Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of cathepsin S expression in gastric adenocarcinoma and in Helicobacter pylori infection

Background Recent experimental studies have suggested a potential link between cathepsin S (CTTS) and gastric adenocarcinoma progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma in patients who underwent curative-intent surgical resection. Methods This was a cross-sectional study that included two groups: gastric adenocarcinoma (n = 42) and gastritis (n = 50). The gastritis group was then subdivided into H. pylori-positive (n = 25) and H. pylori-negative (n = 25) groups. Gastric tissue samples were analysed to determine CTTS expression through immunohistochemistry. Samples were obtained by oesophagogastroduodenoscopy or surgical specimens. Results In patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric adenocarcinoma, the age ranged from 37 to 85 years. Among them, 50% were male. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. Alternatively, among patients with gastric adenocarcinoma, 19% had expression between 25–50%, 14.3% between 51–75%, and 26.2% had expression higher than 75% (p < 0.001). In the gastritis group, CTTS expression was significantly higher in patients with a positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001). There was no statistically significant association between CTTS positivity and clinicopathological variables, including tumour staging, histological type, angiolymphatic invasion, recurrence, current status and death. Conclusion CTTS expression is higher in gastric adenocarcinoma samples. Patients with gastritis due to H. pylori also show a higher expression of CTTS than patients with negative results for this bacterium.
Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4–/– mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase–dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4–/– mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.
Emotion differentiation in early recovery from alcohol use disorder: Associations with in‐the‐moment affect and 3‐month drinking outcomes

Abstract Background Early recovery from alcohol use disorder (AUD) is commonly associated with high levels of negative affect, stress, and emotional vulnerability, which confer significant relapse risk. Emotion differentiation—the ability to distinguish between discrete emotions—has been shown to predict relapse after treatment for a drug use disorder, but this relationship has not been explored in individuals recovering from AUD. Methods The current study used thrice daily random and up to thrice daily self‐initiated ecological momentary assessment surveys (N = 42, observations = 915) to examine whether 1) moments of high affective arousal are characterized by momentary differences in emotion differentiation among individuals in the first year of a current AUD recovery attempt, and 2) individuals’ average emotion differentiation would predict subsequent alcohol use measured by the timeline follow‐back over a 3‐month follow‐up period. Results Multilevel models showed that moments (Level 1) of higher‐than‐average negative affect (p < 0.001) and/or stress (p = 0.033) were characterized by less negative emotion differentiation, while moments of higher‐than‐average positive affect were characterized by greater positive emotion differentiation (p < 0.001). At the between‐person level (Level 2), participants with higher stress overall had lower negative emotion differentiation (p = 0.009). Linear regression showed that average negative, but not positive, emotion differentiation was inversely associated with percent drinking days over the subsequent 3‐month follow‐up period (p = 0.042). Neither form of average emotion differentiation was associated with drinking quantity. Conclusions We found that for individuals in early AUD recovery, affective states are associated with acute shifts in the capacity for emotion differentiation. Further, we found that average negative emotion differentiation prospectively predicts subsequent alcohol use.
MES-FPMIPv6: MIH-Enabled and enhanced secure Fast Proxy Mobile IPv6 handover protocol for 5G networks*^

Fast Proxy Mobile IPv6 (FPMIPv6) is an extension of the PMIPv6 mobility management deployed as part of the next-generation internet protocol. It allows location-independent routing of IP datagrams, based on local mobility to IPv6 hosts without involvement of stations in the IP address signaling. A mobile node keeps its IP address constant as it moves from link to link, which avoids signaling overhead and latency associated with changing IP address. Even though local mobility requirements hold, it entails security threats such as Mobile Node, Mobile Access Gateway, as well as Local Mobility Anchor impersonation that go beyond those already exist in IPv6. As mobile station keeps moving across different serving networks, its IP remains constant during handover, and location privacy may not also be preserved. Moreover, homogeneous network dependence of PMIPv6 is one of the gaps, which FPMIPv6 could not mitigate. FPMIPv6 does not support heterogeneous network handover, for which numerous researchers have proposed Media Independent Handover (MIH) enabled FPMIPv6 schemes to allow fast handover among heterogeneous networks, but in the absence of security solutions. As a comprehensive solution, we propose a new handover authentication scheme and a key agreement protocol for the ‘MIH-enabled Network Only FPMIPv6’ model. As one of the basic requirements, mobility management should minimize signaling overhead, handover delay and power consumption of the mobile node. The proposed scheme improves wireless link overhead (mobile node overhead) by 6-86% as cell radius, wireless failure probability and number of hop vary. The security of the proposed scheme has also been analyzed under BAN logic and Automated Validation of Internet Security Protocols and Applications (AVISPA) tool and its performance has numerically been evaluated through a pre-determined performance matrix and found to be effective and preferably applicable compared with other schemes.
Selective endocytosis of Ca2+-permeable AMPARs by the Alzheimer’s disease risk factor CALM bidirectionally controls synaptic plasticity

AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission, and the plastic modulation of their surface levels determines synaptic strength. AMPARs of different subunit compositions fulfill distinct roles in synaptic long-term potentiation (LTP) and depression (LTD) to enable learning. Largely unknown endocytic mechanisms mediate the subunit-selective regulation of the surface levels of GluA1-homomeric Ca2+-permeable (CP) versus heteromeric Ca2+-impermeable (CI) AMPARs. Here, we report that the Alzheimer’s disease risk factor CALM controls the surface levels of CP-AMPARs and thereby reciprocally regulates LTP and LTD in vivo to modulate learning. We show that CALM selectively facilitates the endocytosis of ubiquitinated CP-AMPARs via a mechanism that depends on ubiquitin recognition by its ANTH domain but is independent of clathrin. Our data identify CALM and related ANTH domain–containing proteins as the core endocytic machinery that determines the surface levels of CP-AMPARs to bidirectionally control synaptic plasticity and modulate learning in the mammalian brain.
Direction of non‐recoverable strain in the glenohumeral capsule following multiple anterior dislocations: Implications for anatomic Bankart repair

The study aimed to analyze the direction of non‐recoverable strain and determine the optimal direction for anatomic capsular plication within four sub‐regions of the inferior glenohumeral capsule following multiple dislocations. Seven fresh‐frozen cadaveric shoulders were dissected. A grid of strain markers was affixed to the inferior glenohumeral capsule. Each joint was mounted in a 6‐degree‐of‐freedom robotic testing system and repeatedly dislocated in the anterior direction 10 times at 60° of abduction and 60° of external rotation of the glenohumeral joint. The 3D positions of the strain markers were compared before and after dislocations to define the non‐recoverable strain. The strain map was divided into four sub‐regions. The angles of deviation between each maximum principle strain vector and the anterior band of the inferior glenohumeral ligament (AB‐IGHL) or posterior band of the IGHL (PB‐IGHL) for the anterior and posterior regions of the capsule were determined. The mean direction of all strain vectors in each sub‐region was categorized. The direction of the non‐recoverable strain in the anterior‐band and anterior‐axillary‐pouch sub‐regions was categorized as parallel to the AB‐IGHL, whereas the posterior‐axillary‐pouch and posterior‐band sub‐regions were mostly perpendicular to the PB‐IGHL. Clinical Significance: Plication of the anteroinferior capsule parallel to the AB‐IGHL may be preferred during arthroscopic Bankart repair to restore anatomy; posteroinferior capsular plication may also be necessary and best performed perpendicular to the PB‐IGHL. The direction of the capsular injury remains the same irrespective of the number of dislocations. This study provides the scientific and quantitative rationale for an anatomic approach to capsular plication.
Kinematic and Kinetic Comparison between Baseball Pitching and Football Passing

Kinematic and kinetic aspects of baseball pitching and football passing were compared. Twenty-six high school and collegiate pitchers and 26 high school and collegiate quarterbacks were analyzed using three-dimensional high-speed motion analysis. Although maximum shoulder external rotation occurred earlier for quarterbacks, maximum angular velocity of pelvis rotation, upper torso rotation, elbow extension, and shoulder internal rotation occurred earlier and achieved greater magnitude for pitchers. Quarterbacks had shorter strides and stood more erect at ball release. During arm cocking, quarterbacks demonstrated greater elbow flexion and shoulder horizontal adduction. To decelerate the arm, pitchers generated greater compressive force at the elbow and greater compressive force and adduction torque at the shoulder. These results may help explain differences in performance and injury rates between the two sports.
Cross‐sectional clinical cancer genomics community of practice survey analysis of provider attitudes and beliefs regarding the use of deceased family member tissue to guide living family member genetic cancer risk assessment

Next‐generation tumor tissue sequencing techniques may result in the detection of putative germline pathogenic variants (PVs), raising the possibility that germline cancer predisposition could be identified from archival medical tissue samples of deceased relatives. The approach, termed traceback, is designed to inform risk management recommendations for living family members. Provider perspectives regarding traceback testing have not yet been explored, so we conducted a cross‐sectional survey of Clinical Cancer Genomics Community of Practice providers regarding their attitudes and beliefs toward traceback testing. Self‐reported demographics, provider characteristics, attitudes and perceived barriers were collected. We evaluated responses in the context of whether providers had previous experience with traceback testing. Data were analyzed using chi‐square and Fisher's exact testing. Among 207 respondents (of 816 eligible), most were women (89.4%), white (85.5%), and not Hispanic or Latino (89.7%). US‐based providers represented the majority of respondents (87.4%). Relatively, few providers 32 of 207 (15.5%) had previous experience with traceback. Among the individuals without experience in traceback, 84.0% thought there would be barriers to implementation; however, only 68.8% of individuals with previous traceback experience agreed (p = .04). Respondents in both groups thought that traceback would be valuable in their practice (82.6%, p = .22) and that they would feel comfortable discussing the concept (83.6%, p = .83), interpreting the results (72.2%, p = .24), and discussing the results with their patients (80.7%, p = .38). Patient interest and cost were seen as less of a barrier by those with experience with traceback testing. Recurrent themes obtained in open‐ended responses are also presented. Overall, providers believe that traceback would be a valuable tool in their practice. Individuals with previous experience identified less barriers with implementation of this testing, highlighting an area for future research and education.
Bisphenol A aggravates renal apoptosis and necroptosis in selenium‐deficient chickens via oxidative stress and PI3K/AKT pathway

Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se‐deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3‐kinase/threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increased reactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx, and superoxide dismutase, downregulated PI3K and AKT expressions, activated Bcl/Bax‐Caspase 9‐Caspase 3, and receptor‐interacting protein kinase 1/mixed lineage kinase domain‐like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA‐exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Se‐deficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.
Can an Aging Leopard Change Its Spots? The Role of Mindset of Aging on Implicit and Explicit Attitudes in Older Adults

Growth mindset of aging (MA) refers to the belief that aging processes are malleable, while fixed MA is the belief that how one ages is predetermined and unchangeable. Using experimental methods, we manipulated MA and explored its impact on implicit old-age attitudes and self-perceptions of aging. Eighty-six older adults were randomly placed into a growth or fixed MA condition. Next, we assessed implicit old-age attitudes and self-perceptions of aging. The experimental manipulation was successful in that group MA scores differed, but MA did not significantly influence implicit old-age attitudes or self-perceptions of aging. However, a regression analysis revealed a novel finding: More growth MA was related to less negative implicit old-age attitudes and more positive self-perceptions of aging. These findings are an important contribution to the MA literature, which is in its infancy.
Mapping wheelchair functions and their associated functional elements for stair climbing accessibility: a systematic review

Abstract Purpose Wheelchair (WC) design elements are subjected to the accessibility and assistive needs of a person with locomotor disability. In order to pursue a holistic design for a stairclimbing WC, there is a need for literature review on WC functions reported for both stair climbing and plane surface movement. Methods A total of 112 Research articles are reviewed for the purpose of extracting the relationship between WC design elements and the functions associated with them. Stairclimbing technologies are reviewed for their technological assessment in terms of functional elements associated with stairclimbing. Cross-functional mapping between functional elements and their dominant function is performed. Heat map for primary user needs and associated design elements is generated from cross mapping. Conclusions A design gap for user’s functional needs is indicated from the review of literature on prototypes and products of WC. The literature in stairclimbing technology is primarily focussed on stair climbing capability and not on the other functional needs, such as safety, ride comfort, seat comfort, manoeuvrability, etc. Implications for rehabilitation For attaining the goal of an effective rehabilitation, it is important to design and develop an assistive technology that can provide maximum accessibility and functioning for a person with disability. In case of locomotor disability, wheelchair (WC) is the most empowering tool that can assist people in both accessibility and activities of daily living. This review of literature was conducted to draw out the functions fulfilled by a WC, such as safety, comfort, propulsion for its users and the associated WC elements like seat, wheels, backrest, etc., that are required to fulfil those functions. WC being the most important technological intervention in the life of a person who cannot walk should be designed with the highest level of empathy. Therefore, each and every aspect of the user’s physical and emotional needs should be catered up to the limits of engineering design. The research on stair climbing technologies has also grown exponentially, fuelled by technological growth in engineering mechanisms, ambient awareness sensors, actuators, etc. The review attempts to envelop such technologies and consolidate them on the basis of their capabilities and efficacies. The virtue of stair climbing has been realized through some novel and innovative mechanisms reviewed in this article that can be integrated with the research in field of functional elements required to carry out primary functions of a disabled person, such as safety, comfort, intuitiveness, etc. This review can help in coupling both of them in a more rational way where a designer who is designing the technology is more empathetic towards the design for accessibility. It can also help user in becoming more confident towards adapting a new assistive technology.
The prognostic impact of preoperative body composition in perihilar and intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is a rare but highly aggressive malignancy of the biliary system. Although it is amenable to surgical resection in early disease, outcomes are frequently dismal. Here, we investigated the prevalence of body composition (BC) alterations and their prognostic role for surgical patients with intrahepatic (iCCA) and perihilar (pCCA) disease. Patients undergoing curative‐intent surgery for iCCA or pCCA between 2010 and 2019 at University Hospital Aachen were included. Axial computed tomography images were retrospectively assessed with a segmentation tool (3D Slicer) at the level of the third lumbar vertebra to determine lumbar skeletal muscle (SM) index, mean SM radiation attenuation, and visceral fat area. The related BC pathologies sarcopenia, myosteatosis, visceral obesity, and sarcopenic obesity were determined using previously described cutoffs. A total of 189 patients (86 with iCCA, 103 with pCCA) were included. Alterations of BC were highly prevalent in iCCA and pCCA, respectively: sarcopenia, 33% (28/86) and 39% (40/103); myosteatosis, 66% (57/86) and 66% (68/103); visceral obesity, 56% (48/86) and 67% (69/103); sarcopenic obesity, 11% (9/86) and 17% (17/103). Sarcopenia and myosteatosis did not have a significant prognostic role for disease‐free survival (DFS) and overall survival (OS). Patients with iCCA with sarcopenic obesity (n = 9) had significantly shorter OS than patients without sarcopenic obesity (n = 7; log‐rank p = 0.002; median OS, 11 months and 31 months; 1‐year mortality, 55.6% [5/9] and 22% [17/77]; 5‐year mortality, 88.9% [8/9] and 61% [47/77], respectively). In multivariable analysis, only tumor‐related risk factors remained prognostic for DFS and OS. Sarcopenic obesity may affect clinical outcomes after curative‐intent surgery for iCCA, indicating that imaging‐based analysis of BC may hold prognostic value for long‐term survival and could aid preoperative patient selection.