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In this article, we examine Differential Fault Attacks (DFA) targeting two stream ciphers, FLIP and FiLIP. We explore the fault model where an adversary flips a single bit of the key at an unknown position. Our analysis involves establishing complexity bounds for these attacks, contingent upon the cryptographic parameters of the Boolean functions employed as filters and the key size. Initially, we demonstrate how the concept of sensitivity enables the detection of the fault position using only a few keystream bits. This represents an enhancement over previous DFA methodologies applied to these ciphers. Subsequently, we leverage the properties of the filter's derivatives to execute attacks. This approach is universally applicable to any filter, and we delineate specific attack strategies for the two function families previously implemented in these ciphers. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia. METHODS: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/ mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year. RESULTS: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%. DISCUSSION: Aligningwith practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion. [ABSTRACT FROM AUTHOR]

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.

Abstract After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site “KUMA”, the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called “FLIP” to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. Graphical Abstract

This study is set in EFL teacher training during the COVID -19 pandemic. The goal of this research study was to examine students' perceptions of the development of their oral abilities by means of weekly Flip video recordings. An action research design was carried out for EFL teacher-training students from a Chilean university. Synchronous English language sessions focusing on oral production were aided by asynchronous practice on the Flip platform. Content analysis was conducted to examine the students' perceptions of the use of Flip to facilitate the development of speaking skills. Cooccurring categories were identified, and related networks were produced to identify relevant nodes. Findings revealed favorable perceptions in both the linguistic and socioaffective aspects of learners' oral performance resulting from the weekly recordings. It was concluded that the use of Flip promoted the students' oral production by heightened positive socioaffective perceptions over the course of one academic semester during the time of COVID-19. [ABSTRACT FROM AUTHOR]

International students, particularly international English as a Second Language (ESL) students who come to the United States with relatively lower levels of English oral language proficiency, are often reluctant to participate in academic discussions. In a graduate-level TESOL program with a majority of international ESL students, a video recording, sharing, and discussion platform, Flip, was utilized in the program's teaching innovation. Flip is widely adopted by educators of all grade levels worldwide, as it enables educators to create a less formal online space to meet the holistic needs of international ESL students, including both academic and social needs. The article explains the teaching context of the practice, four stages of course integration with Flip, reasons for the integration, reflections, and future pedagogical directions. Incorporating Flip in this program promotes linguistic benefits, teacher identity and skill development, a community of belonging, and increased equity in assessment. Practical pedagogical considerations are also provided at the end of the article. [ABSTRACT FROM AUTHOR]

After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site "KUMA", the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called "FLIP" to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. [ABSTRACT FROM AUTHOR]

This study evaluated the perceived impact of using Flip (Microsoft Corp.) to facilitate a group project in a socially distanced environment. Student groups were assigned a self-care scenario, and students independently traveled to local pharmacies to identify a pertinent nonprescription product. Students individually recorded a review of the product using Flip. Subsequently, students reviewed and replied to group member videos to compare products. Students worked as a group to develop consensus regarding the most appropriate product recommendation for their scenario. At semester end, students completed a questionnaire about their experiences using Flip for the project. Sixty-eight students (91%) completed the perceptions questionnaire at course conclusion. Students found Flip enjoyable (68%) and easy to use (74%). The majority of students (82%) viewed all of their group members' Flip videos, and most (88%) agreed or strongly agreed Flip facilitated group work in a socially distanced environment. Students overall perceived Flip as enjoyable and easy to use. Though utilization of Flip was initially due social distancing requirements, the positive student feedback encouraged continued use of this platform asynchronously. Flip provides a unique mechanism for facilitating group projects in multiple different environments. [ABSTRACT FROM AUTHOR]

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Finding creative and effective ways to support student experiences and student learning in the classroom is an important goal for instructors, especially as remote and hybrid formats become more common and new, educational technologies are recommended. The current work involved the creation and implementation of a curricular innovation using Flip to encourage the use of evidence-based learning strategies and promote a sense of community in a college classroom. A survey was developed and administered as extra credit in a large Introduction to Psychology class in Spring 2021, with questions focused on examining student perceptions of using Flip in the classroom. Results revealed that students enjoyed using Flip for assignments, believed that Flip assignments helped their learning of class content, and recommended the instructor keeping using Flip in future semesters. The current work highlights the versatility and benefit of using Flip as an instructional tool in the classroom. [ABSTRACT FROM AUTHOR]

With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints' workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation. [ABSTRACT FROM AUTHOR]

Several combinatorial actions of the affine Weyl group of type C ˜ n on triangulations, trees, words and permutations are compared. Addressing a question of David Vogan, we show that, modulo a natural involution, these permutation representations are multiplicity-free. The proof uses a general construction of Gelfand subgroups in the affine Weyl groups of types C ˜ n and B ˜ n. [ABSTRACT FROM AUTHOR]

Let n , d ∈ N and n > d. An (n − d) -domino is a box I 1 × ⋯ × I n such that I j ∈ { [ 0 , 1 ] , [ 1 , 2 ] } for all j ∈ N ⊂ [ n ] with | N | = d and I i = [ 0 , 2 ] for every i ∈ [ n ] ∖ N. If A and B are two (n − d) -dominoes such that A ∪ B is an (n − (d − 1)) -domino, then A , B is called a twin pair. If C , D are two (n − d) -dominoes which form a twin pair such that A ∪ B = C ∪ D and { C , D } ≠ { A , B } , then the pair C , D is called a flip of A , B. A family D of (n − d) -dominoes is a tiling of the box [ 0 , 2 ] n if interiors of every two members of D are disjoint and ⋃ B ∈ D B = [ 0 , 2 ] n. An (n − d) -domino tiling D ′ is obtained from an (n − d) -domino tiling D by a flip, if there is a twin pair A , B ∈ D such that D ′ = (D ∖ { A , B }) ∪ { C , D } , where C , D is a flip of A , B. A family of (n − d) -domino tilings of the box [ 0 , 2 ] n is flip-connected, if for every two members D , E of this family the tiling E can be obtained from D by a sequence of flips. In the paper a flip-connected class of (n − d) -domino tilings of the box [ 0 , 2 ] n is described. [ABSTRACT FROM AUTHOR]

The uncontrolled proliferation of malignant cells in growing tumors results in the generation of different stressors in the tumor microenvironment, such as nutrient shortage, hypoxia and acidosis, among others, that disrupt endoplasmic reticulum (ER) homeostasis and may lead to ER stress. As a response to ER stress, both normal and tumor cells launch a set of signaling pathways known as the unfolded protein response (UPR) to restore ER proteostasis and maintain cell viability and function. However, under sustained ER stress, an apoptotic cell death process can be induced and this has been the subject of different review articles, although the role of the TRAIL-R2/DR5-activated extrinsic pathway of apoptosis has not yet been thoroughly summarized. In this Review, we provide an updated overview of the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress and discuss the role of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) in the final outcome of UPR signaling. Particularly, we focus on the mechanisms controlling cellular FLICE-like inhibitory protein (FLIP) levels in tumor cells undergoing ER stress, which may represent a potential target for therapeutic intervention in cancer. [ABSTRACT FROM AUTHOR]

Phytoplankton patterns have been observed widely in aquatic systems. Although pattern formation has been investigated based on many PDEs, discrete models on aquatic systems can provide more complex dynamics. A discrete toxic-phytoplankton–zooplankton model is studied in this paper, with the consideration of Allee effect and cross-diffusion. Focusing on Allee effect coefficient, flip and Neimark–Sacker bifurcation analyses are carried out. And focusing on cross-diffusion coefficient, Turing bifurcation analyses are carried out. Parameter conditions and bifurcation diagram of these bifurcations are obtained correspondingly. Numerical simulations are then performed which are consistent with results of theoretical analysis. Irregular patterns can be formed by flip bifurcation. Spirals can be formed by Neimark–Sacker bifurcation. Spots and stripes can be formed by Turing bifurcation. When Turing and flip, or Turing and Neimark–Sacker bifurcations both occur, special patterns can be obtained. [ABSTRACT FROM AUTHOR]

The ongoing co-circulation of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains necessitates advanced methods such as high-throughput multiplex pseudovirus systems for evaluating immune responses to different variants, crucial for developing updated vaccines and neutralizing antibodies (nAbs). We have developed a quadri-fluorescence (qFluo) pseudovirus platform by four fluorescent reporters with different spectra, allowing simultaneous measurement of the nAbs against four variants in a single test. qFluo shows high concordance with the classical single-reporter assay when testing monoclonal antibodies and human plasma. Utilizing qFluo, we assessed the immunogenicities of the spike of BA.5, BQ.1.1, XBB.1.5, and CH.1.1 in hamsters. An analysis of cross-neutralization against 51 variants demonstrated superior protective immunity from XBB.1.5, especially against prevalent strains such as "FLip" and JN.1, compared to BA.5. Our finding partially fills the knowledge gap concerning the immunogenic efficacy of the XBB.1.5 vaccine against current dominant variants, being instrumental in vaccine-strain decisions and insight into the evolutionary path of SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The esophagogastric junction (EGJ) is a complex anti-reflux barrier whose integrity relies on both the intrinsic lower esophageal sphincter (LES) and extrinsic crural diaphragm. During hiatal hernia repair, it is unclear whether the crural closure or the fundoplication is more important to restore the anti-reflux barrier. The objective of this study is to analyze changes in LES minimum diameter (Dmin) and distensibility index (DI) using the endoluminal functional lumen imaging probe (FLIP) during hiatal hernia repair. Methods: Following implementation of a standardized operative FLIP protocol, all data were collected prospectively and entered into a quality database. This data were reviewed retrospectively for all patients undergoing hiatal hernia repair. FLIP measurements were collected prior to hernia dissection, after hernia reduction, after cruroplasty, and after fundoplication. Additionally, subjective assessment of the tightness of crural closure was rated by the primary surgeon on a scale of 1 to 5, 1 being the loosest and 5 being the tightest. Results: Between August 2018 and February 2020, 97 hiatal hernia repairs were performed by a single surgeon. FLIP measurements collected using a 40-mL volume fill without pneumoperitoneum demonstrated a significant decrease in LES Dmin (13.84 ± 2.59 to 10.27 ± 2.09) and DI (6.81 ± 3.03 to 2.85 ± 1.23 mm2/mmHg) after crural closure (both p < 0.0001). Following fundoplication, there was a small, but also statistically significant, increase in both Dmin and DI (both p < 0.0001). Additionally, subjective assessment of crural tightness after cruroplasty correlated well with DI (r = − 0.466, p < 0.001) and all patients with a crural tightness rating ≥ 4.5 (N = 13) had a DI < 2.0 mm2/mmHg. Conclusion: Cruroplasty results in a significant decrease in LES distensibility and may be more important than fundoplication in restoring EGJ competency. Additionally, subjective estimation of crural tightness correlates well with objective FLIP evaluation, suggesting surgeon assessment of cruroplasty is reliable. [ABSTRACT FROM AUTHOR]

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a leading cause of food bolus impaction in children and adults. The mechanism of dysphagia in EoE, particularly non-obstructive dysphagia, remains incompletely understood. While fibrostenotic processes appear to be critical in the development of dysphagia, somatosensory dysfunction and dysmotility also contribute. This review considers potential mechanisms of dysphagia and evaluates the utility of current and future treatment strategies in this context. [ABSTRACT FROM AUTHOR]

Background. There are growing interests from practicing endoscopists to implement the functional lumen imaging probe (FLIP) impedance planimetry system. We present a simulation-based curriculum using an "into the fire" approach with hands-on pre- and post-tests to teach the use of this technology. Methods. The curriculum consists of a series of pre-tests, didactic content, mentored hands-on instructions, and post-tests. Pre- and post-testing included a knowledge-based written test, a confidence survey, and an assessment form specific to the hands-on performance of FLIP. Result. Twenty-two practicing physicians completed the curriculum. After course completion, participants had improved knowledge-based written test scores from 6.8±1.7 to 8.9±0.9 (P <0.001), confidence scores from 10.0±5.9 to 22.1±2.6 (P <0.001), and hands-on performance score from 11.4±3.4 to 23.1±2.0 (P <0.001) with significant improvement in all components of the hands-on skills. Conclusion. Our simulation curriculum is effective in improving confidence, knowledge, and technical proficiency when teaching the use of FLIP to practicing physicians. [ABSTRACT FROM AUTHOR]

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment. [ABSTRACT FROM AUTHOR]

Let X be a normal Q-factorial projective variety with at most log canonical singularities. We shall give a sufficient condition for the existence of at most finitely many KX-negative extremal rays R(C NE(X) of divisorial type. As an application, we show that for a nonisomorphic surjective endomorphism f:X - X of a normal projective Q-factorial terminal 3-fold X with (X) > 0, a suitable power fk (k > 0) of f descends to a nonisomorphic surjective endomorphism g:Xmin - Xmin of a minimal model Xmin of X. [ABSTRACT FROM AUTHOR]

Background: Endoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent of the pyloromyotomy continues to present a challenge as there are no standardized tools for measuring changes in pyloric distensibility during the procedure. The objective of this study was to evaluate the utility of using impedance planimetry with endoscopic functional luminal imaging probe (FLIP) to measure changes in pyloric distensibility after POP, and to compare these changes with improvement in symptoms and objective gastric emptying. Methods: Patients with medically refractory gastroparesis underwent POP with FLIP measurements of the pylorus (EndoFLIP®, Medtronic, Fridley MN). FLIP measurements, as well as changes in symptoms measured by the validated gastroparesis cardinal symptom index (GCSI) and scintigraphic gastric emptying studies (GES), were evaluated before and after POP. Results: A total of 14 patients underwent measurement with FLIP during POP, 12 of whom had pre- and post-POP measurements. Mean pyloric diameter increased by 1.4 mm, from 13.9 mm to 15.3 mm (p = 0.0012). Mean distensibility index increased from 6.2 mm2/mmHg to 9.1 mm2/mmHg (p = 0.0074). Successful division of the pylorus was achieved in 100% of patients with a mean operative time of 36 min and no perioperative complications. The mean length of stay was 0.7 days (0–3 days). Post-POP mean GCSI score improved from 2.97 to 2.28 at a mean follow-up time of 27 days (p < 0.001). Objective improvement in gastric emptying was observed in 80% of patients with scintigraphic GES, with mean four-hour retention decreasing from 46.3% to 32.4% (p < 0.007). Conclusions: FLIP is a safe and feasible tool to provide objective measurements during POP. Larger cohorts with longer follow-up are required to determine if measured improvements in pyloric diameter and distensibility are predictive of sustained improvements in GCSI and GES. [ABSTRACT FROM AUTHOR]

In this article, we propose key recovery attack on two stream ciphers: Kreyvium and FLIP $_{530}(42,128,360)$ 530 (42 , 128 , 360) using Differential Fault Attack (DFA) technique. These two ciphers are being used in Fully Homomorphic Encryption (FHE) due to their low error growth during keystream generation. Kreyvium is an NFSR-based stream cipher and FLIP is a permutation-based stream cipher. We first show that the complete state of the Kreyvium can be recovered by injecting 3 faults and considering 450 many keystream bits. In case of FLIP, we show that if there is a 1-bit fault in the state of the cipher then from 9000 normal and faulty keystream bits the state (i.e., the secret key) of the cipher can be recovered. For single bit fault, one will require to solve a system of equations for each 530 possible fault locations to recover the correct key of FLIP. To the best of our knowledge, this is the first article which analyzes the security of these two FHE supported stream ciphers under DFA and it has been observed that DFA completely reveals the secret keys of these two ciphers with very minimal faults. [ABSTRACT FROM AUTHOR]

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF-α inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF-α by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-α to assess the function of TNF-α in TP/LPS co-treatment. Additionally, time-dependent NF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro. Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-κB-mediated pro-survival protein, was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-α, revealing the role of TNF-α in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-κB dependent pro-survival signals, especially FLIP, induced by LPS/TNF-α. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in vitro. Mice and hepatocytes treated with TP were sensitive to TNF-α, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

Objectives: Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. Methods: An in vitro peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1β, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1β and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. Results: Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1β and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1β and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. Discussion: Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD.

COVID-19 pandemic is casting a long shadow, and the appearance of the JN.1 variety calls attention to the necessity of maintaining heightened awareness. It considers the strength that has been developed via immunization programs and the necessity of global collaboration to find a solution in light of the emergence of new strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Phylogenetically, the SARS-CoV-2 Omicron XBB lineages, which include EG.5.1 and HK.3, are different from the SARS-CoV-2 BA.2.86 lineage, which was initially discovered in August 2023. More than 30 mutations in the spike (S) protein are carried by BA.2.86 compared to XBB and BA.2, suggesting a high potential for immune evasion. JN.1 (BA.2.86.1.1), a descendant of BA.2.86, appeared in late 2023 after the format had undergone evolution. JN.1 carries three mutations in proteins that do not include S, as well as S:L455S. As previously demonstrated, the HK.3 and other "FLip" variations possess the S:L455F mutation, which enhances transmissibility and immune escape capacity in comparison to the parental EG.5.1 variety. This mutation is a characteristic of JN.1. The COVID-19 virus is dynamic and evolves over time. New varieties can sometimes spread more quickly or effectively after these alterations. If that happens, the new variant has a chance to outpace the current varieties in terms of frequency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints’ workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation.

The uncontrolled proliferation of malignant cells in growing tumors results in the generation of different stressors in the tumor microenvironment, such as nutrient shortage, hypoxia and acidosis, among others, that disrupt endoplasmic reticulum (ER) homeostasis and may lead to ER stress. As a response to ER stress, both normal and tumor cells launch a set of signaling pathways known as the unfolded protein response (UPR) to restore ER proteostasis and maintain cell viability and function. However, under sustained ER stress, an apoptotic cell death process can be induced and this has been the subject of different review articles, although the role of the TRAIL-R2/DR5-activated extrinsic pathway of apoptosis has not yet been thoroughly summarized. In this Review, we provide an updated overview of the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress and discuss the role of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) in the final outcome of UPR signaling. Particularly, we focus on the mechanisms controlling cellular FLICE-like inhibitory protein (FLIP) levels in tumor cells undergoing ER stress, which may represent a potential target for therapeutic intervention in cancer.

Background: The functional luminal imaging probe (FLIP) can be used to measure the esophagogastric junction distensibility index (DI) during myotomy for achalasia and increased DI has been shown to predict superior clinical outcomes. The objective of this study was to determine if the intraoperative DI and the changes produced by per oral endoscopic myotomy (POEM) differed between achalasia subtypes.Methods: FLIP measurements were performed during POEM for achalasia at a single institution. DI (defined as the minimum cross-sectional area (CSA) at the EGJ divided by distensive pressure) was measured at three time points: after induction of anesthesia, after submucosal tunneling, and after myotomy. Measurements were reported at the 40 mL fill volume for the 8 cm FLIP (EF-325) and at the 60 mL fill volume for the 16 cm FLIP (EF-322). Measurements were compared using chi-square and Kruskal-Wallis tests.Results: 142 patients had intraoperative FLIP performed during POEM for achalasia between 2012 and 2019 (30 type I, 68 type II, 27 type III, and 17 variant). Patients with type I achalasia had a significantly higher induction DI (median 1.7 mm2/mmHg) than type II (0.8 mm2/mmHg), type III (0.9 mm2/mmHg), and variants (1.1 mm2/mmHg; p < 0.001). These differences persisted after submucosal tunneling and final DI after myotomy was also significantly higher in type I patients (median 8.0 mm2/mmHg) compared to type II (5.8 mm2/mmHg), type III (3.9 mm2/mmHg), and variants (5.4 mm2/mmHg; p < 0.001). Achalasia subtypes were found to have similar CSA at all time points, whereas pressure differed with type I having the lowest pressure and type III the highest.Conclusion: The DI at each operative step during POEM was found to differ significantly between achalasia subtypes. These differences in DI were due to pressure, as CSA was similar between subtypes. Achalasia subtype should be accounted for when using FLIP as an intraoperative calibration tool and in future studies examining the relationship between DI and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Esophagogastric junction distensibility index (DI), measured using the functional luminal imaging probe (FLIP), correlates with symptomatic outcomes after interventions for achalasia. The objective of this study was to determine if the intraoperative measurement of DI using FLIP was associated with improved clinical outcomes following per-oral endoscopic myotomy (POEM) for achalasia when compared with procedures in which FLIP was not utilized. Methods: Patients undergoing POEM from 2012 to 2017 at a single institution by a single surgeon were studied. Use of FLIP during this time period was based on catheter and technician availability, resulting in two patient cohorts. In patients in whom FLIP was used, operative video recordings were reviewed to determine when DI measurements led to the performance of additional myotomy. Postoperative Eckardt symptom scores (ES) at 12 months and postoperative physiologic studies were compared between patients with and without intraoperative FLIP. Associations were assessed using Mann–Whitney U and Chi-square tests. Results: 143 patients were included in the analysis (61 with intraoperative FLIP and 82 without FLIP). Video recordings were available for 85% of the FLIP cohort. Review of these operative recordings revealed that 65% of patients who underwent FLIP had additional myotomy performed following the initial postmyotomy FLIP measurement. At 12 months after POEM, the FLIP cohort had significantly more clinical successes (defined as ES ≤ 3) than patients in whom FLIP was not used (93% vs. 81%, p < 0.05). Conclusions: Use of intraoperative FLIP during POEM resulted in the surgeon performing additional myotomy in over half of cases and was associated with improved clinical outcomes. This study demonstrates the potential for a FLIP-tailored myotomy to improve outcomes in patients undergoing surgical myotomy for achalasia. [ABSTRACT FROM AUTHOR]

Introduction: The Endoluminal Functional Lumen Imaging Probe (Endoflip™) is a balloon-based catheter that provides real-time, objective feedback regarding the distensibility of any sphincter in the gastrointestinal tract. Usage of the Functional Lumen Imaging Probe (FLIP) has not been standardized, which has limited the interpretation and generalizability of published data. The purpose of this consensus statement is to provide a standardized protocol for obtaining FLIP measurements in order to create a more uniform approach to data collection.Methods: Five expert foregut surgeons, all of whom utilize the FLIP system in their daily practice, convened on March 19, 2019, to create a standardized protocol for obtaining FLIP measurements during hiatal hernia repair and fundoplication, magnetic sphincter augmentation, laparoscopic Heller myotomy, and peroral endoscopic myotomy. Existing literature was presented and reviewed. Each step of the protocol was discussed in detail until a unanimous consensus was reached.Results: A standardized protocol was developed for obtaining FLIP measurements during hiatal hernia repair and fundoplication, magnetic sphincter augmentation, laparoscopic Heller myotomy, and peroral endoscopic myotomy.Conclusion: The FLIP impedance planimetry system is the only technology available that provides surgeons an objective way to assess the tightness of a fundoplication or adequacy of a myotomy during an operation. While considerable research remains to correlate FLIP measurements to patient outcomes, this consensus statement will provide standardization of data collection among FLIP users that will enhance the understanding of future study results. [ABSTRACT FROM AUTHOR]

Regulation of anti-apoptotic protein FLICE-like inhibitory protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) remains a crucial step in the cell fate determination and thus targeting these anti-apoptotic proteins could be a viable strategy for the treatment of cancer. However the regulation of FLIP and XIAP is not very well established till date. Here we have shown that ROS decreased XIAP and FLIP by activation of ubiquitin-proteasomal pathway in imatinib resistant K562 cells. Activation of the components of MAPK pathway, ERK and JNK, played a crucial role in XIAP and FLIP degradation because ectopic expression or knock down of ERK and JNK changed the pattern of ROS mediated down-regulation of these two proteins. We have also found that JNK and ERK differentially regulates FLIP and XIAP, respectively. Moreover, our data suggests that activated ERK decreased Akt phosphorylation and thus its binding to and stabilization of XIAP. On the other hand, JNK activation increased E3 ubiquitin ligase ITCH expression and its binding to FLIP which leads to its degradation. Thus, we have, for the first time elucidated that ROS mediated ERK-Akt crosstalk regulates XIAP. We have also shown for the first time that ROS regulates ITCH expression which controls FLIP degradation. [Display omitted] • We have, for the first time, shown that ERK and PI3K/Akt pathways crosstalk in the regulation of XIAP in presence of ROS. • We have also shown for the first time that ROS increases expression of ITCH which, by its association with FLIP, degrades it via proteasome pathway. [ABSTRACT FROM AUTHOR]