A Volcano Correlation between Catalytic Activity for Sulfur Reduction Reaction and Fe Atom Count in Metal Center.

Sulfur reduction reaction (SRR) facilitates up to 16 electrons, which endows lithium-sulfur (Li-S) batteries with a high energy density that is twice that of typical Li-ion batteries. However, its sluggish reaction kinetics render batteries with only a low capacity and cycling life, thus remaining the main challenge to practical Li-S batteries, which require efficient electrocatalysts of balanced atom utilization and site-specific requirements toward highly efficient SRR, calling for an in-depth understanding of the atomic structural sensitivity for the catalytic active sites. Herein, we manipulated the number of Fe atoms in iron assemblies, ranging from single Fe atom to diatomic and triatomic Fe atom groupings, all embedded within a carbon matrix. This led to the revelation of a "volcano peak" correlation between SRR catalytic activity and the count of Fe atoms at the active sites. Utilizing operando X-ray absorption and X-ray diffraction spectroscopies, we observed that polysulfide adsorption-desorption and electrochemical conversion kinetics varied up and down with the incremental addition of even a single iron atom to the catalyst's metal center. Our results demonstrate that the metal center with exactly two iron atoms represents the optimal configuration, maximizing atom utility and adeptly handling the conversion of varied intermediate sulfur species, rendering the Li-S battery with a high areal capacity of 23.8 mAh cm-2 at a high sulfur loading of 21.8 mg cm-2. Our results illuminate the pivotal balance between atom utilization and site-specific requirements for optimal electrocatalytic performance in SRR and diverse electrocatalytic reactions.

In vitro and in vivo study of andrographolide nanoparticles for the treatment of Mycoplasma pneumoniae pneumonia.

OBJECTIVE(S): The emergence of antibiotic resistance has led to suboptimal treatment outcomes for Mycoplasma pneumoniae pneumonia (MPP). Exploring naturally occurring drug components that are both effective against MPP and non-toxic may be a promising choice. This study aimed to investigate the therapeutic effect of andrographolide nanoparticles on pneumonia caused by Mycoplasma pneumoniae infection. METHODS: Andrographolide alginate-poloxamer nanoparticles (AND-ALG-POL/NPs) were obtained by wet medium grinding, and the characterization and in vitro release of the prepared andrographolide nanoparticles were examined by high performance liquid chromatography, particle size analyzer, zeta potential meter and transmission electron microscopy. The cytotoxicity and anti-inflammatory effects of AND-ALG-POL/NPs were evaluated in vitro by MP-infected lung epithelial cells BEAS-2B. Symptoms of pneumonia, total cell count, total protein content and inflammatory factor levels in BALF were assessed by MP-induced pneumonia in BALB/c mice treated with AND-ALG-POL/NPs, and histopathological studies were performed on lung tissues from experimental animals. RESULTS: The results showed that the prepared AND-ALG-POL/NPs were homogeneous spherical with a diameter of 180 ± 23 nm, a zeta potential of (-14.4 ± 2.1) mV, an average encapsulation rate of 87.74 ± 0.87 %, and an average drug loading of 13.17 ± 0.54 %. AND-ALG-POL/NPs were capable of slow release in vitro and showed significant inhibitory ability against MP (P < 0.001). However, AND-ALG-POL/NPs were not cytotoxic to normal cells and alleviated MP infection-induced apoptosis and elevated inflammatory factors. In the in vivo experiments, AND-ALG-POL/NPs alleviated the symptoms of pneumonia in MPP mice, reduced the abnormally elevated total cell count, total protein content and inflammatory factor levels in BALF, and alleviated lung tissue edema, inflammatory cell infiltration and apoptosis (P < 0.001). Meanwhile, the therapeutic effects of AND-ALG-POL/NPs on MPP were similar to those of azithromycin (AZM) and higher than those of andrographolide (AND) free monotherapy (P < 0.001). CONCLUSION: In summary, the prepared AND-ALG-POL/NPs can effectively inhibit MPP in vitro and in vivo, and the effect is similar to that of AZM. Therefore, AND- ALG - POL/NPs have the potential to replace AZM as a potential drug for the treatment of MPP.

Case weighted power priors for hybrid control analyses with time-to-event data.

We develop a method for hybrid analyses that uses external controls to augment internal control arms in randomized controlled trials (RCTs) where the degree of borrowing is determined based on similarity between RCT and external control patients to account for systematic differences (e.g., unmeasured confounders). The method represents a novel extension of the power prior where discounting weights are computed separately for each external control based on compatibility with the randomized control data. The discounting weights are determined using the predictive distribution for the external controls derived via the posterior distribution for time-to-event parameters estimated from the RCT. This method is applied using a proportional hazards regression model with piecewise constant baseline hazard. A simulation study and a real-data example are presented based on a completed trial in non-small cell lung cancer. It is shown that the case weighted power prior provides robust inference under various forms of incompatibility between the external controls and RCT population.

Estimating treatment effect in randomized trial after control to treatment crossover using external controls.

In clinical trials, it is common to design a study that permits the administration of an experimental treatment to participants in the placebo or standard of care group post primary endpoint. This is often seen in the open-label extension phase of a phase III, pivotal study of the new medicine, where the focus is on assessing long-term safety and efficacy. With the availability of external controls, proper estimation and inference of long-term treatment effect during the open-label extension phase in the absence of placebo-controlled patients are now feasible. Within the framework of causal inference, we propose several difference-in-differences (DID) type methods and a synthetic control method (SCM) for the combination of randomized controlled trials and external controls. Our realistic simulation studies demonstrate the desirable performance of the proposed estimators in a variety of practical scenarios. In particular, DID methods outperform SCM and are the recommended methods of choice. An empirical application of the methods is demonstrated through a phase III clinical trial in rare disease.

Evaluating hybrid controls methodology in early-phase oncology trials: A simulation study based on the MORPHEUS-UC trial.

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase statistical precision. Here we assess combining two sources of Roche HTD to construct a hybrid control in targeted therapy for decision-making via an extensive simulation study. Our simulations are based on the real data of one of the experimental arms and the control arm of the MORPHEUS-UC Phase Ib/II study and two Roche HTD for atezolizumab monotherapy. We consider potential complications such as model misspecification, unmeasured confounding, different sample sizes of current treatment groups, and heterogeneity among the three trials. We evaluate two frequentist methods (with both Cox and Weibull accelerated failure time [AFT] models) and three different commensurate priors in Bayesian dynamic borrowing (with a Weibull AFT model), and modifications within each of those, when estimating the effect of treatment on survival outcomes and measures of effect such as marginal hazard ratios. We assess the performance of these methods in different settings and the potential of generalizations to supplement decisions in early-phase oncology trials. The results show that the proposed joint frequentist methods and noninformative priors within Bayesian dynamic borrowing with no adjustment on covariates are preferred, especially when treatment effects across the three trials are heterogeneous. For generalization of hybrid control methods in such settings, we recommend more simulation studies.

Building Porous Ni(Salen)-Based Catalysts from Waste Styrofoam via Autocatalytic Coupling Chemistry for Heterogeneous Oxidation with Molecular Oxygen.

The development of robust and industrially viable catalysts from plastic waste is of great significance, and the facile construction of high performance heterogeneous catalyst systems for phenol-quinone conversions remains a grand challenge. Herein, a feasible strategy is demonstrated to reclaim Styrofoam into hierarchically porous nickel-salen-loaded hypercrosslinked polystyrene (PS@Ni-salen) catalysts with high activities through an unusual autocatalytic coupling route. The salen is immobilized onto PS chain by Friedel-Crafts alkylation of benzyl chloride derivatives, and the generated hydrogen chloride coordinately promotes the simultaneous crosslinking and bridge formation between aromatic rings via a Scholl coupling route, leading to hierarchically porous networks. After the metallization with Ni, the resultant networks exhibit high catalytic activity for the oxidation of 2,3,6-trimethylphenol to 2,3,5-trimethyl-1,4-benzoquinone under mild conditions (303 K, 1 bar of O2 ). This catalyst also demonstrates attractive recycling performance without an obvious loss of catalytic efficiency over five consecutive cycles. This methodology might provide a potential sustainable alternative to construct environmentally benign and cost-effective catalysts for specific organic transformation.

Covariate handling approaches in combination with dynamic borrowing for hybrid control studies.

Borrowing data from external control has been an appealing strategy for evidence synthesis when conducting randomized controlled trials (RCTs). Often named hybrid control trials, they leverage existing control data from clinical trials or potentially real-world data (RWD), enable trial designs to allocate more patients to the novel intervention arm, and improve the efficiency or lower the cost of the primary RCT. Several methods have been established and developed to borrow external control data, among which the propensity score methods and Bayesian dynamic borrowing framework play essential roles. Noticing the unique strengths of propensity score methods and Bayesian hierarchical models, we utilize both methods in a complementary manner to analyze hybrid control studies. In this article, we review methods including covariate adjustments, propensity score matching and weighting in combination with dynamic borrowing and compare the performance of these methods through comprehensive simulations. Different degrees of covariate imbalance and confounding are examined. Our findings suggested that the conventional covariate adjustment in combination with the Bayesian commensurate prior model provides the highest power with good type I error control under the investigated settings. It has desired performance especially under scenarios of different degrees of confounding. To estimate efficacy signals in the exploratory setting, the covariate adjustment method in combination with the Bayesian commensurate prior is recommended.

A frequentist approach to dynamic borrowing.

There has been growing interest in leveraging external control data to augment a randomized control group data in clinical trials and enable more informative decision making. In recent years, the quality and availability of real-world data have improved steadily as external controls. However, information borrowing by directly pooling such external controls with randomized controls may lead to biased estimates of the treatment effect. Dynamic borrowing methods under the Bayesian framework have been proposed to better control the false positive error. However, the numerical computation and, especially, parameter tuning, of those Bayesian dynamic borrowing methods remain a challenge in practice. In this paper, we present a frequentist interpretation of a Bayesian commensurate prior borrowing approach and describe intrinsic challenges associated with this method from the perspective of optimization. Motivated by this observation, we propose a new dynamic borrowing approach using adaptive lasso. The treatment effect estimate derived from this method follows a known asymptotic distribution, which can be used to construct confidence intervals and conduct hypothesis tests. The finite sample performance of the method is evaluated through extensive Monte Carlo simulations under different settings. We observed highly competitive performance of adaptive lasso compared to Bayesian approaches. Methods for selecting tuning parameters are also thoroughly discussed based on results from numerical studies and an illustration example.

Non-trivial Contribution of Carbon Hybridization in Carbon-based Substrates to Electrocatalytic Activities in Li-S Batteries.

Appling an electrochemical catalyst is an efficient strategy for inhibiting the shuttle effect and enhancing the S utilization of Li-S batteries. Carbon-based materials are the most common conductive agents and catalyst supports used in Li-S batteries, but the correlation between the diversity of hybridizations and sulfur reduction reaction (SRR) catalytic activity remains unclear. Here, by establishing two forms of carbon models, i.e., graphitic carbon (GC) and amorphous carbon (AC), we observe that the nitrogen atom doped in the GC possesses a higher local charge density and a lower Gibbs free energy towards the formation of polysulfides than in the AC. And the GC-based electrode consistently inherits considerably enhanced SRR kinetics and superior cycling stability and rate capability in Li-S batteries. Therefore, the function of carbon in Li-S batteries is not only limited as conductive support but also plays an unignorable contribution to the electrocatalytic activities of SRR.

Regulating Sodium Deposition through Gradiently-Graphitized Framework for Dendrite-Free Na Metal Anode.

Na metal anode (NMA) is one of the most promising candidate materials for next-generation low-cost sodium metal batteries. However, the preferred deposition of Na metal at the anode/separator interface increases the risk of dendrite penetration of the separator, consequently, reduces safety and life of batteries with NMA. In this study, a Na deposition-regulating strategy is shown by designing a gradiently graphitized 3D carbon fiber (CF) framework as host (grad-CF), whereby Na is guided to deposit preferentially at the bottom of the anode, safely away from the separator. The obtained Na anode significantly reduces the probability of dendrite-induced short circuits. The grad-CF host enables NMA stable cycling at a high current density of 6 mA cm-2 . When the Na@grad-CF is applied as anode in full cells pared with Na3 V2 (PO4 )3 (NVP) cathode, it exhibits a reversible capacity of 73 mA h g-1 after 500 cycles with a low decay rate of 0.13%.

CAR T targets and microenvironmental barriers of osteosarcoma.

Osteosarcoma (OS) is one of the most common malignancies in children and adolescents. Multimodal chemotherapy and aggressive surgical resection have improved the prognosis of patients with osteosarcoma. However, the prognosis of OS patients with unresectable advanced tumors, distant metastasis or chemotherapy is still poor. Chimeric antigen receptor (CAR) T cells have achieved remarkable success in the treatment of hematologic malignancies, injecting new vitality into the field of adoptive cell therapy. However, the efficacy in solid tumors has been largely limited. The reason for the poor curative effect of solid tumors is mainly the heterogeneity of solid tumor antigen, immune escape, tumor microenvironment barrier, resistance of immunosuppressive cells and inhibitory factors, which lead to the obstruction of CAR T cell infiltration and the aggravation of failure. Potential antigenic targets for osteosarcoma CAR T cell therapy are under continuous exploration. Some of the antigenic targets, such as anti-HER2-CAR T cells, have achieved good results in preclinical studies, and some of them have entered clinical studies and achieved certain clinical effects. In this review, we discuss the research progress of potential antigen targets and osteosarcoma microenvironment of CAR T cells in the treatment of osteosarcoma.

Chained multimediator model of sexual orientation disclosure, sexual minority stigma, sexual minority identity, social support, and resilience among ymsms.

INTRODUCTION: This study aimed to investigate sexual orientation disclosure and mental health among young men who have sex with men (YMSMs). To this end, we constructed a chained multimediator model of sexual minority stigma, sexual minority identity, social support, and resilience, with the moderator of sexual orientation disclosure. METHODS: We conducted a cross-sectional survey of 345 YMSMs in Nanning, China. Bivariate analysis was used to evaluate factors associated with sexual orientation disclosure. Sexual minority stigma was used to predict identity, with social support as the step 1 mediator and resilience as the step 2 mediator. Sexual minority identity was analyzed using a chained moderated mediation model; sexual orientation disclosure was included as a moderator in all models to control its confounding effect. RESULTS: The average age of YMSMs was 20.0 ± 1.3 years. Bivariate analysis indicated that YMSMs who disclosed sexual orientation may have experienced less stigma (15.49 ± 3.02 vs 16.21 ± 2.74), obtained more social support (65.98 ± 11.18 vs 63.19 ± 11.13), had strong psychological resilience (37.40 ± 8.57 vs 35.39 ± 7.73), and had a more positive self-identity (104.12 ± 21.10 vs 95.35 ± 16.67); differences between subgroups were statistically significant (p < 0.05). Sexual minority stigma, perceived stigma, and enacted stigma were significantly associated with social support and resilience. The association between sexual minority stigma and sexual minority identity was significantly mediated by social support (indirect effect [95% CI] = - 3.307 [- 4.782, - 1.907]). Resilience significantly mediated the same association for identity (- 2.544 [- 4.052, - 1.114]). The chained relationship from sexual minority stigma to social support, resilience, and identity was also significant, with an indirect effect of - 0.404 [- 0.621, - 0.249]. CONCLUSION: Among YMSMs in China, sexual minority stigma affects sexual minority identity through social support and resilience. Given the psychological effects of stigma, social support and resilience must be considered to better promote positive self-identity and mental health among YMSMs.

Individual and network factors associated with HIV self-testing among men who have sex with men in resource-limited settings in China.

BACKGROUND: HIV self-testing (HIVST) is a potential strategy to overcome challenges of HIV testing among men who have sex with men (MSM). However, for resource-limited settings, technology and diagnostic devices are lagging. Hence, we estimated the status and correlates of HIVST among MSM in resource-limited settings in China to inform the development of HIVST to reach United Nations Programme on HIV and AIDS (UNAIDS) targets to end HIV by 2030. METHODS: A cross-sectional study was conducted among MSM in Nanning, Guangxi, China, between August 2019 and January 2020. The HIVST status was collected and data on social network features, sociodemographic information, risk behaviours, etc. were compared between prior- and non-HIVST MSM. Logistic regression analyses were conducted to examine the correlates of HIVST. RESULTS: The prevalence of HIVST among 446 MSM was 40.4% (95% confidence interval [CI] 35.8-44.9%). The main component of sociocentric network contains more prior-HIVST MSM (38.3%) than non-HIVST MSM (28.6%, P =0.031). More MSM with individual features such as substance use during anal sex (22.8% vs 15.4%, P =0.049) and multiple sexual partners (76.1% vs 59.4%, P <0.001) were detected among prior-HIVST MSM. In multivariable analysis, prior HIVST was associated with the strong strength of ego-alter ties in the egocentric network (adjusted odds ratio [aOR] 1.72; 95% CI 1.09-2.71), HIV-infected partners (aOR, 7.17; 95% CI, 1.40-36.60), and vaginal intercourse (aOR, 0.38; 95% CI, 0.17-0.85). CONCLUSIONS: HIVST coverage among MSM in resource-limited settings is suboptimal. Integrating social networks into testing services may be viable to promote HIVST in MSM within resource-limited settings.

Characterization of carbaryl-degrading strain Bacillus licheniformis B-1 and its hydrolase identification.

Pesticides introduced inadvertently or deliberately into environment by anthropogenic activity have caused growing global public concern, therefore the search of approaches for elimination of such xenobiotics should be encouraged. A cypermethrin-degrading bacterial strain Bacillus licheniformis B-1 was found to efficiently degrade carbaryl in LB medium at concentrations of 50-300 mg L-1 within 48 h, during which temperature and pH played important roles as reflected by increase in pollutant depletion. A stimulatory effect of Fe3+ and Mn2+ on microbial growth was observed, whereas Cu2+ caused inhibition of degradation. Results showed that 1-naphthol was a major transformation product of carbaryl which was further metabolised. An approximately 29 kDa carbaryl-degrading enzyme was purified from B-1 with 15.93-fold purification and an overall yield of 6.02% was achieved using ammonium sulphate precipitation, DEAE-Sepharose CL-6B anion-exchange chromatography and Sephadex G-100 gel filtration. The enzyme was identified through nano reversed-phase liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry as a phosphodiesterase (PDE). This is the first report on the characterization of carbaryl-degrading by Bacillus spp. and the role of a PDE in carbaryl-detoxifying. Also, strain B-1 showed versatile in carbosulfan, isoprocarb and chlorpyrifos degradation, demonstrating as ideal candidate for environment bioremediation.

Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial.

BACKGROUND: Initial results from the ongoing GALLIUM trial have shown that patients with follicular lymphoma have a longer progression-free survival after first-line immunochemotherapy with obinutuzumab than with rituximab. The aim of this secondary analysis was to evaluate the prognostic value of PET-CT responses after first-line immunochemotherapy in the GALLIUM study. METHODS: GALLIUM is an open-label, parallel-group randomised, phase 3 trial, which recruited previously untreated patients with CD20-positive follicular lymphoma (grades 1-3a; disease stage III/IV, or stage II with largest tumour diameter ≥7 cm) who were aged 18 years or older and met the criteria for needing treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous administration of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, then day 1 of subsequent cycles) or rituximab (375 mg/m2 on day 1 of each cycle), in six 21-day cycles with cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP; oral administration) followed by two 21-day cycles of antibody alone, or eight 21-day cycles cyclophosphamide, vincristine, and prednisone (known as CVP; oral administration), or six 28-day cycles with bendamustine, followed by maintenance antibody every 2 months for up to 2 years. The primary endpoint of the trial, investigator-assessed progression-free survival, has been reported previously. This secondary analysis reports PET and CT-based responses at end-of-induction therapy and explains their relation with progression-free and overall survival outcomes in patients with available scans. As per protocol, during the trial, PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional thereafter), acquired at baseline and end of induction (PET population), were assessed prospectively by investigators and an independent review committee (IRC) applying International Harmonisation Project (IHP) 2007 response criteria, and retrospectively by the IRC only applying current Lugano 2014 response criteria. IRC members (but not study investigators) were masked to treatment and clinical outcome when assessing response. The landmark analyses excluded patients who died or progressed (contrast enhanced CT-based assessment of progressive disease, or started next anti-lymphoma treatment) before or at end of induction. GALLIUM is registered at ClinicalTrials.gov, number NCT01332968. FINDINGS: 1202 patients were enrolled in GALLIUM between July 6, 2011, and Feb 4, 2014, of whom 595 were included in the PET population; 533 (IHP 2007; prospective analysis), and 508 (Lugano 2014; retrospective analysis) were analysed for progression-free survival (landmark analysis). At end of induction, 390 of 595 patients (65·5% [95% CI 61·6-69·4]) achieved PET complete response according to IHP 2007 criteria, and 450 (75·6% [95% CI 72·0-79·0]) obtained PET complete metabolic response according to Lugano 2014 criteria. With a median of 43·3 months of observation (IQR 36·2-51·8), 2·5-year progression-free survival from end of induction was 87·8% (95% CI 83·9-90·8) in PET complete responders and 72·0% (63·1-79·0) in non-complete responders according to IRC-assessed IHP 2007 criteria (hazard ratio [HR] 0·4, 95% CI 0·3-0·6, p<0·0001). According to Lugano 2014 criteria, 2·5-year progression-free survival in complete metabolic responders was 87·4% (95% CI 83·7-90·2) and in non-complete metabolic responders was 54·9% (40·5-67·3; HR 0·2, 95% CI 0·1-0·3, p<0·0001). INTERPRETATION: Our results suggest that PET is a better imaging modality than contrast-enhanced CT for response assessment after first-line immunochemotherapy in patients with follicular lymphoma. PET assessment according to Lugano 2014 response criteria provides a platform for investigation of response-adapted therapeutic approaches. Additional supportive data are welcomed. FUNDING: F Hoffmann-La Roche.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival.

OBJECTIVES: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN: Multicenter prospective study of in-hospital cardiac arrest. SETTING: Five medical centers in the United States and the United Kingdom. PATIENTS: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95-100) and 93% positive predictive value (95% CI, 66-100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1-2 (area under the curve, 0.79; 95% CI, 0.70-0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46-95), 72% specificity (95% CI, 65-79), and 98% negative predictive value (95% CI, 93-100) for cerebral performance category 1-2. CONCLUSIONS: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

Robotic approaches may offer benefit in colorectal procedures, more controversial in other areas: a review of 168,248 cases.

INTRODUCTION: While the penetrance of robotic surgery into field of urology and gynecology has been significant, general surgeons have been slower adopters. We sought to compare laparoscopy and RAS among five different general surgical procedures with various penetrance of MIS. METHODS: Following IRB approval, the New York Statewide Planning and Research Cooperative System administrative data were used to identify five common laparoscopic general surgery procedures: cholecystectomy, colectomy, esophageal fundoplication (EF), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) between 2008 and 2012. ICD-9 codes were used to select laparoscopic versus robotic procedures. Procedures were compared based on any complication and hospital length of stay (HLOS). Following descriptive analysis, propensity score analysis was used to estimate the population average differences between patients who underwent robotic-assisted and laparoscopic procedures. RESULTS: There were 1458 patients who had undergone robotic-assisted surgery and 166,790 patients who had undergone laparoscopic surgery among the five procedures between 2008 and 2012. Of the 1458 robotic cases, 186 were cholecystectomy, 307 were RYGB, 118 were SG, 288 were EF, and 559 were colectomy. Initial univariate analysis showed a significantly higher rate of overall complications and HLOS in the laparoscopic group compared to the robotic-assisted group. Laparoscopic colectomy had a significantly higher rate of complications and longer length of stay compared to robotic approaches. No difference in complications or HLOS was seen in the cholecystectomy group. Following propensity score analysis, patients who had undergone robotic-assisted colectomy had significantly lower rate of complications compared to those who underwent conventional laparoscopic procedure (p value = 0.0022). In addition, patients who underwent robotic-assisted SG had on average 1.22 days longer HLOS (p value = 0.0037). CONCLUSION: Robotic approaches may facilitate safer adoption of minimally invasive approaches in areas where penetrance of conventional laparoscopy is low, such as in colorectal surgery.

A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*.

OBJECTIVE: A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. DESIGN: An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. SETTING: Tertiary medical center. PATIENTS: In-hospital cardiac arrest patients (n = 34). MAIN RESULTS: Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). CONCLUSIONS: The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker.

Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help to improve diagnostic accuracy but have a minimal prognostic value. The goals of the current study were to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1750 proteins identified by proteomic analyses, keratin 4 (KRT4) and keratin 17 (KRT17) showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that KRT4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, KRT17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. KRT17 was also highly expressed in immature squamous metaplasia and in endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of KRT17 expression were significantly associated with poor survival of squamous cell carcinoma patients (Hazard ratio=14.76, P=0.01). In summary, both KRT4 and KRT17 expressions are related to the histopathology of the cervical squamous mucosa; KRT17 is highly overexpressed in immature squamous metaplasia, in HSIL, and in squamous cell carcinoma and the level of KRT17 in squamous cell carcinoma may help to identify patients who are at greatest risk for cervical cancer mortality.

Graphene Oxide-Silver-Coated Sulfonated Polyetheretherketone (Ag/GO-SPEEK): A Broad-Spectrum Antibacterial Artificial Bone Implants.

Polyetheretherketone (PEEK), particularly its sulfonated form (SPEEK), has emerged as a promising synthetic biomaterial for artificial bone implants, providing an alternative to conventional titanium metal. However, postoperative infections pose a critical challenge, driven by diverse and antibiotic-resistant bacteria. To address this issue, we propose the modification of the SPEEK surface using a thin graphene oxide (GO) film containing silver (Ag) ions. The resulting coating exhibits substantial antibacterial effects against various pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Experimental assessments elucidate the coating's impact on bacterial adhesion, biofilm formation, and morphology. The results suggest that hindered bacterial growth stems from reduced biofilm production and the controlled release of Ag ions facilitated by the GO coating. The Ag/GO-SPEEK material holds promise as a bioactive implant, addressing the challenges associated with bacterial targeting in bone tissue engineering applications.