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The purpose of this paper is to provide a new method for solving the problem of the 3D source localization in indoor environments with weak airflow by the experimental study on the multi-robot method. For this purpose, we developed a 3D MRO (mobile robot olfaction) system consisting of three mobile robots. The gas sensor carried with each robot has a moving range of 0.5 m to 1.5 m on the Z-axis. A total of 60 experiments were conducted to validate and compare the standard whale optimization algorithm (SWOA) and the standard particle swarm optimization (SPSO) methods in a 7.65 m×4.1 m experimental area with two source heights (0.75 m and 1.05 m). For two source heights, the success rate and localization step of the SPSO method are 56.7% (17/30) and 31.4 steps, respectively. In addition, the success rate and localization step of the SWOA method are 80% (24/30) and 32.9 steps, respectively. These results show that the SWOA method has strong application potential in indoor environments with weak airflow.

The electric dipole polarizabilities and the tune-out wavelengths for the n3S1 (n = 2, 3) states of Be2+ are determined through the application of the relativistic full-configuration-interaction approach. Our calculations directly integrate the mass shift operator into the Dirac-Coulomb-Breit Hamiltonian and further assess the quantum electrodynamics (QED) correction to the dynamic dipole polarizabilities using perturbation theory. The results reveal that the static electric dipole polarizability of the 23S1 and 33S1 states, as well as the 93 nm tune-out wavelength of the 23S1 state and the 238 nm tune-out wavelength of the 33S1 state, exhibits a high sensitivity to QED correction, which exceeds 80 ppm, providing a sensitive test for atomic structure theory., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Aims: To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD)., Methods and Results: The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings., Conclusion: Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The storage of hydrogen is key to its applications. Developing adsorbent materials with high volumetric and gravimetric storage capacities, both of which are essential for the efficient use of hydrogen as a fuel, is challenging. Here we report a controlled catenation strategy in hydrogen-bonded organic frameworks (RP-H100 and RP-H101) that depends on multiple hydrogen bonds to guide catenation in a point-contact manner, resulting in high volumetric and gravimetric surface areas, robustness and ideal pore diameters (~1.2-1.9 nm) for hydrogen storage. This approach involves assembling nine imidazole-annulated triptycene hexaacids into a secondary hexagonal superstructure containing three open channels through which seven of the hexagons interpenetrate to form a seven-fold catenated superstructure. RP-H101 exhibits high deliverable volumetric (53.7 g l -1 ) and gravimetric (9.3 wt%) capacities for hydrogen under a combined temperature and pressure swing (77 K/100 bar → 160 K/5 bar). This work illustrates the virtues of supramolecular crystals as promising candidates for hydrogen storage., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To investigate the most common concomitant symptoms and the urgent demand of solution in the breast cancer patients undergoing postoperative endocrine treatment, as well as the acceptance and expectation of acupuncture in the patients so as to provide the scientific data for promoting the application of acupuncture in the breast cancer patients., Methods: Breast cancer patients treated in Tianjin Medical University Cancer Institute and Hospital from January 2022 to March 2023 were randomly selected as the subjects. Using "questionnaire star" website, the questionnaire was conducted to investigate the relevant concomitant symptoms of the patients in postoperative endocrine treatment and the questions related to acupuncture treatment., Results: In this study, 229 questionnaires were distributed and 211 valid ones were collected, with the response rate of 92.1%. Among these patients, the first three common symptoms were sleep disorders (157 cases, 74.4%), hot flashes (138 cases, 65.4%) and joint / muscle pain (118 cases, 55.9%)；the top three symptoms to be solved the most urgently were sleep disorders (131 cases, 62.1%), joint / muscle pain (62 cases, 29.4%) and hot flashes (45 cases, 21.3%). 79.1% of the patients (167 cases) were willing to receive acupuncture treatment because of the high expectations on its potential effect (93%). 20.9% of them (44 cases) refused acupuncture because they were worried not to be treated by the experienced physicians of TCM (52%) or afraid of needling feelings (48%). The average expectation value of acupuncture treatment was 4.02 points (5 points for the total score) among patients willing to receive acupuncture treatment. The main purposes of receiring acupuncture for the patients undergoing endocrine treatment were to strengthen the immune function (92%), reduce the adverse reactions (83%), and improve the physical condition (75%), et al., Conclusions: Sleep disorder is one of the most concerned symptoms in endocrine treatment for the patients after breast cancer surgery. The patients highly expect for acupuncture treatment even though some patients dislike the needling sensation. How to provide the acceptable and high-quality acupuncture services for cancer patients will be one of the major directions of acupuncture research in the future.

Durable and conductive interfaces that enable chronic and high-resolution recording of neural activity are essential for understanding and treating neurodegenerative disorders. These chronic implants require long-term stability and small contact areas. Consequently, they are often coated with a blend of conductive polymers and are crosslinked to enhance durability despite the potentially deleterious effect of crosslinking on the mechanical and electrical properties. Here the grafting of the poly(3,4 ethylenedioxythiophene) scaffold, poly(styrenesulfonate)-b-poly(poly(ethylene glycol) methyl ether methacrylate block copolymer brush to gold, in a controlled and tunable manner, by surface-initiated atom-transfer radical polymerization (SI-ATRP) is described. This "block-brush" provides high volumetric capacitance (120 F cm ─3 ), strong adhesion to the metal (4 h ultrasonication), improved surface hydrophilicity, and stability against 10 000 charge-discharge voltage sweeps on a multiarray neural electrode. In addition, the block-brush film showed 33% improved stability against current pulsing. This approach can open numerous avenues for exploring specialized polymer brushes for bioelectronics research and application., (© 2024 Wiley‐VCH GmbH.)

Background: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT)., Methods: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS)., Results: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS., Conclusion: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis., Competing Interests: Disclosure The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Electrotactile stimulus is a form of sensory substitution in which an electrical signal is perceived as a mechanical sensation. The electrotactile effect could, in principle, recapitulate a range of tactile experience by selective activation of nerve endings. However, the method has been plagued by inconsistency, galvanic reactions, pain and desensitization, and unwanted stimulation of nontactile nerves. Here, we describe how a soft conductive block copolymer, a stretchable layout, and concentric electrodes, along with psychophysical thresholding, can circumvent these shortcomings. These purpose-designed materials, device layouts, and calibration techniques make it possible to generate accurate and reproducible sensations across a cohort of 10 human participants and to do so at ultralow currents (≥6 microamperes) without pain or desensitization. This material, form factor, and psychophysical approach could be useful for haptic devices and as a tool for activation of the peripheral nervous system.

The Australian culturally and linguistically diverse (CALD) communities may be at higher risk of salt intake than recommended given the use of a combination of discretionary sources and exposure to processed foods within a western country. This survey aimed to understand the knowledge, attitudes, and behaviors toward dietary salt and the acceptability of salt substitutes in the CALD communities. An online cross-sectional survey was conducted among adults who self-reported being a part of a CALD community, which was defined as non-Indigenous cultural groups in Australia having cultural or linguistic connections with their overseas place of birth, ancestry or ethnic origin, religion, preferred language or language spoken at home. A total of 218 respondents opened the survey link. A total of 196 completed the entire survey. The majority of respondents (162, 83%) were aware that high salt intake causes serious health problems. Altogether 134 (69%) respondents were aware that there is a recommended amount for daily salt consumption although only 59 (44%) knew precise recommendations as <5 g salt per day. Around one quarter of the respondents rarely or never looked for ‟low in salt'' or ‟reduced salt'' messages on food labels when shopping. Over half specified they always or often added salt during cooking or preparing foods in the household. Almost 4 in 5 CALD respondents were willing to reduce their salt intake for health and 3 in 4 were open to trying a salt substitute. Further research into the utility of a salt substitute intervention in the Australian CALD community is warranted., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

Allosteric regulation is common in protein-protein interactions and is thus promising in drug design. Previous experimental and simulation work supported the presence of allosteric regulation in the SARS-CoV-2 spike protein. Here the route of allosteric regulation in SARS-CoV-2 spike protein is examined by all-atom explicit solvent molecular dynamics simulations, contrastive machine learning, and the Ohm approach. It was found that peptide binding to the polybasic cleavage sites, especially the one at the first subunit of the trimeric spike protein, activates the fluctuation of the spike protein's backbone, which eventually propagates to the receptor-binding domain on the third subunit that binds to ACE2. Remarkably, the allosteric regulation routes starting from the polybasic cleavage sites share a high fraction (39-67%) of the critical amino acids with the routes starting from the nitrogen-terminal domains, suggesting the presence of an allosteric regulation network in the spike protein. Our study paves the way for the rational design of allosteric antibody inhibitors.

Context: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined., Objective: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma., Design: Cross-sectional study., Patients: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma., Methods: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal., Main Outcome Measure: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma., Results: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS., Conclusion: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion.

Introduction: Older adults are usually perceived as warmer but less competent than younger adults. This study examined how these stereotypes are related to domain-specific attributes and how individuals' values may moderate the association., Methods: We recruited 560 Chinese participants (mean age [SD]: 23.14 ± 7.08 years old, ranging from 18 to 60 years old) and 479 American participants (mean age [SD]: 31.37 ± 7.19 years old, ranging from 18 to 57 years old). Participants rated perceived warmth and competence of older adults based on vignettes with varying descriptions of specific domains (i.e., three relational domains: number of friends, family relationship quality, and engagement in neighbourhood activities; and three individualistic domains: income, depression, and memory) and personal attributes (i.e., gender, age, and independence)., Results: Firstly, the results showed that relational domains predict warmth, whereas individualistic domains predict competence in both samples from China and the USA. Secondly, in both samples, people with higher communal values attributed more relevance to relational domains on judgement of warmth. Lastly, only in the US sample did people with higher agentic values attribute more relevance to individualistic domains on judgement of competence., Discussion/conclusion: The study revealed that personal values, when determined relatively, contribute to stereotypes of older adults in the two independent samples., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing., (© 2023. The Author(s).)

Background: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy., Methods: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups., Results: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery., Conclusion: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

For a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) film employed in a device stack, charge must pass through both the bulk of the film and interfaces between adjacent layers. Thus, charge transport is governed by both bulk and contact resistances. However, for ultrathin films (e.g., flexible devices, thin-film transistors, printed electronics, solar cells), interfacial properties can dominate over the bulk properties, making contact resistance a significant determinant of device performance. For most device applications, the bulk conductivity of PEDOT:PSS is typically improved by blending additives into the solid film. Doping PEDOT:PSS with secondary dopants (e.g., polar small molecules), in particular, increases the bulk conductivity by inducing a more favorable solid morphology. However, the effects of these morphological changes on the contact resistance (which play a bigger role at smaller length scales) are relatively unstudied. In this work, we use transfer length method (TLM) measurements to decouple the bulk resistance from the contact resistance of PEDOT:PSS films incorporating several common additives. These additives include secondary dopants, a silane crosslinker (typically used to stabilize the PEDOT:PSS film), and multi-walled carbon nanotubes (conductive fillers). Using conductive atomic force microscopy, Kelvin probe force microscopy, Raman spectroscopy, and photoelectron spectroscopy, we connect changes in the contact resistance to changes in the surface morphology and energetics as governed by the blended additives. We find that the contact resistance at the PEDOT:PSS/silver interface can be reduced by (1) increasing the ratio of PEDOT to PSS chains, (2) decreasing the work function, (3) decreasing the benzoid-to-quinoid ratio at the surface of the solid film, (4) increasing the film uniformity and contact area, and (5) increasing the phase-segregated morphology of the solid film.

Objective: To investigate the oncologic and surgical safety of the fused fascia method for immediate breast reconstruction with implants. Methods: The clinical data of 343 patients with immediate breast reconstruction with implants in Tianjin Medical University Cancer Hospital from 2014-2017 were retrospectively analyzed to compare the 5-year local recurrence-free survival, 5-year disease-free survival and 5-year overall survival of patients with breast reconstruction by fusion fascia and other methods, and to analyze the complication incidences of implant removal between different implant groups. Results: Of the 343 patients with breast reconstruction, 95 were in the fused fascia group (fascia group) and 248 were in the non-fascia group (25 in the bovine pericardial patch group and 223 in the muscle flap group). At a median follow-up of 49 months, the differences in 5-year local recurrence-free survival (90.1% and 94.9%, respectively), 5-year disease-free survival (89.2% and 87.6%, respectively), and 5-year overall survival (95.2% and 95.1%, respectively) between patients in the fascial and non-fascial groups were not statistically significant ( P >0.05). The complication incidence of implant removal was 24.0% (6/25) in the patch group and 2.1% (2/95) and 2.2% (5/223) in the fascia and muscle flap groups, respectively. Conclusion: Immediate breast reconstruction with fused fascial combined with implant is safe and feasible, less invasive than muscle flaps, more economical and with fewer complications than patches.

Perovskite solar cells (PSCs) have delivered a power conversion efficiency (PCE) of more than 25% and incorporating polymers as hole-transporting layers (HTLs) can further enhance the stability of devices toward the goal of commercialization. Among the various polymeric hole-transporting materials, poly(triaryl amine) (PTAA) is one of the promising HTL candidates with good stability; however, the hydrophobicity of PTAA causes problematic interfacial contact with the perovskite, limiting the device performance. Using molecular side-chain engineering, a uniform 2D perovskite interlayer with conjugated ligands, between 3D perovskites and PTAA is successfully constructed. Further, employing conjugated ligands as cohesive elements, perovskite/PTAA interfacial adhesion is significantly improved. As a result, the thin and lateral extended 2D/3D heterostructure enables as-fabricated PTAA-based PSCs to achieve a PCE of 23.7%, improved from the 18% of reference devices. Owing to the increased ion-migration energy barrier and conformal 2D coating, unencapsulated devices with the new ligands exhibit both superior thermal stability under 60 °C heating and moisture stability in ambient conditions., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Aims: Multiple studies have suggested a likely association between breech presentation and assisted reproductive technology (ART) for conception. The aims were to determine whether conception via in vitro fertilisation (IVF) and ovulation induction (OI) is associated with fetal malpresentation at birth and to ascertain what mediating factors most significantly contribute to fetal malpresentation., Methods: This whole-population-based cohort study included 355 990 singleton pregnancies born in Queensland, Australia, between July 2012 and July 2018. Multinomial logistic regression models estimated the adjusted odds of breech, transverse/shoulder and face/brow malpresentations in pregnancies conceived via spontaneous conception, OI (OI group) and IVF with or without intracytoplasmic sperm injection (ART group)., Results: After adjustment for potential confounding factors, breech presentation occurred approximately 20% more often in singleton pregnancies conceived via both ART (adjusted odds ratio: 1.20, 95% confidence interval: 1.10-1.30, P < 0.001) and OI (1.21, 95% confidence interval: 1.04-1.39, P < 0.05). No significant associations were observed between the three modes of conception and transverse/shoulder or face/brow presentations. Low birthweight was found to be the most significant mediating factor for breech presentation in pregnancies conceived via ART and OI., Conclusions: Similar levels of increased odds of breech presentation are present in pregnancies conceived via OI and ART, suggesting a shared underlying mechanism for the aetiology of breech presentation. For women who are considering or have conceived via these methods, counselling with respect to this increased risk is recommended., (© 2023 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Purpose: Surgical meshes are often used in retro-pectoral implant-based breast reconstruction (IBBR) to improve lower pole expansion. However, using of surgical meshes is associated with increased complications and costs. To solve this problem, we have adopted a modified fascia-based IBBR technique using fasciae of pectoral major, serratus anterior, and external oblique muscles to form a sling covering the lower pole of prosthesis since 2014., Methods: Data of 788 retro-pectoral IBBR cases, including 250 fascia-based IBBR cases (fascial group) and 538 traditional IBBR cases (control group), treated between 2014 and 2019 were retrospectively analyzed. The surgical outcomes of the fascial and control group were compared. The primary endpoint was the rate of post-operative complications requiring interventions. The secondary endpoint was the rate of explantation. The exploratory endpoint was the time from surgery to complication and explantation., Results: The fascial group had significantly lower rates of developing major post-operative complications (1.2 vs. 6.1%, p = 0.002) and losing prostheses (1.2 vs. 4.3%, p = 0.025), as compared with the control group. The median time from surgery to complication and explantation were 61 (range, 35-115) days and 92 (range, 77-134) days for the fascial group and 35 (range, 6-239) days and 63 (range, 23-483) days for the control group, respectively., Conclusion: Fascia-based IBBR technique had low rates of major post-operative complications and explantation. Fascia-based IBBR technique could be considered as an alternative reconstruction method in properly selected patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The π-conjugated backbone of semiconducting polymers gives rise to both their electronic properties and structural rigidity. However, current computational methods for understanding the rigidity of polymer chains fail in one crucial way. Namely, standard torsional scan (TS) methods do not satisfactorily capture the behavior of polymers exhibiting a high degree of steric hindrance. This deficiency in part stems from the method by which torsional scans decouple energy related to electron delocalization from that related to nonbonded interactions. These methods do so by applying classical corrections of the nonbonded energy to the quantum mechanical (QM) torsional profile for polymers that are highly sterically hindered. These large corrections to the energy from nonbonded interactions can substantially skew the calculated QM energies related to torsion, resulting in an inaccurate or imprecise estimation of the rigidity of a polymer. As a consequence, simulations of the morphology of a highly sterically hindered polymer using the TS method can be highly inaccurate. Here, we describe an alternative, generalizable method by which the delocalization energy can be decoupled from the energy associated with nonbonded interactions─the "isolation of delocalization energy" (DE) method. From torsional energy calculations, we find that the relative accuracy of the DE method is similar to the TS method (within 1 kJ/mol) for two model polymers (P3HT, PTB7) when compared to quantum mechanical calculations. However, the DE method significantly increased the relative accuracy for simulations of PNDI-T, a highly sterically hindered polymer (8.16 kJ/mol). Likewise, we show that comparison of the planarization energy (i.e., backbone rigidity) from torsional parameters is significantly more precise for both PTB7 and PNDI-T when using the DE method as opposed to the TS method. These differences affect the simulated morphology, with the DE method predicting a significantly more planar configuration of PNDI-T.

Conventional processes for depositing thin films of conjugated polymers are restricted to those based on vapor, liquid, and solution-phase precursors. Each of these methods bear some limitations. For example, low-bandgap polymers with alternating donor-acceptor structures cannot be deposited from the vapor phase, and solution-phase deposition is always subject to issues related to the incompatibility of the substrate with the solvent. Here, a technique to enable deposition of large-area, ultra-thin films (≈20 nm or more), which are transferred from the surface of water, is demonstrated. From the water, these pre-solidified films can then be transferred to a desired substrate, circumventing limitations such as solvent orthogonality. The quality of these films is characterized by a variety of imaging and electrochemical measurements. Mechanical toughness is identified as a limiting property of polymer compatibility, along with some strategies to address this limitation. As a demonstration, the films are used as the hole-transport layer in perovskite solar cells, in which their performance is shown to be comparable to controls formed by spin-coating., (© 2023 Wiley-VCH GmbH.)

Aims: The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia., Methods: In this prospective study, fifty adult inpatients who were taking prednisolone ≥20 mg/day and experienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed., Results: The participants age was 69 ± 10 years, daily prednisolone dose was 34 ± 10 mg, HbA1c was 7.7 ± 2.0 % (61 ± 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r 2  = 0.11, p = 0.024). A multivariate model comprising sex, HbA1c, a prior diagnosis of diabetes, diabetes treatment and weight explained nearly-two thirds of the variability in daily insulin dose (r 2  = 0.65, p < 0.001)., Conclusions: In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing., 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 Elsevier B.V. All rights reserved.)

Adrenal adenomas are incidentally identified in up to 5% of computer tomography scans performed for unrelated indications. A proportion of these adrenal incidentalomas are found to autonomously secrete cortisol based on definitions in current guidelines. Epidemiological studies suggest that chronic exposure to mild glucocorticoid excess from adrenal incidentalomas is associated with significantly increased cardiometabolic risk. However, current management guidelines adopt a conservative approach as no large prospective randomized studies have demonstrated that these patients benefit from surgery. This narrative review examines the epidemiological and mechanistic studies related to three common clinical settings of mild glucocorticoid excess to gain further insight into the potential benefits of treating patients with adrenal incidentaloma and possible autonomous cortisol secretion., (© 2022 John Wiley & Sons Ltd.)

Supramolecules have been drawing increasing attention recently in addressing healthcare challenges caused by infectious pathogens. We herein report a novel class of guanidinium-perfunctionalized polyhedral oligomeric silsesquioxane (Gua-POSS) supramolecules with highly potent antimicrobial activities. The modular structure of Gua-POSS T m -C n consists of an inorganic T10 or T8 core ( m = 10 or 8), flexible linear linkers of varying lengths ( n = 1 or 3), and peripherally aligned cationic guanidinium groups as the membrane-binding units. Such Gua-POSS supramolecules with spherically arrayed guanidinium cations display high antimicrobial potency against Gram-positive ( Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria, as well as fungus ( Candida albicans ), with the best showing excellently low minimal inhibitory concentrations (MICs) of 1.7-6.8 μM in media, yet with negligible hemolytic activity and low in vitro cytotoxicity to mammalian cells. More significantly, they can inhibit biofilm formation at around their MICs and near-completely break down preestablished difficult-to-break biofilms at 250 μg mL -1 (∼50 μM). Their strong antiviral efficacy was also experimentally demonstrated against the enveloped murine hepatitis coronavirus as a surrogate of the SARS-CoV species. Overall, this study provides a new design approach to novel classes of sphere-shaped organic-inorganic hybrid supramolecular materials, especially for potent antimicrobial, anti-biofilm, and antiviral applications.

Purpose: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD., Methods: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states., Results: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity ( P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity ( P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity ( P = 0.018 and 0.024, respectively)., Conclusions: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.] .

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHN Vgat+ ) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHN Vgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHN Vgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHN Vgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance., (© 2022. The Author(s).)

Objective: To establish whether increased variability in macular thickness in neovascular age-related macular degeneration (nAMD) patients affects visual outcomes in clinical practice DESIGN: Retrospective cohort study PARTICIPANTS: Treatment-naive nAMD patients studied over 24 months METHODS: Central subfield thickness (CST) values from optical coherence tomography were collected quarterly from baseline to 24 months, and standard deviations (SDs) were calculated. The relationship was modeled with mixed-effects regression between CST SD and 24-month change in visual acuity (VA). Linear regression modeling determined predictors of CST SD., Results: A total of 422 eyes with nAMD were studied. Baseline and 24-month CST values (mean ± SD) were 331.2 ± 97.6 and 253.4 ± 53.6 μm (Δ = -77.8 ± 104.7 μm, p < 0.001), with CST SD across 24 months of 42.0 ± 32.8 μm. Baseline and 24-month VA were 58.8 ± 19.2 and 62.4 ± 20.6 Early Treatment of Diabetic Retinopathy Study letters (Δ = +3.7 ± 20.8 letters, p = 0.008). CST SD over 24 months was a statistically significant negative predictor of 24-month change in VA (-15.41 [-20.98, -9.83] letters per 100 μm, p < 0.001). Quartile analysis of 24-month VA by CST SD showed a +11.2-letter difference between the first and last quartiles (p < 0.001). Baseline CST was a predictor of 24-month CST SD (24.88 [22.69, 27.06] μm per 100 μm, p < 0.001)., Conclusions: Higher macular thickness fluctuations are related to poorer visual outcomes at 24 months in patients with nAMD treated with anti-vascular endothelial growth factor injections. Macular thickness variability may be an important prognostic factor of visual outcomes in nAMD eyes., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

We have developed a deep learning aging clock using blood test data from the China Health and Retirement Longitudinal Study, which has a mean absolute error of 5.68 years. We used the aging clock to demonstrate the connection between the physical and psychological aspects of aging. The clock detects accelerated aging in people with heart, liver, and lung conditions. We demonstrate that psychological factors, such as feeling unhappy or being lonely, add up to 1.65 years to one's biological age, and the aggregate effect exceeds the effects of biological sex, living area, marital status, and smoking status. We conclude that the psychological component should not be ignored in aging studies due to its significant impact on biological age.

Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction., Competing Interests: Conflict of Interest Statement The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Spiradiclisliboensis L. Wu & W. J. Liu, a new species in tribe Ophiorrhizeae of Rubiaceae from limestone mountain areas of Guizhou, south-western China, is described and illustrated. It is similar to S.guangdongensis and S.jingxiensis , but differs from the latter two by the following traits: stipule triangular, inflorescence sessile or with peduncle up to 0.5 mm long, pedicel 0.8-2.2 mm long, corolla white, salverform, corolla tube 1.6-2.2 cm long, corolla tube of long-styled morph inside with a villous ring and stigmas positioned at the throat of the corolla tube. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria., (Xiao-Fei Song, Wen-Jian Liu, Ao-Xue Chen, Zheng-Ming Yao, Hong-Bo Lan, Lei Wu.)

Background and Objective: This study characterizes the impact of race, ethnicity, insurance status, and geographic location on anti-vascular endothelial growth factor (VEGF) use for the treatment of diabetic macular edema (DME)., Patients and Methods: This study is a retrospective cohort study. The American Academy of Ophthalmology Intelligent Research in Sight Registry was queried for patients diagnosed with DME who received at least one anti-VEGF injection between 2012 and 2020 ( n = 203,707). Multivariate regression analyses investigated associations between race, ethnicity, insurance status, and geographic location and anti-VEGF use and visual outcomes., Results: White race, non-Hispanic/Latino ethnicity, and private insurance were associated with higher use of anti-VEGF injections during a 60-month period (incidence rate ratio, 1.2, 1.25, and 1.17, respectively; P < .01). Furthermore, being of non-Hispanic/Latino ethnicity and having private health insurance were associated with higher longitudinal visual acuity (odds ratio, 1.44 [ P = .02] and odds ratio, 1.43 [ P < .01], respectively)., Conclusion: Ethnicity and insurance status are associated with anti-VEGF use and visual acuity outcomes in DME. [ Ophthalmic Surg Lasers Imaging Retina 2022; 53:380-391.] .

Purpose: To evaluate retinal thickness fluctuations in patients with diabetic macular oedema (DMO) treated with anti-vascular endothelial growth factor (anti-VEGF) injections., Methods: Visual acuity (VA) and central subfield thickness (CST) were collected at baseline, 3, 6, 9 and 12 months. Retinal thickness fluctuation was quantified by standard deviation (SD) of CST across 12 months. A mixed effects regression model evaluated the relationship between CST SD and VA at 12 months. Multiple linear regression analysis was performed to investigate predictors of CST SD., Results: Mean baseline and 12-month VAs were 63.5 ± 15.7 and 69.0 ± 13.8 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (change = +5.1 ± 16.1 letters, p < 0.001). Mean baseline and 12-month CSTs were 396.9 ± 109.7 and 337.7 ± 100.7 μm (change = -59.2 ± 114.8 μm, p < 0.001). Retinal thickness variability across the first 12 months was 59.4 ± 43.6 μm. Stratification of patient eyes by CST SD demonstrated 9.7 letters difference in 12-month VA between first and fourth quartiles. Significant predictors of CST SD include baseline CST, injection type, laser treatment, and DR stage., Conclusions: Larger retinal thickness fluctuations are associated with poorer visual outcomes in eyes with DMO treated with anti-VEGF injections. Retinal thickness variability may be an important prognostic biomarker for DMO patients., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ&#95;0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ&#95;0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ&#95;0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ&#95;0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ&#95;0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ&#95;0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ&#95;0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ&#95;0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ&#95;0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ&#95;0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ&#95;0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ&#95;0043533 would serve as a novel therapeutic target for PCOS., (Copyright © 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3 + T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3 + CD8 + cytotoxic T cells (CTLs, p = .0079), CD3 + CD4 + FOXP3 - T helper cells (T h , p = .0010), and CD3 + CD4 + FOXP3 + regulatory T cells (Tregs, p = .0089) with no difference in CD68 + macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor., Competing Interests: YMS has recieved funding from Regeneron. BTF has financial interests in both Regeneron and Thermo Fisher Scientific. GAM is a consultant for CEND Biopharma and Synthekine, and has recieved funding from MERCK, Roche, BioLine, and Regeneron. None of the disclosures listed are related to this work., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

In a recently published article, Melenhorst et al. performed a longitudinal analysis on chimeric antigen receptor (CAR) T cells isolated from patients over 10 years after therapy, revealing expansion of a long-lived CD4 + CAR T-cell population with a cytotoxic phenotype., (© 2022 Australian and New Zealand Society for Immunology, Inc.)

Background: Currently, there is no validated and available method internationally to determine the contents of nicotine and aerosolizing agents, namely glycerol and propylene glycol, added onto the heatsticks for use in heated smoking devices., Objective: To determine the concentrations of nicotine, propylene glycol, glycerol and triacetin in heated tobacco products (HTPs) which is essential to understanding their health effects on smokers as well as secondhand smokers., Methods: A simple methodology was developed and validated to simultaneously determine nicotine, propylene glycol, glycerol, and triacetin concentrations present in heatsticks. The tobacco material was extracted with a mixture of methanol-acetonitrile (7 + 3, by volume) with 1,3-butanediol and n-heptadecane as internal standards and analyzed with gas chromatography with flame-ionization detection (GC-FID)., Results: Good linearity was achieved over the following concentration ranges: 0.1-1.0 mg/mL for nicotine, 0.03-2.0 mg/mL for propylene glycol, 0.5-10.0 mg/mL for glycerol, and 0.1-4.0 mg/mL triacetin, with a coefficient of determination ≥0.995. The limits of detection and quantification were 0.0009 and 0.003 mg/mL for nicotine, 0.02 and 0.02 mg/mL for propylene glycol, 0.03 and 0.09 mg/mL for glycerol, and 0.005 and 0.02 mg/mL for triacetin, respectively. Good recoveries were obtained for nicotine at 89.8-102.0%, propylene glycol at 95.5-102.5%, glycerol at 95.2-102.6%, and triacetin at 90.6-103.1%., Conclusion: This method provides an affordable and reliable technique for routine analysis of nicotine and aerosolizing chemicals present in HTPs which is necessary to assess their impact to public health., Highlights: Many gaps remain in research on HTPs, in particular, country levels information on the content of the products are limited. This article contains information on a newly developed method to simultaneously determine nicotine, propylene glycol, glycerol and triacetin present in the tobacco material and butts of heatsticks for HTPs., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The conductive polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is ubiquitous in research dealing with organic electronic devices (e.g., solar cells, wearable and implantable sensors, and electrochemical transistors). In many bioelectronic applications, the applicability of commercially available formulations of PEDOT:PSS (e.g., Clevios) is limited by its poor mechanical properties. Additives can be used to increase the compliance but pose a risk of leaching, which can result in device failure and increased toxicity (in biological settings). Thus, to increase the mechanical compliance of PEDOT:PSS without additives, we synthesized a library of intrinsically stretchable block copolymers. In particular, controlled radical polymerization using a reversible addition-fragmentation transfer process was used to generate block copolymers consisting of a block of PSS (of fixed length) appended to varying blocks of poly(poly(ethylene glycol) methyl ether acrylate) (PPEGMEA). These block copolymers (PSS (1) - b -PPEGMEA ( x ) , where x ranges from 1 to 6) were used as scaffolds for oxidative polymerization of PEDOT. By increasing the lengths of the PPEGMEA segments on the PEDOT:[PSS (1) - b -PPEGMEA (1-6) ] block copolymers, ("Block-1" to "Block-6"), or by blending these copolymers with PEDOT:PSS, the mechanical and electronic properties of the polymer can be tuned. Our results indicate that the polymer with the longest block of PPEGMEA, Block-6, had the highest fracture strain (75%) and lowest elastic modulus (9.7 MPa), though at the expense of conductivity (0.01 S cm -1 ). However, blending Block-6 with PEDOT:PSS to compensate for the insulating nature of the PPEGMEA resulted in increased conductivity [2.14 S cm -1 for Blend-6 (2:1)]. Finally, we showed that Block-6 outperforms a commercial formulation of PEDOT:PSS as a dry electrode for surface electromyography due to its favorable mechanical properties and better adhesion to skin.

Objective: To investigate the effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats. Methods: The experimental research method was used. Fifty-one no matter male or female Sprague-Dawley rats aged 7-10 weeks were selected, and two round full-thickness skin defect wounds with a diameter of 2 cm were created on the back of each rat at a distance about 1.0 cm to the spine. The rats were divided into temperature-sensitive hydrogel group, gel group, and blank control group according to the random number table, with 17 rats and 34 wounds in each group. Wounds of rats in the first two groups were applied respectively with 0.3 mL temperature-sensitive hydroxybutyl chitosan hydrogel and carboxymethyl chitosan hydrogel immediately after injury, and the wounds of rats in blank control group received no treatment. The wounds of rats in the three groups were all covered with vaseline oil gauze. The states of temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group and carboxymethyl chitosan hydrogel in wounds of rats in gel group were observed every day when the dressings were changed, and the difficulty of vaseline oil gauze removal was recorded. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound healing of rats in the three groups was observed and the wound healing rates were calculated. On the 3rd, 7th, 10th, 14th, and 21st day after injury, tissue from 4 wounds of 2 rats in each group was collected for the following observation and detection. The infiltration of inflammatory cells, angiogenesis, and re-epithelialization were observed by hematoxylin eosin staining. The regeneration and remodeling of collagen fibers were observed by Masson staining, and the collagen volume fraction was calculated. The expressions of interleukin-6 (IL-6), transforming growth factor β 1 (TGF-β 1 ), and matrix metalloproteinase-1 (MMP-1) were detected by enzyme-linked immunosorbent assay method. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test. Results: The carboxymethyl chitosan gel in wounds of rats in gel group was liquid gel and could flow with the body position, while the temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group was solid gel and could not flow with the body position, and the distribution of the latter was more uniform. The vaseline oil gauzes were easily removed in wounds of rats in temperature-sensitive hydrogel group, while the vaseline oil gauzes were difficult to remove in the other two groups. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound granulation tissue of rats grew well in temperature-sensitive hydrogel group and gel group, with no obvious infection, and two rats in blank control group died of wound infection on the 3rd and 5th day after injury. On the 7th, 10th, 14th, and 21st day after injury, the wound healing rates of rats in temperature-sensitive hydrogel group and gel group were significantly higher than that in blank control group ( P <0.01). On the 10th day after injury, the wound healing rate of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group ( P <0.05). A large number of neutrophils and lymphocytes infiltrated into the wounds of rats in the three groups on the 3rd day after injury. The infiltration of inflammatory cells was gradually reduced and the wound healed gradually in rats of temperature-sensitive hydrogel group and gel group from the 7th to 21st day after injury, and the epidermis and dermis could be seen, without hair follicles and other skin appendages. The wounds of rats in blank control group did not heal completely on 21st day after injury. From the 3rd to 10th day after injury, the newly formed collagen fibers increased gradually in the wounds of rats in the three groups. On the 14th and 21st day after injury, the collagen fibers in the wounds of rats in temperature-sensitive hydrogel group and gel group were denser and more orderly than those in blank control group. On the 10th, 14th, and 21st day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group and gel group was significantly higher than that in blank control group ( P <0.01). On the 14th day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group ( P <0.01). On the 3rd, 7th, and 10th day after injury, the expressions of IL-6 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P <0.01), and the expressions of IL-6 in wounds of rats in gel group were significantly lower than those in blank control group ( P <0.01). On the 3rd, 7th, and 10th day after injury, the expressions of TGF-β 1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P <0.01). The expressions of TGF-β 1 in wounds of rats in gel group were significantly lower than those in blank control group on the 3rd and 7th day after injury ( P <0.01), and the expression of TGF-β 1 in wounds of rats in gel group was significantly higher than that in blank control group on the 10th day after injury ( P <0.01). On the 14th day after injury, the expression of TGF-β 1 in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group ( P <0.01). On the 21st day after injury, the expression of TGF-β 1 in wounds of rats in temperature-sensitive hydrogel group was significantly lower than that in gel group and blank control group ( P <0.01), and the expression of TGF-β 1 in wounds of rats in gel group was significantly lower than that in blank control group ( P <0.01). On the 7th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group ( P <0.01). On the 10th, 14th, and 21st day after injury, the expressions of MMP-1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group ( P <0.01). On the 10th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly lower than that in blank control group ( P <0.01). On the 14th and 21st day after injury, the expressions of MMP-1 in wounds of rats in gel group were significantly higher than those in blank control group ( P <0.01). Conclusions: Temperature-sensitive hydroxybutyl chitosan hydrogel can promote the healing of full-thickness skin defect wounds in rats by increasing the expressions of IL-6, TGF-β 1 , and MMP-1, regulating the wound healing environment, inhibiting inflammatory reaction, improving the strength of tissue repair, and promoting collagen synthesis or decomposition.

Objective: To evaluate visual acuity (VA) outcomes, prognostic factors, and changes in disease severity in patients with age-related macular degeneration (AMD) undergoing cataract surgery., Design: Retrospective cohort study PARTICIPANTS: Patients with AMD or healthy control patients who underwent cataract surgery between 2012 and 2017., Methods: Eyes were categorized into 3 AMD groups-intermediate AMD (iAMD), fovea-involving geographic atrophy (GA), neovascular AMD (nAMD)-and 3 preoperative VA-matched control groups (iAMDc), fovea-involving geographic atrophy control (GAc), neovaascular AMD control (nAMDc)., Results: We compared 216 iAMD, 35 GA, and 184 nAMD eyes with 130, 31, and 129 controls. At postoperative month 12 (POM12), VA increased significantly in iAMD and nAMD (+10.1 ± 14.5 and +9.7 ± 18.9 letters, p < 0.001), but not in GA (p = 0.68). All control groups showed significant VA gains (iAMDc: +17.1 ± 9.7, GAc: +30 ± 12.9, and nAMDc: +26.4 ± 15.6 letters, p < 0.001). For AMD groups, POM12 VA and gain in VA were significantly lower than that of controls (p < 0.01), and better preoperative VA predicted smaller VA gains (p ≤ 0.007). Longer duration of AMD in iAMD, ellipsoid zone disruption in nAMD, and lower central subfield thickness in GA were associated with poorer VA outcomes (p < 0.05). Development of nAMD occurred in 8 iAMD eyes and was associated with longer duration of disease (p = 0.001). For nAMD eyes, injection frequency did not vary between the 12-month pre- and postoperative periods (p = 0.051)., Conclusions: Cataract surgery improves VA for patients with iAMD and nAMD, albeit not to the level of those without retinal pathology. Preoperative VA, AMD duration, and optical coherence tomography parameters may be important prognostic factors for cataract surgery in patients with AMD., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The mechanical properties of π-conjugated (semiconducting) polymers are a key determinant of the stability and manufacturability of devices envisioned for applications in energy and healthcare. These properties─including modulus, extensibility, toughness, and strength─are influenced by the morphology of the solid film, which depends on the method of processing. To date, the majority of work done on the mechanical properties of semiconducting polymers has been performed on films deposited by spin coating, a process not amenable to the manufacturing of large-area films. Here, we compare the mechanical properties of thin films of regioregular poly(3-heptylthiophene) (P3HpT) produced by three scalable deposition processes─interfacial spreading, solution shearing, and spray coating─and spin coating (as a reference). Our results lead to four principal conclusions. (1) Spray-coated films have poor mechanical robustness due to defects and inhomogeneous thickness. (2) Sheared films show the highest modulus, strength, and toughness, likely resulting from a decrease in free volume. (3) Interfacially spread films show a lower modulus but greater fracture strain than spin-coated films. (4) The trends observed in the tensile behavior of films cast using different deposition processes held true for both P3HpT and poly(3-butylthiophene) (P3BT), an analogue with a higher glass transition temperature. Grazing incidence X-ray diffraction and ultraviolet-visible spectroscopy reveal many notable differences in the solid structures of P3HpT films generated by all four processes. While these morphological differences provide possible explanations for differences in the electronic properties (hole mobility), we find that the mechanical properties of the film are dominated by the free volume and surface topography. In field-effect transistors, spread films had mobilities more than 1 magnitude greater than any other films, likely due to a relatively high proportion of edge-on texturing and long coherence length in the crystalline domains. Overall, spread films offer the best combination of deformability and charge-transport properties.

Purpose: This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME)., Design: Retrospective, cross-sectional study., Participants: The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707)., Methods: Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features., Main Outcome Measures: Visual acuity and DR severity., Results: Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01)., Conclusions: There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The purpose of the current study is to examine how nonmodifiable sociodemographic, disease, appointment, management, and survey factors correlate with provider rating. This was a retrospective cross-sectional study conducted on 29 857 patient Clinician and Group Consumer Assessment of Healthcare Providers and Systems surveys collected from January 2017 to January 2019 at a tertiary eye center. We included surveys of patients aged 18 years or older, who answered at least 4 of 6 subfield questions, and completed the survey within 90 days of the appointment. The main outcome was the odds of receiving top box score (TBS) of 10/10 on the survey question regarding overall provider rating. The results showed that the variables with higher odds of TBS included higher overall appointment attendance (odds ratio [OR]: 2.66 [95% CI: 1.23-5.75], P = .013); older patient age (OR 2.44 [95% CI: 2.08-2.87], P < .001]; higher percentage of survey questions completed (OR: 2.02 [95% CI: 1.79-2.27], P < .001); better best corrected visual acuity (OR: 1.85 [95% CI: 1.3-2.64], P = .001); optometry clinic visit (OR: 1.25 [95% CI: 1.15-1.36], P < .001); having procedures (OR: 1.19 [95% CI: 1.04-1.36], P = .013), surgery scheduled (OR: 1.18 [95% CI: 1.03-1.36], P = .020], or refraction done (OR: 1.16 [95% CI: 1.08-1.25], P < .001); being seen by male providers (OR: 1.11 [95% CI: 1.04-1.17], P = .001); and having additional eye testing performed (OR: 1.06 [95% CI: 1.00-1.13], P = .048). Variables associated with lower odds of TBS included longer time to complete survey (OR: 0.42 [95% CI: 0.3-0.58], P = .001); new patient encounter (OR: 0.62 [95% CI: 0.58-0.65], P < .001); and glaucoma (OR: 0.66 [95% CI: 0.59-0.75], P < .001), cornea (OR: 0.79 [95% CI: 0.71-0.87], P < .001), or comprehensive clinic visits (OR: 0.86 [95% CI: 0.79-0.94], P < .001). Thus, nonmodifiable factors may affect the provider rating, and these factors should be studied further and accounted for when interpreting the results of patient experience surveys., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MH: None. JH: None. AXC: None. TG: None. TC: None. SLR: None. RPS: Genentech/Roche (personal fees), Alcon/Novartis (personal fees), Apellis (grant), Graybug (grant), Zeiss (personal fees), Bausch + Lomb (personal fees), Ophthea (personal fees), Regeneron Pharmaceuticals, Inc. (personal fees). AVR: AR: Alcon, Novartis, Zeiss, Allergan, Regeneron, Genentech, Samsara (all personal fees); Novartis, Genentech (research)., (© The Author(s) 2021.)