High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

Shape-changing electrode array for minimally invasive large-scale intracranial brain activity mapping.

Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces.

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

Epidemiologic characteristics and a prognostic nomogram for patients with vulvar cancer: results from the Surveillance, Epidemiology, and End Results (SEER) program in the United States, 1975 to 2016.

OBJECTIVE: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. METHODS: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). RESULTS: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. CONCLUSIONS: The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

Association between ABO blood type and type I endometrial cancer: a retrospective study.

This study aimed to assess the association between ABO blood type and incident of type I endometrial cancer (EC), as well as the stage and differentiation. 213 patients with type I EC and 300 healthy controls were included. As a result, the frequencies of A, B, O, and AB blood types among patients with type I EC were 51 (23.9%), 59 (27.7%), 93 (43.7%) and 10 (4.7%), respectively. There were no significant differences in age, body mass index, and other baseline covariates between groups of ABO blood types (p > .05). Logistic regression model showed that women with blood type O was more likely to develop type I EC than those with type A (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.05-2.63). However, there was no significant association of ABO blood type with stage and differentiation of type I EC (p > .05). In conclusion, blood type O was the most prevalent ABO blood type among patients with type I EC and was associated with increased risk of type I EC, while ABO blood type was not significantly associated with stage or differentiation of type I EC.IMPACT STATEMENTWhat is already known on this subject? Previous studies have produced inconsistent findings on association of ABO blood type with EC. Those studies also did not explore the relationship between ABO blood type and stage or differentiation of type I EC.What the results of this study add? The present study showed that women with blood type O was more likely to develop type I EC than those with type A and there was no significant association of ABO blood type with stage or differentiation of type I EC.What the implications are of these findings for clinical practice and/or further research? Gynaecologists should pay more attention to women with blood type O, who should undergo more active EC screening.

Stable, long-term single-neuronal recording from the rat spinal cord with flexible carbon nanotube fiber electrodes.

Objective.Flexible implantable electrodes enable months-long stable recording of single-unit signals from rat brains. Despite extensive efforts in the development of flexible probes for brain recording, thus far there are no conclusions on their application in long-term single neuronal recording from the spinal cord which is more mechanically active. To this end, we realized the chronic recording of single-unit signals from the spinal cord of freely-moving rats using flexible carbon nanotube fiber (CNTF) electrodes.Approach.We developed flexible CNTF electrodes for intraspinal recording. Continuousin vivoimpedance monitoring and histology studies were conducted to explore the critical factors determining the longevity of the recording, as well as to illustrate the evolution of the electrode-tissue interface. Gait analysis were performed to evaluate the biosafety of the chronic intraspinal implantation of the CNTF electrodes.Main results.By increasing the insulation thickness of the CNTF electrodes, single-unit signals were continuously recorded from the spinal cord of freely-moving rats without electrode repositioning for 3-4 months. Single neuronal and local field potential activities in response to somatic mechanical stimulation were successfully recorded from the spinal dorsal horns. Histological data demonstrated the ability of the CNTF microelectrodes to form an improved intraspinal interfaces with greatly reduced gliosis compared to their stiff metal counterparts. Continuous impedance monitoring suggested that the longevity of the intraspinal recording with CNTF electrodes was determined by the insulation durability. Gait analysis showed that the chronic presence of the CNTF electrodes caused no noticeable locomotor deficits in rats.Significance.It was found that the chronic recording from the spinal cord faces more stringent requirements on the electrode structural durability than recording from the brain. The stable, long-term intraspinal recording provides unique capabilities for studying the physiological functions of the spinal cord relating to motor, sensation, and autonomic control in both health and disease.

High-speed Fourier ptychographic microscopy for quantitative phase imaging.

Fourier ptychographic microscopy (FPM), as an emerging computational imaging method, has been applied to quantitative phase imaging with resolution bypassing the physical limit of the detection objective. Due to the weak illumination intensity and long image acquisition time, the achieved imaging speed in current FPM methods is still low, making them unsuitable for real-time imaging applications. We propose and demonstrate a high-speed FPM method based on using laser illumination and digital micro-mirror devices for illumination angle scanning. In this new, to the best of our knowledge, FPM method, we realized quantitative phase imaging and intensity imaging at over 42 frames per second (fps) with around 1 µm lateral resolution. The quantitative phase images have revealed membrane height fluctuations of red blood cells with nanometer-scale sensitivity, while the intensity images have resolved subcellular features in stained cancer tissue slices.

Outcomes of reproduction following cesarean scar pregnancy treatment: A systematic review and meta-analysis.

OBJECTIVES: To explore the reproductive outcomes of women with a history of cesarean scar pregnancy (CSP) and the influence of various treatments on subsequent pregnancy outcomes. STUDY DESIGN: The PubMed, Embase, Medline, Cochrane Library and ClinicalTrial.gov databases were searched for studies with the outcomes of pregnancy after CSP treatment. Studies that reported reproductive outcomes after CSP with more than 5 followed cases were included. The main data collected includes the treatment methods of CSP and subsequent pregnancy outcomes. The main information includes intrauterine pregnancy, recurrent CSP (RCSP), and spontaneous miscarriage, while the secondary information includes complications during pregnancies and the outcomes of childbirths. According to different treatments (conservative treatment, surgical treatment without resection of cesarean scar, and surgical treatment with resection of cesarean scar), a stratified analysis was carried out to compare the influence of treatments on subsequent pregnancy outcomes. RESULTS: A total of 32 studies including 3380 cases of CSP met the inclusion criteria, of which 583 cases conceived again after treatment (including 292 cases of unexpected pregnancy), and finally 178 cases delivered successfully. The follow-up time ranged from 3 to 72 months. Among women with fertility requirements, a total of 291 cases in 403 women were successfully conceived during the follow-up period in 15 studies. Thence the pregnancy rate of women with fertility requirements was 76.2 %. Among all of the 583 successfully conceived women, 83.4 % of them had intrauterine pregnancy, while 15.3 % of cases were RCSP. The total ectopic pregnancy rate reached 16.6 %, covering RCSP and other sites of ectopic pregnancy. 14.6 % of intrauterine pregnancy experienced spontaneous miscarriage. The intrauterine pregnancy rates of the conservative treatment group, the surgical treatment without resection of cesarean scar group, and the surgical treatment with resection of cesarean scar group were 93.1 %, 80.1 % and 86.0 % respectively; the corresponding RCSP rates were 6.9 %, 15.6 % and 14.0 % respectively; and the corresponding spontaneous miscarriage rates were 20.7 %, 13.9 % and 22.2 % respectively. CONCLUSION: The outcomes of reproduction after CSP included intrauterine pregnancy, RCSP and other sites of ectopic pregnancy. Women with a history of CSP still have a high pregnancy rate, but the risk of RCSP and spontaneous miscarriage is also increased. It is impossible to clarify the effect of different treatments on subsequent pregnancy. Whether the resection and repair of cesarean scar can ameliorate reproductive outcomes needs to be further assessed. Further large-scale prospective studies, even RCTs with long-term follow-up are needed to expound the outcomes of reproduction after CSP and the effect of different treatments on subsequent reproductive outcomes.

Retroperitoneal ectopic pregnancy: A literature review of reported cases.

To provide reference for the diagnosis and treatment of retroperitoneal ectopic pregnancy (REP), we conducted a review on all of the reported cases in English by summarizing their clinical manifestation, diagnosis, management and prognosis. A total of 25 literatures including 26 REP cases were collected from PubMed database. 40 % (10/25) of the patients had a history of tubal pregnancy, 65.4 % (17/26) was spontaneous pregnancy, and the average period of amenorrhea was 56.7 days. Abdominal pain is the most common (53.8 %, 14/26) symptom of REP. Ultrasound is the main method of diagnosing REP. Only 30.8 % (8/26) were diagnosed as REP at the initial visit, and 55.6 % (10/18) of those who were misdiagnosed received unnecessary invasive treatment. The pregnancy sites of REP are complex, and it can be simply divided into pelvic REP and abdominal REP. Due to preoperative misdiagnosis, 46.2 % (9/26) of REP experienced two or more treatments. Except for 2 patients who received local methotrexate (MTX) injection in the gestational sac, the other 24 patients underwent surgical treatment, and all patients had a good prognosis. Due to insufficient knowledge, the rate of misdiagnosis and mistreatment of REP is high. The key to diagnosing REP is to consider the possibility of REP and the scanning field during examination can cover the site of pregnancy. Local MTX injection and surgical resection are both effective methods for the treatment of REP.

Single-dose versus multidose metronidazole for the treatment of vaginal trichomoniasis: A meta-analysis.

OBJECTIVE: The purpose of this meta-analysis is to further explore the effectiveness of multidose metronidazole (MTZ) and single-dose MTZ in the treatment of trichomoniasis. STUDY DESIGN: Search all the literature on MTZ for trichomoniasis in the Pubmed, Ovid Embase, Ovid MEDLIN and Cochrane Library databases. The search period is from the establishment of the database to September 10, 2020. Two authors independently screened the literatures based on inclusion and exclusion criteria, and independent extraction and integration of literature data. The main observation indicators were treatment failure rate and side-effects. Data analysis was performed using RevMan5.2 software. The risk ratio (RR) and 95 % confidence interval (CI) were used as the effect scale indicators of the counting data. P < 0.05 was considered to be statistically significant. RESULTS: A total of 2114 articles were retrieved. After screening, a total of 7 articles were included, including 5 randomized controlled trial (RCT) studies and 2 case-control studies. 745 cases were treated with single-dose MTZ, and 732 cases were treated with multidose MTZ. The single-dose MTZ had a higher failure rate for trichomoniasis than the multidose MTZ, and the difference was statistically significant (RR = 1.07, 95 %CI, 1.03-1.11, P = 0.0003). When a HIV-positive study was excluded, the failure rate of the single-dose MTZ was still significantly higher than that of the multidose MTZ (RR = 1.62, 95 %CI, 1.19-2.22, P = 0.002). The side-effects of the single-dose MTZ were higher than those of the multidose MTZ, but the difference was not statistically significant (RR = 1.06, 95 %CI, 0.88-1.27, P = 0.53). CONCLUSION: Although based on available data, multidose MTZ is more effective than single-dose MTZ for trichomoniasis, this advantage is not as obvious as previously proven. This small advantage may be lower if considering the compliance of multidose MTZ in the real world. Therefore, more high-quality studies are needed to confirm this before suggesting a multidose MTZ as the first line treatment for HIV-negative trichomoniasis.

Photoelectrochemical competitive immunosensor for 17ß-estradiol detection based on ZnIn2S4@NH2-MIL-125(Ti) amplified by PDA NS/Mn:ZnCdS.

A competitive-type PEC immunosensor for 17ß-estradiol (E2) detection was successfully fabricated using ZnIn2S4@NH2-MIL-125(Ti) composite as matrix. The excellent PEC behavior of ZnIn2S4@NH2-MIL-125(Ti) composite could be attributed to that the Ti4+-Ti3+ intervalence cycles in the titanium oxo-cluster of NH2-MIL-125(Ti) as well as the matching energy level between ZnIn2S4 and NH2-MIL-125(Ti) promote the migration and separation of photocarrier. Besides, polydopamine (PDA) with abundant amino- and quinone-groups was selected to further improve the PEC signals and capture antibody, which implement through the covalent bonding of PDA and BSA-E2 or carboxyl-group functionalized Mn:ZnCdS QDs in the competitive-type strategy. Concretely, the quinone functional groups in PDA film was applied to immobilize BSA-E2 through Michael reactions, and the PDA nanosphere loaded Mn:ZnCdS quantum dot (PDA NS/Mn:ZnCdS QDs) was used as antibodies' labels to amplify PEC signals. After PDA NS/Mn:ZnCdS-anti-E2 immobilized on the modified electrode, a remarkable increase of photocurrent signal was observed owing to the specific bonding of antigen and antibody. Based on the competitive binding of PDA NS/Mn:ZnCdS-anti-E2 with either free E2 or bovine serum albumin (BSA)-E2 causing the change of the photocurrent signal, the standard sample free E2 could be accuracy detect. Under optimal conditions, the competitive-type PEC immunosensor exhibited the linear range from 0.0005 ng/mL to 20 ng/mL and a limit detection of 0.3 pg/mL (S/N = 3). Meanwhile, the acceptable stability, selectivity and reproducibility of the proposed PEC immunosensing platform indicating the promising detection of small molecular environmental pollutants.

Gas-Permeable, Irritation-Free, Transparent Hydrogel Contact Lens Devices with Metal-Coated Nanofiber Mesh for Eye Interfacing.

An electronic "smart" contact lens device with high gas permeability and optical transparency, as well as mechanical compliance and robustness, offers daily wear capability in eye interfacing and can have broad applications ranging from ocular diagnosis to augmented reality. Most existing contact lens electronics utilize gas-impermeable substrates, electronic components, and interfacial adhesion layers, which impedes them from applications requiring continuous daily wear. Here we report on the design and fabrication of an eye interfacing device with a commercial ocular contact lens as the substrate, metal-coated nanofiber mesh as the conductor, and in situ electrochemically deposited poly(3,4-ethylenedioxythiophene) (PEDOT) /poly(styrene sulfonate) (PSS) as the adhesion material. This hydrogel contact lens device shows high gas permeability, wettability, and level of hydration, in addition to excellent optical transparency, mechanical compliance, and robustness. Using a rabbit model, we found that the animals wearing these hydrogel contact lens devices continuously for 12 hours showed a level of corneal fluorescein staining comparable to those wearing pure hydrogel contact lenses for same period of time, with no obvious corneal abrasion or irritation, indicating their high level of safety for continuous daily wear. Finally, full-field electroretinogram (ERG) recordings on rabbits were carried out to demonstrate the functionality of this device. We believe that the strategy of integrating nanofiber mesh-based electronic components demonstrated here can offer a general platform for hydrogel electronics with the advantages of preserving the physiological and mechanical properties of the hydrogel, thus enabling seamless integration with biological tissues and providing various wearable or implantable sensors with improved biocompatibility for health monitoring or medical treatment.