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The article "The Prairie Dog Conundrum" explores the complex relationship between prairie dogs and humans in the Western U.S. Prairie dogs, once abundant, are now among the most maligned and persecuted animal species in the region. Despite being considered pests, prairie dogs play a crucial role as ecosystem engineers, supporting the survival of various species like black-footed ferrets and mountain plovers. Efforts are being made to conserve prairie dogs and the prairie ecosystems that depend on them, with researchers exploring innovative methods like tracking collars and oral vaccines to protect prairie dogs from threats like plague. [Extracted from the article]

The article explores the issue of protecting migration routes for mule deer, pronghorn, and elk in the Western United States. These animals rely on these routes to find food and survive harsh conditions, but their paths are increasingly obstructed by human development. Conservation efforts face opposition from lawmakers, landowners, and industry leaders. The article emphasizes the importance of tracking and mapping these migrations and highlights the significance of migration for the survival and well-being of these species. It specifically focuses on the efforts in Wyoming to protect migration corridors for mule deer and pronghorn, including the designation of corridors and the implementation of measures like easements and wildlife overpasses. However, challenges remain, such as resistance from some landowners and ongoing development. The article also discusses the need for collaboration among stakeholders to ensure the preservation of migration routes. [Extracted from the article]

IMPORTANCE: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress. OBJECTIVE: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing. DESIGN, SETTING, AND PARTICIPANTS: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US residents, and had access to the internet and a health care professional. Previous cancer genetic testing or counseling was exclusionary. In the family history cohort, participants had a personal or family history of breast or ovarian cancer. In the familial pathogenic variant (PV) cohort, participants reported 1 biological relative with a PV in an actionable cancer susceptibility gene. Data analysis was performed between December 13, 2020, and May 31, 2023. INTERVENTION: Participants completed baseline questionnaires, watched an educational video, and were randomized to 1 of 4 arms: the control arm with pretest and/or posttest genetic counseling, or 1 of 3 study arms without pretest and posttest counseling. Genetic counseling was provided by phone appointments and testing was done using home-delivered saliva kits. MAIN OUTCOMES AND MEASURES: The primary outcome was participant distress measured by the Impact of Event Scale 3 months after receiving the results. Secondary outcomes included completion of testing, anxiety, depression, and decisional regret. RESULTS: A total of 3839 women (median age, 44 years [range 22-91 years]), most of whom were non-Hispanic White and college educated, were randomized, 3125 in the family history and 714 in the familial PV cohorts. In the primary analysis in the family history cohort, all experimental arms were noninferior for distress at 3 months. There were no statistically significant differences in anxiety, depression, or decisional regret at 3 months. The highest completion rates were seen in the 2 arms without pretest counseling. CONCLUSIONS AND RELEVANCE: In the MAGENTA clinical trial, omitting individualized pretest counseling for all participants and posttest counseling for those without PV during remote genetic testing was not inferior with regard to posttest distress, providing an alternative care model for genetic risk assessment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02993068

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment−naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. MAIN OUTCOMES AND MEASURES: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. RESULTS: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. CONCLUSIONS AND RELEVANCE: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.

Binfet wanted to know whether a lion had killed this calf, and if so, whether the calf was infected with chronic wasting disease, or CWD, when it died. Binfet also wanted to know if anecdotal stories about lions and coyotes avoiding the carcasses of deer killed by CWD were true, or just that - stories. FEATURE JUSTIN BINFET, A BIOLOGIST with the Wyoming Game and Fish Department, strode down a sagebrush-covered hill in the Deer Creek Range of central Wyoming, his phone in his hand. While Binfet and his team concentrate on lions, Jakopak focuses on deer. [Extracted from the article]

Introduction: Antibiotic use is a risk factor for Clostridioides difficileinfection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. Methods: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficilewas identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. Results: On univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05–4.36] p= 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09–6.50] p= 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseriwere associated with protection from severe CDI (p< 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. Conclusion: Use of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53mutation and/or deletion, ATMdeletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10–4sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were in MRD + CR at venetoclax initiation). U-MRD4 at 12mo was 57%. 32/45 (71%) had U-MRD at the completion of venetoclax: 22/32 stopped ibrutinib; 10 continued ibrutinib. At a median of 41 months from venetoclax initiation, 5/45 patients have progressed; none have died from CLL or Richter Transformation. In 32 patients with BM U-MRD4, peripheral blood (PB) MRD4 was analyzed every 6 months; 10/32 have had PB MRD re-emergence at a median of 13 months post-venetoclax. In summary, the addition of venetoclax in patients treated with ≥12mo of ibrutinib achieved high rate of BM U-MRD4 and may achieve durable treatment-free remission.

IMPORTANCE: Previously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors’ previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures. OBJECTIVE: To examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral robotic surgery plus RT/CRT for OPC at a single-institution comprehensive cancer center. EXPOSURES: Adherence to speech pathology swallowing intervention during RT coded as (1) eat: oral intake at end of RT (nothing by mouth [NPO]; partial oral intake [PO], with feeding tube [FT] supplement; full PO); and (2) exercise: swallowing exercise adherence (nonadherent vs partial/full adherence). MAIN OUTCOMES AND MEASURES: Feeding tube and diet (Performance Status Scale for Head and Neck Cancer) patient-reported swallowing-related quality of life (MD Anderson Dysphagia Inventory; MDADI) and clinician-graded dysphagia severity grade (videofluoroscopic Dynamic Imaging Grade of Swallowing Toxicity; DIGEST) were collected at baseline, 3 to 6 months, and 18 to 24 months post-RT. RESULTS: A total of 595 patients (mean [SD] age, 65 [10] years; 532 [89%] male) who underwent primary RT (111 of 595 [19%]), CRT (434 of 595 [73%]), or primary transoral robotic surgery plus RT/CRT (50 of 595 [8%]) were included in this cohort study. At the end of RT, 55 (9%) patients were NPO, 115 (19%) were partial PO, 425 (71%) were full PO, and 340 (57%) reported exercise adherence. After multivariate adjustment, subacute return to solid diet and FT were independently associated with oral intake (odds ratio [OR], 2.0; 95% CI, 1.0-4.1; OR, 0.1; 95% CI, 0.0-0.2, respectively) and exercise (OR, 2.9; 95% CI, 1.9-4.5; OR, 0.3; 95% CI, 0.1-0.5, respectively). Subacute MDADI (β = 6.5; 95% CI, 1.8-11.2), FT duration (days; β = −123.4; 95% CI, −148.5 to −98.4), and less severe dysphagia per DIGEST (OR, 0.6; 95% CI, 0.3-1.0) were independently associated with oral intake, while exercise was independently associated with less severe laryngeal penetration/aspiration per DIGEST-safety (OR, 0.7; 95% CI, 0.4-1.0). DIGEST grade associations with oral intake were not preserved long-term; however, exercise was associated with a higher likelihood of solid diet intake and better swallow safety per DIGEST. CONCLUSIONS AND RELEVANCE: The findings of this cohort study extend the authors’ previously published findings that oral intake and swallowing exercise during RT are associated with favorable functional outcomes, now demonstrated with broader domains of function using validated measures. Patterns of benefit differed in this study. Specifically, better subacute recovery of swallow-related quality of life and less severe dysphagia were found among patients who maintained oral intake independent of exercise adherence, and shorter FT utilization and better long-term diet and swallowing safety were found among those who exercised independent of oral intake.

THE FUTURES OF CONSERVATION THE GOLDEN EAGLE did not fly, even when Hannah Nikonow pulled over, climbed out of her car and approached the bird on a cold January day. From 2008 to 2018 in Arizona, thanks in part to a consistent hunter-education campaign, 88% of hunters in a major deer-hunting area located in critical condor habitat either switched to non-lead ammunition or removed their gut piles from the field. Wyoming hunter Erik Kramer picked up his first box of non-lead bullets after drawing a tag for a special hunt in Grand Teton National Park, which required non-lead ammo. The debate over the use of lead bullets by hunters has been brewing for years in hunting and conservation communities. [Extracted from the article]

Richter’s Syndrome (RS) is an aggressive transformation of CLL, usually clonally-related diffuse large B-cell lymphoma (DLBCL), characterized by frequent TP53 mutations, intrinsic chemoresistance and poor survival. TP53-independent treatments are needed. We conducted a single center, phase 2, investigator-initiated study of high dose blinatumomab (maximum 112 mcg/d after initial, weekly dose escalation), NCT03121534, given for an 8-week induction and 4-week consolidation cycle. Responses were assessed by Lugano 2014 criteria. Serial multi-parameter flow cytometry from blood was performed to identify patient-specific biomarkers for response. Nine patients were treated. Patients had received a median of 4 and 2 prior therapies for CLL and RS, respectively. Five of 9 had del(17p) and 100% had complex karyotype. Four patients had reduction in nodal disease, including one durable complete response lasting >1 y. Treatment was well tolerated, with no grade >3 cytokine release syndrome and 1 case of grade 3, reversible neurotoxicity. Immunophenotyping demonstrated the majority of patients expressed multiple immune checkpoints, especially PD1, TIM3 and TIGIT. The patient who achieved CR had the lowest levels of immune checkpoint expression. Simultaneous targeting with immune checkpoint blockade, especially PD1 inhibition, which has already demonstrated single-agent efficacy in RS, could achieve synergistic killing and enhance outcomes.

Understanding the dynamic changes at the active site during catalysis is a fundamental challenge that promises to improve catalytic properties. While performing Arrhenius studies during H2oxidation over Au/TiO2catalysts, we found different apparent activation energies (Eapp) depending on the feedwater pressure. This is partially attributed to changing numbers of metal–support interface (MSI) sites as water coverage changes with temperature. Constant water coverage studies showed two kinetic regimes: fast heterolytic H2activation directly at the MSI (Eapp∼ 25 kJ/mol) and significantly slower heterolytic H2activation mediated by water (Eapp∼ 45 kJ/mol). The two regimes had significantly different kinetics, suggesting a complicated mechanism of water poisoning. Density functional theory (DFT) showed water has minor effects on the reaction thermodynamics, primarily attributable to intrinsic differences in surface reactivity of different Au sites in the DFT model. The DFT model suggested significant surface restructuring of the TiO2support during heterolytic H2adsorption; evidence for this phenomenon was observed during in situinfrared spectroscopy experiments. A monolayer of water on the hydroxylated TiO2surface increased the H2dissociation activation barrier by ∼0.2 eV, in good agreement the difference in experimentally measured values. DFT calculations suggested H2activation goes through a proton-coupled electron-transfer-like mechanism. During proton transfer to a basic support hydroxyl group, electron density is distributed through the gold nanorod and partially localized on the protonated support hydroxyl group. Water slows H2activation by slowing this H+transfer, forcing negative charge buildup on the Au and increasing the transition state energy.

Patients with chronic lymphocytic leukemia (CLL) who achieve blood or bone marrow (BM) undetectable minimal residual disease (U-MRD) status after first-line fludarabine, cyclophosphamide, and rituximab (FCR) have prolonged progression-free survival (PFS), when assessed by an assay with sensitivity 10-4 (MRD4). Despite reaching U-MRD4, many patients, especially those with unmutated IGHV, subsequently relapse, suggesting residual disease <10-4 threshold and the need for more sensitive MRD evaluation. MRD evaluation by next-generation sequencing (NGS) has a sensitivity of 10-6 (MRD6). To better assess the depth of remission following first-line FCR treatment, we used NGS (Adaptive Biotechnologies Corporation) to assess MRD in 62 patients, all of whom had BM U-MRD by multicolor flow cytometry (sensitivity 10-4) at end-of-FCR treatment. Samples from these patients included 57 BM samples, 29 peripheral blood mononuclear cell (PBMC) samples, and 32 plasma samples. Only 27.4% of the 62 patients had U-MRD by NGS. Rate of U-MRD by NGS was lowest in BM (25%), compared with PBMC (55%) or plasma (75%). No patient with U-MRD by NGS in BM or PBMC was MRD+ in plasma. Patients with mutated IGHV were more likely to have U-MRD by NGS at the end of treatment (EOT; 41% vs 13%, P = .02) than those with unmutated IGHV. Median follow-up was 81.6 months. Patients with U-MRD at EOT had superior PFS vs MRD+ patients, regardless of sample type assessed (BM, P = .02, median not reached [NR] vs 67 months; PBMC, P = .02, median NR vs 74 months). More sensitive MRD6 testing increases prognostic discrimination over MRD4 testing.

Patients with chronic lymphocytic leukemia (CLL) who achieve blood or bone marrow (BM) undetectable minimal residual disease (U-MRD) status after first-line fludarabine, cyclophosphamide, and rituximab (FCR) have prolonged progression-free survival (PFS), when assessed by an assay with sensitivity 10−4(MRD4). Despite reaching U-MRD4, many patients, especially those with unmutated IGHV, subsequently relapse, suggesting residual disease <10−4threshold and the need for more sensitive MRD evaluation. MRD evaluation by next-generation sequencing (NGS) has a sensitivity of 10−6(MRD6). To better assess the depth of remission following first-line FCR treatment, we used NGS (Adaptive Biotechnologies Corporation) to assess MRD in 62 patients, all of whom had BM U-MRD by multicolor flow cytometry (sensitivity 10−4) at end-of-FCR treatment. Samples from these patients included 57 BM samples, 29 peripheral blood mononuclear cell (PBMC) samples, and 32 plasma samples. Only 27.4% of the 62 patients had U-MRD by NGS. Rate of U-MRD by NGS was lowest in BM (25%), compared with PBMC (55%) or plasma (75%). No patient with U-MRD by NGS in BM or PBMC was MRD+in plasma. Patients with mutated IGHVwere more likely to have U-MRD by NGS at the end of treatment (EOT; 41% vs 13%, P= .02) than those with unmutated IGHV. Median follow-up was 81.6 months. Patients with U-MRD at EOT had superior PFS vs MRD+patients, regardless of sample type assessed (BM, P= .02, median not reached [NR] vs 67 months; PBMC, P= .02, median NR vs 74 months). More sensitive MRD6 testing increases prognostic discrimination over MRD4 testing.

According to Ayurveda, the traditional medical system of India, doshasare a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest.

This phase 2 study was conducted to prospectively evaluate how clinical and biological factors correlate with outcome in patients with treatment-naive (TN) and relapsed (R) chronic lymphocytic leukemia (CLL) treated with lenalidomide and rituximab. Oral lenalidomide 10 mg was administered daily starting on day 9 of cycle 1. IV rituximab 375 mg/m2 was administered weekly during cycle 1 and every 4 weeks for cycles 3 to 12. Sequencing of a custom panel of 295 genes was performed in pretreatment bone marrow samples. The study included 61 patients with TN CLL and 59 with R CLL; the overall response rate (ORR) was 73% and 64%, respectively. A baseline β2-microglobulin level <4 mg/L was associated with higher ORR in both groups (both, P = .03), and absence of mutations in the NOTCH signaling pathway showed a trend for association with higher ORR in R CLL (P = .10). Median PFS was 50 months in TN patients and 28 months in R patients. On multivariate analysis, age ≥65 years (P = .02) was associated with shorter PFS in TN patients, whereas according to univariate analysis, >2 previous therapies (P = .02) was the only factor associated with shorter PFS in R patients. A trend for association between mutations in the NOTCH pathway and shorter PFS was observed in TN CLL (P = .15). Further exploration of the NOTCH pathway may help optimize the efficacy of this combination in patients with CLL. This study protocol was approved by the University of Texas MD Anderson Cancer Center institutional review board and registered at clinicaltrials.gov (#NCT01446133).

This phase 2 study was conducted to prospectively evaluate how clinical and biological factors correlate with outcome in patients with treatment-naive (TN) and relapsed (R) chronic lymphocytic leukemia (CLL) treated with lenalidomide and rituximab. Oral lenalidomide 10 mg was administered daily starting on day 9 of cycle 1. IV rituximab 375 mg/m2was administered weekly during cycle 1 and every 4 weeks for cycles 3 to 12. Sequencing of a custom panel of 295 genes was performed in pretreatment bone marrow samples. The study included 61 patients with TN CLL and 59 with R CLL; the overall response rate (ORR) was 73% and 64%, respectively. A baseline β2-microglobulin level <4 mg/L was associated with higher ORR in both groups (both, P= .03), and absence of mutations in the NOTCH signaling pathway showed a trend for association with higher ORR in R CLL (P= .10). Median PFS was 50 months in TN patients and 28 months in R patients. On multivariate analysis, age ≥65 years (P= .02) was associated with shorter PFS in TN patients, whereas according to univariate analysis, >2 previous therapies (P= .02) was the only factor associated with shorter PFS in R patients. A trend for association between mutations in the NOTCH pathway and shorter PFS was observed in TN CLL (P= .15). Further exploration of the NOTCH pathway may help optimize the efficacy of this combination in patients with CLL. This study protocol was approved by the University of Texas MD Anderson Cancer Center institutional review board and registered at clinicaltrials.gov(#NCT01446133).

ABSTRACTIntroduction: RX-3117 is an oral, small molecule cytidine analog anticancer agent with an improved pharmacological profile relative to gemcitabine and other nucleoside analogs. The agent has excellent activity against various cancer cell lines and xenografts including gemcitabine-resistant variants and it has excellent oral bioavailability; it is not a substrate for the degradation enzyme cytidine deaminase. RX-3117 is being evaluated at a daily oral schedule of 700 mg (5 days/week for 3 weeks) which results in plasma levels in the micromolar range that have been shown to be cytotoxic to cancer cells. It has shown clinical activity in refractory bladder cancer and pancreatic cancer.Areas covered: The review provides an overview of the relevant market and describes the mechanism of action, main pharmacokinetic/pharmacodynamic features and clinical development of this investigational small molecule.Expert opinion: RX-3117 is selectively activated by uridine-cytidine kinase 2 (UCK2), which is expressed only in tumors and has a dual mechanism of action: DNA damage and inhibition of DNA methyltransferase 1 (DNMT1). Because of its tumor selective activation, novel mechanism of action, excellent oral bioavailability and candidate biomarkers for patient selection, RX-3117 has the potential to replace gemcitabine in the treatment of a spectrum of cancer types.Trial registration:ClinicalTrials.gov identifier: NCT02030067.Trial registration:ClinicalTrials.gov identifier: NCT03189914.

Water adsorbed at the metal–support interface (MSI) plays an important role in multiple reactions. Due to its importance in CO preferential oxidation (PrOx), we examined H2oxidation kinetics in the presence of water over Au/TiO2and Au/Al2O3catalysts, reaching the following mechanistic conclusions: (i) O2activation follows a similar mechanism to that proposed in CO oxidation catalysis; (ii) weakly adsorbed H2O is a strong reaction inhibitor; (iii) fast H2activation occurs at the MSI, and (iv) H2activation kinetics are inconsistent with traditional dissociative H2chemisorption on metals. Density functional theory (DFT) calculations using a supported Au nanorod model suggest H2activation proceeds through a heterolytic dissociation mechanism, resulting in a formal hydride residing on the Au and a proton bound to a surface TiOH group. This potential mechanism was supported by infrared spectroscopy experiments during H2adsorption on a deuterated Au/TiO2surface, which showed rapid H–D scrambling with surface hydroxyl groups. DFT calculations suggest that the reaction proceeds largely through proton-mediated pathways and that typical Brønsted–Evans Polanyi behavior is broken by introducing weak acid/base sites at the MSI. The kinetics data were successfully reinterpreted in the context of the heterolytic H2activation mechanism, tying together the experimental and computational evidence and rationalizing the observed inhibition by physiorbed water on the support as blocking the MSI sites required for heterolytic H2activation. In addition to providing evidence for this unusual H2activation mechanism, these results offer additional insight into why water dramatically improves CO PrOx catalysis over Au.

Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10−4). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo, p< 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%, p< 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo, p< 0.001), but similar for <0.01% vs 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders.