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The weight of characters is a crucial step in different population analyses. We propose a new formula to facilitate this while establishing a scale that follows the criteria of the probability of change in each character. This method is described for drawing of median-joining networks, yet it could also be used for other methods in which the weight of the characters is required. Am J Phys Anthropol 143:488-492, 2010. [c] 2010 Wiley-Liss, Inc. KEY WORDS character weight; mathematical scale; median-joining networks DOI 10.1002/ajpa.21366

El título nobiliario de Marqués del Valle del Toxo, conocido comúnmente como Marqués de Yavi, era el más importante en el territorio del virreinato del Río de la Plata y se extendía por toda la Puna argentina y diversos municipios de Bolivia. Hubo cuatro marqueses desde su creación en 1708 por la Real Cédula emitida por Felipe V, rey de España, hasta su disolución en 1820 luego del fallecimiento del cuarto marqués Juan José Feliciano Fernández Campero. La abundancia de referencias históricas sobre el Marquesado de Yavi, el reciente interés político por recuperar la figura histórica del último Marqués sumado al encuentro social de sus descendientes ofreció la extraordinaria posibilidad de realizar una reconstrucción detallada de la genealogía de la familia Campero y relacionarla con el estudio molecular de sus descendientes. Se analizaron muestras de 30 individuos Campero a través de 6 microsatélites del cromosoma Y (DYS:19, 389a y b, 390,392,393) Se encontraron 8 linajes paternos bien definidos, 16 muestras comparten un linaje único, el segundo linaje congrega a 5 individuos, el tercero y cuarto linaje cuentan con 2 individuos cada uno y en 5 muestras se encontraron linajes individuales no relacionados con los anteriores. De estos resultados se interpreta que en la Genealogía Campero coexisten linajes diferentes, de los cuales uno de ellos, el mayoritario, probablemente sea el linaje fundador de esta genealogía. Se discuten estos resultados a la luz de la información genealógica e histórica.

Background: Earlier studies have shown that 1-2mg of 4-hydroxytamoxifen (4-OHT) gel applied to the breast skin reduced cell proliferation in estrogen receptor (ER) positive invasive cancers to a similar degree as oral tamoxifen (TAM), with significantly lower plasma levels. We now report results of a Phase IIB pre-surgical window trial of women with DCIS, designed to obtain pilot data in early lesions. Our ultimate goal is to develop transdermal 4-OHT as an alternative to oral TAM for women at high risk for breast cancer and those with DCIS. The study was closed early because the manufacturer discontinued the drug supply, but remains blinded until all biomarker analysis is complete. Here we report the plasma and breast adipose tissue concentration of TAM metabolites from the topical 4-OHT gel group (4 mg) in comparison with the oral TAM group (20mg). Methods: Women with DCIS were enrolled, and randomized to 4-OHT gel (4mg/day, 2mg per breast, E: Z isomers = 1:1,) or to oral (Z) TAM (20mg/day) for 4-10 weeks before surgery. Blood was collected on the day of surgery, and breast adipose tissue was collected at surgery. There were a total of 22 patients with matched blood and breast adipose tissue. The concentration of TAM metabolites in plasma and breast tissue was determined with liquid chromatography/tandem mass spectrometry. We assumed that the subjects with detectable N-desmethyl TAM (NDT) in plasma belong to the oral TAM group because NDT is not a product of 4-OHT metabolism. Under this assumption, 13 subjects were categorized into oral TAM group, and 9 subjects into the topical 4-OHT group. Wilcoxon rank-sum test was used for statistical analysis. Results: The results are shown in the table. The concentration is presented as mean ± SD; the lowest quantitation limit (LQL) was 1 ng/mL for plasma, and 3 ng/g for tissue. TAM and its metabolites were found in the plasma of the presumed oral TAM group, with high levels of TAM and NDT. In the presumed 4-OHT gel group, only (Z) 4-OHT was found in the plasma although both (E) and (Z) forms were applied. The mean plasma level of 4-OHT in the gel group was 70% lower than the mean of 4-OHT in the oral TAM group (p = 0.004). In breast tissue, similar amounts of (E) and (Z) forms of 4-OHT were found in the 4-OHT gel group, with the (Z) 4-OHT level being equivalent to that in the oral TAM group (p = 0.48). Endoxifen was only found in the oral TAM group. We saw no evidence of further metabolic transformation of 4-OHT in the breast following topical administration. Conclusions: With 4 mg of 4-OHT gel daily applied to the breasts of DCIS patients, the mean plasma level of 4-OHT was significantly lower and the mean breast tissue level of 4-OHT was similar to that in women taking oral TAM 20 mg daily, thus confirming the results from previous studies. We are still evaluating efficacy of topical 4-OHT in terms of reduction of cell proliferation (Ki67). [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers., Methods: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs)., Results: FcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed in TAMs in human glioblastoma, most robustly at diagnosis. Notably, FcE-aCTLA-4-mediated selective depletion of intratumoral regulatory T cells (Tregs) via TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, a chemotherapeutic drug with immunomodulatory functions, was found to upregulate FcγRIIIA on TAMs in glioblastoma patients who received doxorubicin and anti-PD-1 with concomitant LIPU/MB. In murine models of immunotherapy-resistant gliomas, a combinatorial regimen of FcE-aCTLA-4, anti-PD-1, and doxorubicin with LIPU/MB, achieved a 90% cure rate, that was associated robust infiltration of activated CD8+ T cells and establishment of immunological memory as evidenced by rejection upon tumor rechallenge., Conclusions: Our findings demonstrate that FcE-aCTLA-4 promotes robust immunomodulatory and anti-tumor effects in murine gliomas and is significantly enhanced when combined with anti-PD-1, doxorubicin, and LIPU/MB. We are currently investigating this combinatory strategy in a clinical trial (clinicaltrials.gov NCT05864534)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM., (© 2024. The Author(s).)

The pleiotropic nature of the apolipoprotein E ( APOE ) gene is associated with complex diseases in different populations. We analyzed APOE polymorphisms in 76 individuals from Jujuy - Argentina using NGS technology. The observed genotypes align with the expected Hardy-Weinberg equilibrium. APOE3 was the most common allele, followed by APOE4 and APOE2 . The allele distribution pattern is consistent with findings in previously studied populations of Native Americans and Asians. The E4 allele's low frequency, always observed in a heterozygous state, raises questions regarding its relevance in explaining dementia and longevity associated with this marker in the Central Andes., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Aggressive estrogen receptor (ER) positive breast cancer is frequently tamoxifen-resistant; alternative endocrine approaches exist for therapy, but not for prevention, particularly in premenopausal women. We examined the efficacy of the selective ER modulator (Z-endoxifen) as monotherapy and in combination with the selective progesterone receptor modulators (onapristone and ulipristal acetate) in the tamoxifen-insensitive C3(1)/SV40TAg mouse mammary tumorigenesis model. Unlike tamoxifen at human equivalent dose (HED) 101 mg/day, endoxifen at HED 24 mg/day significantly increased latency and reduced tumor growth relative to untreated controls. Ulipristal acetate (UPA) at HED 81 mg/day also significantly increased latency however failed to inhibit tumor growth, while onapristone (HED 98 mg/day) had no tumor prevention efficacy in this model. Addition of UPA to endoxifen did not enhance preventive efficacy over endoxifen alone. The expression of genes associated with cell cycle, cell proliferation and extracellular matrix remodeling was similarly repressed by endoxifen and UPA however only endoxifen significantly downregulated prominent genes associated with poor prognosis (Col11a1, Il17b, Pdgfa, Tnfrsf11a). Our results indicate that endoxifen can prevent breast cancers, even when tamoxifen-resistant, through its role in favorable tissue remodeling and immunomodulation., Competing Interests: Conflict of Interest Statement No potential conflicts of interest were disclosed by all authors., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma., Methods: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m 2 , 80 mg/m 2 , 135 mg/m 2 , 175 mg/m 2 , 215 mg/m 2 , and 260 mg/m 2 ) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual., Findings: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m 2 ), and 12 patients were treated at dose level 6 (260 mg/m 2 ). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m 2 , encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m 2 in the case of the grade 3 encephalopathy, and to 215 mg/m 2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m 2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 μM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562-1·747] in non-sonicated brain to 5·878 μM [3·462-9·980] μM in sonicated brain [5·9-times increase], p=0·0001)., Interpretation: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing., Funding: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family., Competing Interests: Declaration of interests AMS and RS have received in-kind (drug) support from Bristol-Myers Squibb, in-kind (ultrasound devices) and research support from and Carthera, and in-kind (drug) and research support from Agenus. AMS, DYZ, VAA, and RS are co-authors of intellectual property filed by Northwestern University related to therapeutic ultrasound. RS has acted or is acting as a scientific advisor or has served on advisory boards for the following companies: Alpheus Medical, AstraZeneca, Boston Scientific, Carthera, Celularity, GT Medical, Insightec, Lockwood (BlackDiamond), Northwest Biotherapeutics, Novocure, Syneos Health (Boston Biomedical), TriAct Therapeutics, and Varian Medical Systems. RVL is on the scientific advisory board and speakers’ bureau for Merck and on the speakers’ bureau for Novocure; has obtained research support from Bristol-Myers Squibb; and has received honoraria for editing from EBSCO INFORMATION services, Medlink, Neurology, and Elsevier. PK participates in advisory boards for Novocure, Janssen, SDP Oncology, Affinia, Sintetica, Mirati; has done consulting for Biocept, Enclear Therapies, Affinia Therapeutics and Bioclinica; and has received research support from Genentech and Novocure. MC, CD, GB, and AC are employees of Carthera, inventors of patents related to the technology, or have stock ownership in Carthera. AC has received funding support from Horizon 2020 European Innovation Council; is a paid consultant of Carthera; and is part of the Board of Directors of Carthera. JB is vice chair of the Neuro Education Track Subcommittee from the American Society of Anesthesiologists., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prevention Relevance: Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer., (©2022 American Association for Cancer Research.)

The settlement of the Americas has been the focus of incessant debate for more than 100 years, and open questions regarding the timing and spatial patterns of colonization still remain today. Phylogenetic studies with complete human Y chromosome sequences are used as a highly informative tool to investigate the history of human populations in a given time frame. To study the phylogenetic relationships of Native American lineages and infer the settlement history of the Americas, we analyzed Y chromosome Q Haplogroup, which is a Pan-American haplogroup and represents practically all Native American lineages in Mesoamerica and South America. We built a phylogenetic tree for Q Haplogroup based on 102 whole Y chromosome sequences, of which 13 new Argentine sequences were provided by our group. Moreover, 1,072 new single nucleotide polymorphisms (SNPs) that contribute to its resolution and diversity were identified. Q-M848 is known to be the most frequent autochthonous sub-haplogroup of the Americas. The present is the first genomic study of Q Haplogroup in which current knowledge on Q-M848 sub-lineages is contrasted with the historical, archaeological and linguistic data available. The divergence times, spatial structure and the SNPs found here as novel for Q-Z780, a less frequent sub-haplogroup autochthonous of the Americas, provide genetic support for a South American settlement before 18,000 years ago. We analyzed how environmental events that occurred during the Younger Dryas period may have affected Native American lineages, and found that this event may have caused a substantial loss of lineages. This could explain the current low frequency of Q-Z780 (also perhaps of Q-F4674, a third possible sub-haplogroup autochthonous of the Americas). These environmental events could have acted as a driving force for expansion and diversification of the Q-M848 sub-lineages, which show a spatial structure that developed during the Younger Dryas period., Competing Interests: The authors have declared that no competing interests exist.

We report a new form of catalyst based on ferromagnetic hexagonal-close-packed (hcp) Co nanosheets (NSs) for selective CO 2 RR to ethanal, CH 3 CHO. In all reduction potentials tested from -0.2 to -1.0 V (vs RHE) in 0.5 M KHCO 3 solution, the reduction yields ethanal as a major product and ethanol/methanol as minor products. At -0.4 V, the Faradaic efficiency (FE) for ethanal reaches 60% with current densities of 5.1 mA cm -2 and mass activity of 3.4 A g -1 (total FE for ethanal/ethanol/methanol is 82%). Density functional theory (DFT) calculations suggest that this high CO 2 RR selectivity to ethanal on the hcp Co surface is attributed to the unique intralayer electron transfer, which not only promotes [OC-CO]* coupling but also suppresses the complete hydrogenation of the coupling intermediates to ethylene, leading to highly selective formation of CH 3 CHO.

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.

Objective: Hydration status after cardiac surgery can be difficult to assess, often requiring invasive measurements. Bioelectrical impedance vector analysis (BIVA) is based on patterns of resistance (R) and reactance (Xc), corrected by height, and has been used in various clinical scenarios to determine body composition and monitor its changes over time. The purpose of the present study was to apply this method in cardiac surgery patients to assess the variation in hydration status and to compare its changes according to the use of extracorporeal circulation., Design: Single-center, observational, prospective study including patients older than 18 years undergoing elective or urgent cardiac surgery., Setting: Intensive cardiac care unit of a tertiary center in a metropolitan area., Participants: The study comprised 76 patients with a median age of 60 years and mostly undergoing coronary artery bypass grafting (CABG) (n = 47 [61.8%]) with extracorporeal circulation (n = 54 [73%])., Interventions: Bioimpedance was measured with a standard tetrapolar single-frequency bioimpedance meter using a standardized procedure and plotted in an R-Xc graph., Measurements and Main Results: The study demonstrated an increase in total body water immediately after surgery that was sustained until producing hyperhydration 24 hours later. Off-pump CABG was associated with a normal hydration status after surgery, whereas on-pump CABG produced a significant increase in total body water., Conclusions: Fluid status assessment with BIVA in cardiac surgery showed an increase in total body water up to 24 hours after surgery. Off-pump surgery prevented overhydration, which partially could explain the reduction in some of the postoperative complications. BIVA could serve as a useful method for monitoring fluid status in the setting of goal-directed therapy to assist in maintaining euvolemia in cardiac surgical patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference-based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment-related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129-treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3-336) in the oral vs. 2.82 (IQR: 1.4-5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R 2  = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Enabling catalysts to promote multistep chemical reactions in a tandem fashion is an exciting new direction for the green chemistry synthesis of materials. Nanoparticle (NP) catalysts are particularly well suited for tandem reactions due to the diverse surface-active sites they offer. Here, we report that AuPd alloy NPs, especially 3.7 nm Au 42 Pd 58 NPs, catalyze one-pot reactions of formic acid, diisopropoxy-dinitrobenzene, and terephthalaldehyde, yielding a very pure thermoplastic rigid-rod polymer, polybenzoxazole (PBO), with a molecular weight that is tunable from 5.8 to 19.1 kDa. The PBO films are more resistant to hydrolysis and possess thermal and mechanical properties that are superior to those of commercial PBO, Zylon. Cu NPs are also active in catalyzing tandem reactions to form PBO when formic acid is replaced with ammonia borane. Our work demonstrates a general approach to the green chemistry synthesis of rigid-rod polymers as lightweight structural materials for broad thermomechanical applications.

Haplogroup Q originated in Eurasia around 30,000 years ago. It is present in Y-chromosomes from Asia and Europe at rather low frequencies. Since America is undoubtedly one of the continents where this haplogroup is highly represented, it has been defined as one of the founding haplogroups. Its M3 clade has been early described as the most frequent, with pan-American representation. However, it was also possible to find several other haplogroup Q clades at low frequencies. Numerous mutations have been described for haplogroup Q, allowing analysis of its variability and assignment of its geographic origin. We have analyzed 442 samples of unrelated men from Argentina and Paraguay belonging to haplogroup Q; here we report specifically on 27 Q (xM3) lineages. We tested 3 single-nucleotide polymorphisms (SNPs) by amplified product-length polymorphism (APLP) analysis, 3 SNPs for restriction fragment length polymorphism (RFLP) analysis, 15 SNPs by Sanger sequencing, and 17 short tandem repeats (STRs). Our approach allowed us to identify five subhaplogroups. Q-M3 and Q-CTS2730/Z780 are undoubtedly autochthonous lineages and represent the most frequent subhaplogroups, with significant representation in self-defined aboriginal populations, and their autochthonous status has been previously described. The aim of present work was to identify the continental origin of the remaining Q lineages. Thus, we analyzed the STR haplotypes for the samples and compared them with haplotypes described by other authors for the rest of the world. Even when haplogroup Q lineages have been extensively studied in America, some of them could have their origin in post-Columbian human migration from Europe and Middle East.

Tuning the performance of nanoparticle (NP) catalysts by controlling the NP surface strain has evolved as an important strategy to optimize NP catalysis in many energy conversion reactions. Here, we present our new study on using an eigenforce model to predict and experiments to verify the strain-induced catalysis enhancement of the oxygen reduction reaction (ORR) in the presence of L1 0 -CoMPt NPs (M = Mn, Fe, Ni, Cu, Ni). The eigenforce model allowed us to predict anisotropic (that is, two-dimensional) strain levels on distorted Pt(111) surfaces. Experimentally, by preparing a series of 5 nm L1 0 -CoMPt NPs, we could push the ORR catalytic activity of these NPs toward the optimum region of the theoretical two-dimensional volcano plot predicted for L1 0 -CoMPt. The best ORR catalyst in the alloy NP series we studied is L1 0 -CoNiPt, which has a mass activity of 3.1 A/mg Pt and a specific activity of 9.3 mA/cm 2 at room temperature with only 15.9% loss of mass activity after 30 000 cycles at 60 °C in 0.1 M HClO 4 .

An efficient CuPd nanoparticle (NP) catalyst (3 nm CuPd NPs deposited on carbon support) is designed for catalyzing electrochemical allylic alkylation in water/isopropanol (1:1 v/v) and 0.2 m KHCO 3 solution at room temperature. The Pd catalysis was Pd/Cu composition-dependent, and CuPd NPs with a Pd/Cu ratio close to one are the most efficient catalyst for the selective cross-coupling of alkyl halides and allylic halides to form C-C hydrocarbons with product yields reaching up to 99 %. This NP-catalyzed electrochemical allylic alkylation expands the synthetic scope of cross-coupling reactions and can be further extended to other organic reaction systems for developing green chemistry electrosynthesis methods., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Similarly to other populations across the Americas, Argentinean populations trace back their genetic ancestry into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to perform population structure analyses at a sub-continental level. Concerning the Native American ancestry, we could identify four Native American components segregating in modern Argentinean populations. Three of them are also found in modern South American populations and are specifically represented in Central Andes, Central Chile/Patagonia, and Subtropical and Tropical Forests geographic areas. The fourth component might be specific to the Central Western region of Argentina, and it is not well represented in any genomic data from the literature. As for the European and African ancestries, we confirmed previous results about origins from Southern Europe, Western and Central Western Africa, and we provide evidences for the presence of Northern European and Eastern African ancestries., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PL provides consulting services to myDNAmap S.L. JMB and JZ are employed by Biocódices S.A. HD is the scientific director of Biocódices S.A. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: Paclitaxel shows little benefit in the treatment of glioma due to poor penetration across the blood-brain barrier (BBB). Low-intensity pulsed ultrasound (LIPU) with microbubble injection transiently disrupts the BBB allowing for improved drug delivery to the brain. We investigated the distribution, toxicity, and efficacy of LIPU delivery of two different formulations of paclitaxel, albumin-bound paclitaxel (ABX) and paclitaxel dissolved in cremophor (CrEL-PTX), in preclinical glioma models., Experimental Design: The efficacy and biodistribution of ABX and CrEL-PTX were compared with and without LIPU delivery. Antiglioma activity was evaluated in nude mice bearing intracranial patient-derived glioma xenografts (PDX). Paclitaxel biodistribution was determined in sonicated and nonsonicated nude mice. Sonications were performed using a 1 MHz LIPU device (SonoCloud), and fluorescein was used to confirm and map BBB disruption. Toxicity of LIPU-delivered paclitaxel was assessed through clinical and histologic examination of treated mice., Results: Despite similar antiglioma activity in vitro , ABX extended survival over CrEL-PTX and untreated control mice with orthotropic PDX. Ultrasound-mediated BBB disruption enhanced paclitaxel brain concentration by 3- to 5-fold for both formulations and further augmented the therapeutic benefit of ABX. Repeated courses of LIPU-delivered CrEL-PTX and CrEL alone were lethal in 42% and 37.5% of mice, respectively, whereas similar delivery of ABX at an equivalent dose was well tolerated., Conclusions: Ultrasound delivery of paclitaxel across the BBB is a feasible and effective treatment for glioma. ABX is the preferred formulation for further investigation in the clinical setting due to its superior brain penetration and tolerability compared with CrEL-PTX., (©2019 American Association for Cancer Research.)

While various effects of physicochemical parameters (e.g., size, facet, composition, and internal structure) on the catalytic efficiency of nanozymes (i.e., nanoscale enzyme mimics) have been studied, the strain effect has never been reported and understood before. Herein, we demonstrate the strain effect in nanozymes by using Pd octahedra and icosahedra with peroxidase-like activities as a model system. Strained Pd icosahedra were found to display 2-fold higher peroxidase-like catalytic efficiency than unstrained Pd octahedra. Theoretical analysis suggests that tensile strain is more beneficial to OH radical (a key intermediate for the catalysis) generation than compressive strain. Pd icosahedra are more active than Pd octahedra because icosahedra amplify the surface strain field. As a proof-of-concept demonstration, the strained Pd icosahedra were applied to an immunoassay of biomarkers, outperforming both unstrained Pd octahedra and natural peroxidases. The findings in this research may serve as a strong foundation to guide the design of high-performance nanozymes.

Purpose: Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors., Patients and Methods: In a double-blind presurgical window trial of oral telapristone acetate (TPA) 12 mg daily versus placebo, 70 patients with early-stage breast cancer were randomized 1:1 (stratified by menopause) and treated for 2 to 10 weeks. The primary endpoint was change in Ki67 between diagnostic biopsy and surgical specimens. Gene expression pre- and posttherapy was assessed using RNA-sequencing and gene set enrichment analysis was performed to determine pathways enriched in response to TPA and placebo treatments., Results: Among 61 evaluable women (29 placebo and 32 telapristone acetate), 91% of tumors were ER/PR positive. The mean Ki67 declined by 5.5% in all women treated with telapristone acetate ( P = 0.003), and by 4.2% in all women treated with placebo ( P = 0.04). After menopausal stratification, the Ki67 decline remained significant in 22 telapristone acetate-treated premenopausal women ( P = 0.03). Differential gene expression analysis showed no significant modulation overall. However, in a subset of tumors that demonstrated ≥30% relative reduction in Ki67 in the telapristone acetate group, genes related to cell-cycle progression, and those in the HER2 amplicon were significantly downregulated. In contrast, no significantly enriched pathways were identified in the placebo group., Conclusions: Patients treated with telapristone acetate whose Ki67 decreased by ≥30% demonstrated a selective antiproliferative signal, with a potentially important effect on HER2 amplicon genes. Evaluation of SPRMs in a neoadjuvant trial is merited, with attention to predictors of response to SPRM therapy, and inclusion of pre- and postmenopausal women., (©2019 American Association for Cancer Research.)