Search

Do Sun Kwon,1,* Yong Jun Choi,2,* Tae Hee Kim,2 Min Kwang Byun,2 Jae Hwa Cho,2 Hyung Jung Kim,2 Hye Jung Park2 1Department of Internal Medicine, Hallym Hospital, Incheon, Korea; 2Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea*These authors contributed equally to this workCorrespondence: Hye Jung Park Department of Internal MedicineGangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul 60273, Republic of KoreaTel +82-2-2019-3302Fax +82-2-3463-3882Email craft7820@yuhs.acPurpose: The forced mid-expiratory flow (FEF25-75%) value is a potentially sensitive marker of obstructive peripheral airflow. We aimed to assess whether FEF25-75% can be an early predictor of chronic obstructive pulmonary disease (COPD).Patients and Methods: Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital. We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later. A FEF25-75% z-score less than − 0.8435 was considered low. We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019.Results: Among 307 patients, 91 (29.6%) had low FEF25-75% at baseline. After 10 years, the incidence rate of COPD in the low FEF25-75% group was significantly higher than that in the normal FEF25-75% group (41.8% vs 7.4%; P-value< 0.001). The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; P-value< 0.001), smoking status (occasional smoker HR, 4.59; P-value< 0.001 and long-term smoker HR, 2.18; P-value=0.023), and low FEF25-75% (HR, 3.31; P-value< 0.001) were predictive factors for the development of COPD.Conclusion: The FEF25-75% value in patients with normal lung function is a useful predictor for the development of COPD. We should carefully monitor patients who present with low FEF25-75% values, even if they have normal lung function.Keywords: COPD, respiratory function tests, tobacco

Background: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infec

BACKGROUND: Endoscopic sphincterotomy (EST) to remove bile-duct stones is the most frequently used endoscopic technique. Few reports exist regarding application of large-balloon dilation (LBD) after EST for treatment of patients with bile-duct stones. OBJECTIVE: To compare the effect of EST plus LBD with that of EST alone. DESIGN: A prospective randomized controlled trial. SETTING: A large tertiary-referral center. PATIENTS AND INTERVENTIONS: Two hundred consecutive patients with bile-duct stones were randomized in equal numbers to EST plus LBD (12- to 20-mm balloon diameter) or EST alone. MAIN OUTCOME MEASUREMENTS: Successful stone removal and complications such as pancreatitis and bleeding. RESULTS: EST plus LBD compared with EST alone resulted in similar outcomes in terms of overall successful stone removal (97.0% vs 98.0%), large size (>15 mm) stone removal (94.4% vs 96.7%), and the use of mechanical lithotripsy (8.0% vs 9.0%). Complications were similar between the 2 groups (5.0% vs 7.0%, P = .767). Complications were as follows for the EST plus LBD group and the EST group: pancreatitis, 4.0% and 4.0%; cholecystitis, 1.0% and 1.0%; and bleeding (delayed), 0% and 2.0%, respectively. CONCLUSIONS: Based on the similar rates of successful stone removal and complications, EST plus LBD should be an effective alternative to EST. EST plus LBD is a safe and effective treatment for endoscopic removal of common bile duct stones. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach., Competing Interests: Declaration of interests M.Z., S.M.B., P.C.B., and D.S.K. are co-inventors on a patent related to this work. P.C.B. serves as a consultant and equity holder of companies in the microfluidics and life sciences industries, including 10x Genomics, GALT/Isolation Bio, Celsius Therapeutics, Next Gen Diagnostics, Cache DNA, Concerto Biosciences, Amber Bio, Stately, Ramona Optics, and Bifrost Biosystems. D.S.K. serves as an equity holder of Day Zero Diagnostics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and bacterial vaginosis (BV). These negative effects may arise from sialidase-mediated degradation of the protective mucus layer in the cervicovaginal environment. Prior biochemical studies of vaginal bacterial sialidases have focused solely on the BV-associated organism Gardnerella vaginalis . Despite their implications for sexual and reproductive health, sialidases from other vaginal bacteria have not been characterized. Here, we show that vaginal Prevotella species produce sialidases that possess variable activity toward mucin substrates. The sequences of sialidase genes and their presence are largely conserved across clades of Prevotella from different geographies, hinting at their importance globally. Finally, we find that Prevotella sialidase genes and transcripts, including those encoding mucin-degrading sialidases from Prevotella timonensis , are highly prevalent and abundant in human vaginal genomes and transcriptomes. Together, our results identify Prevotella as a critical source of sialidases in the vaginal microbiome, improving our understanding of this detrimental bacterial activity., Competing Interests: Competing interests statement:J.R. is a cofounder of LUCA Biologics, a biotechnology company focusing on translating microbiome research into live biotherapeutic drugs for women’s health. D.S.K. serves as equity holder of Day Zero Diagnostics.

Introduction: Early detection of pancreatic cancer continues to be a challenge due to the difficulty in accurately identifying specific signs or symptoms that might correlate with the onset of pancreatic cancer. Unlike breast or colon or prostate cancer where screening tests are often useful in identifying cancerous development, there are no tests to diagnose pancreatic cancers. As a result, most pancreatic cancers are diagnosed at an advanced stage, where treatment options, whether systemic therapy, radiation, or surgical interventions, offer limited efficacy., Methods: A two-stage weakly supervised deep learning-based model has been proposed to identify pancreatic tumors using computed tomography (CT) images from Henry Ford Health (HFH) and publicly available Memorial Sloan Kettering Cancer Center (MSKCC) data sets. In the first stage, the nnU-Net supervised segmentation model was used to crop an area in the location of the pancreas, which was trained on the MSKCC repository of 281 patient image sets with established pancreatic tumors. In the second stage, a multi-instance learning-based weakly supervised classification model was applied on the cropped pancreas region to segregate pancreatic tumors from normal appearing pancreas. The model was trained, tested, and validated on images obtained from an HFH repository with 463 cases and 2,882 controls., Results: The proposed deep learning model, the two-stage architecture, offers an accuracy of 0.907   ±   0.01, sensitivity of 0.905   ±   0.01, specificity of 0.908   ±   0.02, and AUC (ROC) 0.903   ±   0.01. The two-stage framework can automatically differentiate pancreatic tumor from non-tumor pancreas with improved accuracy on the HFH dataset., Discussion: The proposed two-stage deep learning architecture shows significantly enhanced performance for predicting the presence of a tumor in the pancreas using CT images compared with other reported studies in the literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mandal, Balraj, Kodamana, Arora, Clark, Kwon and Rathore.)

In this work, the impact of a tungsten oxide (WO 3 ) seed and capping layer for ferroelectric La-doped (Hf, Zr)O 2 (La:HZO) based capacitors, designed with back-end-of-line (BEOL) compatibility, is systematically investigated. The WO 3 capping layer supplies oxygen to the La:HZO layer throughout the fabrication process and during device cycling. This facilitates the annihilation of oxygen vacancies (V o ) within the La:HZO layer, thereby stabilizing its ferroelectric orthorhombic phase and resulting in an increase of the remanent polarization (P r ) value in the capacitor. Moreover, the effectiveness of the WO 3 capping layer depends on the seed layer of the HZO film, suggesting that proper combination of the seed and capping layers should be employed to maximize the ferroelectric response. Finally, a TiN/TiO 2 seed layer/La:HZO/WO 3 capping layer/TiN capacitor is successfully fabricated and optimized by a complete set of atomic layer deposition (ALD) processes, achieving a superior 2P r value and endurance value of more than 10 9 cycles at an electric field of 2.5 MV/cm. The WO 3 capping layer is anticipated to offer a viable solution for doped HZO capacitors with reduced thickness, addressing the challenge of elevated V o levels that favor the tetragonal phase and result in low 2P r values.

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm 2 /s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety., (© 2024. The Author(s).)

The ever-increasing demand for rechargeable battery systems in the era of electric vehicles has spurred extensive research into developing polymeric components for batteries, such as separators, polymer electrolytes, and binders. However, current battery systems rely on expensive and nonrenewable resources, which potentially have a negative environmental impact. Therefore, polymer materials derived from natural resources have gained significant attention, primarily due to their cost-effective and environmentally sustainable features. Moreover, natural feedstocks often possess highly polar functional groups and high molecular weights, offering desirable electro-chemo-mechanical features when applied as battery materials. More recently, various recycling and upcycling strategies for polymeric battery components have also been proposed given the substantial waste generation from end-of-life batteries. Recycling polymeric materials includes an overall process of recovering the components from spent batteries followed by regeneration into new materials. Polymer upcycling into battery materials involves transforming daily-used plastic waste into high-value-added battery components. This review aims to give a state-of-the-art overview of contemporary methods to develop sustainable polymeric materials and recycling/upcycling strategies for various battery applications., (© 2024 Wiley-VCH GmbH.)

The shape of flexible endoscopic surgical robot should be obtained to increase control accuracy and prevent unwanted tissue damage. To estimate the shape of flexible manipulator, space efficiency, cost-effectiveness, system complexity, and ease of calibration should be considered to integrate sensors into the manipulator. In this article, we propose a real-time method to estimate the shape of a hyper-redundant manipulator having embedded coiled fiber sensors. The main advantage of this method is guaranteeing shape recognition even when the manipulator is subjected to an external load. The fiber sensors are highly flexible, compact, and inexpensive, as well as they can functionally measure both compressive and tensile strain of hyper-redundant manipulator. The sensor design was optimized to achieve durability and sensitivity. The numbers of sensor and the placements were determined by the analysis of the kinematics and moment distribution of the manipulator. The accuracy of shape estimation was validated experimentally under both free-loading and loading conditions. The proposed method achieved real-time estimating capability with a mean maximum error of each joint position smaller than 3.54% in free-loading condition and 5.47% in loading condition.

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease., (© 2024. The Author(s).)

The high explosiveness of hydrogen gas in the air necessitates prompt detection in settings where hydrogen is used. For this reason, hydrogen sensors are required to offer rapid detection and possess superior sensing characteristics in terms of measurement range, linearity, selectivity, lifetime, and environment insensitivity according to the publicized protocol. However, previous approaches have only partially achieved the standardized requirements and have been limited in their capability to develop reliable materials for spatially accessible systems. Here, an electrical hydrogen sensor with an ultrafast response (∼0.6 s) satisfying all demands for hydrogen detection is demonstrated. Tailoring structural engineering based on the reaction kinetics of hydrogen and palladium, an optimized heating architecture that thermally activates fully suspended palladium (Pd) nanowires at a uniform temperature is designed. The developed Pd nanostructure, at a designated temperature distribution, rapidly reacts with hydrogen, enabling a hysteresis-free response from 0.1% to 10% and durable characteristics in mechanical shock and repetitive operation (>10,000 cycles). Moreover, the device selectively detects hydrogen without performance degradation in humid or carbon-based interfering gas circumstances. Finally, to verify spatial accessibility, the wireless hydrogen detection system has been demonstrated, detecting and reporting hydrogen leakage in real-time within just 1 s.

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to Mycobacterium tuberculosis ( Mtb ) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current and never smokers by performing single-cell RNA sequencing (scRNA-seq), flow cytometry, and functional assays. We observed the enrichment of immature inflammatory monocytes in the lungs of smokers compared with nonsmokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease. Using integrative scRNA-seq and flow cytometry, we identified CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provided evidence that the recruitment of monocytes into the lung was mediated by CCR2-binding chemokines, including CCL11. We also show that these cells exhibit elevated inflammatory responses upon exposure to Mtb and accelerated intracellular growth of Mtb compared with mature macrophages. This elevated Mtb growth could be inhibited by anti-inflammatory small molecules, providing a connection between smoking-induced pro-inflammatory states and permissiveness to Mtb growth. Our findings suggest a model in which smoking leads to the recruitment of immature inflammatory monocytes from the periphery to the lung, which results in the accumulation of these Mtb -permissive cells in the airway. This work defines how smoking may lead to increased susceptibility to Mtb and identifies host-directed therapies to reduce the burden of TB among those who smoke.

Diverse and non- Lactobacillus -dominated vaginal microbial communities are associated with adverse health outcomes such as preterm birth and the acquisition of sexually transmitted infections. Despite the importance of recognizing and understanding the key risk-associated features of these communities, their heterogeneous structure and properties remain ill-defined. Clustering approaches are commonly used to characterize vaginal communities, but they lack sensitivity and robustness in resolving substructures and revealing transitions between potential sub-communities. Here, we address this need with an approach based on mixed membership topic models. Using longitudinal data from cohorts of pregnant and non-pregnant study participants, we show that topic models more accurately describe sample composition, longitudinal changes, and better predict the loss of Lactobacillus dominance. We identify several non- Lactobacillus -dominated sub-communities common to both cohorts and independent of reproductive status. In non-pregnant individuals, we find that the menstrual cycle modulates transitions between and within sub-communities, as well as the concentrations of half of the cytokines and 18% of metabolites. Overall, our analyses based on mixed membership models reveal substructures of vaginal ecosystems which may have important clinical and biological associations.

A central challenge in practically using high-capacity silicon (Si) as anode materials for lithium-ion batteries is alleviating significant volume change of Si during cycling. One key to resolving the failure issues of Si is exploiting carefully designed polymer binders exhibiting mechanical robustness to retain the structural integrity of Si electrodes, while concurrently displaying elasticity and toughness to effectively dissipate external stresses exerted by the volume changes of Si. Herein, a highly elastic and tough polymer binder is proposed by interweaving polyacrylic acid (PAA) with poly(urea-urethane) (PUU) elastomer for Si anodes. By systematically tuning molecular parameters, including molecular weights of hard/soft segments and structures of hard segment components, it is demonstrated that the mechanical properties of polymer binders, such as elasticity, toughness, and stress relaxation ability, strongly affect the cycling performance of Si electrodes. This study provides new insight into the rational design of polymer binders capable of accommodating the volume changes of Si, primarily by judicious modulation of the mechanical properties of polymer binders., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Lead is the most widely used X-ray-shielding material, but it is heavy (density ≈ 11.34 g/cm 3 ) and toxic. Therefore, the replacement of Pb with lightweight, ecofriendly materials would be beneficial, and such materials would have applications in medicine, electronics, and aerospace engineering. However, the shielding ability of Pb-free materials is significantly lower than that of Pb itself. To maximize the radiation attenuation of non-Pb-based shielding materials, a high-attenuation cross-section, normal to the incoming X-ray direction, must be achieved. In this study, we developed efficient X-ray-shielding materials composed of sulfated cerium oxide (S-CeO 2 ) and bismuth halides. Crucially, the materials are lightweight and mechanically flexible because of the absence of heavy metals (for example, Pb and W). Further, by pre-forming the doped metal oxide as a porous sponge matrix, and then incorporating the bismuth halides into the porous matrix, uniform, compact, and intimate composites with a high-attenuation cross-section were achieved. Owing to the synergetic effect of the doped metal oxide and bismuth halides, the resultant thin (approximately 3 mm) and lightweight (0.85 g·cm -3 ) composite achieved an excellent X-ray-shielding rate of approximately 92% at 60 kV, one of the highest values reported for non-heavy-metal shielding materials.

The vaginal ecosystem is closely tied to human health and reproductive outcomes, yet its dynamics in the wake of childbirth remain poorly characterized. Here, we profile the vaginal microbiota and cytokine milieu of participants sampled longitudinally throughout pregnancy and for at least one year postpartum. We show that delivery, regardless of mode, is associated with a vaginal pro-inflammatory cytokine response and the loss of Lactobacillus dominance. By contrast, neither the progression of gestation nor the approach of labor strongly altered the vaginal ecosystem. At 9.5-months postpartum-the latest timepoint at which cytokines were assessed-elevated inflammation coincided with vaginal bacterial communities that had remained perturbed (highly diverse) from the time of delivery. Time-to-event analysis indicated a one-year postpartum probability of transitioning to Lactobacillus dominance of 49.4%. As diversity and inflammation declined during the postpartum period, dominance by L. crispatus, the quintessential health-associated commensal, failed to return: its prevalence before, immediately after, and one year after delivery was 41%, 4%, and 9%, respectively. Revisiting our pre-delivery data, we found that a prior live birth was associated with a lower odds of L. crispatus dominance in pregnant participants-an outcome modestly tempered by a longer ( > 18-month) interpregnancy interval. Our results suggest that reproductive history and childbirth in particular remodel the vaginal ecosystem and that the timing and degree of recovery from delivery may help determine the subsequent health of the woman and of future pregnancies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure., Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites., Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease., Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention., (© 2023. The Author(s).)

Background: Although various endoscopic surgery robots developed in previous studies are versatile and have high lesion accessibility, they have limitations in terms of reaching the target lesion through the curved path in the large intestine and providing a stable tasking environment for the operator., Methods: An endoscopic surgery robot was developed for performing surgery in the large intestine. The robot was easily inserted into the target lesion in the curved colon through the mounted soft actuator and demonstrated high structural stiffness through the insertion of the sigmoidal auxiliary tendons., Results: The robot was able to access the target lesion in the curved colon through teleoperation alone. Further, it was confirmed that the high structural stiffness overtube improved the overall task performance in the user test., Conclusions: The proposed robotic system demonstrated the possibility and potential of performing advanced endoscopic surgery in the large intestine., (© 2022 John Wiley & Sons Ltd.)

A highly stretchable and tissue-adhesive multifunctional sensor based on structurally engineered islets embedded in ultra-soft hydrogel is reported for monitoring of bladder activity in overactive bladder (OAB) induced rat and anesthetized pig. The use of hydrogel yielded a much lower sensor modulus (1 kPa) compared to that of the bladder (300 kPa), while the strong adhesiveness of the hydrogel (adhesive strength: 260.86 N/m) allowed firm attachment onto the bladder. The change in resistance of printed liquid metal particle thin-film lines under strain were used to detect bladder inflation and deflation; due to the high stretchability and reliability of the lines, surface strains of 200% could be measured repeatedly. Au electrodes coated with Platinum black were used to detect electromyography (EMG). These electrodes were placed on structurally engineered rigid islets so that no interfacial fracture occurs under high strains associated with bladder expansion. On the OAB induced rat, stronger signals (change in resistance and EMG root-mean-square) were detected near intra-bladder pressure maxima, thus showing correlation to bladder activity. Moreover, using robot-assisted laparoscopic surgery, the sensor was placed onto the bladder of an anesthetized pig. Under voiding and filling, bladder strain and EMG were once again monitored. These results confirm that our proposed sensor is a highly feasible, clinically relevant implantable device for continuous monitoring OAB for diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The overtube of an endoscopic surgery robot is fixed when performing tasks, unlike those of commercial endoscopes, and this overtube should have high structural stiffness after reaching the target lesion so that sufficient tension can be applied to the lesion tissue with the surgical tool and there are fewer changes in the field of view of the endoscopic camera from this reaction force. Various methods have been proposed to reinforce the structural stiffnesses of hyper-redundant manipulators. However, the safety, rapid response, space efficiency, and cost-effectiveness of these methods should be considered for use in actual clinical environments, such as the gastrointestinal tract. This study proposed a method to minimize the positional changes of the overtube end tip due to external forces using only auxiliary tendons in the optimized path without additional mechanical structures. Overall, the proposed method involved moving the overtube to the target lesion through the main driving tendon and applying tension to the auxiliary tendons to reinforce the structural stiffness. The complete system was analyzed in terms of energy, and the sigmoidal auxiliary tendons were verified to effectively reinforce the structural stiffness of the overtube consisting of rolling joints. In addition, the design guidelines of the overtube for actual endoscopic surgery were proposed considering hollowness, retroflexion, and high structural stiffness. The positional changes due to external forces were confirmed to be reduced by 60% over the entire workspace.

Background: The majority of studies characterizing female genital tract microbiota have focused on luminal organisms, while the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that these communities may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a cohort of Kenyan female sex workers., Results: We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners-dominated luminal samples had a corresponding Gardnerella-dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbial community was associated with epithelial remodeling and pro-inflammatory pathways. Tissue-adherent communities dominated by L. iners and Gardnerella were associated with lower host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, although with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity., Conclusion: We identified ectocervical tissue-adherent bacterial communities in all study participants of a female sex worker cohort. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. We further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community could possibly act as a reservoir that seed the lumen with less optimal, non-Lactobacillus, bacteria. Video Abstract., (© 2023. The Author(s).)

The air suspension and location specification properties of nanowires are crucial factors for optimizing nanowires in electronic devices and suppressing undesirable interactions with substrates. Although various strategies have been proposed to fabricate suspended nanowires, placing a nanowire in desired microstructures without material constraints or high-temperature processes remains a challenge. In this study, suspended nanowires were formed using a thermally aggregated electrospun polymer as a template. An elaborately designed microstructure enables an electrospun fiber template to be formed at the desired location during thermal treatment. Moreover, the desired thickness of the nanowires is easily controlled with the electrospun fiber templates, resulting in the parallel formation of suspended nanowires that are less than 100 nm thick. Furthermore, this approach facilitates the formation of suspended nanowires with various materials. This is accomplished by evaporating various materials onto the electrospun fiber template and by removing the template. Palladium, copper, tungsten oxide (WO 3 ), and tin oxide nanowires are formed as examples to demonstrate the advantage of this approach in terms of nanowire material selection. Hydrogen (H 2 ) and nitrogen dioxide (NO 2 ) gas sensors comprising palladium and tungsten oxide, respectively, are demonstrated as exemplary devices of the proposed method., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2023.)

The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that antigens were rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions, whereas low protease activity and antigen degradation rates were detected in the vicinity of follicular dendritic cells (FDCs). Correlated with these findings, immunization regimens designed to target antigen to FDCs led to germinal centers dominantly targeting intact antigen, whereas traditional immunizations led to much weaker responses that equally targeted the intact immunogen and antigen breakdown products. Thus, spatially compartmentalized antigen proteolysis affects humoral immunity and can be exploited.

Purpose: Using a new robotic endoscopic platform system developed for retrograde intrarenal surgery (RIRS) called easyUretero (ROEN Surgical Inc.), we evaluated the feasibility and safety of renal stone retrieval in a porcine model., Materials and Methods: Six female pigs were used for our in vivo study. First, 0.3-cm-sized phantom stones were inserted into the kidneys of each pig via the ureteral access sheath. Next, renal stone retrieval was attempted using manual RIRS in three pigs and robotic RIRS in three pigs. Three surgeons performed extraction of 10 stones in each session., Results: The mean stone retrieval time by manual RIRS was significantly shorter than that by robotic RIRS (399.9±185.4 sec vs. 1127.6±374.5 sec, p =0.001). In contrast, the questionnaire regarding usability showed high satisfaction in the surgeons' fatigue category for surgeons using robotic RIRS. The radiation exposure dose was also lower in robotic RIRS than in manual RIRS (0.14 µSv vs. 45.5 µSv). Postoperative ureteral injury assessment revealed Grade 0 in manual RIRS cases and Grades 0, 1, and 2 in robotic RIRS cases., Conclusion: The easyUretero system is a new robotic RIRS system that was developed in Korea. The results of the present study suggest that using easyUretero for stone retrieval during RIRS is safe and ergonomic., (© Copyright: Yonsei University College of Medicine 2022.)

Background: In robotic surgery, a surgeon controls a surgical robot through a master manipulator in motion scaled teleoperation environment. However, there are no clear criteria for the master's workspace., Methods: From the user experiment, we proposed an Ergonomic Comfort Workspace considering ergonomics and performed a verification experiment using the actual surgeons' dataset., Results: From the user experiment, with comfortable posture, there was no significant difference (p-value < 0.05) between the master workspace when the task space is increased, and the workspace is defined as an ergonomic comfort workspace. Using the JIGSAWS dataset, elementary surgical tasks using surgical robots, verify the effectiveness of the ergonomic comfort workspace (ECW). It was confirmed that more than 95% of surgical task data were almost included in the ECW., Conclusions: The proposed ECW of the master for robotic laparoscopic surgery enables surgeons to perform surgery with high comfort and precision., (© 2022 John Wiley & Sons Ltd.)

Purpose: To test the safety and feasibility of laser lithotripsy for midsize renal stones using a newly developed robotic retrograde intrarenal surgery (RIRS) system (easyUretero) in a porcine model. Materials and Methods: Three urologic surgeons representing three different RIRS experience levels (beginner, intermediate, and expert) participated. Four female pigs (aged 6 months) underwent manual or robotic RIRS. Under general anesthesia, a nephrostomy tract was created ventrally, and calcium stones (diameter, 1.0-1.5 cm) were inserted at renal calices. For manual RIRS, surgeons operated a flexible ureteroscope. For robotic RIRS, the ureteroscope was attached to the robotic slave device. The Auriga XL™ Holmium laser was used for lithotripsy. Lasering and stone retrieval time were measured. Kidneys and ureters were inspected for injury at the end of each session. Results: For the expert, both lasering and stone retrieval by manual RIRS were quicker than by robotic RIRS (22.8 ± 11.0 s/stone vs 234.5 ± 102.5 s/stone, p  = 0.02; 41.5 ± 0.5 s/stone vs 79.3 ± 8.1 s/stone, p  = 0.02). For the intermediate and beginner, lasering and stone retrieval times were not significantly different between manual and robotic procedures (127.8 ± 93.2 s/stone vs 284.8 ± 112.3 s/stone, p  = 0.08; 86.0 ± 30.5 s/stone vs 84.1 ± 21.4 s/stone, p  = 0.92). All stones were removed. Grade 1 ureteral and renal injuries occurred in both manual RIRS and robotic RIRS. Conclusions: The laser lithotripsy using the easyUretero robotic system is safe and feasible in a porcine model, even for less-experienced surgeons.

Background: A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions., Results: Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture and growth of the L. crispatus consortia on-chip was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the vagina chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines., Conclusion: This study demonstrates the potential of applying human organ chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. Video Abstract., (© 2022. The Author(s).)

Purpose: To investigate the usefulness and ergonomics of a newly developed robotic system for flexible ureteroscopy (easyUretero)., Materials and Methods: During in vitro testing, six participants performed renal stone removal four times in an artificial kidney-ureter-bladder model. Each participant manipulated a single-use digital flexible ureteroscope (LithoVue) with their hands and the robotic system, sequentially. We compared the task completion times of each participant. The ergonomics of and operational satisfaction with each procedure were assessed by questionnaires. In vivo tests evaluated the operability and safety of the robotic system in two live female pigs. We checked that all the steps of flexible lithotomy for renal stones could be completed individually., Results: The task completion time with the robotic system during in vitro testing was significantly longer than with manual ureteroscopy regardless of the operator's competence level (expert professors: 282.6±92.4 seconds vs. 73.6±43.3 seconds, p<0.001; fellows: 247.5±57.7 seconds vs. 95.8±43.7 seconds, p<0.001; residents: 281.3±111.0 seconds vs. 188.6±138.6 seconds, p<0.001). The residents took more time to remove the upper and mid caliceal stones with the robotic system. The ergonomic evaluation was better for the robotic system, but operational satisfaction was lower, and there was no statistical difference among the groups. In vivo tests showed that all the steps of robotic flexible ureteroscopy could be completed without difficulty. No safety issues were encountered during the procedure., Conclusions: The robotic system (easyUretero) was ergonomic and safe for flexible ureteroscopy and laser lithotripsy for renal stones., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Sodium metal batteries have been emerging as promising candidates for post-Li battery systems owing to the natural abundance, low costs, and high energy density of Na metal. However, exploiting an Na metal anode is accompanied by uncontrolled Na electrodeposition, particularly concerning dendrite growth, hampering practical Na metal battery applications. Herein, we propose sodiophilic gel polymer electrolytes with a porosity-gradient Janus structure to alleviate Na dendrite growth. Tethering only 1.1 mol % sodiophilic poly(ethylene glycol) to poly(vinylidene fluoride- co -hexafluoropropylene) suppresses Na dendrites by regulating homogeneous Na + distribution, which relies on molecular-level coordination between Na + and the sodiophilic functional groups. By exploiting the porosity-gradient Janus structure, we have demonstrated that regular porosity and well-defined morphology of polymer electrolytes, particularly at the Na/electrolyte interface, significantly impact dendrite growth. This study provides new insights into the rational design of Na dendrite-suppressing polymer electrolytes, primarily focusing on the ion-regulating ability achieved by surface engineering.

Bacterial vaginosis (BV), the overgrowth of diverse anaerobic bacteria in the vagina, is the most common cause of vaginal symptoms worldwide. BV frequently recurs after antibiotic therapy, and the best probiotic treatments only result in transient changes from BV-associated states to "optimal" communities dominated by a single species of Lactobacillus. Therefore, additional treatment strategies are needed to durably alter vaginal microbiota composition for patients with BV. Vaginal microbiota transplantation (VMT), the transfer of vaginal fluid from a healthy person with an optimal vaginal microbiota to a recipient with BV, has been proposed as one such alternative. However, VMT carries potential risks, necessitating strict safety precautions. Here, we present an FDA-approved donor screening protocol and detailed methodology for donation collection, storage, screening, and analysis of VMT material. We find that Lactobacillus viability is maintained for over six months in donated material stored at - 80 °C without glycerol or other cryoprotectants. We further show that species-specific quantitative PCR for L. crispatus and L. iners can be used as a rapid initial screening strategy to identify potential donors with optimal vaginal microbiomes. Together, this work lays the foundation for designing safe, reproducible trials of VMT as a treatment for BV., (© 2022. The Author(s).)

Background: Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking., Methods: Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV-) female sex workers (FSWs), and HIV- lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing., Results: MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV- FSW groups. The TRAV1-2-TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome., Conclusions: MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2-TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The camera of an endoscope is fixed to the device, and the image rotates together with the endoscope. This can lead to visual confusion for the user and incorrect image reading. The problem also occurs with endoscopic robots. Using a master device with the same degrees of freedom as the endoscope to control an endoscopic robot causes visual-motor misorientation, making intuitive control difficult., Methods: The roll misorientation between the image and master device handle was removed by measuring and correcting for the roll axis displacement of the master device. This enabled intuitive manipulation of the master device. The work speed and number of mistakes were experimentally measured with and without image correction., Results: The tasks were completed significantly faster and more accurately with image orientation correction than without., Conclusions: The proposed method enables intuitive manipulation of the master device by correcting the image orientation in endoscopic robot control., (© 2022 John Wiley & Sons Ltd.)