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Abstract Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2− stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4–5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer. Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009

As multiple UN fora develop parallel rules for sharing benefits from digital sequence information, we urge better coordination. International policymakers should focus on harmonizing new benefit-sharing rules to ensure open access to data, database interoperability, and better benefit sharing outcomes.

Purpose: To determine the role of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) in differentiating the inflammatory process and malignant lymphoma of the lacrimal gland. Methods: A retrospective analysis of all subjects who underwent lacrimal gland biopsy and magnetic resonance (MR) imaging with DWI sequences during a 10-year period at the Sheba Medical Center, Israel. The lacrimal glands’ ADC values were documented bilaterally by blinded observers and correlated with the final histology verified diagnoses. Results: Twenty-eight patients were included, with 19 females (68%) with a mean ± SD age of 48.1 ± 25.7 years. The right orbit was involved in 14 cases (50%) and the left in 13 (46%); one patient (4%) had bilateral involvement. Seventeen cases (61%) had a final diagnosis of idiopathic inflammation or dacryoadenitis, and six cases (21%) were diagnosed with lymphoma. Additional diagnoses included pleomorphic adenoma in 3 (11%), adenoid cystic carcinoma, and solitary fibrous tumor. Lower mean ADC values were observed in the lymphoma versus inflammatory group (1.03 × 10-3 Vs. 1.45 × 10-3, P = 0.02). Conclusion: Restricted diffusion on MR imaging can serve as a diagnostic tool in the differentiation between inflammatory processes of the lacrimal gland and lymphoma.

Abstract Background The effects of post‐coronavirus disease 2019 (COVID‐19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed to evaluate the effects of a 12‐week telerehabilitation programme on cardiorespiratory and muscular fitness and body composition in older patients with post‐COVID‐19 syndrome. Methods One hundred twenty older patients with post‐COVID‐19 syndrome were randomly assigned to one of two groups: patients who carried out the telerehabilitation programme (n = 60; age: 65.0 ± 5.2; female: 14.2%) and a control group (n = 60; age: 64.3 ± 5.0; female: 24.5%). An incremental cardiopulmonary exercise testing, isokinetic strength test, and bioelectrical impedance analysis were performed to compare cardiorespiratory and muscle strength responses and body composition between telerehabilitation and control groups. Results A significant increase in the cardiopulmonary exercise testing duration was found in the telerehabilitation group compared to the control group (mean difference = 88.9 s, P = 0.001). Peak oxygen uptake increased in the telerehabilitation group (mean difference = 3.0 mL·kg−1·min−1, P

The ability to freely control the polarization of X-rays enables measurement techniques relying on circular or linear dichroism, which have become indispensable tools for characterizing the properties of chiral molecules or magnetic structures. Therefore, the demand for polarization control in X-ray free-electron lasers is increasing to enable polarization-sensitive dynamical studies on ultrafast time scales. The soft X-ray branch Athos of SwissFEL was designed with the aim of providing freely adjustable and arbitrary polarization by building its undulator solely from modules of the novel Apple X type. In this paper, the magnetic model of the linear inclined and circular Apple X polarization schemes are studied. The polarization is characterized by measuring the angular electron emission distributions of helium for various polarizations using cold target recoil ion momentum spectroscopy. The generation of fully linear polarized light of arbitrary angle, as well as elliptical polarizations of varying degree, are demonstrated.

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify host genetic factors influencing the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single-nucleotide polymorphisms (SNPs) previously associated with the innate immune response in a total of 97 elderly (age > 65 years) residents of three long-term care facilities located in Barcelona, Spain. Individuals were PCR-tested during the SARS-CoV-2 outbreaks between September and November 2020. SARS-CoV-2 PCR tests revealed infections in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2 seronegative until vaccination (January and February 2021). After adjusting for sex and age, we found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility—MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2 infection was found for 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in the gene encoding oligoadenylate synthetase (OAS). Our results indicate that MMS19/rs2236575_A and IFIH1/rs1990760_TC genetic variants were associated with a resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors.

This conceptual methods article parallels remarks given at the 2022 American Association on Intellectual and Developmental Disabilities conference highlighting the importance of including the voices of people with intellectual disability in research processes. The purpose of this article was to put forth a call to action to disability researchers to advance, expect, and model inclusive research practices and consider this action as a form of scholarly activism and allyship toward the intellectual and developmental disabilities community. This conceptual article is organized to engage existing inclusive research literature and offers a method of inclusive research team design with practical suggestions for consideration. Finally, implications for research policy are also presented.

Neural efficiency, adaptability, and synchronization, or the ability to recruit, dynamically modulate, and coordinate neural resources on an "as needed" basis, have been proposed as hallmarks of skilled reading. The current study explored the relation between these aspects of neural functioning during reading, as measured by electroencephalography (EEG), and individual differences in inhibitory control, as measured by performance on the Simon task. Wireless 16-channel EEG headsets were used to record eyes-closed resting-state EEG and EEG during reading (recorded while participants completed a reading comprehension test). Results from 140 participants showed a significant correlation between inhibitory control and neural efficiency in the theta frequency band within the right posterior region-of-interest, but no significant correlations with neural adaptability or synchronization. Given the established relation between theta-based activity and linguistic processes, this finding suggests that readers with better inhibitory control demonstrate more efficient use of their language network while reading.

The green spaces in Wat Pah play an important role in forest conservation in Thailand. This study identified and analyzed the structures and patterns of landscape ecology in Wat Pah Nanachart, Ubon Ratchathani Province, to guide a conceptual framework for green space conservation in forest monasteries. Spatial analysis and modeling using geoinformatics technology were employed to recognize and characterize these landscapes. Information on the green space conservation and management of Wat Pah was also obtained using an in-depth interview and site observation. The results revealed that most of the green space in Wat Pah is forest, characterized by an ecological matrix and a dry evergreen forest. The forest structure can be divided into three canopies, dominated by the Dipterocarpaceae family, which has regenerated into upper and lower canopies. It is an edge matrix and ecological corridor connected to the internal and external green spaces of Wat Pah. It plays an important role in supporting cultural, religious, and aesthetic activities for ordained monks and Buddhists. The spatial landscape model can be divided into three main zones: Thoranisangha, Buddhawas, Sanghawas. Thoranisangha is an open space covered with traditional and artificially planted tree species. It is located in front of the temple and designed for public utilities in the context of managing and conserving the remaining trees. Buddhawas is a semi-open space mostly covered with traditional tree species. It represents Buddhism’s identity and uniqueness and is used for religious ceremonies and dissemination—listening to sermons, meditating, and praying. Meanwhile, Sanghawas is covered with natural forest and contains residences for monks that are designed to be in harmony with the forest ecosystem.

This article presents a demonstration of the improved performance of an X-ray free-electron laser (FEL) using the optical klystron mechanism and helical undulator configuration, in comparison with the common planar undulator configuration without optical klystron. The demonstration was carried out at Athos, the soft X-ray beamline of SwissFEL. Athos has variable-polarization undulators, and small magnetic chicanes placed between every two undulators to fully exploit the optical klystron. It was found that, for wavelengths of 1.24 nm and 3.10 nm, the required length to achieve FEL saturation is reduced by about 35% when using both the optical klystron and helical undulators, with each effect accounting for about half of the improvement. Moreover, it is shown that a helical undulator configuration provides a 20% to 50% higher pulse energy than planar undulators. This work represents an important step towards more compact and high-power FELs, rendering this key technology more efficient, affordable and accessible to the scientific community.

Abstract This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated β-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated β-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.