A harmonized public resource of deeply sequenced diverse human genomes.

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also show substantial added value from this data set compared with the prior versions of the component resources, typically combined via liftOver and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared with previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality-control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.

Multiracial Reading the Mind in the Eyes Test (MRMET): An inclusive version of an influential measure.

Can an inclusive test of face cognition meet or exceed the psychometric properties of a prominent less inclusive test? Here, we norm and validate an updated version of the influential Reading the Mind in the Eyes Test (RMET), a clinically significant neuropsychiatric paradigm that has long been used to assess theory of mind and social cognition. Unlike the RMET, our Multiracial Reading the Mind in the Eyes Test (MRMET) incorporates racially inclusive stimuli, nongendered answer choices, ground-truth referenced answers, and more accessible vocabulary. We show, via a series of large datasets, that the MRMET meets or exceeds RMET across major psychometric indices. Moreover, the reliable signal captured by the two tests is statistically indistinguishable, evidence for full interchangeability. We thus present the MRMET as a high-quality, inclusive, normed and validated alternative to the RMET, and as a case in point that inclusivity in psychometric tests of face cognition is an achievable aim. The MRMET test and our normative and validation data sets are openly available under a CC-BY-SA 4.0 license at osf.io/ahq6n.

Antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses.

Atmospheric-pressure, non-thermal plasma destroys microorganisms by directly reacting with hydrocarbon molecules in the cell wall and/or by damaging the cytoplasmic membrane, proteins, and DNA with charged particles and reactive species. The aim of our study was to evaluate the antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses on various pathogen preparations. The resultant antibacterial and anticandidal effects were assessed by evaluating percent and log reduction values for pathogen colonies. Nitrogen-plasma pulses emitted at an energy of 1.5 J and argon-plasma pulses generated at 0.5 J elicited remarkable antibacterial effects on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) and anticandidal effects on Candida albicans. Nitrogen-plasma pulses at a pulse count of five elicited remarkable antibacterial effects on Cutibacterium acnes at the energy settings of 1.75, 2.5, and 3 J, but not at 1 J. Meanwhile, argon-plasma pulses showed antibacterial effects on C. acnes at an energy of 0.5 and 0.65 J. Nitrogen- or argon-plasma pulses exert antibacterial and anticandidal effects on bacterial and fungal pathogens.

Lupeol-induced nitric oxide elicits apoptosis-like death within Escherichia coli in a DNA fragmentation-independent manner.

Lupeol is known to be plentiful in fruits or plant barks and has an antimicrobial effect, however, its mode of action(s) has yet to be determined. To elucidate lupeol generates nitric oxide (NO), which is recognized for possessing an antimicrobial activity, intracellular NO was measured in Escherichia coli using DAF-FM. Using the properties of NO passing through plasma membrane easily, increased malondialdehyde levels have shown that lupeol causes lipid peroxidation, and the resulting membrane depolarization was confirmed by DiBAC4(3). These data indicated that lupeol-induced NO is related to the destruction of bacterial membrane. Further study was performed to examine whether NO, known as a cell proliferation inhibitor, affects bacterial cell division. As a result, DAPI staining verified that lupeol promotes cell division arrest, and followed by early apoptosis is observed in Annexin V/PI double staining. Even though these apoptotic hallmarks appeared, the endonuclease failed to perform properly with supporting data of decreased intracellular Mg2+ and Ca2+ levels without DNA fragmentation, which is confirmed using a TUNEL assay. These findings indicated that lupeol-induced NO occurs DNA fragmentation-independent bacterial apoptosis-like death (ALD). Additionally, lupeol triggers DNA filamentation and morphological changes in response to DNA repair system called SOS system. In accordance with the fact that ALD deems to SOS response, and that the RecA is considered as a caspase-like protein, increase in caspase-like protein activation occurred in E. coli wild-type, and no ΔRecA mutant. In conclusion, these results demonstrated that the antibacterial mode of action(s) of lupeol is an ALD while generating NO.

Contribution of SOS genes to H2O2-induced apoptosis-like death in Escherichia coli.

Hydrogen peroxide (H2O2) is a debriding agent that damages the microbial structure and function by generating various reactive oxygen species (ROS). H2O2-produced hydroxyl radical (OH∙) also exerts oxidative stress on microorganisms. The spread of antibiotic-resistance in bacteria is a serious issue worldwide, and greater efforts are needed to identify and characterize novel antibacterial mechanisms to develop new treatment strategies. Therefore, this study aimed to clarify the relationship between H2O2 and Escherichia coli and to elucidate a novel antibacterial mechanism(s) of H2O2. Following H2O2 exposure, increased levels of 8-hydroxydeoxyguanosine and malondialdehyde indicated that H2O2 accelerates oxidation of bacterial DNA and lipids in E. coli. As oxidative damage worsened, the SOS response was triggered. Cell division arrest and resulting filamentous cells were identified in cells, indicating that LexA was involved in DNA replication. It was also verified that RecA, a representative SOS gene, helps self-cleavage of LexA and acts as a bacterial caspase-like protein. Our findings also showed that dinF is essential to preserve E. coli from H2O2-induced ROS, and furthermore, demonstrated that H2O2-induced SOS response and SOS genes participate differently in guarding E. coli from oxidative stress. As an extreme SOS response is considered apoptosis-like death (ALD) in bacteria, additional experiments were performed to examine the characteristics of ALD. DNA fragmentation and membrane depolarization appeared in H2O2-treated cells, suggesting that H2O2 causes ALD in E. coli. In conclusion, our investigations revealed that ALD is a novel antibacterial mode of action(s) of H2O2 with important contributions from SOS genes.

Naringin-generated ROS promotes mitochondria-mediated apoptosis in Candida albicans.

Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O2- ) and hydroxyl radicals (OH- ). Reactive oxygen species (ROS) have a serious impact on Ca2+ signaling and the production of mitochondrial ROS. After exposure to enhanced O2- and OH- , mitochondrial Ca2+ overload and mitochondrial O2- generation were confirmed in C. albicans. It was verified that mitochondrial O2- transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca2+ accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin-generated O2- and OH- damage the mitochondria and that mitochondrial dysfunction-mediated apoptosis is novel antifungal mechanism of naringin.

Cognitive test scores vary with choice of personal digital device.

Mobile- and web-based psychological research are a valuable addition to the set of tools available for scientific study, reducing logistical barriers for research participation and allowing the recruitment of larger and more diverse participant groups. However, this comes at the cost of reduced control over the technology used by participants, which can introduce new sources of variability into study results. In this study, we examined differences in measured performance on timed and untimed cognitive tests between users of common digital devices in 59,587 (Study 1) and 3818 (Study 2) visitors to TestMyBrain.org , a web-based cognitive testing platform. Controlling for age, gender, educational background, and cognitive performance on an untimed vocabulary test, users of mobile devices, particularly Android smartphones, showed significantly slower performance on tests of reaction time than users of laptop and desktop computers, suggesting that differences in device latency affect measured reaction times. Users of devices that differ in user interface (e.g. screen size, mouse vs. touchscreen) also show significant differences (p < 0.001) in measured performance on tests requiring fast reactions or fine motor movements. By quantifying the contribution of device differences to measured cognitive performance in an online setting, we hope to improve the accuracy of mobile- and web-based cognitive assessments, allowing these methods to be used more effectively.

Nitric oxide-inducing Genistein elicits apoptosis-like death via an intense SOS response in Escherichia coli.

Increasing prevalence of multidrug-resistant untreatable infections has prompted researchers to trial alternative treatments such as a substitute for traditional antibiotics. This study endeavored to elucidate the antibacterial mechanism(s) of this isoflavone, via analysis of relationship between genistein and Escherichia coli. Furthermore, this investigation analyzed whether genistein generates nitric oxide (NO) in E. coli as NO contributes to cell death. RecA, an essential protein for the bacterial SOS response, was detected through western blot, and the activated caspases decreased without RecA. The results showed that the NO induced by genistein affected the bacterial DNA. Under conditions of acute DNA damage, an SOS response called apoptosis-like death occurred, affecting DNA repair. These results suggested that RecA was bacterial caspase-like protein. In addition, NO was toxic to the bacterial cells and induced dysfunction of the plasma membrane. Thus, membrane depolarization and phosphatidylserine exposure were observed similarly to eukaryotic apoptosis. In conclusion, the combined results demonstrated that the antibacterial mode of action(s) of genistein was a NO-induced apoptosis-like death, and the role of RecA suggested that it contributed to the SOS response of NO defense. KEY POINTS: • Genistein generates nitric oxide in E. coli. • Genistein exhibits intense SOS response in E. coli. • Genistein-induced NO causes apoptosis-like death in E. coli.

Effects of argon and nitrogen plasma pulses on the skin and skin appendages in an in vivo animal model.

BACKGROUND: For medical purposes, plasma can be generated from inert gaseous sources in a device by ultra-high-frequency generators and emitted to target tissue at a pulse duration in the milliseconds. OBJECTIVE: To evaluate argon and nitrogen plasma pulse-induced tissue reactions in the skin and skin appendages of an in vivo animal model. METHODS: Argon and nitrogen plasma pulses were non-invasively delivered to in vivo rat skin at various experimental settings. Specimens were histologically evaluated following hematoxylin and eosin and Masson's trichrome staining. RESULTS: At low-energy settings of 1.0, 1.5, and 2.0 J, nitrogen plasma treatments generated noticeable tissue coagulation at the depths of 31.5 ± 8.3, 94.9 ± 16.9, and 171.6 ± 19.7 µm, respectively, at Day 0. At high-energy settings of 2.5 and 3.0 J, nitrogen plasma treatments generated marked tissue coagulation at the depths of 381.7 ± 33.6 µm and 456.3 ± 75.7 µm, respectively, at Day 0. CONCLUSIONS: Treatment with argon plasma induces microscopic changes in the epidermis, dermis, and sebaceous glands without generating excessive thermal injury, whereas that with nitrogen plasma elicits energy-dependent thermal coagulation in the epidermis and dermis with remarkable neocollagenesis.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Sequential delivery of long-pulsed 755-nm alexandrite laser and long-pulsed 1,064-nm neodymium:yttrium-aluminum-garnet laser treatment for pigmented disorders.

BACKGROUND: Long-pulsed (LP) lasers at pulse durations of 1-300 ms have been used to destroy nests of nevi cells by selectively targeting pigment chromophores. OBJECTIVE: To evaluate dual-wavelength LP laser-induced tissue reactions. METHODS: The patterns of LP 755-nm alexandrite (Alex) and/or 1064-nm neodymium (Nd):yttrium-aluminum-garnet (YAG) laser-induced tissue reactions were macroscopically evaluated using a tattoo-embedded phantom. Additionally, a pilot in vivo human study was performed for common acquired melanocytic nevus, of which dermoscopic images and high-speed cinematographs were obtained. RESULTS: Combinations of Nd:YAG and Alex laser treatments at interpulse intervals of 10 or 20 ms generated round to oval zones of photothermal and photoacoustic injury in two distinctive areas containing disintegrated tattoo particles. Treatment at interpulse intervals of 10 or 20 ms between Alex and Nd:YAG pulses elicited lesser degrees of thermal damage to surrounding tissues, compared to treatment at 100 or 200 ms. Immediately after combined LP laser treatment of human nevus lesions in vivo, Nd:YAG-Alex treatment at a 20-ms interpulse interval exhibited more remarkable crusting and erosive appearances than Alex-Nd:YAG treatment. CONCLUSION: For treating pigmented disorders, sequential delivery of LP Nd:YAG and Alex pulses at short interpulse intervals of 10-20 ms can effectively destroy nests of pigment chromophores.

Broadband light treatment using static operation and constant motion techniques for skin tightening in Asian patients.

BACKGROUND: Broadband light (BBL) devices irradiate photons of different wavelength to induce photothermal reactions on various aging-related chromophores. OBJECTIVES: To evaluate three BBL treatment settings for skin tightening in Asian patients. METHODS: A total of 27 patients underwent three sessions of BBL treatment via (1) an 800-nm cutoff filter using a static operation technique and a 695-nm cutoff filter using a constant motion technique (group 1, N = 9), (2) an 800-nm cutoff filter using a constant motion technique (group 2, N = 9), and (3) a 590-nm cutoff filter using a constant motion technique (group 3, N = 9). RESULTS: The patients in group 1 presented marked clinical improvements in zygomatic wrinkles, nasolabial folds, and marionette lines, with a median overall global aesthetic improvement scale (GAIS) score of 3. Meanwhile, patients in group 2 exhibited noticeable improvements in zygomatic wrinkles, nasolabial folds, perioral expression wrinkles at the cheek, and marionette lines, with a median GAIS score of 3. Patients in group 3 experienced improvement in skin tone and texture, zygomatic wrinkles, nasolabial folds, and marionette lines, with a median GAIS score of 2. CONCLUSIONS: Our data demonstrated that BBL treatment for nonablative, noninvasive skin tightening elicits satisfactory clinical outcomes.

Pattern analysis of 532- and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin.

Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532 nm and 1064 nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5 µm × 70.2 ± 17.3 µm (31-mm distance step) and 91.0 ± 44.7 µm × 81.2 ± 36.3 µm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1 µm × 83.3 ± 37.4 µm (single-pulse mode) and 100.8 ± 40.4 µm × 83.1 ± 29.4 µm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.

Multimodal Approach for Treating Horizontal Neck Wrinkles Using Intensity Focused Ultrasound, Cohesive Polydensified Matrix Hyaluronic Acid, and IncobotulinumtoxinA.

BACKGROUND: For the restoration of horizontal neck wrinkles, multimodal approaches using neuromodulators, intensity focused ultrasound (IFU), and fine line fillers are recommended. OBJECTIVE: To evaluate the efficacy and safety of a 1-day, multimodal approach for horizontal neck wrinkles. METHODS: Twelve female patients with horizontal neck wrinkles were treated with a combined treatment of IFU, cohesive polydensified matrix hyaluronic acid (CPMHA), and incobotulinumtoxinA. Therapeutic outcomes were assessed on Day 0 and 1, 2, 3, and 6 months thereafter. RESULTS: Horizontal neck wrinkles decreased significantly in length from a median at baseline of 269.75 mm (interquatile range [IQR], 235.35-302.94 mm) to 91.5 mm (IQR, 51.4-108.61 mm) at 1 month, 92.3 mm (IQR, 69.66-132.07 mm) at 2 months, 101.88 mm (IQR, 86-146.77 mm) at 3 months, and 109.48 mm (IQR, 85.06-148.17 mm) at 6 months after the combined treatment. The median global aesthetic improvement scale scores were 3.5 (IQR, 2-4) at 1 month, 3 (IQR, 3-3.5) at 2 months, 3 (IQR, 2-4) at 3 months, and 3 (IQR, 3-3) at 6 months. Post-treatment petechiae resolved completely within 7 days, and CPMHA-induced lumps disappeared within 1 month. CONCLUSION: The present data demonstrated that the multimodal, combined treatment used in the present study provides satisfactory and long-lasting therapeutic outcomes by targeting different pathogenetic factors of horizontal neck wrinkles.

Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss: an evaluator-blinded, split-scalp study.

Laser- or light-assisted therapies have been used to improve the perifollicular environment by upregulating the expression of growth factors and signaling molecules for hair restoration. The aim of our study was to preclinically and clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an in vivo human skin environmental scanning electron microscopy (ESEM) study were performed with different power and energy settings. Thereafter, an evaluator-blinded, split-scalp study was conducted to evaluate hair thickness and density in 10 PHL patients treated with 12 sessions of fractionated thulium laser treatment with or without post-laser treatment application of a growth factor-containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped zones of thulium laser-induced tissue coagulation (LITC) were noted immediately after treatment in the epidermis and upper to mid-dermis without remarkable ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non-ablative LITC on the surface of the stratum corneum of a human subject immediately after laser irradiation. In PHL patients, 12 sessions of thulium laser monotherapy at 1-week intervals resulted in significantly increased hair density and thickness. Post-laser treatment application of GF solution offered additional therapeutic efficacy by improving hair density and thickness on the split scalp. The use of a fractionated thulium laser with or without post-laser therapy application of GF solution to treat PHL elicited remarkable improvements in hair thickness and hair counts.

Investigation on the Cutaneous Change Induced by Face-Lifting Monodirectional Barbed Polydioxanone Thread.

BACKGROUND: Owing to its potentially greater mechanical force on the implanted tissue, barbed thread is frequently used in face-lifting procedures. However, the long-term durability thereof remains controversial. Moreover, reports on underlying histologic and molecular changes resulting from face-lifting procedures are scarce. OBJECTIVE: To evaluate histologic and molecular changes induced by absorbable, barbed face-lifting thread in an animal model. MATERIALS AND METHODS: Fragments of monofilament, monodirectionally barbed polydioxanone thread were implanted in dorsal skin from 12 guinea pigs. Tissue samples were harvested at 1, 3, and 7 months thereafter. Histopathologic analysis and quantification of Type 1 collagen and transforming growth factor beta 1 (TGF-ß1) levels were performed. RESULTS: Implantation of a single fragment induced fibrous capsule around the thread. Tissue reactions were strongest at 1 month after implantation, showing marked infiltration of inflammatory cells and fibroblasts, which gradually decreased. On molecular analysis, Type 1 collagen and TGF-ß1 levels were significantly increased, compared to normal skin, throughout the 7-month study period. CONCLUSION: Our results suggest that implantation of barbed thread induces strong anchorage to skin tissue. Quantitative analysis of collagen and its downstream signaling molecule TGF-ß supports the long-term durability of the thread. Therefore, the authors expect potential beneficial effect for rejuvenation on its clinical application.

Pressure- and dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution for the treatment of atrophic skin disorders.

BACKGROUND: Needleless transcutaneous pneumatic injections (TPIs) are a minimally invasive way to deliver the solution into the skin for therapeutic purposes. The suggested action mechanisms of TPI therapy include mechanical stimulation, immediate tissue shrinkage and late wound healing. METHODS: Thirteen Korean patients were treated with TPI for atrophic skin disorders, including acne scars, striae albae, post-furuncle, or carbuncle scars, and horizontal wrinkles with lipoatrophy. At each TPI treatment session, a single pass was made along with the atrophic skin lesions without overlapping. Thereafter, two dermatologists objectively evaluated the clinical improvement in the lesions in the photographs via the global aesthetic improvement scale (GAIS). RESULTS: One month after the final treatment, the overall mean GAIS score was 2.3 ± 0.8. Six of the 13 (46.2%) patients exhibited clinical improvement of grade 3, five (38.5%) patients grade 2 and two (15.4%) patients grade 1. The overall mean subjective satisfaction score with the TPI treatment was 2.3 ± 0.9. Six of the 13 (46.2%) patients achieved subjective satisfaction of grade 3, six (46.2%) patients grade 2 and one (7.7%) patient grade 0. CONCLUSIONS: The present study demonstrated that the TPI treatment is effective and safe for treating atrophic skin disorders of varying causes in Korean patients.

The critical size of hydrogen-bonded alcohol clusters as effective Brønsted bases in solutions.

The alkyl oxonium ion, which is a protonated alcohol, has long been proposed as a key reaction intermediate in alcohol dehydration. Nonetheless, the dynamics and structure of this simple but important intermediate species have not been adequately examined due to the transient nature of the oxonium ion. Here, we devised a model system for the key step in the alcohol dehydration reaction, in which a photoacid transfers a proton to alcohols of different basicity in the acetonitrile solvent. Using time-resolved spectroscopy and computation, we have found that the linkage of at least two alcohol molecules via hydrogen bonding is critical for their enhanced reactivity and extraction of the proton from the acid. This finding addresses the cooperative role of the simplest organic protic compounds, namely alcohols, in nonaqueous acid-base reactions.

Metastatic melanomas of unknown primary show better prognosis than those of known primary: a systematic review and meta-analysis of observational studies.

BACKGROUND: Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion. OBJECTIVE: We sought to identify the prognosis of MUP compared with melanoma of known primary (MKP). METHODS: We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP. RESULTS: Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP. LIMITATIONS: Diverse observational studies were reviewed, and selection and reporting biases are possible. CONCLUSIONS: The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage.

Synergistic growth of nickel and platinum nanoparticles via exsolution and surface reaction.

Bimetallic catalysts combining precious and earth-abundant metals in well designed nanoparticle architectures can enable cost efficient and stable heterogeneous catalysis. Here, we present an interaction-driven in-situ approach to engineer finely dispersed Ni decorated Pt nanoparticles (1-6 nm) on perovskite nanofibres via reduction at high temperatures (600-800 oC). Deposition of Pt (0.5 wt%) enhances the reducibility of the perovskite support and promotes the nucleation of Ni cations via metal-support interaction, thereafter the Ni species react with Pt forming alloy nanoparticles, with the combined processes yielding smaller nanoparticles that either of the contributing processes. Tuneable uniform Pt-Ni nanoparticles are produced on the perovskite surface, yielding reactivity and stability surpassing 1 wt.% Pt/γ-Al2O3 catalysts for CO oxidation. This approach heralds the possibility of in-situ fabrication of supported bimetallic nanoparticles with engineered compositional distributions and performance.