Boehmeria Nivea Extract (BNE-RRC) Reverses Epithelial-Mesenchymal Transition and Inhibits Anchorage-Independent Growth in Tumor Cells.

The epithelial-mesenchymal transition (EMT) phenotype, identified as a significant clinical indicator in regard to cancer, manifests as a biological process wherein cells transition from having epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responses to various types of tissue damage. This study investigated the impact of BNE-RRC on oral cancer cells (KB) and revealed its significant effects on cancer cell growth, migration, invasion, and the EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing the EMT to a mesenchymal-epithelial transition (MET). Extraordinarily, sustained culturing of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting that BNE-RRC is a potential therapeutic agent for cancer. These findings highlight the promise of BNE-RRC as a comprehensive therapeutic agent for cancer treatment that acts by inhibiting cancer cell growth, migration, and invasion while also orchestrating a reversal of the EMT process. In this study, we propose that BNE-RRC could be an effective agent for cancer treatment.

Epidermal phyB requires RRC1 to promote light responses by activating the circadian rhythm.

Phytochrome B (phyB) expressed in the epidermis is sufficient to promote red light responses, including the inhibition of hypocotyl elongation and hypocotyl negative gravitropism. Nonetheless, the downstream mechanism of epidermal phyB in promoting light responses had been elusive. Here, we mutagenized the epidermis-specific phyB-expressing line (MLB) using ethyl methanesulfonate (EMS) and characterized a novel mutant allele of RRC1 (rrc1-689), which causes reduced epidermal phyB-mediated red light responses. The rrc1-689 mutation increases the alternative splicing of major clock gene transcripts, including PRR7 and TOC1, disrupting the rhythmic expression of the entire clock and clock-controlled genes. Combined with the result that MLB/prr7 exhibits the same red-hyposensitive phenotypes as MLB/rrc1-689, our data support that the circadian clock is required for the ability of epidermal phyB to promote light responses. We also found that, unlike phyB, RRC1 preferentially acts in the endodermis to maintain the circadian rhythm by suppressing the alternative splicing of core clock genes. Together, our results suggest that epidermal phyB requires RRC1 to promote light responses by activating the circadian rhythm in Arabidopsis thaliana.

5G Security Threat Assessment in Real Networks.

Advances in mobile communication networks from 2G to 5G have brought unprecedented traffic growth, and 5G mobile communication networks are expected to be used in a variety of industries based on innovative technologies, fast not only in terms of extremely low latency but massive access devices. Various types of services, such as enhanced mobile broadband (eMBB), massive machine type communication (mMTC), and ultra-reliable and low latency communication (uRLLC), represent an increase in the number of attacks on users' personal information, confidential information, and privacy information. Therefore, security assessments are essential to verify and cope with these various attacks. In this research, we (1) looked at 5G mobile communication network backgrounds and problems to investigate existing vulnerabilities and (2) assessed the current situation through evaluation of 5G security threats in real-world mobile networks in service.

Current US neurosurgical resident involvement, interest, and barriers in global neurosurgery.

OBJECTIVE: It is estimated that nearly 47 million preventable deaths occur annually due the current worldwide deficit in surgical care; subsequently, the World Health Organization resolved unanimously to endorse a decree to address this deficit. Neurosurgeons from industrialized nations can help address the needs of underserved regions. Exposure during training is critical for young neurosurgeons to gain experience in international work and to cultivate career-long interest. Here, the authors explore the opinions of current residents and interest in global neurosurgery as well as the current state of international involvement, opportunities, and barriers in North American residency training. METHODS: An internet-based questionnaire was developed using the authors' university's REDCap database and distributed to neurosurgical residents from US ACGME (Accreditation Council for Graduate Medical Education)-approved programs. Questions focused on the resident's program's involvement and logistics regarding international rotations and the resident's interest level in pursuing these opportunities. RESULTS: A 15% response rate was obtained from a broad range of training locations. Twenty-nine percent of respondents reported that their residency program offered elective training opportunities in developing countries, and 7.6% reported having participated in these programs. This cohort unanimously felt that the international rotation was a beneficial experience and agreed that they would do it again. Of those who had not participated, 81.3% reported interest or strong interest in international rotations. CONCLUSIONS: The authors' results indicate that, despite a high level of desire for involvement in international rotations, there is limited opportunity for residents to become involved. Barriers such as funding and rotation approval were recognized. It is the authors' hope that governing organizations and residency programs will work to break down these barriers and help establish rotations for trainees to learn abroad and begin to join the cause of meeting global surgical needs. To meet overarching international neurosurgical needs, neurosurgeons of the future must be trained in global neurosurgery.

Use of Referential Discourse Contexts in L2 Offline and Online Sentence Processing.

The present study aimed to investigate (a) the extent to which Chinese-speaking learners of English in Taiwan use referential noun phrase (NP) information contained in discourse contexts to complete ambiguous noun/verb fragments in a sentence completion task, and (b) whether and when they use the contexts to disambiguate main verb versus reduced relative clause (MV/RRC) ambiguities in real time. Results showed that unlike native English speakers, English learners did not create a marked increase in RRC completions in biasing two-NP-referent discourse contexts except for advanced learners. Nevertheless, like native speakers, the learners at elementary, intermediate, and advanced English proficiency levels all used the information in a later stage of resolving the MV/RRC ambiguities in real time. The delayed effect of referential context information observed suggests that L2 learners, like native speakers, are able to construct syntax-to-discourse mappings in real time. It also suggests that processing of syntactic information takes precedence over integration of syntactic information with discourse information during L1 and L2 online sentence processing.

Current status of surgery in dermatology.

An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein.

Mesoscopic Analysis of Rounded and Hybrid Aggregates in Recycled Rubber Concrete.

Recycled rubber concrete (RRC), a sustainable building material, provides a solution to the environmental issues posed by rubber waste. This research introduces a sophisticated hybrid random aggregate model for RRC. The model is established by combining convex polygon aggregates and rounded rubber co-casting schemes with supplemental tools developed in MATLAB and Fortran for processing. Numerical analyses, based on the base force element method (BFEM) of the complementary energy principle, are performed on RRC's uniaxial tensile and compressive behaviors using the proposed aggregate models. This study identified the interfacial transition zone (ITZ) around the rubber as RRC's weakest area. Here, cracks originate and progress to the aggregate, leading to widespread cracking. Primary cracks form perpendicular to the load under tension, whereas bifurcated cracks result from compression, echoing conventional concrete's failure mechanisms. Additionally, the hybrid aggregate model outperformed the rounded aggregate model, exhibiting closer peak strengths and more accurate aggregate shapes. The method's validity is supported by experimental findings, resulting In detailed stress-strain curves and damage contour diagrams.

Redox-stress response resistance (RRR) mediated by hyperoxidation of peroxiredoxin 2 in senescent cells.

Aging is closely related to redox regulation. In our previous work, we proposed a new concept, "redox-stress response capacity (RRC)," and found that the decline in RRC was a dynamic characteristic of aging. However, the mechanism of RRC decline during aging remains unknown. In this study, using the senescent human fibroblast cell model and Caenorhabditis elegans model, we identified that peroxiredoxin 2 (PRDX2), as a hydrogen peroxide (H2O2) sensor, was involved in mediating RRC. PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C. elegans also showed decreased RRC. The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells. Moreover, the level of PRDX2 hyperoxidation also increased in old C. elegans. Simultaneous overexpression of both PRDX2 and sulfiredoxin (SRX) rescued the reduced RRC and delayed senescence. The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity, resulting in the decreased cellular response to H2O2, which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity. Treatment of young cells with a high level of H2O2 to induce a higher level of PRDX2-SO3 resulted in mimicking the RRC decline in senescent cells, which is also similar to a model of insulin resistance induced by high levels of insulin. All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells, we named it redox-stress response resistance, RRR. RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.

Identification of the redox-stress signaling threshold (RST): Increased RST helps to delay aging in C. elegans.

Reactive oxygen species (ROS) play a dual role since they can be either beneficial or harmful to living systems. With increasing ROS concentrations, the roles of ROS change from advantageous to detrimental. There seems to be a concentration threshold that determines the transition from their advantageous to detrimental effects. If we purposefully increase the threshold, that is, increase the range of ROS that plays an advantageous role, it should be beneficial for individuals. To test this hypothesis, in C. elegans, the effects of oxidative challenge induced by different concentrations of paraquat (PQ) on nematode lifespan were evaluated. We found that there is a maximum level below which redox stress has benefits and named this threshold as "Redox-stress Signaling Threshold (RST)". Furthermore, we found that starvation (or heat stress or exercise) stimuli at early stage in C. elegans could increase the RST, indicating that this value is not fixed and can be increased by the adaptive response. More intriguingly, we found that increasing RST could improve Redox-stress Response Capacity (RRC) and healthspan, suggesting that increasing the RST value through early stimulation will be an effective strategy to delay aging.

Dermatology residency research policies: A 2021 national survey.

BACKGROUND: In this follow-up study to previous work, the authors survey the availability of key measures and resources pertaining to residency research in U.S. Accreditation Council for Graduate Medical Education-accredited dermatology residency programs, including potential policy changes following the COVID-19 pandemic. OBJECTIVE: The chief objective of this survey was to evaluate and compare dermatology programs' resident research requirements and guidelines. METHODS: This cross-sectional study employed a 13-item survey administered online in early 2021 to assess the degree to which dermatology residency programs require and support their new physician graduates in scholarly research endeavors. RESULTS: A total of 32 program directors representing 30 dermatology residency programs (30 of 138 accredited programs contacted [22%]) responded to the survey. Almost all programs described quality improvement project requirements for residents and were able to provide funding for resident conference participation. Most programs also reported resident publication requirements and the availability of research electives. However, the vast majority did not have required research rotations or a formal mentorship program. The COVID-19 pandemic did not have a substantial impact on residency research requirements. CONCLUSION: Our survey provides objective data about the current dermatology resident research requirements across the United States. These findings may prove valuable to prospective applicants, residency programs, and accrediting agencies in improving, advancing, and structuring dermatology residency guidelines and resources with the aim of encouraging new physician trainees to pursue research.

"Filler-ins" to Physicians: History of the Otolaryngology Training Program at Mayo Clinic.

The first officially recognized otolaryngology resident at Mayo Clinic started training in 1908. In the following years, the residency program evolved through emerging national standards and regulations for medical education, declining and resurgent interest in the specialty, and radical changes in otolaryngology as a practice. This article details the growth of the Mayo Clinic otolaryngology residency program, often in the words of the pioneering physicians involved in the process, from "filler-ins" for the staff to today's nationally recognized program.

The Impact of Regulation on Resident International Experiences: A Multispecialty Review of Current ACGME and RRC Standards for International Electives.

OBJECTIVE: Partnerships between industrialized and nonindustrialized institutions have accelerated the growth of surgery and surgical subspecialties in the developing world. The results of these partnerships include qualitive and quantitative clinical benefits as well as unique opportunities for the development of resident clinical and surgical skills. Surveys demonstrate surgical residents have a strong interest in international humanitarian work. Ultimately, the opportunities for residents to participate in international work as a program elective are subject to the regulations of the Accreditation Council of Graduate Medical Education (ACGME) and the Residency Review Committees (RRC) that govern residency accreditation. The regulations from accreditation bodies serve to ensure resident safety and educational value; however, excessive regulation can be a major hurdle to programs initiating international electives. Though the regulations are publicly available there is no comparison of various subspecialty standards in the literature. Nor is there a review of how standards affect resident education and safety or the ability for individual residencies to initiate international electives. METHODS: The regulations as defined by the ACGME and RRC of 7 surgical specialties (general, plastics, neurological, otolaryngology, ophthalmology, orthopedics, and urology) were reviewed from the available data on the ACGME website. RESULTS: The regulations demonstrate a great deal of diversity in how the specialties regulate international work. On one end of spectrum, 2 programs have robust guidelines and an approval process that ultimately allows residents to claim credit for cases performed internationally. On the other end, the regulations for some programs make little mention of international rotations other than to deny that cases be counted for credit. CONCLUSIONS: ACGME regulations have a strong effect on resident experiences while training internationally. Ideally, regulations should ensure resident safety and education without being overly cumbersome and preventing smaller programs from developing international electives. This would allow more residents access to the educational benefits available through meaningful international electives. Beyond the educational benefits, resident participation in international training creates a foundation for continued international work throughout their career. This could, in turn, increase the number of surgeons willing to travel internationally and bolster the development and consistency of international humanitarian e`fforts.

The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.

Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/ß. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging.

Multiclassifier system with hybrid learning applied to the control of bioprosthetic hand.

In this paper the problem of recognition of the intended hand movements for the control of bio-prosthetic hand is addressed. The proposed method is based on recognition of electromiographic (EMG) and mechanomiographic (MMG) biosignals using a multiclassifier system (MCS) working in a two-level structure with a dynamic ensemble selection (DES) scheme and original concepts of competence function. Additionally, feedback information coming from bioprosthesis sensors on the correct/incorrect classification is applied to the adjustment of the combining mechanism during MCS operation through adaptive tuning competences of base classifiers depending on their decisions. Three MCS systems operating in decision tree structure and with different tuning algorithms are developed. In the MCS1 system, competence is uniformly allocated to each class belonging to the group indicated by the feedback signal. In the MCS2 system, the modification of competence depends on the node of decision tree at which a correct/incorrect classification is made. In the MCS3 system, the randomized model of classifier and the concept of cross-competence are used in the tuning procedure. Experimental investigations on the real data and computer-simulated procedure of generating feedback signals are performed. In these investigations classification accuracy of the MCS systems developed is compared and furthermore, the MCS systems are evaluated with respect to the effectiveness of the procedure of tuning competence. The results obtained indicate that modification of competence of base classifiers during the working phase essentially improves performance of the MCS system and that this improvement depends on the MCS system and tuning method used.

The 2016 AANS Presidential Address: Leading the way.

This AANS presidential address focuses on enduring values of the neurosurgical profession that transcend the current political climate. The address was delivered by Dr. Batjer during a US presidential election year, but the authors have intentionally avoided discussing the current chaos of the American health care system in the knowledge that many pressing issues will change depending on the outcome of the 2016 elections. Instead, they have chosen to focus on clarifying what neurosurgeons, and the American Association of Neurological Surgeons, in particular, stand for; identifying important challenges to these fundamental principles and values; and proposing specific actions to address these challenges. The authors cite "de-professionalism" and commoditization of medicine as foremost among the threats that confront medicine and surgery today and suggest concrete action that can be taken to reverse these trends as well as steps that can be taken to address other significant challenges. They emphasize the importance of embracing exceptionalism and never compromising the standards that have characterized the profession of neurosurgery since its inception.

Choice both affects and reflects preferences.

The free-choice paradigm is a widely used paradigm in psychology. It has been used to show that after a choice between two similarly pleasant stimuli, the pleasantness of the chosen one tends to increase, whereas the pleasantness of the rejected one tends to decrease-a spreading of alternatives. However, the methodological validity of the free-choice paradigm to study choice-induced preference change has recently been seriously questioned [Chen, K. M., & Risen, J. L. (2010). How choice affects and reflects preferences: Revisiting the free-choice paradigm. Journal of Personality and Social Psychology, 99, 573-594. doi:10.1037/a0020217]. According to this criticism, the classically reported spreading of alternatives between the first and second rating sessions cannot be unambiguously interpreted to reflect a true change in preferences and can be observed even for completely static preferences. Here, we used two measurement sequences, a classical Rating 1-choice-Rating 2 sequence and a control Rating 1-Rating 2-choice sequence, to disentangle the spreading of alternatives driven by the effect of choice from the artefactual effect highlighted by Chen and Risen. In two studies using different stimulus material (faces and odours), we find that choice has a robust modulatory impact on preferences for rejected odours, but not for chosen odours and not for faces.

Comparable operative times with and without surgery resident participation.

BACKGROUND: Both physicians and patients may perceive that having surgical residents participate in operative procedures may prolong operations and worsen outcomes. We hypothesized that resident participation would prolong operative times and potentially adversely affect postoperative outcomes. OBJECTIVE: To evaluate the effect of general surgery resident participation in surgical procedures on operative times and postoperative patient outcomes. DESIGN: Retrospective study of general surgery procedures performed during two 1-year time periods, 2007 without residents and 2011 with residents. Procedures included laparoscopic appendectomy and cholecystectomy, thyroidectomy, breast procedure, hernia repair, lower extremity amputation, tunneled venous catheter, and percutaneous endoscopic gastrostomy. The primary outcome was operative time and secondary outcomes included length of stay (LOS) and mortality. SETTING: Academic general surgery residency program. RESULTS: There were 2280 operative procedures performed during the 2 periods: 1150 with resident involvement (RES group) and 1130 without residents (NORES group). The RES and NORES groups were similar for patient age (42 vs 41, p = 0.14) and male gender (46% vs 45%, p = 0.68), and there was no difference in overall operative time (68min vs 66min, p = 0.58). More specifically there was no difference in operative time (minutes) for specific procedures including laparoscopic appendectomy (67 vs 71, p = 0.8), thyroidectomy (125 vs 109, p = 0.16), breast procedure (38 vs 26, p = 0.79), hernia repair (61 vs 60, p = 0.74), lower extremity amputation (65 vs 77, p = 0.16), tunneled venous catheter (49 vs 47, p = 0.75), and percutaneous endoscopic gastrostomy (49 vs 46, p = 0.76). However, laparoscopic cholecystectomy took slightly longer in the RES group (71 vs 66, p = 0.02). LOS was shorter during the year with resident involvement (2.6 days vs 3.7 days, p = 0.0004) and there was no difference in mortality (0.17% vs 0.35%, p = 0.45). CONCLUSIONS: There is no difference in operative time for common general surgery procedures with or without resident involvement. In addition, resident involvement is associated with a decrease in LOS. This information should be used to change physician and patient negative perceptions regarding resident involvement while performing surgical procedures.

Early experience in establishing and evaluating an ACGME-approved international general surgery rotation.

BACKGROUND: In 2011, the Accreditation Council for Graduate Medical Education Surgery Residency Review Committee first provided guidelines for elective international general surgery rotations. The Vanderbilt general surgery residency program received Surgery Residency Review Committee approval for a fourth-year elective in Kenya beginning in the 2011-2012 academic year. Because this rotation would break ground culturally and geographically, and as an educational partnership, a briefing and debriefing process was developed for this ground-breaking year. OBJECTIVES: Our objectives were to prepare residents to maximize the experience without competing for cases with local trainees or overburdening the host institution and to perform continuous quality assessment and improvement as each resident returned back. METHODS: Briefing included health protection strategies, a procedures manual containing step-by-step preparation activities, and cultural-sensitivity training. Institutional Review Board exemption approval was obtained to administer a questionnaire created for returning residents concerning educational value, relations with local trainees, physical environment, and personal perceptions that would provide the scaffold for the debriefing conference. RESULTS: The questionnaire coupled with the debriefing discussion for the first 9 participants revealed overall satisfaction with the rotation and the briefing process, good health, and no duty hours or days-off issues. Other findings include the following: (1) emotional effect of observing African families weigh cost in medical decision making; (2) satisfactory access to educational resources; (3) significant exposure to specialties such as urology and radiology; and (4) toleration of 4 weeks as a single and expressed need for leisure activity materials such as books, DVDs, or games. The responses triggered adjustments in the briefing sessions and travel preparation. The host institution invited the residents to return for the 2012-2013 year as well as 2013-2014. CONCLUSION: Detailed preparation and the follow-up evaluation for assessment and improvement of this nascent international surgery experience are associated with resident satisfaction and the host institution has agreed to continue the rotation.

Dysferlin interacts with calsequestrin-1, myomesin-2 and dynein in human skeletal muscle.

Dysferlinopathies are a group of progressive muscular dystrophies characterized by mutations in the gene DYSF. These mutations cause scarcity or complete absence of dysferlin, a protein that is expressed in skeletal muscle and plays a role in membrane repair. Our objective was to unravel the proteins that constitute the dysferlin complex and their interaction within the complex using immunoprecipitation assays (IP), blue native gel electrophoresis (BN) in healthy adult skeletal muscle and healthy cultured myotubes, and fluorescence lifetime imaging-fluorescence resonance energy transfer (FLIM-FRET) analysis in healthy myotubes. The combination of immunoprecipitations and blue native electrophoresis allowed us to identify previously reported partners of dysferlin - such as caveolin-3, AHNAK, annexins, or Trim72/MG53 - and new interacting partners. Fluorescence lifetime imaging showed a direct interaction of dysferlin with Trim72/MG53, AHNAK, cytoplasmic dynein, myomesin-2 and calsequestrin-1, but not with caveolin-3 or dystrophin. In conclusion, although IP and BN are useful tools to identify the proteins in a complex, techniques such as fluorescence lifetime imaging analysis are needed to determine the direct and indirect interactions of these proteins within the complex. This knowledge may help us to better understand the roles of dysferlin in muscle tissue and identify new genes involved in muscular dystrophies in which the responsible gene is unknown.