Predicting Postoperative Outcomes in Patients Undergoing Esophagectomy: A Prospective Study
Authors: YUAN Tingting , Maimaiti Mijiti , LI Dan , Ta’ati Zhaenhaer , YAN Rui
Published: July 2023

Purpose
Frailty, a clinical syndrome characterized by a reduced physiological reserve and decreased resistance to stressors, is extremely common in oncology patients. Given that esophagectomy is associated with significant postoperative adverse outcomes, the early identification of high-risk patients is critical. This study compared the utility of the Modified 5-Factor Frailty Index (mFI-5) and the Modified Charlson Comorbidity Index (mCCI) in predicting postoperative outcomes in patients undergoing esophagectomy.
Method
We reviewed the records of patients who underwent esophagectomy between 2019 and 2022. Two validated risk stratification tools measured the burden of comorbidity: mFI-5 and mCCI. The primary outcomes included a prolonged postoperative hospital stay and major and minor postoperative complications.
Result
A total of 359 patients were included (mean age 63.1 ± 8.6 years; 74.4% were males). The length of postoperative hospital stay was 30.0 (IQR 25.0,39.5) days, with 37 patients (10.3%) experiencing major postoperative complications and 192 patients (53.5%) experiencing minor postoperative complications. In multivariate analysis, mCCI remained a significant predictor of major postoperative complications (OR = 1.52, 95% CI 1.01–2.3, p = 0.046), but was no longer a significant predictor of prolonged postoperative hospital stay or minor complications. In addition, the mFI-5 score was no longer a significant predictor of any of the three postoperative outcomes.
Conclusion
This is the first study to compare the utility of the mFI-5 and mCCI in predicting adverse postoperative outcomes in patients undergoing esophagectomy. Our findings suggest that mCCI is a valid predictor of major complications in this patient group, whereas the role of mFI-5 is limited. This should be further investigated in a prospective multicenter cohort study.
The role of specific isoforms of CaV2 and the common C-terminal of CaV2 in calcium channel function in sensory neurons of Aplysia
Authors: Dunn Tyler W , Fan Xiaotang , Lee Jiwon , Smith Petranea , Gandhi Rushali , Sossin Wayne S
Published: July 2023

Habituation is the diminishing of a physiological response to a frequently repeated stimulus. In Aplysia, habituation to touch is mediated by the depression of the response to sensory neuron firing mediated by a decrease in transmitter release even after modest rates of action potential firing. This depression is not common among Aplysia synaptic connections suggesting the presence of a release apparatus specialized for this depression. This depression can be reversed through activation of protein kinase C and this is thought to underlie the behavior of dishabituation. We have previously noted that the calcium channel required for release, ApCaV2, has many splice isoforms in Aplysia. We found that specific splice forms of ApCaV2 and splice forms for interacting partners of ApCaV2 are preferentially used in sensory neurons, consistent with a specialized release apparatus. However, we were not able to find a specific splice uniquely required for synaptic depression. The C-terminus of ApCaV2 alpha1 subunit retains conserved binding sites for Aplysia rab-3 interacting molecule (ApRIM) and ApRIM-binding protein (ApRBP) and the C-terminus is required for full synaptic expression of ApCaV2.
Efficacy of ultrasound-guided stellate ganglion block on relieving acute postoperative pain: systematic review and meta-analysis
Authors: Zhao Yan , Xiao Xiangli
Published: July 2023

Background
The efficacy of stellate ganglion block (SGB) in alleviating postoperative pain remains uncertain. This meta-analysis aimed to determine the efficacy of ultrasound-guided SGB in relieving acute postoperative pain in patients undergoing surgery with general anesthesia.
Methods
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted comparing SGB with control or placebo. The primary outcome was pain score at 24h after surgery. Secondly outcomes included postoperative pain scores at other times (0, 2, 4, 6, 8, 12h) and postoperative nausea and vomiting. A random effects model was used to calculate mean difference (MD) or risk ratio (RR) with 95% confidence intervals.
Results
Eight studies, with a total of 470 patients, were included in this meta-analysis. Ultrasound-guided SGB was associated with lower pain score at 24h after surgery (MD − 0.71; 95% CI: −1.26, − 0.16, p = 0.01, I2 = 86%), with low level of evidence. Ultrasound-guided SGB was also linked to a lower pain score at postoperative 8h (MD − 0.65; 95% CI: −1.03, − 0.28, p = 0.01, I2 = 29%), with moderate level of evidence. There was no difference in pain scores at 0, 2, 4, 6,12 hours after surgery.
Conclusion
Ultrasound-guided SGB is effective in alleviating acute postoperative pain. However, given the low level of evidence and a limited number of trials, more large-scale and high-quality RCTs are required in the future researches.
Fronto-temporal cortical grey matter thickness and surface area in the at-risk mental state and first-episode schizophrenia: A magnetic resonance imaging study
Authors: Rasser Paul E. , Ehlkes Tim , Consortium MinT , Schall Ulrich
Published: July 2023

Background
Studies to date examining cortical thickness and surface area in young individuals At Risk Mental State (ARMS) of developing psychosis have revealed inconsistent findings, either reporting increased, decreased or no differences compared to mentally healthy individuals. The inconsistencies may be attributed to small sample sizes, varying age ranges, different ARMS identification criteria, lack of control for recreational substance use and antipsychotic pharmacotherapy, as well as different methods for deriving morphological brain measures.
Methods
A surfaced-based approach was employed to calculate fronto-temporal cortical grey matter thickness and surface area derived from magnetic resonance imaging (MRI) data collected from 44 young antipsychotic-naïve ARMS individuals, 19 young people with first-episode schizophrenia, and 36 age-matched healthy volunteers. We conducted group comparisons of the morphological measures and explored their association with symptom severity, global and socio-occupational function levels, and the degree of alcohol and cannabis use in the ARMS group.
Results
Grey matter thickness and surface areas in ARMS individuals did not significantly differ from their age-matched healthy counterparts. However, reduced left-frontal grey matter thickness was correlated with greater symptom severity and lower function levels; the latter being also correlated with smaller left-frontal surface areas. ARMS individuals with more severe symptoms showed greater similarities to the first-episode schizophrenia group. The morphological measures in ARMS did not correlate with the level of alcohol or cannabis use.
Conclusions
Our findings suggest that a decline in function levels and worsening mental state are associated with morphological changes in the left frontal cortex in ARMS but to a lesser extent than those seen in first-episode schizophrenia. Alcohol and cannabis use did not confound these findings. However, the cross-sectional nature of our study limits our ability to draw conclusions about the potential progressive nature of these morphological changes in ARMS.
The effectiveness of theory-based smoking cessation interventions in patients with chronic obstructive pulmonary disease: A meta-analysis
Authors: Han Mengjing , Fu Yingping , Ji Quanyue , Deng Xiaoli , Fang Xuewen
Published: July 2023

Background Smoking cessation can effectively reduce the risk of death, alleviate respiratory symptoms, and decrease the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Effective smoking cessation strategies are crucial for the prevention and treatment of COPD. Currently, clinical interventions based on theoretical frameworks are being increasingly used to help patients quit smoking and have shown promising results. However, theory-guided smoking cessation interventions have not been systematically evaluated or meta-analyzed for their effectiveness in COPD patients. In order to improve smoking cessation rates, this study sought to examine the effects of theory-based smoking cessation interventions on COPD patients. Methods Our research adopted a meta-analysis design. Two researchers conducted a search and evaluation of randomized controlled trials (RCTs) that met the inclusion criteria. The Cochrane Library, Web of Science, PubMed, Embase, Wanfang Knowledge Service Platform, China National Knowledge Infrastructure (CNKI), VIP Information Services Platform, and China Biomedical Literature Service System were among the databases that were searched. The retrieval deadline for this search is from the establishment of the database up until April 20, 2023. Results A total of 11 RCTs involving 3,830 patients were included in the meta-analysis. Results showed that theory-based smoking cessation interventions improved smoking cessation rates, quality of life, and lung function in COPD patients compared to conventional nursing. However, these interventions did not significantly affect the level of nicotine dependence in patients. Conclusion Theory-based smoking cessation intervention as a non-pharmacologically assisted smoking cessation strategy has a positive impact on motivating COPD patients to quit smoking and improving their lung function and quality of life.
High-intensity acute exercise impacts motor learning in healthy older adults
Authors: Coxon James , Taylor Eleanor , Cadwallader Claire , Curtin Dylan , Chong Trevor , Hendrikse Joshua
Published: July 2023

Healthy aging is associated with a decline in motor sequence learning. Acute cardiorespiratory exercise has emerged as a potential intervention to improve motor learning, however research in healthy older adults is limited. The current study investigated the impact of high-intensity interval exercise on a subsequent sequential motor learning task. Twenty-four older adults (aged 55–75 years) completed either 20-minutes of cycling, or an equivalent period of active rest before practicing a sequential force grip task. Skill learning was assessed during acquisition and at a 6-hour retention test. In contrast to expectation, exercise was associated with reduced accuracy during skill acquisition compared to rest, particularly for older participants. However, improvements in motor skill were retained in the exercise condition, while a reduction in skill was observed following rest. Our findings suggest the impact of high intensity exercise on motor performance varies depending on age. Importantly, our findings indicate that high-intensity exercise can facilitate early offline consolidation of a novel skill in older adults which may have implications for motor rehabilitation.
Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer
Authors: Nagatani Yoshiaki , Kiyota Naomi , Imamura Yoshinori , Koyama Taiji , Funakoshi Yohei , Komatsu Masato , Itoh Tomoo , Teshima Masanori , Nibu Ken-Ichi , Sakai Kazuko , Nishio Kazuto , Shimomura Manami , Nakatsura Tetsuya , Ikarashi Daiki , Nakayama Takayuki , Kitano Shigehisa , Minami Hironobu
Published: July 2023

Although immune checkpoint inhibitors (ICPi) for salivary grand cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi. We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing. ACC and MEChigh showed the lowest and higher infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumor. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumor showed a positive correlation with PD-L1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumor (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumor (r = -0.049). The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune inflamed type, and this may support the rationale of ICPi for this pathological subtype.
Feelings of loneliness and meaning in life in subjects with Asperger's syndrome
Authors: Sipowicz Kasper , Pietras Tadeusz , Kosmalski Marcin
Published: July 2023

Introduction: Subjects with Asperger's syndrome without intellectual disabilities have significant difficulties in establishing social relationships despite their IQ being within the normal range. One of the effects of social deficit is depression. The question arises whether loneliness and dimensions of meaning in life correlate with the severity of depression and whether the average severity of depression, loneliness and dimensions of meaning in life differentiate the following groups: people with Asperger's syndrome and depression, people with Asperger's syndrome without depression, people with depression without Asperger's syndrome and healthy subjects.
Material & Methods: The study was conducted on a total of 170 people, including: 43 people with Asperger's syndrome and depression, 41 people with Asperger's syndrome without depression, 40 people with depression without Asperger's syndrome and 46 healthy people (without Asperger's syndrome and without depression). All were administered a demographic survey, Beck Depression Inventory II (BDI-II), De Jong Gierveld Loneliness Scale (DJGLS), Life Attitude Profile-Revised (LAP-R). Asperger's syndrome and depressive episodes were diagnosed on the basis of ICD-10 research criteria still applicable in Poland.
Results:In the group with Asperger's syndrome and depression the highest levels of loneliness and the lowest values of the dimensions of the sense of meaning in life, except for the acceptance of death, were observed. This result was significantly different from the results obtained in the other study groups. Both in people with Asperger's syndrome without depression and in people with depression without Asperger's syndrome, the values of the dimensions of the sense of meaning in life and the level of loneliness differ significantly from the results obtained in the control group. The BDI-II scores correlated positively with the loneliness values and negatively with the sense of meaning in life values in all groups.
Discussion: The results indicate that both suffering from depression and having Asperger's syndrome are associated with an increased sense of loneliness and a reduced sense of meaning in life. People with Asperger's syndrome and depression have the highest values of loneliness and the lowest values of dimensions of the sense of meaning of life compared to the other groups studied. The limitation of the work is the deliberate selection of groups, because it would be interesting to answer the question whether Asperger's syndrome is a risk factor for depression in the population.
Effective triclosan removal by using porous aromatic frameworks in continuous fixed-bed column studies
Authors: Li Ye , Gong Fuxin , Yang Wu , Liu Bingxin
Published: July 2023

Triclosan (TCS) has been regarded as an emerging contaminant in aquatic systems, so its efficient removal holds great significance. In this study, NPVMo@iPAF-1, with specific surface area of 665 m2/g, prepared by incorporating (NH4)5H6PV8Mo4O40 into porous aromatic frameworks (PAF) was obtained. And fixed-bed columns packed with NPVMo@iPAF-1 were employed for TCS removal. The experiment data strongly correlated with the Thomas and Yoon-Nelson models under different operation conditions. The pore preservation, electrostatic effect and the synergistic effect of π-π interaction contributed to the effective adsorption of TCS onto NPVMo@iPAF-1. The NPVMo@iPAF-1 fixed-bed column could be effectively regenerated by in-situ ozonation for more than 10 regeneration cycles. NPVMo@iPAF-1 turned out to be a promising adsorbent for removing TCS not only from pure water but also from reclaimed water and surface water samples.
Tuning of centrifugal pendulum vibration absorbers operating in a fluid
Authors: Shaw Steven W. , Bahadori Reza
Published: July 2023

The linear and nonlinear tuning of centrifugal pendulum vibration absorbers operating in a fluid is addressed. These devices are used to reduced engine order torsional vibrations in rotating machinery. They are frequently housed in a rotating enclosure filled with a fluid, an important example of which is the automotive torque converter. The pressure field in the rotating fluid generates an effective buoyancy on the pendulum mass, thereby affecting its oscillation frequency. This effect is well known for simple pendulums operating in a static fluid under gravity, and is herein generalized to the case of a finite-sized centrifugal pendulum operating in a rotating fluid. A sample shape for the pendulum absorber is considered in detail, showing how the the expected results from a simple, small volume absorber can be generalized to account for more realistic geometries. The main results provide a convenient method for tuning the linear and nonlinear dynamics of the pendulum motion to account for the effects of the surrounding fluid. It is also shown that ignoring the fluid effect can lead to ineffective, and even catastrophic, operation of the pendulum absorber.
Sick sinus syndrome diagnosed after a sinus arrest during treatment for zygomatic fracture: a case report
Authors: Hayashi Hiroki , Abe Atsushi , Oguma Tetsushi , Ito Yu , Nakayama Atsushi
Published: July 2023

Background
Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report.
Case presentation
Sick sinus syndrome is caused by damage to the sinoatrial node or surrounding tissue, and is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. Sinus arrest occurred during and after cheek bone open reduction. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations.
Conclusions
The patient developed sinus arrest during treatment of a zygomatic fracture and was diagnosed as having sinus failure syndrome. In cases of cardiogenic syncope with injuries to the maxillofacial region, the cause of syncope should be thoroughly investigated to avoid complications due to abnormalities of the circulatory system.
Linking replication stress with replication dynamics in Vicia faba root meristem cells
Authors: Musiałek Marcelina W. , Rybaczek Dorota
Published: July 2023

DNA replication faces many challenges, both internally and externally, generally described as factors that induce replication stress. In this article, we describe how prolonged replication stress affects the dynamics of replication and fork activity in V. faba root meristem cells. V. faba seems to have a highly effective stress response system that includes a reaction to replication stress. We used 2.5 mM hydroxyurea (HU) for prolonged stress induction (32 hours) and measured changes in replication and fork activity after initial stress induction, prolonged exposure and after regeneration time in water. We also induced premature chromosome condensation (PCC) as a reference, to compare cells that express valid ATR/Chk1 S-phase checkpoint with cells that lack ATR functions. Our results included general changes in replication activity, obtained with 5-ethynyl-2'-deoxyuridine (EdU) labeling as well as an extended analysis of replication fork progression facilitated by double-labeling with EdU and 5-iodo-2’-deoxyuridine (IdU) which we found to be an appealing alternative to commonly used labeling with 5-chloro-2’-deoxyuridine (CldU) and IdU. A preliminary analysis of minichromo-some maintenance complex component 2 (MCM2), a subunit of minichromosome maintenance protein complex (MCM), were shown. We were able to pinpoint a mechanism that may contribute to the replication stress resistance of V. faba cells the most. We have also demonstrated that it is not only cells with ATR malfunctions where heterochromatin areas are extensively affected by replication stress.
NF-κB target TFAM to modulate mtDNA copies involved in lung injury of mice induced by radon
Authors: Xu Chenlan , Pei Weiwei , Jiang Huihui , Cui Yangchen , Liu Shiyi , Zhang Qi , Zhang Shuyu , Yang Zhao , Jiao Yang , Nie Jihua
Published: July 2023

Radon is the second causative agent of lung cancer after cigarette smoke, it has been identified as a class I carcinogen. However, the exact mechanism of lung cancer caused by radon is still unclear. To examine the underlying mechanism of radon-induced lung injury, a combination of dose- and time-dependent toxic effects in vivo and vitro, NF-κB/TFAM/mtDNA pathway was employed. Radon-induced toxicity occurred in a dose- and time-dependent manners and was characterized by inflammatory cell infiltration, the alveolar septum thickened and the alveolar wall ruptured, moreover, TFAM, NF-κB p65, COXⅡ, ROS and mtDNA signaling pathways were the vital steps in radon-induced pulmonary toxicity. Finally, mitochondrial was identified as a potential target organelle for the further explore of radon-induced lung cancer.
Internationalization of Medical Education in China: A Case Study of Policy and Practice in University Staff and Faculty Members’ Outward Mobility
Authors: Jiang Qin , Sun Hong , Li Yuandong , Liu Shuang , Wang Linlin , Liu Shenjun
Published: July 2023

Background Due to the impact of globalization, especially in the light of COVID-19 pandemic, internationalization of medical education is critical. As the key agent in the progress of higher education internationalization, university staff and faculty members were understudied. This study aims to investigate internationalization of medical university staff and faculty member with a longitudinal quantitative study on their outward mobility.Methods The subject of this study was a cohort of university staff and faculty members who went mobile during their employment. The number of participation in overseas activity is the index to the character of mobility. Descriptive statistics was applied using Microsoft Excel. Certain variables were considered: the ratio of outward staff to the population, purpose of mobility, time length of overseas stay and destinations. Data were classified and summarized, calculations were made by percentage.Results Although there was a rising tendency of international involvement among university staff, a considerably large proportion was disengaged from cross-border activities. For those with outward mobility experiences, there might be a lack of individual willingness for internationalization. While being mobile, most of them were research focused, less attention was paid in either teaching or service. Administrative staff and laboratory staff did not receive the requisite level of training for adaptation to internationalization.Conclusions This is the first study describing the outward mobility of university staff and faculty members with longitudinal quantitative research method in Internationalisation of Higher Education and Internationalisation of Medical Education, complementing the literature with a Chinese format. Although this study was conducted in medical context, the findings resonate with those in Internationalisation of Higher Education literature. In future endeavors, more emphasis are recommended to shift toward internationalization for all members, integrating the different dimensions of internationalization.
A Multimodal Machine Learning Model for Predicting Dementia Conversion in Alzheimer’s Disease
Authors: Lee Min-Woo , Kim Hye Weon , Choe Yeong Sim , Yang Hyeon Sik , Lee Ji Yeon , Lee Hyunji , Yong Jung Hyeon , Kim Donghyeon , Lee Minho , Kang Dong Woo , Jeon So Yeon , Son Sang Joon , Lee Young-Min , Kim Hyug-Gi , Kim Regina E.Y. , Lim Hyun Kook
Published: July 2023

Alzheimer's disease (AD) accounts for 60–70% of the population with dementia. Despite the integration of MRI and PET in AD clinics and research, there is a lack of validated models for predicting dementia conversion from MCI. Thus, we aimed to investigate and validate a machine learning model to predict this. A total of 196 subjects were enrolled from four hospitals and the Alzheimer’s Disease Neuroimaging Initiative dataset. Volumes of the ROI, white matter hyperintensity, and regional SUVR were analyzed using T1, T2-FLAIR MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores and Fazekas scales. Compared with the GBM model trained solely on demographics, AUC of the cross-validation models incorporating T1 image features (pBonferroni=0.03) and T1 and αPET image features (pBonferroni<0.001). The two cross-validated models (pBonferroni=0.08) did not differ significantly in their predictive measures. After performing the inference, the model combining T1 and αPET image features exhibited the highest AUC (0.875), which was comparable to that of the model using only T1 image features (0.835). Our machine learning model utilizing Solitaire T1 MRI features shows promising predictive value for dementia conversion within a 4-year timeframe, making it applicable in circumstances where αPET is unavailable.
Effects of environmental factors and intraspecific niche overlap on the body and ecological characteristics of red-tongued pit vipers (Gloydius ussuriensis)
Authors: Do Min Seock , Son Seok-Jun , Jung Ji-Hwa , Lee Sang-Cheol , Choi Green , Nam Hyung-Kyu
Published: July 2023

The body condition of a snake species provides important physiological, morphological, and ecological information that elucidates its habits, life cycle, and competitive relationships. We measured the body size and condition of the wild Gloydius ussuriensis population in South Korea from 2018 to 2022, analyzed the degree of intraspecific niche overlap, and identified the geographic and climatic factors affecting their body condition. We found that the females were longer than the males. The body condition index (BCI) of G. ussuriensis differed depending on sex and season; the BCI of the females and males was highest in August and October, respectively. Environmental factors related to altitude and temperature affected the body condition of G. ussuriensis; BCI increased as the mean annual temperature and winter temperature increased; however, it increased when the annual temperature range decreased. The mean Pinaka index was 0.96, indicating a high degree of niche overlap; however, the niche overlap among the neonates was less than that among the adults and juveniles. To elucidate the causes of niche overlap and mechanisms behind the intraspecific competition among G. ussuriensis individuals, the habitat and utilization of food resources at different development stages of G. ussuriensis should be further investigated.
Influence of Clearance Between Cradle and Barrel on Nonlinear Dynamic Response of The Artillery System
Authors: Lu Shaojie , Gao Zhiying , Zhang Haifeng , Liao Maolin
Published: July 2023

The artillery weapon system,characterized as a complex nonlinear mechanical system , is influenced by various factors affecting its muzzle vibration response.Thus, taking the model of the artillery system with variable cross-section and multi-step barrel as the object, the equation of bending deformation of the barrel is obtained.Subsequently, the equation of the fundamental frequency of the vertical vibration of the muzzle is obtained based on Hooke’s law and Rayleigh method.And the reliability of both equation is verified by the modal testing and the FEM method under the constraint boundary.Then, the equivalent non-linear dynamic model of the vertical vibration of the muzzle is established ,considering the clearance between the barrel and cradle. Furthermore, the amplitude-frequency curves of the equivalent model under the sinusoidal excitation is obtained based on the multi-scale analysis method for analyzing the impact of clearance and sinusoidal excitation.Finally, the vibration research system of the model of the artillery system is constructed to study the vibration characteristics of the muzzle.The study shows that the proposed theoretical model of bending deformation and fundamental frequency exhibits a higher level of accuracy .In addition, the system demonstrates a reduction in stiffness and a escalation in the maximum amplitude of the amplitude-frequency curve with the increase of the magnitude of the excitation.While, the system demostrates a escalation in both the stiffness and the maximum amplitude with the increase of the clearance value.
Hepatorenal pathologies in TNF-transgenic mouse model of rheumatoid arthritis are alleviated by anti-TNF treatment
Authors: Li Xuefei , Wang Yi , Chen Ziqiang , Ruan Ming , Yang Chan , Zhou Maolin , Li Ning , Xing Lianping , Xu Hao , Yang Ling , Shi Qi , Wang Yongjun , Chen Jinman , Liang Qianqian
Published: July 2023

Objective
To examine and quantify liver and kidney lesions and their response to anti-TNF therapy in TNF-Tg mouse model of rheumatoid arthritis.
Methods
Female TNF-Tg (Tg3647) mice were used as the animal model of chronic rheumatoid arthritis. Ultrasound, immunofluorescence and histology staining, serology test and real-time PCR were used to examine the pathological changes in liver and kidney.
Results
TNF-Tg mice showed a significant decrease in body weight and a dramatic increase in the volumes of gallbladder, knee cavity, and popliteal lymph nodes. Liver and kidney of TNF-Tg mice were demonstrated increased chronic inflammation, accumulation of immune cells, fibrosis and senescence, compared to the wide-type (WT) mice. Moreover, up-regulation of inflammatory factors and impaired normal function were also observed in the liver and kidney of TNF-Tg mice. The inflammation infiltration, fibrosis and senescence in liver and kidney of female TNF-Tg mice were improved after anti-TNF treatment, and better treatment effects were achieved at 8 weeks of intervention.
Conclusions
We found that TNF drives the development of liver and kidney pathology in female TNF-Tg mice, and there are limitations in the loss of utility of Anti-TNF for prolonged treatment of RA-associated hepatic and renal injury. This study provided a reliable and high clinically relevant animal model for the further study to explore the molecular mechanisms and drug discovery of hepatorenal pathologies in RA.
The societal economic impact of vision impairment in adults 40 years and above: Findings from the National Eye Survey of Trinidad and Tobago
Authors: Braithwaite Tasanee , Bailey Henry , Bartholomew Debra , Maharaj Vedatta , Fraser Amandi , Deomansingh Frank , Ramsewak Shivaa , Tripathi Vrijesh , Sharma Subash , Ramsewak Samuel , Bourne Rupert , Gray Alastair
Published: July 2023

Background
Understanding and mitigating the societal economic impact of vision impairment (VI) is important for achieving the Sustainable Development Goals.
Aim
To estimate the prevalent societal economic impact of presenting VI in Trinidad and Tobago using bottom-up cost and utilisation data from the 2014 National Eye Survey of Trinidad and Tobago.
Methods
We took a societal perspective to combine comprehensive, individual-level cost and utilisation data, with population-based prevalence estimates for VI, and additional data from a contemporaneous national eyecare system survey. We included direct (medical and non-medical) and indirect (productivity loss) costs, and intangible losses in total cost estimates, presented in 2014 Trinidad & Tobago(TT) dollars and UK sterling equivalent. We considered but excluded transfer payments and dead weight losses. Sensitivity analyses explored impact on total cost of parameter uncertainty and assumptions.
Results
Individual utilisation and cost data were available for 65.5%(n = 2792/4263) and 59.0%(n = 2516/4263) eligible participants aged ≥ 40 years, respectively. Participant mean age was 58.4(SD 11.8, range 40–103) years, 56.3% were female. We estimated total societal cost of VI in 2014 at UK£365,650,241 (TT$3,842,324,655), equivalent to £675 per capita (population ≥ 40 years). Loss of wellbeing accounted for 73.3%. Excluding this, the economic cost was UK£97,547,222 (TT$1,025,045,399), of which indirect costs accounted for 70.5%, followed by direct medical costs (17.9%), and direct non-medical costs (11.6%).
Conclusion
This study provides robust estimates of the economic impact of vision loss in a Caribbean country, and highlights the extent to which affected individuals and their families bear the societal economic cost of vision impairment.
Corrosion in reinforced concrete: Diagnostics through Potential Corrosion Technique
Authors: Reginato Lucas Alexandre , Lorenzi Alexandre , de Oliveira Leonardo Covatti , Lorenzi Luciani Somensi , Filho Luiz Carlos Pinto da Silva
Published: July 2023

Among the processes that accelerate the loss performance of reinforced concrete structures, considering their frequent occurrence and severity, reinforcement corrosion can be seen as one of the most important. A worrying factor is that most buildings in the Brazilian urban centers are between 40 and 50 years old, a time when repairs and maintenance become more routine. Therefore, the problems related to the corrosion of the reinforcements tend to accentuate in the coming years, and the identification of corrosion will play an important role. Thus, this research has the purpose to analyze the application of the diagnosis through potential corrosion techniques. For this, full-scale reinforced concrete beams were corrosion analyzed. Corrosion was stimulated by the Modified Immersion Accelerated Corrosion - CAIM method, at three levels of mass loss: 5, 10 and 15%. The diagnostic technique through the corrosion potential was applied, in which it was observed that there is uncertainty in the corrosion evaluation for the mass loss levels of 5 and 10%, resulting in a corrosion uncertainty interval, but at 15%, the potential technique proved to be satisfactory.
Harnessing the power of whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation
Authors: Lisowski Leszek , Cabanes-Creus Marti , Liao Sophia H.Y. , Navarro Renina Gale , Knight Maddison , Nazareth Deborah , Lau Ngee-Soon , Ly Mark , Zhu Erhua , Roca-Pinilla Ramon , Delgado Ricardo Bugallo , Baltazar Grober , Westhaus Adrian , Merjane Jessica , Crawford Michael , McCaughan Geoffrey , Ezquerro Carmen María Unzu , González-Aseguinolaza Gloria , Alexander Ian , Pulitano Carlo
Published: July 2023

Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important in the era of personalized medicine. Liver-directed gene therapies present a unique challenge due to the complexity of the human liver. In this work, we describe the application of whole human liver explants in an ex situ normothermic perfusion system to evaluate a set of fourteen natural and bioengineered adeno-associated viral (AAV) vectors directly in human liver, in the presence and absence of neutralizing human sera. Under non-neutralizing conditions, the recently developed AAV variants, AAV-SYD12 and AAV-LK03, emerged as the most functional variants in terms of cellular uptake and transgene expression. However, when assessed in the presence of human plasma containing anti-AAV neutralizing antibodies (NAbs), vectors of human origin, specifically those derived from AAV2/AAV3b, were extensively neutralized, whereas AAV8- derived variants performed efficiently. This study establishes the use of normothermic liver perfusion as an invaluable preclinical model for evaluating liver-targeted gene therapies and providing guidance for making essential decisions that promote the most effective translational programs.
Significance of phosphorus leaching during potato production in coarse soil
Authors: Liu Xiaoyu , Ma Zhong , Qin Yonglin , Shi Xiaohua , Yu Jing , Jia Liguo , Fan Mingshou
Published: July 2023

Phosphorus (P) loss through vertical leaching has been considered insignificant in potato production in Inner Mongolia of China. However, the coarse-textured soil in this potato production region has lower water and nutrient retention capacity, which may result in significant P leaching, leading to increased environmental risk and lower P-use efficiency in potato production. The objective of this study was to evaluate phosphorus leaching in coarse soil during potato production under varied phosphorus application rates and irrigation volumes in Inner Mongolia, by collecting leachate from 60 cm deep soil. Results obtained over the course of four years indicate that accumulative P leaching during the potato production ranged from 0.61 to 4.67 kg/ha, and it increased significantly with increasing P application rate or irrigation volume. This P leaching is of concern to both crop production and the health of aquatic ecosystems, it suggests it is of importance to develop both P fertilizer management and irrigation technique for diminishing P leaching and improving P-use efficiency in potato production on coarse soil.
RETRACTED: Impact of germination conditions on nutritional, nutraceutical, functional and anti-nutritional factors of Pseudocereals grown in Northern Himalayas
Authors: Bhat Tashooq , Habib Huraiya , Kumar Ashwani , Amin Tawheed , ALI GOWHAR , HAMID AFLAQ
Published: July 2023

The authors have requested that this preprint be removed from Research Square.