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Background Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer. Methods We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured. Results Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025). Conclusion Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.

As the field of wearable electronics continues to expand, the integration of inorganic thermoelectric (TE) materials into fabrics has emerged as a promising development due to their excellent TE properties. However, conventional thermal methods for fabricating TE fabrics are unsuitable for wearable applications because of their high temperatures, resulting in rigid TE materials. Herein, a nonthermally fabricated silver selenide (Ag2Se) TE fabric is developed that can be effectively integrated into wearable applications. Ag2Se nanoparticles are densely formed within the fabric through a simple in situ chemical reduction process, resulting in remarkable electrical stability even after 10 000 cycles of mechanical deformation, such as stretching and compression. Notably, the fabricated Ag2Se TE fabric exhibits superior stretchability, stretching ≈1.36 times more than the thermally treated Ag2Se TE fabrics, while retaining its excellent electrical conductivity. Moreover, the TE unit exhibits 9.80 μW m−1 K−2 power factor, 134.45 S cm−1 electrical conductivity, and −26.98 μV K−1 Seebeck coefficient at 370 K. A haptic sensing glove based on the Ag2Se TE fabric as a sensor for detecting potential hazards is demonstrated. The glove effectively distinguishes between simple touch, physical pain, and high‐temperature hazards, ensuring user safety and prompt response.

Background: The gut microbiome is a diverse system within the gastrointestinal tract composed of trillions of microorganisms (gut microbiota), along with their genomes. Accumulated evidence has revealed the significance of the gut microbiome in human health and disease. Due to its ability to alter drug/xenobiotic pharmacokinetics and therapeutic outcomes, this once-forgotten “metabolic organ” is receiving increasing attention. In parallel with the growing microbiome-driven studies, traditional analytical techniques and technologies have also evolved, allowing researchers to gain a deeper understanding of the functional and mechanistic effects of gut microbiome. Aim of review: From a drug development perspective, microbial drug metabolism is becoming increasingly critical as new modalities (e.g., degradation peptides) with potential microbial metabolism implications emerge. The pharmaceutical industry thus has a pressing need to stay up-to-date with, and continue pursuing, research efforts investigating clinical impact of the gut microbiome on drug actions whilst integrating advances in analytical technology and gut microbiome models. Our review aims to practically address this need by comprehensively introducing the latest innovations in microbial drug metabolism research— including strengths and limitations, to aid in mechanistically dissecting the impact of the gut microbiome on drug metabolism and therapeutic impact, and to develop informed strategies to address microbiome-related drug liability and minimize clinical risk. Key scientific concepts of review: We present comprehensive mechanisms and co-contributing factors by which the gut microbiome influences drug therapeutic outcomes. We highlight in vitro, in vivo, and in silico models for elucidating the mechanistic role and clinical impact of the gut microbiome on drugs in combination with high-throughput, functionally oriented, and physiologically relevant techniques. Integrating pharmaceutical knowledge and insight, we provide practical suggestions to pharmaceutical scientists for when, why, how, and what is next in microbial studies for improved drug efficacy and safety, and ultimately, support precision medicine formulation for personalized and efficacious therapies.

Background: Keloids are a common fibrotic disease of the skin, with the pathological hallmark of excessive extracellular matrix synthesis due to abnormal fibroblast activity. Since keloids clinically arise in areas of high mechanical tension, the mechanotransductory pathway may be attributed to its pathogenesis. We aimed to establish a preclinical platform to elucidate the underlying mechanism of keloid development and its clinical persistence. Methods: We fabricated a mechanically stretchable polydimethylsiloxane cell culture platform; with its mimicry of the in vivo cyclic stretch of skeletal muscles, cells showed higher proliferation compared with conventional modalities. Results: In response to mechanical strain, TGF-β and type 1 collagen showed significant increases, suggesting possible TGF-β/Smad pathway activation via mechanical stimulation. Protein candidates selected by proteomic analysis were evaluated, indicating that key molecules involved in cell signaling and oxidative stress were significantly altered. Additionally, the cytoskeletal network of keloid fibroblasts showed increased expression of its components after periodic mechanical stimulation. Conclusions: Herein, we demonstrated and validated the existing body of knowledge regarding profibrotic mechanotransduction signaling pathways in keloid fibroblasts. Cyclic stretch, as a driving force, could help to decipher the tension-mediated biomechanical processes, leading to the development of optimized therapeutic targets.

ABSTRACTThe gut microbiota affects hepatic drug metabolism. However, gut microbial factors modulating hepatic drug metabolism are largely unknown. In this study, using a mouse model of acetaminophen (APAP)-induced hepatotoxicity, we identified a gut bacterial metabolite that controls the hepatic expression of CYP2E1 that catalyzes the conversion of APAP to a reactive, toxic metabolite. By comparing C57BL/6 substrain mice from two different vendors, Jackson (6J) and Taconic (6N), which are genetically similar but harbor different gut microbiotas, we established that the differences in the gut microbiotas result in differential susceptibility to APAP-induced hepatotoxicity. 6J mice exhibited lower susceptibility to APAP-induced hepatotoxicity than 6N mice, and such phenotypic difference was recapitulated in germ-free mice by microbiota transplantation. Comparative untargeted metabolomic analysis of portal vein sera and liver tissues between conventional and conventionalized 6J and 6N mice led to the identification of phenylpropionic acid (PPA), the levels of which were higher in 6J mice. PPA supplementation alleviated APAP-induced hepatotoxicity in 6N mice by lowering hepatic CYP2E1 levels. Moreover, PPA supplementation also reduced carbon tetrachloride-induced liver injury mediated by CYP2E1. Our data showed that previously known PPA biosynthetic pathway is responsible for PPA production. Surprisingly, while PPA in 6N mouse cecum contents is almost undetectable, 6N cecal microbiota produces PPA as well as 6J cecal microbiota in vitro, suggesting that PPA production in the 6N gut microbiota is suppressed in vivo. However, previously known gut bacteria harboring the PPA biosynthetic pathway were not detected in either 6J or 6N microbiota, suggesting the presence of as-yet-unidentified PPA-producing gut microbes. Collectively, our study reveals a novel biological function of the gut bacterial metabolite PPA in the gut-liver axis and presents a critical basis for investigating PPA as a modulator of CYP2E1-mediated liver injury and metabolic diseases.

Behavioral approaches have been successful in challenging the rational actor model of international legal analysis and supplementing that model with empirical evidence. Yet observing a set of features about the world requires ignoring or bracketing others. Behavioral approaches retain their own inevitable blind spots, which are not necessarily products of flawed experimental design, but stem from the paradigmatic traits of these approaches. These blind spots derive from an emphasis on methodological individualism, positivism, and experimentation. This emphasis may obscure the social aspects of international legal decision-making. For example, behavioral approaches to international law often use experimental data to describe cognitive tendencies. In doing so, these approaches may not seek and likely will not have tools to discover the meaning of a state action, or the human actions that produce that state action. That latter inquiry requires “historical, ethnographic and other sociological methods that analyze social life outside of the experimental setting.” In sum, behavioral approaches pursue both theoretical and empirical concerns different from those pursued in an interpretive mode of meaning-making.

A simple method of investigating the effect of joint clearances on landing gear retraction failure is presented and applied to the main landing gear with a single sidestay and a hydraulic actuator. A geometric model is presented with assumptions of each link as a rigid body and their relative positions geometrically determined by considering the size of the clearances. We conducted a sensitivity analysis based on a geometric model of the main landing gear. The model was calibrated using the data from the technical order. A Monte Carlo simulation (MCS) was conducted, and whose input was the distance of each clearance based on the experimental design that combined the modified Latin hypercube sampling (LHS) and central composite design (CCD). As a result, we were able to find that the joint had a high potential to operate abnormally. We validated the model by using the actual failure data. Finally, the physical meaning of the sensitivity analysis results was interpreted by comparing them with the values obtained through an amplification index method that is a modified linearization method.

Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes) was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold) higher basal glutathione levels and (~2 fold) lower basal (mRNA and activity) levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

Why do nations obey custom? The conventional model of the law of nations or customary international law (CIL) countenances a separation thesis that CIL is comprised of two discrete elements: state practice (usus) and a legal consciousness (opinio). This Article argues that the separation thesis is attributable to the time-honored philosophical dilemma in comprehending the reality known as Cartesian “mind-body” dualism. As innocuous as it might sound, the dualism-inspired separation thesis tends to generate grave conceptual and practical quandaries, such as the circularity and dogmatic competition between the two constitutive elements, i.e., state practice and legal consciousness. This Article submits that state practice and state mind should not be separated in the first place, and aims to reinstate an ontological unity between the two elements to better ascertain CIL. The holistic and dynamic thesis proposed by this Article focuses not on the static substances comprising CIL, but on the evolving relations among states leading to the development of CIL. In a given legal community (nomos), each CIL rule undergoes a normative life-cycle: rule-formation (externalization), rule-recognition (objectivation) and rule-following (internalization). Under this sociological approach, a particular behavioral pattern among states emerges from a shared belief in its legal reality. Such behavioral regularity among states, once performed, in turn further strengthens the original belief of legal bindingness. [ABSTRACT FROM AUTHOR]

The world trade system is in disarray. Trade wars and the impasse over the appointment of new Appellate Body members at the World Trade Organization (WTO) have all threatened to destabilize the current world trade order. At the center of the storms confronting the current world trade order is China, whose state-driven economic and trade policies have fueled trade conflicts with other WTO members. Yet the distinction between market capitalism and state capitalism is rather artificial, and it is high time that the world trade community builds a new, consensus-based world trade order that could accommodate both styles of capitalism. This Article has three goals. First, it debunks the ostensible orthodoxy of pure market capitalism and demonstrates the false choice between market capitalism and state capitalism. The practice of state intervention in market capitalism and state capitalism differs only in degree, not in kind. Second, this Article discusses how the recent politicization of trade relations has undermined the global economic governance system symbolized by the WTO. Such politicization nullifies the hard-won institution of rule of law in trade relations that the world trade community has painstakingly built in the past decades. Finally, this Article proposes that WTO members establish a subsidy community in which WTO members share the meaning and scope of countervailable subsidies based on a process of social learning. Such a thematic community can launch a discursive platform of "Specific Subsidy Concerns." Data-driven, intensive peer review through specific subsidy concerns can open up a black box of subsidy structure and enable WTO members to focus on how a given subsidy system actually functions, rather than on what it may lack. [ABSTRACT FROM AUTHOR]

Summary: Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca2+ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.

Why do judges commonly predicate their own decisions on earlier decisions authored by others? What makes those otherwise discrete and separate decisions of the past nonetheless hang together and form a powerful system of reference to subsequent cases? While legal justification for legal precedent remains remarkably limited, a leading account attributes this ostensibly puzzling authority to its efficiency-enhancing properties. However, conservation of judicial resources can hardly motivate judges to abide by past decisions. Moreover, the consequentialist nature of the rationalist explanation tends to exaggerate the predictive force of legal precedent. No legal precedent guarantees a particular court ruling, while an overarching logic of judicial efficiency might allude in such direction. In an effort to fill such analytical gap, this Article reconstructs legal precedent as a socio-anthropological phenomenon, i.e., “ritual.” The central claim of this Article is twofold. First, legal precedent is explicable in cultural terms, such as symbol and language; second, legal precedent holds a structural-systematic value as it exists for its own sake. This novel approach to legal precedent, this Article argues, can enrich mindsets of legal scholars and practitioners and help them expand their discursive horizons, so as to produce globally relevant decisions. This Article applies the new framework to the jurisprudence of the World Trade Organization (WTO) in order to reconfigure the boundaries of legal precedent in a global dimension. [ABSTRACT FROM AUTHOR]

The Trump administration has recently pushed the World Trade Organization (WTO) into a crisis by gutting its court and waging trade wars. Conventional narratives on this crisis have been state-centered as they ascribe origins of the crisis to domestic politics in key WTO members, especially the United States. This Article divulges both analytical and normative blind spots left by these narratives. This Article, in a Copernican turn, submits a system-driven alternative, in terms of the "World Trade Constitution" (WTC), which generates rich insights in both diagnosing and prescribing the crisis. The WTC, for the purpose of the Article, does not denote a formal document; rather, it signifies a broad sense of "constitutionalism" consonant with a total set of fundamental normative products, such as practice and precedent, which have historically emerged in the world trading community. This Article tests the resiliency of the WTC by demonstrating various system-maintaining behaviors of WTO members in the face of the crisis. This Article posits that the WTC is culturally stickier than many would believe in that its stakeholders incorporate, by reference, the WTC into the domestic legal and political discourse, even without a formal transposition mechanism. The very fact that the Biden administration was pressured to return to the WTO normalcy is emblematic of the WTC's resiliency. The legal gravitational force of the WTC can also shape daily operations of private businesses at a granular level, even if such force may remain unrecognizable on a surficial level. This Article finally argues that political constitutionalism, through a collective decision-making mechanism (voting), must complement the WTC for the latter's lasting sustainability. [ABSTRACT FROM AUTHOR]

Mobile cranes are essential for transporting heavy materials at construction sites, but their operation carries significant safety risks, particularly due to the potential for overturning accidents. These accidents can be classified into two main categories: mechanical accidents, which are caused by factors such as outrigger failure, excessive load weight, and operator skill, and environmental accidents, which arise from ground subsidence due to groundwater and sinkholes. While numerous studies have addressed the causes and prevention of mechanical accidents, there has been a lack of research focusing on the prevention of environmental accidents. This study presents the development of an Electrical Resistivity Measurement System (ERMS) designed to prevent overturning accidents caused by ground subsidence at mobile crane work sites. The ERMS, mounted on a mobile crane, continuously monitors the ground conditions in real time and predicts the likelihood of ground subsidence to prevent accidents. Unlike typical buried electrode methods, the proposed system features a foldable electrode mechanism and a water supply device, thereby making installation and removal more efficient. Furthermore, it uses a ground stability determination algorithm that qualitatively assesses soft ground conditions, which are the primary cause of ground subsidence. The performance of the ERMS was validated through comparisons with commercial equipment, and its applicability was further confirmed through field tests conducted at mobile crane installations. The ERMS is expected to significantly reduce the risk of accidents caused by ground subsidence during mobile crane operations and to contribute to enhancing overall safety in construction environments.

Conventional narratives explicate the recent trade war between the United States and China in realist terms, such as a hegemonic struggle symbolized by the "Thucydides trap." Yet this universalist heuristic fatally omits ideational factors, such as beliefs that are capable of contextualizing a particular foreign affair. The U.S.-China economic conflicts of today are characterized as much by past convictions as by simple power politics. This Article aims to remedy this analytical blind spot by employing the concept of "collective memory." The central claim is that the particular ways and forms in which the U.S. elites and the public remember, and evoke, momentous economic conflicts of the past elucidate a recidivistic pattern of exceptionalist trade policies of the United States. While drawing from the past, collective memories manifest themselves in the present tense for the present purpose. Three decades ago, the Cold War and Japan-Bashing planted collective memories on economic warfare in the minds of U.S. policymakers and the public. Those collective memories, this Article argues, shape how the Trumpian trade war is waged in the present time. The Article also warns that false analogies triggered by such collective memories may seriously distort the legal and economic reality of the contemporary global sphere. This Article concludes that the United States needs to be more susceptible to external opinions different from its own, thereby cultivating counter-memories that can disabuse the United States of those myths subscribed to by its power elites. [ABSTRACT FROM AUTHOR]

Populists are trying to take down the global economic order and its institutions. While some of those forces might be fueled by racism, they also play to legitimate social concerns that include massive plant closings and deindustrialization, inadequate skills programs, and lack of decent jobs. Some of these problems also concern the Global South, as workers there face exploitation, unhealthy working conditions, and other social ills caused by global capitalism. In light of these problems, this Article argues that the International Labor Organization (ILO) should design new conventions on lead firm liability and mass layoffs. While other scholars and policymakers have already argued that lead firms should shoulder employer responsibilities of their suppliers, contractors, and franchisees, this is the first law review article that calls for an ILO convention that can diffuse such rules globally. The Article also calls on the World Trade Organization (WTO) to advise the ILO on these labor-protective conventions. The WTO, as an expert trade body, can better ensure stakeholders that these new conventions will comply with international trade law and policy, including with WTO "public morals" exception rules and with rules on technical barriers on trade and tax and subsidies. In doing so, the WTO can guarantee that the new conventions, far from hurting trade, will help to enhance the global trade regime. Moreover, the WTO, through its "peer review" practice, where stakeholders can discuss how to create and implement new labor and trade policies, can help coordinate a muchneeded global dialogue for a more inclusive globalization. This is also true of the ILO conventions that we advocate for here. We conclude by addressing likely arguments against our proposal, including from scholars and policymakers skeptical of the role that international law can have on the current political turmoil. After addressing those objections to our proposal, we maintain that collaboration between the ILO and the WTO, while certainly not the panacea for all the complex and daunting problems of our times, remains critical to restore legitimacy to the global economic order in a postpopulist era. [ABSTRACT FROM AUTHOR]

Category: Trauma; Ankle Introduction/Purpose: Ankle fracture is one of the most common fractures over the age of 50 years. However, there is a lack of research on osteoporotic ankle fractures compared to other osteoporotic fractures. Recently, some studies have been published that Hounsfield Unit(HU) measuring bone attenuation from CT scan is used for assessing the bone density of not only the hip and spine but also extremities such as the distal radius and proximal humerus. This study aims to evaluate the correlation between HU of distal tibia without ankle fracture and DEXA-BMD and determine the cut-off value of HU for osteoporosis diagnosis. Additionally, this study determines whether the HU of the distal tibia obtained from the preoperative CT scan of ankle fractures helps evaluate patients with osteoporotic ankle fractures. Methods: From June 2016 to August 2020, We retrospectively studied foot and ankle traumatic patients who are postmenopausal women or men over 50 years. They conducted a foot or ankle CT scan containing the axial images of the distal tibia and DEXA- BMD within three months. Patients with open fractures with severe displacement or arthritic change were excluded. The mean HU was obtained from two sequential axial images of the distal tibial metaphysis's largest region of interest (ROI), more than 1cm proximal to the tibial plafond. We divided the patients into Group A without ankle fractures and Group B with distal tibia or fibula fractures in the ankle. The correlation analysis was done between the distal tibial HU and DEXA-BMD. We obtained the cut-off value of the distal tibial HU for osteoporosis using receiver operating characteristic(ROC) curves and compared the results between the two groups. Results: Group A was 38 cases(mean age 69.9), and Group B was 59 (mean age 71.0). There were no statistical differences in patients' characteristics, the mean distal tibial HU, bone density, T-score, and rate of osteoporosis in BMD. All HU values in both groups showed excellent inter- and intra-observer reliability(All intraclass coefficients>0.9). Both groups had significant correlations between the distal tibial HU and DEXA-BMD, especially in the femur neck and L3 spine(r=0.706, 0.622, p< 0.001 in Group A, r=0.625,0.499, p< 0.001 in Group B). The cut-off value for osteoporosis of the distal tibial HU was 153.15(sensitivity 73.9%, specificity 86.7%; area under the curve(AUC) 0.841, 95% CI 0.716-0.965, p< 0.001) in Group A. The cut-off value of Group B was 167.35(sensitivity 66.7%, specificity 75.9%; AUC 0.737, 95% CI 0.610-0.865, p=0.002). Conclusion: The distal tibial HU values on the axial images on the CT showed a significant correlation with the central bone of DEXA-BMD. The distal tibial HU value showed excellent reliability with or without fracture. HU value can be easily obtained using a preoperative ankle CT scan without additional cost & radiation exposure to patients with ankle fractures. Therefore, it can help treat osteoporotic ankle fractures by screening for osteoporosis and deciding the fixation method of surgery.