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Micronutrient deficiencies, a global concern affecting vulnerable populations, including pregnant women, pose significant public health challenges. Specifically, micronutrient deficiencies in iron, vitamin A, iodine and folate have been of greatest public health concern among pregnant women. This study aimed to evaluate the co-occurrence of selected multiple micronutrient deficiencies among pregnant women attending Antenatal Care (ANC) in Mbeya, Tanzania. Employing a cross-sectional design, data were gathered from 420 pregnant women aged 15-49 years attending ANC in Mbeya Region. Semi-structured questionnaires captured socio-demographic data, and blood samples were collected for biomarkers assessment. The study used Stata 17.0 to analyze the data. Results revealed that six out of ten pregnant women exhibited at least one form of micronutrient deficiency, with 15.0% experiencing double deficiencies and 2.2% experiencing triple deficiencies. Iron Deficiency Anemia (IDA) was prevalent among 61.7% of anaemic pregnant women. Individual micronutrient deficiency rates were as follows: folate (21.7%), vitamin B12 (9.9%), iron (38.4%), vitamin A (9.8%), with a median Urinary Iodine Concentration (UIC) of 279.4μg/L. Pregnant women with anemia were more likely to have Multiple Micronutrient Deficiencies (MMD) compared to non-anemic counterparts (p-value <0.005). Additionally, those in the second trimester were at a higher risk of MMD than those in the first trimester (p-value <0.005). A higher wealth quantile appeared to protect against MMD (p-value <0.005). The study highlights the co-occurrence of MMD among pregnant women in Tanzania, indicates the necessity for an improved strategy to enhance multiple micronutrients intake through dietary diversity, MMS and fortified foods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mchau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bioremediation is an effective and environment-friendly treatment used to clean up hydrocarbon-contaminated soil. However, the effectiveness of this treatment is often limited by the low bioavailability of the target contaminants. Surfactants addition thus appears as a way to increase solubility of these hydrophobic molecules and consequently improve their bioavailability. The use of biological surfactants is often favoured over synthetic ones because they are claimed to be non-toxic to the environment though few studies have addressed this issue. The present work evaluated the effects of a synthetic surfactant, sodium dodecyl sulphate (SDS) and a biosurfactant (rhamnolipids) on germination and growth of ryegrass over a wide range of concentrations, between one up to ten times their respective critical micellar concentration (CMC). Experimental results showed that SDS inhibited seed germination of Lolium multiflorum at high concentrations (10 × CMC), unlike rhamnolipids, which did not induce any toxicity symptom at germination stage. At the growth stage, high rhamnolipid concentrations induced chronic phytotoxicity by significantly reducing root length, decreasing biomass production and disrupting the enzymatic defence system. Thus, biosurfactants are less toxic than synthetic ones but their application at high doses in bioremediation treatments might still induce phytotoxicity symptoms and thus negatively affect the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab., Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III-IVB p16-negative HNSCC or unfavourable stage I-III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m 2 1 week before radiotherapy then 250 mg/m 2 weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment., Findings: Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64-77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9-3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5-59·8) in the durvalumab group versus 63·7% (51·3-76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84-2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group)., Interpretation: Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population., Funding: US National Cancer Institute and AstraZeneca., Competing Interests: Declaration of interests MJA declares grants or contracts from the National Institutes of Health (NIH; R21 for phase 1 trial DEHART), receipt of equipment, materials, drugs, medical writing, gifts, or other services from Genentech for drug only support for NIH R21. JEB declares clinical trial grants from Aveo, Celldex, CUE, Genentech, and Moderna, and consulting fees from Bluedot Bio and Exelixis. ND declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca. CH declares participation on a medical advisory board for EMD Serono, and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid as co-chair of the Young Investigators Committee of the Head and Neck Cancer International Group. RCJ declares royalties or license from Elsevier for a textbook authorship. Q-TL declares a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid as Radiation Therapy Oncology group chair for NRG Oncology. LKM declares grants or contracts from AstraZeneca and Merck to their institution, consulting fees from Pfizer, and payment for expert testimony from Arnold & Porter. HSP declares grants or contracts from RefleXion and Merck to their institution, consulting fees from AstraZeneca and RefleXion, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb and G1 Therapeutics, and participation on a data safety monitoring board or advisory board at AstraZeneca and Galera. SP declares grants or contracts from Merck, Bristol Myers Squibb, Pfizer, Actuate, Vyriad, Nanobiotix, Seattle Genetics, AstraZeneca, Molecular Templates, and Sorrento to their institution, consulting fees from Bristol Myers Squibb to their institution, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alkermes to their institution. CPR declares grants or contracts from AstraZeneca, Ayala, BMS, Cue Biopharma, Merck, Prelude, Sanofi Aventis, and Seagen to their institution, consulting fees from Vaccitech and Adaptimmune, and participation on a data safety monitoring board or advisory board at Pionyr Therapeutics. AGS declares grants or contracts from Merck, Bicara, AstraZeneca, Genentech/Roche, ALX Oncology, Regeneron, and Infinity Pharmaceuticals to their institution, consulting fees from Bicara, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from i3Health. VT declares grants or contracts from NIH and Veteran's Administration, support for attending meetings or travel from the American Society for Radiation Oncology and the American Board of Radiology, and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Cardiff Oncology. PAT-S declares support for the current manuscript from NRG Oncology Statistics and Data Management Center grant from NCI. TW-D declares grants or contracts from Bristol Myers Squibb, Merck, Janssen, AstraZeneca/Medimmune, and Tesaro/GSK, and participation on a data safety monitoring board or advisory board at Merck. SSY declares grants or contracts from Bristol Myers Squibb and EMD Serono to their institution, honoraria for editorship from Elsevier, and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at ASTRO for editorship. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Knowing where people are is crucial for policymakers, particularly for the efficient allocation of resources in their country and the development of effective, people-centred policies. However, rural population distribution maps suffer from biases related to the type of dataset used to predict population density, such as the use of nighttime lights datasets in areas without electricity. This renders widely used datasets irrelevant in rural areas and biases nationwide models towards urban areas. To compensate for such biases, we aim at understanding the importance and relationship between water-related covariates and population densities in a random forest model across the urban-rural gradient. By extending a recursive feature elimination framework, we show that commonly used covariates are only selected when modelling the whole country. However, once the highest density areas are removed, water-related characteristics (especially distance to boreholes) become important covariates of population density outside of densely populated areas. This has important implications for modelling population in rural areas, including for a better estimation of the size of remote communities. When seeking to produce country-level population maps, we encourage further studies to explicitly account for rural areas by considering the urban-rural gradient and encourage the use of water-related datasets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Visée et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anisakis simplex larvae, commonly found in marine fish, cause anisakiasis in humans, resulting in gastric to gastro-allergic symptoms. Despite known health risks, the impact of Anisakidae larvae on fish hosts is less understood. This study aimed to investigate this interaction by assessing the feeding strategy of A. simplex. Anisakis larvae were isolated from North Sea Merluccius merluccius tissues (stomach, body cavity, liver and muscle) and were analysed for carbon (δ 13 C) and nitrogen (δ 15 N) isotope values. Significant differences in δ 13 C values were found among host tissues, with the liver differing from muscle and stomach tissues. In contrast, no differences were noted for the associated parasites. Additionally, δ 15 N values indicated that the host occupied a significantly higher relative trophic position than its parasite. This suggests a lack of direct nutrient transfer from host to parasite, as the parasite would typically exhibit higher stable isotope values than the tissue they feed on. Therefore, A. simplex's stable isotope values might reflect those of its previous host (crustacean and/or small fish), providing insights into diet and movement of the paratenic M. merluccius host. Further research is needed to confirm these findings across different fish species and to explore A. simplex as a proxy for trophic ecology., (© 2024 John Wiley & Sons Ltd.)

Tularemia is a deadly disease caused by Francisella tularensis , an emerging intracellular bacterial pathogen that can be disseminated rapidly through aerosols and vector-borne transmission. Recent surveillance data demonstrate an increasing incidence in several countries. Although clinical isolates of Francisella strains are sensitive to currently used antibiotics, engineered or horizontal acquisition of antibiotic resistance is a constant threat to public health. Therefore, the identification of antibiotics that target previously undrugged pathways is required to safeguard human health. An environmental pesticide that is registered for use in multiple countries, tolfenpyrad, shows promising activity to block Francisella growth; however, it is not a suitable antimicrobial candidate for use in vivo due to potential toxicity in humans and other animals. In this study, we applied a structure-activity relationship approach to tolfenpyrad to generate compounds with improved antibacterial activity and reduced toxicity. Through screening of a library of derivatives, we identified analogs with improved therapeutic windows compared with tolfenpyrad. Although structural diversity exists among these analogs, they inhibit the growth of Francisella species but not other Gram-negative or Gram-positive species. These compounds block intramacrophage growth of F. novicida and pathogenesis in an in vivo arthropod model of infection. Although the biochemical activity of these drugs is unknown, they appear to target the same pathway as the parent molecule because F. novicida mutants that are resistant to tolfenpyrad are also resistant to its analogs. Taken together, these findings suggest that these tolfenpyrad-derived compounds comprise a new class of Francisella -targeted antimicrobials and merit further evaluation and development.

Background: The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented., Methods: The microbial composition of 77 longitudinal fecal samples obtained from 35 patients (CC, n = 15; EC, n = 20) was characterized using 16S rRNA gene sequencing. Analyses included assessment of alpha (Shannon index) and beta diversity (weighted UniFrac), unbiased hierarchical clustering, and linear discriminant analysis effect size. Correlative studies with demographics, disease characteristics, safety, efficacy, and immune monitoring data were performed., Results: Significant enrichment in multiple bacterial taxa was associated with the occurrence or resistance to severe treatment-related adverse events (overall or gastrointestinal toxicity specifically). Consistent differences in GM taxonomic composition before pembrolizumab initiation were observed between patients with favorable efficacy (e.g., enriched with Blautia genus) and those with poor efficacy (e.g., enriched with Enterobacteriaceae family and its higher-level taxa up to the phylum level, as well as Clostridium genus and its Clostridiaceae family). Two naturally occurring GM clusters with distinct bacterial compositions were identified. These clusters showed a more than four-fold differential risk for death (hazard ratio, 4.4 [95 % confidence interval, 1.9 to 10.3], P < 0.001) and were associated with interesting (but non-significant) trends in peripheral immune monitoring data., Conclusion: Although exploratory, this study offers initial insights into the intricate interplay between the GM and clinical outcomes in patients with CC and EC treated with a pembrolizumab-based regimen., Trial Registration: ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97)., Competing Interests: Declaration of competing interest EAD: travel and accommodation expenses (institutional, not personal) from AstraZeneca, GSK, and Pfizer. AMTV: became an employee for GSK during the publication development. PV: consulting or advisory role (personal) from Eli Lily and Company, MSD, Mundipharma, Novartis, Pfizer, and Roche; research funding from Tesaro. SH: consulting or advisory role (personal) from AstraZeneca, BMSi, Gilead Sciences, Merck, MSD Oncology, Novartis, and Sanofi. SA: consulting or advisory role (institutional, not personal) for MSD, Sanofi, Roche, BMS, and Pfizer; research funding (institutional, not personal) from Sanofi. AD: research funding (institutional, not personal) from AstraZeneca. EN: travel and accommodation expenses (institutional, not personal) from AstraZeneca, Novartis, Pfizer, PharmaMar, Roche, and Teva. FA: consulting or advisory role (institutional, not personal) for MiMark. KV: travel and accommodation expenses (institutional, not personal) from PharmaMar. HGD: travel and accommodation expenses (institutional, not personal) from Amgen, AstraZeneca, Eli Lily and Company, GSK, MSD, Novartis, Pfizer, PharmaMar, Roche, Tesaro, and Teva; research funding (institutional, not personal) from Roche. HH, ST, LL, RB, XBT, PAV, AH, OD, KKV, and BV: declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A mechanism for the concerted pathway of coupled electron- and phase-transfer reactions (CEPhT) is proposed. CEPhT at three-phase interfaces formed by a solid electrode, an insulating organic solvent, and an aqueous electrolyte is driven by electric double layer (EDL) spillover, with significant electrostatic potential gradients extending a few nanometers into the insulating phase. This EDL spillover phenomenon is studied using scanning electrochemical cell microscopy to interrogate the oxidation of ferrocene in toluene to ferrocenium in water, (Fc) tol → (Fc + ) aq + e - . Finite element method simulations of the electrostatic potential distribution and species concentration profiles enable the calculation of complete i - E curves that incorporate mass transport, electron transfer, phase transfer, and the EDL structure. Simulated and experimental i - E traces show good agreement in the current magnitude and the effect of the supporting electrolyte, identifying an unexpected dependence of overall reaction kinetics on the concentration of the supporting electrolyte in the aqueous phase due to EDL spillover. An interfacial toluene/water mixing region generates a unique electrochemical microenvironment where concerted electron transfer and solvent shell replacement facilitate CEPhT. Kinetic expressions for concerted and sequential CEPhT mechanisms highlight the role of this interfacial environment in controlling the rate of CEPhT. These combined experimental and simulated results are the first to support a concerted mechanism for CEPhT where (Fc) tol is transported to the interfacial mixing region at the three-phase interface, where it undergoes oxidation and phase transfer. EDL spillover can be leveraged for engineering sample geometries and electrostatic microenvironments to drive electrochemical reactivity in classically forbidden regions, e.g., insulating solvents and gases.

Changes in metabolic activity are key regulators of macrophage activity. Pro-inflammatory macrophages upregulate glycolysis, which promotes an inflammatory phenotype, whereas pro-repair macrophages rely upon oxidative metabolism and glutaminolysis to support their activity. Work to understand how metabolism regulates macrophage phenotype has been done primarily in macrophage cell lines and bone marrow-derived macrophages (BMDM). Our study sought to understand changes in metabolic activity of murine tissue-resident alveolar macrophages (AM) in response to LPS stimulation and to contrast them to BMDM. These studies also determined the contribution of glutamine metabolism using the glutamine inhibitor, DON. We found that compared to BMDM, AM have higher rates of oxygen consumption and contain a higher concentration of intracellular metabolites involved in fatty acid oxidation. In response to LPS, BMDM but not AM increased rates of glycolysis. Inhibition of glutamine metabolism using DON altered the metabolic activity of AM but not BMDM. Within AM, glutamine inhibition led to increases in intracellular metabolites involved in glycolysis, the TCA cycle, fatty acid oxidation, and amino acid metabolism. Glutamine inhibition also altered the metabolic response to LPS within AM but not BMDM. Our data reveal striking differences in the metabolic activity of AM and BMDM.

Background: Models of care that are culturally responsive, trauma-informed and provide continuity of care(r), are important components of care for Aboriginal and Torres Strait Islander parents during the broad perinatal period (pregnancy to 2 years after birth; first 1000 days). Many health services do aim to incorporate these concepts in care provision, but often focus on only one., Aim: To identify practical toolkits that guide implementation of culturally responsive care, trauma-informed care, or continuity of care(r) in the perinatal period, and map the key elements., Methods: A scoping review was conducted. Relevant databases and grey literature were searched to identify toolkits that guided implementation of any one of the aforementioned concepts in the perinatal period. Toolkit context, principles, core components and processes were extracted and synthesised., Findings: Thirteen toolkits, from both Indigenous and non-Indigenous contexts, met the inclusion criteria. Six related to culturally responsive care, nine to trauma-informed care, and eight to continuity of care(r), with some overlap. Key principles included continuity of carer, collaboration, woman (or family) centred care, safety and holistic care. Individualised care, team work, having a safe service environment and continuity of care/r were highlighted as core components. Key processes related to planning, implementation, monitoring and evaluation, and sustainability., Discussion: There are no available resources that support holistic implementation of all three concepts of culturally responsive, trauma-informed continuity of care(r), spanning the first 1000 days, for Aboriginal and Torres Strait Islander families. A synthesised toolkit of key principles, core components and key processes would assist implementation of this., Statement of Significance: Problem: Aboriginal and Torres Strait Islander families experience health inequalities and poorer perinatal outcomes due to a legacy of colonisation and ongoing discrimination., What Is Already Known: Culturally responsive care, trauma-informed care and continuity of care(r) are elements of perinatal care shown to improve outcomes and experiences., What This Paper Adds: This review synthesises key aspects of culturally responsive, trauma-informed and continuity of care(r) models. It highlights the lack of resources to support services implementing models pertaining to these three concepts across the full First 1000 days, for Aboriginal and Torres Strait Islander families., Competing Interests: Declaration of Competing Interest There are no competing interests to declare., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Hydrogels are often synthesized through photoinitiated step-, chain-, and mixed-mode polymerizations, generating diverse network topologies and resultant material properties that depend on the underlying network connectivity. While many photocrosslinking reactions are available, few afford controllable connectivity of the hydrogel network. Herein, a versatile photochemical strategy is introduced for tuning the structure of poly(ethylene glycol) (PEG) hydrogels using macromolecular monomers functionalized with maleimide and styrene moieties. Hydrogels are prepared along a gradient of topologies by varying the ratio of step-growth (maleimide dimerization) to chain-growth (maleimide-styrene alternating copolymerization) network-forming reactions. The initial PEG content and final network physical properties (e.g., modulus, swelling, diffusivity) are tailored in an independent manner, highlighting configurable gel mechanics and reactivity. These photochemical reactions allow high-fidelity photopatterning and 3D printing and are compatible with 2D and 3D cell culture. Ultimately, this photopolymer chemistry allows facile control over network connectivity to achieve adjustable material properties for broad applications., (© 2024 Wiley‐VCH GmbH.)

Study Question: What is the relative length variance of the luteal phase compared to the follicular phase within healthy, non-smoking, normal-weight, proven normally ovulatory, premenopausal women with normal-length menstrual cycles?, Summary Answer: Prospective 1-year data from 53 premenopausal women with two proven normal-length (21-36 days) and normally ovulatory (≥10 days luteal) menstrual cycles upon enrollment showed that, despite 29% of all cycles having incident ovulatory disturbances, within-woman follicular phase length variances were significantly greater than luteal phase length variances., What Is Known Already: Many studies report menstrual cycle variability, yet few describe variability in follicular and luteal phase lengths. Luteal lengths are assumed 'fixed' at 13-14 days. Most studies have described follicular and luteal phase variability between-women., Study Design, Size, Duration: This study was a prospective, 1-year, observational cohort study of relative follicular and luteal phase variability both between and within community-dwelling women with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Eighty-one women enrolled in the study and 66 women completed the 1-year study. This study analyzed data from 53 women with complete data for ≥8 cycles (mean 13)., Participants/materials, Setting, Methods: Participants were healthy, non-smoking, of normal BMI, ages 21-41 with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Participants recorded first morning temperature, exercise durations, and menstrual cycle/life experiences daily in the Menstrual Cycle Diary. We analyzed 694 cycles utilizing a twice-validated least-squares Quantitative Basal Temperature method to determine follicular and luteal phase lengths. Statistical analysis compared relative follicular and luteal phase variance in ovulatory cycles both between-women and within-woman. Normal-length cycles with short luteal phases or anovulation were considered to have subclinical ovulatory disturbances (SOD)., Main Results and the Role of Chance: The 1-year overall 53-woman, 676 ovulatory cycle variances for menstrual cycle, follicular, and luteal phase lengths were 10.3, 11.2, and 4.3 days, respectively. Median variances within-woman for cycle, follicular, and luteal lengths were 3.1, 5.2, and 3.0 days, respectively. Menstrual cycles were largely of normal lengths (98%) with an important prevalence of SOD: 55% of women experienced >1 short luteal phase (<10 days) and 17% experienced at least one anovulatory cycle. Within-woman follicular phase length variances were greater than luteal phase length variances (P < 0.001). However, follicular (P = 0.008) and luteal phase length (P = 0.001) variances, without differences in cycle lengths, were greater in women experiencing any anovulatory cycles (n = 8) than in women with entirely normally ovulatory cycles (n = 6)., Limitations, Reasons for Caution: Limitations of this study include the relatively small cohort, that most women were White, initially had a normal BMI, and the original cohort required two normal-length and normally ovulatory menstrual cycles before enrollment. Thus, this cohort's data underestimated population menstrual cycle phase variances and the prevalence of SOD., Wider Implications of the Findings: Our results reinforce previous findings that the follicular phase is more variable than the luteal phase in premenopausal women with normal-length and ovulatory menstrual cycles. However, our study adds to the growing body of evidence that the luteal phase is not predictably 13-14 days long., Study Funding/competing Interest(s): This medical education project of the University of British Columbia was funded by donations to the Centre for Menstrual Cycle and Ovulation Research. The authors do not have any conflicts of interest to disclose., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Aim: The aim was to investigate whether COVID-19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post-infection., Materials and Methods: Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID-19 (H-COVID-19, n = 511), T1D patients with COVID-19 but not hospitalized for COVID-19 (NH-COVID-19, n = 306) and T1D patients without a positive COVID-19 test on record (non-COVID-19, n = 1547). COVID-19 patients were those with a positive polymerase-chain-reaction test on record, and non-COVID-19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks., Results: Compared to non-COVID-19 patients, both H-COVID-19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH-COVID-19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non-COVID-19 patients, both H-COVID-19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH-COVID-19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non-COVID-19 patients, both H-COVID-19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH-COVID-19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow-up., Conclusion: T1D patients with COVID-19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID-19., (© 2024 John Wiley & Sons Ltd.)

Background: CpG oligonucleotides (ODNs) are synthetic single-stranded DNA sequences that act as immunostimulants. They have been increasingly used to treat several cancers; however, thrombocytopenia is a potential recognized side effect of some sequences., Objectives: We tested the ability of 2 CpG ODNs (ODN 2395 and ISIS 120704) to induce thrombocytopenia when administered to BALB/c mice and determined mechanisms associated with thrombocytopenia., Methods: BALB/c mice were prebled and then injected with titrated doses of CpG ODNs, and platelet counts were determined. The mice were treated with intravenous immunoglobulin (IVIg) or various inhibitors and antagonists of toll-like receptor 9 (TLR9) and spleen tyrosine kinase (Syk) to determine their effects on thrombocytopenia., Results: Compared with saline-treated mice or mice treated with 2'-O-methoxyethyl-modified antisense ODN, both ODN 2395 and ISIS 120704 induced acute dose-dependent thrombocytopenia within 3 and 24 hours, respectively. The thrombocytopenia was associated with significant increases in plasma monocyte chemoattractant protein 1. IVIg administration significantly rescued the CpG ODN-induced thrombocytopenia, as did treatment with either a Syk inhibitor or TLR9 antagonists. In vitro, CpG ODN could activate human platelets and this correlated significantly with enhanced IVIg- and Syk-dependent phagocytosis by THP-1 monocytes., Conclusion: These results suggest that CpG ODNs induce acute inflammatory-associated (IVIg-sensitive) thrombocytopenia that can be alleviated by Syk- or TLR9-blockade, and an IVIg- and Syk-dependent platelet clearance pathway appears primarily responsible for the thrombocytopenia., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study investigates the electronic interactions and charge redistribution at the dopant-support interface using a Cu/Co 6 Se 8 cluster construct. Specifically, the redox cluster series [Cu 3 Co 6 Se 8 L 6 ] n ([ 1 -Cu 3 ] n ; n = 0, -1, -2, -3; L = Ph 2 PNTol - , Ph = phenyl, Tol = p -tolyl) spanning four distinct oxidation states is synthesized and characterized using a multitude of techniques, including multinuclear NMR, UV-vis, XANES, and X-ray crystallography. Structural investigations indicate that the clusters are isostructural and chiral, adopting a pseudo- D 3 symmetry. Paramagnetic 31 P NMR spectroscopy and solution-phase magnetic measurements together with DFT calculations are employed to interrogate the electronic structure and spin-state changes across the [ 1 -Cu 3 ] 3- to 1 -Cu 3 redox series, revealing that the copper edge sites retain a +1 oxidation state while the Co/Se core becomes increasingly oxidized, yielding a highly zwitterionic cluster.

The imidophosphorane ligand, [NP t Bu 3 ] - ( t Bu=tert-butyl), enables isolation of a pseudo-tetrahedral, tetravalent praseodymium complex, [Pr 4+ (NP t Bu 3 ) 4 ] (1-Pr), which is characterized by a suite of physical characterization methods including single-crystal X-ray diffraction, electron paramagnetic resonance, and L 3 -edge X-ray near-edge spectroscopies. Variable-temperature direct-current magnetic susceptibility data, supported by multiconfigurational quantum chemical calculations, demonstrate that the electronic structure diverges from the isoelectronic Ce 3+ analogue, driven by increased crystal field. The four-coordinate environment around Pr 4+ in 1-Pr, which is unparalleled in reported extended solid systems, provides a unique opportunity to study the interplay between crystal field splitting and spin-orbit coupling in a molecular tetravalent lanthanide within a pseudo-tetrahedral coordination geometry., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Abstract: Voltage-gated sodium (Nav) channels present untapped therapeutic value for better and safer pain medications. The Nav1.8 channel isoform is of particular interest because of its location on peripheral pain fibers and demonstrated role in rodent preclinical pain and neurophysiological assays. To-date, no inhibitors of this channel have been approved as drugs for treating painful conditions in human, possibly because of challenges in developing a sufficiently selective drug-like molecule with necessary potency not only in human but also across preclinical species critical to the preclinical development path of drug discovery. In addition, the relevance of rodent pain assays to the human condition is under increasing scrutiny as a number of mechanisms (or at the very least molecules) that are active in rodents have not translated to humans, and direct impact on pain fibers has not been confirmed in vivo. In this report, we have leveraged numerous physiological end points in nonhuman primates to evaluate the analgesic and pharmacodynamic activity of a novel, potent, and selective Nav1.8 inhibitor compound, MSD199. These pharmacodynamic biomarkers provide important confirmation of the in vivo impact of Nav1.8 inhibition on peripheral pain fibers in primates and have high translational potential to the clinical setting. These findings may thus greatly improve success of translational drug discovery efforts toward better and safer pain medications, as well as the understanding of primate biology of Nav1.8 inhibition broadly., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

[ 18 F]FE-PE2I PET is a promising alternative to single positron emission computed tomography-based dopamine transporter (DAT) imaging in Parkinson's disease. While the excellent discriminative power of [ 18 F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [ 18 F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson's disease, Hoehn-Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson's disease with 2-year follow-up) cohorts. In the cross-sectional cohort, DAT availability in the putamen and substantia nigra of patients with Parkinson's disease showed a significant negative association with total motor severity ( r = -0.59, P = 0.002 for putamen; r = -0.46, P = 0.018 for substantia nigra), but not tremor severity. To our knowledge, this is the first observed association between motor severity in Parkinson's disease and DAT availability in the substantia nigra. The associations with motor severity in most nigrostriatal regions improved if tremor scores were excluded from motor scores. Further, we found significant asymmetry in DAT availability in the putamen (∼28% lower DAT availability within the more-affected side of the putamen), and DAT-based asymmetry index for the putamen was correlated with asymmetry in motor severity ( r = -0.60, P = 0.001). In the longitudinal study, [ 18 F]FE-PE2I PET detected significant annual percentage reduction of DAT availability at the individual level in the putamen (9.7 ± 2.6%), caudate (10.5 ± 3.8%) and ventral striatum (5.5 ± 2.7%), but not the substantia nigra. Longitudinal per cent reduction in DAT availability within the putamen was strongly associated with increase in motor severity ( r = 0.91, P = 0.011) at follow-up, demonstrating the high sensitivity of [ 18 F]FE-PE2I PET in tracking longitudinal changes. These results provide further evidence for the utility of [ 18 F]FE-PE2I as an important in vivo PET biomarker in future clinical trials of Parkinson's disease., Competing Interests: R.C. and S.J.F. are full-time employees of AbbVie, but their employment does not constitute any competing interest for the content presented in this article. All other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

A universal nomenclature of the anatomic extent of lung cancer has been critical for individual patient care as well as research advances. As progress occurs, new details emerge that need to be included in a refined system that aligns with contemporary clinical management issues. The ninth edition TNM classification of lung cancer, which is scheduled to take effect in January 2025, addresses this need. It is based on a large international database, multidisciplinary input, and extensive statistical analyses. Key features of the ninth edition include validation of the significant changes in the T component introduced in the eighth edition, subdivision of N2 after exploration of fundamentally different ways of categorizing the N component, and further subdivision of the M component. This has led to reordering of the TNM combinations included in stage groups, primarily involving stage groups IIA, IIB, IIIA, and IIIB. This article summarizes the analyses and revisions for the TNM classification of lung cancer to familiarize the broader medical community and facilitate implementation of the ninth edition system., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. J. G. reports honoraria from AstraZeneca, Daiichi Sanyo, and Regeneron (all unrelated to the topic). H. S. P. reports institutional grants from RefleXion and Merck; and consulting fees from RefleXion and AstraZeneca. S. D. reports honoraria from AstraZeneca and Medscape; and is the chair of the IASLC pathology committee. G. A. W. reports grants from the American Cancer Society and the International Lung Cancer Foundation; a career enhancement grant from the Yale SPORE in lung cancer; and consulting fees from AstraZeneca. None declared: (F. C. D., A. S. B., L. T. T.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The Ghanaian elderly population is increasing at the fastest rate and this has become a burden as the rate is not proportional to the investment in health to meet their deteriorating health needs. This creates discrepancies and inequalities in healthcare access and coupled with poor healthcare provider services, the inequalities widen. Poor care services are related to poor knowledge and bad attitudes of care providers hence this study seeks to explore the health practitioners' level of knowledge, attitude, and practice (KAP) toward geriatric care., Methods: The study used a cross-sectional survey design with a simple stratified random technique to select study participants. Out of 257 participants who were sampled for the study, 215 responses were received, representing 83.6% response rate. However, 200 questionnaires were complete (93%) and valid for analysis, which consisted of 166 nurses, representing 83% valid responses, and 34 medical officers, physician assistants, and other allied health care providers, representing 17% valid responses from these professionals. A structured questionnaire was used to assess KAP using the knowledge about Older Patients Quiz (KOP-Q) and Kogan's Attitudes toward Old People Scale (KAOP). Using a mean score of 80%, knowledge, attitude, and practice were dichotomized into good or bad. The Kruskal-Wallis H test was used to compare mean rank across health professionals' knowledge, attitude, and practice of geriatric care., Results: It shows that the majority (94%) of participants have low levels of knowledge in geriatric care. The majority (84%) of participants do not practice good geriatric care. Differences in knowledge exist among health providers and were statistically significant ( P  = .045). Doctors had the lowest mean knowledge score (78.61). Nurses (100.27) and physician assistants (106.15) had moderate mean knowledge score ranks. Although not statistically significant, the rank order for practice scores from highest to lowest was: physician assistants (112.95), nurses (99.19), and doctors (79.21). There were however no statistically significant differences between professions in practice scores ( P  = .067), or attitude scores ( P  = .097)., Conclusion: Health care providers have low knowledge and, bad attitude toward aged care and this may be related to their service delivery which may affect the aged patronage of healthcare services. This is a wake-up call for authorities to organize continuous professional development to enable care providers to improve their service delivery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: This study aimed to evaluate the prospective associations of baseline personal characteristics with utilization frequency and expenditure of chiropractic care in US adults (≥18 years)., Methods: Data are from the 1358 respondents to the 2014 to 2016 Medical Expenditure Panel Survey who utilized chiropractic care. Individual, familial, health-related, and behavioral factors were included as covariates in the multivariate analytic model. Poisson and multinominal logistic regressions were modeled to examine the associations between the predictors and chiropractic utilization and expenditure., Results: The mean annual number of visits was 8.2 visits (95% confidence interval [CI]: 7.9, 8.5), with annual expenditure of $677.43 U.S. dollars (95% CI: $595.47-$759.39) and $84.84 (95% CI: $77.89-$91.78) per visit. Female sex was associated with a 19% higher number of visits (rate ratio [RR] = 1.19, 95% CI: 1.01, 1.41) than males. Publicly insured and uninsured were associated with a 44% higher (RR = 1.44, 95% CI: 1.14, 1.82) and 36% lower (RR = 0.64, 95% CI: 0.48, 0.86) visit frequency, respectively, than those privately insured. Rheumatoid arthritis was associated with 7.38 times the risk of high expenditure (95% CI: 2.61, 24.67) than medium expenditure, compared to no arthritis. Relative to physically active individuals, physical inactivity was associated with a 27% higher visit frequency (RR = 1.27, 95% CI: 1.09, 1.49) and an 82% higher risk (relative risk ratio = 1.82, 95% CI: 1.05, 3.14) of high expenditure than low expenditure., Conclusion: This analysis found distinct usage and expenditure patterns that vary according to specific baseline predictors. Female sex, being publicly insured, having rheumatoid arthritis, and physically inactive were associated with variance in expenditure. Results from this study may help identify chiropractic patients with tendencies for higher utilization or spending and may indirectly assist in predicting patients with slower response to care., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study aimed to examine the trends in the utilization and expenditure of chiropractic care in a representative sample of US adults, aged ≥18 years., Methods: Serial cross-sectional data (2007-2016) from the Medical Expenditure Panel Survey (MEPS) were examined. Weighted descriptive statistics were analyzed to obtain national estimates of chiropractic utilization and expenditure, and time-series linear regression was used to assess trends over time. Socio-demographic characteristics and musculoskeletal diagnoses associated with chiropractic use were also reported., Results: A statistically significantly increasing trend was observed for the number of adults receiving chiropractic care (p < .05), number of visits (p < .05) and utilization rate (P < .05) from 2007 to 2016. A similar trend was not found for chiropractic expenditure during this period (P > .05). The mean number of visits was 8.3 visits per year, with a mean expenditure of $86.94 USD per visit and $721.43 USD per person per year. Mean age of adult chiropractic users each year ranged between 48.6 and 51.2 years old, and users were primarily female (56.3%-60.4%), White persons (90.1%-93.5%), and privately insured (77.3%-82.8%). The most prevalent musculoskeletal diagnoses associated with chiropractic use were low back conditions (45.4%-58.1%), inflammatory/degenerative disc or joint conditions (21.2%-26.8%) and head and neck complaints (9.8%-13.7%)., Conclusion: The findings showed statistically significant increasing trends for the number of adult chiropractic users, the number of visits, and percent utilization of chiropractic care from 2007 to 2016. Conversely, we found a statistically null trend for the total annual expenditure on chiropractic care during the same time period. Findings from this analysis imply that, while chiropractic care appears to be growing, it may still be under-utilized, and more efforts should be devoted to ensuring sustained growth and a larger role in the management of musculoskeletal health., (Copyright © 2024. Published by Elsevier Inc.)

This statement from the Pediatric Academic Societies Maternal Child Health: First 1,000 Days Special Interest Group provides an overview of the rationale, evidence, and key action steps needed to engage Community Health Workers (CHWs) into team-based well-child care (WCC) for families in low-income communities. CHWs have been defined as public health workers who have a trusted and valued connection to a community. Integrating CHWs into early childhood WCC can allow for greater cultural relevancy for families, reduce the burden on clinicians to provide the wide range of WCC services, many of which do not require the expertise of a high-level clinician, and improve preventive care services to families during the vulnerable but critical period of early childhood. There are evidence-based approaches to integrating CHWs into early childhood WCC, as well as payment models that can support them. Implementation and spread of these models will require collaboration and engagement across health systems, clinics, payors, and CHWs; flexibility for local adaptation of these models to meet the needs of clinics, practices, CHWs, and communities; publicly available training resources for CHW education; and research findings to guide effective implementation that incorporates parent and caregiver engagement as well as sustainable payment models., (© 2024. The Author(s).)

Cereal wastes such as rice bran and cereal dust are valuable yet underutilised by-products of grain processing. This study aimed to bio-convert these wastes into bacterial cellulose (BC), an emerging sustainable and renewable biomaterial, via an inexpensive solid-state fermentation (SSF) pre-treatment using three mould isolates. Medium substitution by directly using untreated rice bran or cereal dust did not significantly increase the yield of bacterial cellulose produced by Novacetimonas sp. (NCBI accession number PP421219) compared to the standard Hestrin-Schramm (HS) medium. In contrast, rice bran fermented with Rhizopus oligosporus yielded the highest bacterial cellulose (1.55 ± 0.6 g/L dry weight) compared to the untreated control (0.45 ± 0.1 g/L dry weight), demonstrating an up to 22% increase in yield. Using the SSF process, the media production costs were reduced by up to 90% compared to the standard HS medium. Physicochemical characterisation using SEM, EDS, FTIR, XPS, XRD, and TGA was performed to gain insights into the internal structure, morphology, and chemical bonding of differently produced BC, which revealed comparable biopolymer properties between BC produced in standard and waste-based media. Hence, our findings demonstrate the effectiveness of fungal SSF for transforming abundant cereal waste into BC, providing a circular economy solution to reduce waste and convert it into by-products to enhance the sustainability of the cereal industry.

Anti-bacterial monoclonal antibody (mAb) therapies either rely on toxin neutralization or opsonophagocytic killing (OPK). Toxin neutralization protects the host from toxin-induced damage, while leaving the organism intact. OPK inducing antibodies clear the bacteria but leave the released toxins unencountered. Infection site targeted anti-toxin antibodies (ISTAbs) that we report here addresses this binary paradigm by combining both functionalities into a single molecule. ISTAbs consist of cell wall targeting (CWT) domains of bacteriophage endolysins fused to toxin neutralizing mAbs (IgG). CWT governs specific binding to the surface of bacteria while the IgG variable domain neutralizes the toxins as they are released. The complex is then cleared by phagocytic cells. As proof of concept, we generated several ISTAb prototypes targeting major toxins from two Gram-positive spore forming pathogens that have a high clinical significance; Clostridium difficile , causative agent of the most common hospital-acquired infection, and Bacillus anthracis , a Category A select agent pathogen. Both groups of ISTAbs exhibited potent toxin neutralization, binding to their respective bacterial cells, and induction of opsonophagocytosis. In mice infected with B. anthracis , ISTAbs exhibit significantly higher efficacy than parental IgG in both pre- and post-challenge models. Furthermore, ISTAbs fully protected against B. anthracis infection in a nonhuman primate (NHP) aerosol challenge model. These findings establish that as a platform technology, ISTAbs are broadly applicable for therapeutic intervention against several toxigenic bacterial pathogens.

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter , Cutibacterium , Alloscardovia , Moryella , and Anaeroglobus , that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium , and Bifidobacterium , exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

Introduction: The multidisciplinary American Radium Society Thoracic Committee was assigned to create appropriate use criteria on cardiac toxicity prevention and management for patients undergoing radiotherapy., Methods: A systematic review of the current literature was conducted. Case variants of patients with thoracic malignancies undergoing radiation were created based on presence or absence of cardiovascular risk factors and treatment-related risks assessed by dose exposure to the heart and cardiac substructures. Modified Delphi methodology was used to evaluate the variants and procedures, with less than or equal to three rating points from median defining agreement/consensus., Results: A total of six variants were evaluated. The panel felt that patients with cardiac comorbidities at high risk for radiation-related cardiac toxicity should undergo a prescreening cardiac-focused history and physical (H&P) examination, electrocardiogram, cardiac imaging including an echocardiogram, and referral to a cardiologist/cardio-oncologist. Recommendations for those without cardiac comorbidities at low risk for cardiac toxicity were to undergo a baseline H&P examination only. Conversely, those without cardiac comorbidities but at high risk for radiation-related cardiac toxicity were recommended to undergo a prescreening electrocardiogram, in addition to a H&P examination. For patients with cardiac comorbidities at low risk for cardiac toxicity, the panel felt that prescreening and postscreening tests may be appropriate., Conclusions: The American Radium Society Thoracic appropriate use criteria panel has developed multidisciplinary consensus guidelines for cardiac toxicity prevention, surveillance, and management after thoracic radiotherapy based on cardiac comorbidities at presentation and risk of radiation-related cardiac toxicity., Competing Interests: Disclosure All panelists were required to declare all conflicts of interest for the previous 36 months before initiating work on this document. These complete disclosure forms are retained by the American Radium Society in perpetuity. The American Radium Society Appropriate Use Criteria Steering Committee reviewed these disclosures with the chair and co-chair of this document and approved participation of the panelists before starting development of this work., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer., Methods: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1., Results: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs., Conclusion: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Acinetobacter baumannii , a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.

Introduction: Definitive radiation therapy is considered standard therapy for medically inoperable early-stage NSCLC. Nevertheless, for patients with tumors located near structures such as the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on managing medically inoperable NSCLC located in a central or ultracentral location relative to critical organs at risk., Methods: Case variants regarding centrally and ultracentrally located lung tumors were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel. A comprehensive review of the English medical literature was performed from January 1 1946 to December 31 2023 to inform consensus guidelines. Modified Delphi methods were used by the panel to evaluate the variants and procedures, with at least three rating points from median defining agreement/consensus. The guideline was then approved by the ARS Executive Committee and released for public comment per established ARS procedures., Results: The Thoracic ARS AUC Panel identified 90 relevant references and obtained consensus in all variants. Radiotherapy alone was considered appropriate, with additional immunotherapy to be considered primarily in the clinical trial setting. Hypofractionated radiotherapy in eight to 18 fractions was considered appropriate for ultracentral lesions near the proximal tracheobronchial tree, upper trachea, and esophagus. For other ultracentral lesions near the heart, great vessels, brachial plexus, and spine, or for non-ultracentral but still central lesions, five-fraction stereotactic body radiation therapy was also considered an appropriate option. Intensity-modulated radiotherapy was considered appropriate and three-dimensional-conformal radiotherapy inappropriate for all variants. Other treatment planning techniques to decrease the risk of overdosing critical organs at risk were also considered., Conclusions: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of stage I NSCLC in a central or ultracentral location., Competing Interests: Disclosure Dr. Park reported personal fees AstraZeneca, Bristol-Myers Squibb, Daichii Sankyo, G1 Therapeutics, Galera Medical, RefleXion Medical, Regeneron, and research funding from Merck Sharp & Dohme. Dr. Rimner reported grants from Varian Medical Systems, AstraZeneca, Merck, Boehringer Ingelheim, Pfizer, and National Institutes of Health and personal fees from AstraZeneca, Merck, and MoreHealth. Dr. Chang reported grants from Bristol Myers Squibb and personal fees from Varian Medical Systems and IBA. Dr. Chun reported personal fees from AstraZeneca, Norton Healthcare, Binaytara Foundation, ViewRay, Japanese Society for Radiation Oncology, Hong Kong Precision Oncology Society, and Curio Science. Dr. Donington reported personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Roche/Genentech. Dr. Edelman reported personal fees from AstraZeneca, Takeda, Glaxo Smith Kline, Omega Therapeutics, Novocure, InterVenn, WindMil, Seattle Genetics, Regeneron/Sanofi, Flame Consulting, Proventus Consulting, GE Healthcare Consulting, BioAlta Consulting, Replimmune Consulting, Coherus Consulting, and AnHeart. Dr. Gubens reported personal fees from AnHeart, AstraZeneca, Atreca, Bristol-Myers Squibb, Cardinal Health, Genzyme, Genentech/Roche, Gilead, Guardant, Invitae, iTeos, Merus, Sanofi, Summit, and Surface and grants from Amgen, JNJ, Merck, OncoMed, and Trizell. Dr. Higgins reported grants from Jazz Pharmaceuticals and other support from AstraZeneca, Janssen Pharmaceuticals, and RefleXion Medical. Dr. Iyengar reported other support from Incyte and AstraZeneca. Dr. Movsas reported grants from Varian Research, Philips Research, and ViewRay Research. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Aqueous solutions containing both the strong oxidant, peroxydisulfate (S 2 O 8 2- ), and the strong reductant, oxalate (C 2 ), are thermodynamically unstable due to the highly exothermic homogeneous redox reaction: S 4 2- ), are thermodynamically unstable due to the highly exothermic homogeneous redox reaction: S 2 O 8 2- + C 2 O 4 = -490 kJ/mol). However, at room temperature, this reaction does not occur to a significant extent over the time scale of a day due to its inherently slow kinetics. We demonstrate that the S 2- → 2 SO 4 2- + 2 CO 2 (Δ G 0 = -490 kJ/mol). However, at room temperature, this reaction does not occur to a significant extent over the time scale of a day due to its inherently slow kinetics. We demonstrate that the S 2 reduction of S 8 2- to form S 2 O 4 2- redox reaction occurs rapidly, once initiated by the Ru(NH 3 . Theoretically, the mediated electrochemical generation of a single molecule of S 6 2+ -mediated 1e - cycle that consumes both S 2 O 8 2- to form S 2 in bulk solution. Several experimental demonstrations of S 8 3•- , which rapidly undergoes bond cleavage to form SO 4 2- and the highly oxidizing radical SO 4 is generated in solution for at least 10 min following a 30-s initiation step. Quantitative bulk electrolysis of S •- . Theoretically, the mediated electrochemical generation of a single molecule of S 2 O 8 3•- is initiated by electrogeneration of immeasurably small quantities of S autocatalytic cycle that consumes both S 2 O 8 2- and C 2 O 4 molecular dynamics simulations, and finite difference simulations of cyclic voltammetric responses are presented that support and provide additional insights into the initiation and mechanism of S 2- in bulk solution. Several experimental demonstrations of S 2 O 8 2- /C 2 O 4 2- autocatalysis are presented. Differential electrochemical mass spectrometry measurements demonstrate that CO 2 is generated in solution for at least 10 min following a 30-s initiation step. Quantitative bulk electrolysis of S 2 O 8 2- in solutions containing excess C 2 O 4 2- is initiated by electrogeneration of immeasurably small quantities of S 2 O 8 3•- . Capture of CO 2 as BaCO 3 during electrolysis additionally confirms the autocatalytic generation of CO 2 . First-principles density functional theory calculations, ab initio molecular dynamics simulations, and finite difference simulations of cyclic voltammetric responses are presented that support and provide additional insights into the initiation and mechanism of S 2 O 8 2- /C 2 O 4 2- autocatalysis. Preliminary evidence indicates that autocatalysis also results in a chemical traveling reaction front that propagates into the solution normal to the planar electrode surface.

Bacillus anthracis , the causative agent of anthrax, is among the most likely bacterial pathogens to be used in a biological attack. Inhalation anthrax is a serious, life-threatening form of infection, and the mortality from acute inhaled anthrax can approach 100% if not treated early and aggressively. Food and Drug Administration-approved antibiotics indicated for post-exposure prophylaxis (PEP) or treatment of anthrax are limited. This study assessed the in vitro activity and in vivo efficacy of omadacycline and comparators against clinical isolates of B. anthracis, including a ciprofloxacin-resistant isolate. Minimum inhibitory concentrations (MICs) of omadacycline, ciprofloxacin, and doxycycline were determined against animal and human clinical isolates of B. anthracis , including the ciprofloxacin-resistant Ames strain BAC r 4-2. Mice were challenged with aerosolized BAC r 4-2 spores, and survival was monitored for 28 days post-challenge. Treatment was initiated 24 h after aerosol challenge and administered for 14 days. Omadacycline demonstrated in vitro activity against 53 B. anthracis isolates with an MIC range of ≤0.008-0.25 µg/mL, and an MIC 50 /MIC 90 of 0.015/0.03 µg/mL. Consistent with this, omadacycline demonstrated in vivo efficacy in a PEP mouse model of inhalation anthrax caused by the Ames BAC r 4-2 ciprofloxacin-resistant B. anthracis isolate. Omadacycline treatment significantly increased survival compared with the vehicle control group and the ciprofloxacin treatment group. As antibiotic resistance rates continue to rise worldwide, omadacycline may offer an alternative PEP or treatment option against inhalation anthrax, including anthrax caused by antibiotic-resistant B. anthracis ., Competing Interests: H.S.H., B.K.P., and G.D. have no conflicts to disclose. D.A., S.K.T., and A.W.S. are employees of Paratek Pharmaceuticals, Inc.

The high specificity of human antibodies to blood group A and B antigens is impressive, especially when considering the structural difference between these antigens (tetrasaccharides) is a NHAc versus a hydroxyl group on the terminal monosaccharide residue. It is well established that in addition to anti-A and anti-B there is a third antibody, anti-A,B capable of recognizing both A and B antigens. To analyze this AB specificity, we synthesized a tetrasaccharide, where the NHAc of the A antigen was replaced with an NH 2 . This NH 2 group was then used to attach the glycan to an affinity resin, creating an AB epitope (AB ep ) adsorbent where the critical site for recognition by A and B antibodies was not accessible, while the rest of the (conformationally compact) tetrasaccharide remained accessible. Anti-AB ep antibodies were then isolated from blood group O donors and found to have expected A,B specificity against immobilized and red cell bound synthetic antigens, including AB ep , and were able to agglutinate both A and B red cells. The amount of these anti-AB ep (anti-A,B) antibodies found in the blood of group O donors was comparable to levels of anti-A and anti-B found in group B and A individuals. Using STD-NMR the location for the AB epitope on the tetrasaccharide was found., (© 2024 Wiley-VCH GmbH.)

Growing demand for pesticides has created an environment prone to deceptive activities, where counterfeit or adulterated pesticide products infiltrate the market, often escaping rapid detection. This situation presents a significant challenge for sensor technology, crucial in identifying authentic pesticides and ensuring agricultural safety practices. Raman spectroscopy emerges as a powerful technique for detecting adulterants. Coupling the electrochemical techniques allows a more specific and selective detection and compound identification. In this study, we evaluate the efficacy of spectroelectrochemical measurements by coupling a potentiostat and Raman spectrograph to identify paraquat, a nonselective herbicide banned in several countries. Our findings demonstrate that applying -0.70 V during measurements yields highly selective Raman spectra, highlighting the primary vibrational bands of paraquat. Moreover, the selective Raman signal of paraquat was discernible in complex samples, including tap water, apple, and green cabbage, even in the presence of other pesticides such as diquat, acephate, and glyphosate. These results underscore the potential of this technique for reliable pesticide detection in diverse and complex matrices., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors have no conflicts of interest to declare.

In treatments based on differential reinforcement of alternative behavior, applied researchers and clinicians often provide multiple, qualitatively different reinforcers (i.e., synthesized reinforcement) rather than a single reinforcer (i.e., isolated reinforcement) contingent on alternative behavior. Some research shows that providing synthesized reinforcement for alternative responses within such treatments produces more rapid and complete suppression of target behavior; however, there is limited research evaluating the durability of these effects during treatment disruptions. Conceptual explanations of resurgence (e.g., resurgence as choice, context theory) suggest that treatments that include synthesized alternative reinforcement may lead to more resurgence of target behavior when alternative reinforcement is disrupted relative to treatments using isolated reinforcement. We evaluated this hypothesis within a three-phase resurgence evaluation. We exposed rats to isolated or synthesized reinforcement for alternative responding in the second phase, and we exposed rats to extinction in the third phase. Synthesized alternative reinforcement produced more rapid and complete suppression of target behavior than did isolated reinforcement in the second phase; however, exposure to extinction following synthesized reinforcement produced more resurgence. We discuss these results in terms of their implications for applied research and their support for current conceptual explanations for resurgence., (© 2024 Society for the Experimental Analysis of Behavior.)

Neptunium is an actinide element sourced from anthropogenic production, and, unlike naturally abundant uranium, its coordination chemistry is not well developed in all accessible oxidation states. High-valent neptunium generally requires stabilization from at least one metal-ligand multiple bond, and departing from this structural motif poses a considerable challenge. Here we report a tetrahedral molecular neptunium(V) complex ([Np 5+ (NPC) 4 ][B(ArF 5 ) 4 ], 1-Np) (NPC = [NP t Bu(pyrr) 2 ] - ; t Bu = C(CH 3 ) 3 ; pyrr = pyrrolidinyl (N(C 2 H 4 ) 2 ); B(ArF 5 ) 4  = tetrakis(2,3,4,5,6-pentafluourophenyl)borate). Single-crystal X-ray diffraction, solution-state spectroscopy and density functional theory studies of 1-Np and the product of its proton-coupled electron transfer (PCET) reaction, 2-Np, demonstrate the unique bonding that stabilizes this reactive ion and establishes the thermochemical and kinetic parameters of PCET in a condensed-phase transuranic complex. The isolation of this four-coordinate, neptunium(V) complex reveals a fundamental reaction pathway in transuranic chemistry., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS)., Methods: Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk., Results: This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01)., Conclusions: The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

Purpose: This retrospective study was conducted to ensure that irradiation of the pelvic lymph node areas associated with simultaneous hypofractionated boost to the prostate according to the protocol implemented at the university hospital of Tours (France) does not result in excess urinary and digestive toxicity in the short and medium term., Materials and Methods: The study population included patients with localized unfavourable intermediate or high-risk prostate cancer. The dose delivered was 65Gy in 25 fractions of 2.6Gy to the prostate and seminal vesicles, and 50Gy in 25 fractions of 2Gy to the pelvic lymph nodes. Acute toxicity events (between the start of radiotherapy and the first follow-up consultation) and medium-term toxicity events (after the first follow-up consultation) were assessed using the CTCAE version 5.0 classification., Results: Sixty-three patients were treated according to the protocol between January 1st, 2020, and October 31st, 2022. The majority of them had high-risk prostate cancer (79%). The median follow-up was 15 months. Very few patients reported grade 3-4 toxicity acutely (6% urinary and 0% digestive toxicity) or in the medium term (7% urinary and 0% and digestive toxicity)., Conclusion: Radiotherapy of pelvic lymph node areas with simultaneous hypofractionated boost to the prostate is feasible, with low rates of severe acute and medium-term toxicity., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Data regarding ocular tuberculosis (OTB) in the United States have not been previously reported. We evaluated trends of OTB compared with other extrapulmonary TB (EPTB)., Methods: We estimated the proportion of all EPTB cases (with or without concurrent pulmonary involvement) with OTB reported to the National Tuberculosis Surveillance System during 1993-2019. We compared demographics and clinical characteristics of people with OTB and other EPTB during 2010-2019. P values were calculated by chi-square test for categorical variables and Kruskal-Wallis for continuous variables., Results: During 1993-2019, 1766 OTB cases were reported, representing 1.6% of 109 834 all EPTB cases: 200 (0.5% of 37 167) during 1993-1999, 395 (1.0% of 41 715) during 2000-2009, and 1171 (3.8% of 30 952) during 2010-2019. In contrast to persons with other EPTB, persons with OTB were older (median, 48 vs 44 years; P < .01), more likely to be US-born (35% vs 28%; P < .01), more likely to have diabetes (17% vs 13%; P < .01), and less likely to have HIV (1% vs 8%; P < .01). OTB was less likely to be laboratory confirmed (5% vs 75%; P < .01), but patients were more likely to be tested by interferon gamma release assay (IGRA; 84% vs 56%; P < .01) and to be IGRA positive (96% vs 80%; P < .01)., Conclusions: Reported OTB increased during 1993-2019 despite decreasing TB, including EPTB; the largest increase occurred during 2010-2019. OTB was rarely laboratory confirmed and was primarily diagnosed in conjunction with IGRA results. More research is needed to understand the epidemiology of OTB to inform clinical and diagnostic practices., Competing Interests: Potential conflicts of interest. The authors declare no conflicts of interest related to the content of this manuscript., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Purpose: [ 18 F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [ 11 C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k 2 and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [ 11 C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [ 18 F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions., Method: Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [ 18 F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate [Formula: see text](ref: CS) and DVR CER (ref: CER) values. For SRTM2, the population average of [Formula: see text] was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated., Results: The 1TC k 2 (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC [Formula: see text] was much higher than 1TC [Formula: see text], SRTMC underestimated BP ND (ref: CS) and DVR CER by an average of 3% and 1% across regions, respectively, due to similar bias in k 2 and [Formula: see text] estimation. SRTM underestimated BP ND (ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVR CER underestimation varied by region (mean 10%). Using population average [Formula: see text] values, SRTM2 BP ND and DVR CER showed the best agreement with 1TC estimates., Conclusion: Our findings support the use of population [Formula: see text] value in SRTM2 with [ 18 F]SynVesT-1 for the estimation of [Formula: see text] or DVR CER , regardless of the choice of reference region., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients., (© 2024. The Author(s).)

The synthesis and solution and solid-state characterization of [Pu 4+ (NPC) 4 ], 1-Pu , (NPC = [NP t Bu(pyrr) 2 ] - ; t Bu = C(CH 3 ) 3 ; pyrr = pyrrolidinyl) and [Pu 3+ (NPC) 4 ][K(2.2.2.-cryptand)], 2-Pu , is described. Cyclic voltammetry studies of 1-Pu reveal a quasi-reversible Pu 4+/3+ couple, an irreversible Pu 5+/4+ couple, and a third couple evincing a rapid proton-coupled electron transfer (PCET) reaction occurring after the electrochemical formation of Pu 5+ . The chemical identity of the product of the PCET reaction was confirmed by independent chemical synthesis to be [Pu 4+ (NPC) 3 (HNPC)][B(ArF 5 ) 4 ], 3-Pu , (B(ArF 5 ) 4 = tetrakis(2,3,4,5,6-pentafluourophenyl)borate) via two mechanistically distinct transformations of 1-Pu : protonation and oxidation. The kinetics and thermodynamics of this PCET reaction are determined via electrochemical analysis, simulation, and density functional theory. The computational studies demonstrate a direct correlation between the changing nature of 5 f and 6 d orbital participation in metal-ligand bonding and the electron density on the N im atom with the thermodynamics of the PCET reaction from Np to Pu, and an indirect correlation with the roughly 5-orders of magnitude faster Pu PCET compared to Np for the An 5+ species.

Objective(s): Describe recent national trends in overall treatment modalities for T1 glottic squamous cell carcinomas (SCC), and identify factors associated with treatment regimens., Methods: National Cancer Database from 2004-2020 was queried for all patients with glottic cT1N0M0 SCC. Treatment patterns over time were analyzed using the Cochran-Armitage test for trend. Multivariable logistic regressions were used to determine the factors associated with treatment regimens., Results: Of the 22,414 patients identified, most patients received RT only (57%), 21% received surgery only, and 22% received dual-modality treatment ("over-treatment"). Over the time period, there was a decreasing trend in rates of over-treatment for T1 glottic SCC (p < 0.001) and an increasing trend in surgery only (p < 0.001). Treatment in 2016-2018 (OR: 1.168 [1.004 to 1.359]), 2013-2015 (OR: 1.419 [1.221 to 1.648]), 2010-2012 (OR: 1.611 [1.388 to 1.871]), 2007-2009 (OR: 1.682 [1.450 to 1.951]), or 2004-2006 (OR: 1.795 [1.548 to 2.081]) versus 2019-2020 was associated with greater likelihood of over-treatment. T1b tumors were less likely to be over-treated (OR: 0.795 [0.707 to 0.894]) versus T1a tumors, and less likely to receive surgery first (OR: 0.536 [0.485 to 0.592]) versus T1a tumors., Conclusion: Over-treatment for T1 glottic SCC has been declining, with increasing rates of surgery only. Year of treatment was significantly associated with the receipt of dual-modality treatment. Finally, patients with T1b disease were more likely to receive RT as the first and only treatment., Level of Evidence: 3 Laryngoscope, 134:3633-3644, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18 F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18 F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters., Methods: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL., Results: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non-highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD., Conclusion: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure-function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Bioremediation is considered to be an effective treatment for hydrocarbon removal from polluted soils. However, the effectiveness of this treatment is often limited by the low availability of targeted contaminants. Biosurfactants produced by some microorganisms can increase organic compound solubility and might then overcome this limitation. Two different inocula producers of biosurfactants (Burkholderia thailandensis E264 and SHEMS1 microbial consortium isolated from a hydrocarbon-contaminated soil) were incubated in Bushnell-Haas medium supplemented with hydrocarbons to investigate their biodegradation potential. Experimental results showed their ability to degrade 9.1 and 6.1% of hydrocarbons respectively after 65 days of incubation with an initial total hydrocarbon concentration of 16 g L -1 . The biodegradation was more effective for the light and medium fractions (C10 to C36). B. thailandensis and SHEMS1 consortium produced surfactants after 14 days of culture during the stationary phase with hydrocarbons as the sole carbon and energy source. However, biosurfactant production did not appear to directly increase hydrocarbon degradation efficiency. The complexity and recalcitrance of hydrocarbon mixture used in this study appeared to continue to limit its biodegradation even in the presence of biosurfactants. In conclusion, B. thailandensis and SHEMS1 consortium can degrade recalcitrant hydrocarbon compounds and are therefore good candidates for the bioremediation of environments polluted by total hydrocarbons., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)