Peripheral Location Research Articles

Dramatic changes in mitochondrial subcellular location and morphology accompany activation of the CO2 concentrating mechanism

Dynamic changes in intracellular ultrastructure can be critical for the ability of organisms to acclimate to environmental conditions. Microalgae, which are responsible for ~50% of global photosynthesis, compartmentalize their Ribulose 1,5 Bisphosphate Carboxylase/Oxygenase (Rubisco) into a specialized structure known as the pyrenoid when the cells experience limiting CO2 conditions; this compartmentalization is a component of the CO2 Concentrating Mechanism (CCM), which facilitates photosynthetic CO2 fixation as environmental levels of inorganic carbon (Ci) decline. Changes in the spatial distribution of mitochondria in green algae have also been observed under CO2 limitation, although a role for this reorganization in CCM function remains unclear. We used the green microalga Chlamydomonas reinhardtii to monitor changes in mitochondrial position and ultrastructure as cells transition between high CO2 and Low/Very Low CO2 (LC/VLC). Upon transferring cells to VLC, the mitochondria move from a central to a peripheral cell location and orient in parallel tubular arrays that extend along the cell's apico-basal axis. We show that these ultrastructural changes correlate with CCM induction and are regulated by the CCM master regulator CIA5. The apico-basal orientation of the mitochondrial membranes, but not the movement of the mitochondrion to the cell periphery, is dependent on microtubules and the MIRO1 protein, with the latter involved in membrane-microtubule interactions. Furthermore, blocking mitochondrial respiration in VLC-acclimated cells reduces the affinity of the cells for Ci. Overall, our results suggest that mitochondrial repositioning functions in integrating cellular architecture and energetics with CCM activities and invite further exploration of how intracellular architecture can impact fitness under dynamic environmental conditions.

Computed tomographic features of pulmonary and extrapulmonary lesions can be useful in prioritizing the diagnosis of hemangiosarcoma metastases in dogs.

The aim of this study was to evaluate the CT features of pulmonary metastases in dogs with hemangiosarcoma (HSA) at various sites. Additionally, the CT characteristics of extrapulmonary metastases in the same population were assessed. Retrospective, observational, and descriptive study conducted from April 2013 to January 2024. Dogs with histologically confirmed HSA and suspected or cytologically/histologically confirmed lung metastases were included. Dogs were excluded if they had a second primary tumor or only 1 unsampled pulmonary nodule. 33 dogs were included, with 26/33 [78.8%] having more than 10 metastatic pulmonary nodules. Most nodules were generalized (24/33 [72.7%]), miliary (29/33 [87.9%]) to subcentimetric (32/33 [97%]) in size, well-defined margins (29/33 [87.9%]), or a perilesional halo sign (24/33 [72.7%]). When more than 10 nodules were present, a generalized distribution was prevalent, while a peripheral location was more common when 2 to 10 nodules were present (P < .0001). In 32/33 (97%) cases, a pulmonary vessel was directly connected to the nodule (feeding vessel). After contrast administration, most lung metastases appeared homogenous (26/33 [78.8%]), although some showed areas of intense enhancement (5/33 [15.1%]) a feature also observed in extrapulmonary metastases with varying frequency (0% to 85.7%). Pulmonary HSA metastases were characterized by generalized, small (miliary/subcentimetric), well-defined nodules, commonly associated with a halo sign and feeding vessel. Intralesional areas of spotty postcontrast linear or amorphous strong hyperdensity were frequently observed especially in extrapulmonary metastases. These features may help radiologists and clinicians orient their diagnosis toward metastatic HSA.

Extremely Rare Coexistence of Peripherally Located Mucous Gland Adenoma and Pulmonary Chondroid Hamartoma.

Pulmonary mucous gland adenomas (MGAs) originating in mucous-secreting cells in the bronchi are extremely rare benign tumours. Pulmonary chondroid hamartomas (PCHs) are the most common benign neoplasms of mesenchymal origin of the lung. This study reports an unusual case where MGA and PCH coexisted in a peripheral intra-parenchymal location. A patient with a 1-cm non-specific nodule in the left lung on a computed tomography scan underwent wedge resection. Microscopically, mesenchymal elements consisting of fat and cartilage tissue were observed. Mucous glands were present around these mesenchymal elements. No cellular atypia or mitosis was observed. This allowed for complete treatment without the need for a segmentectomy.

Remote Diagnosis of Retinal Detachment in an Emergency Department Using Nonmydriatic Hybrid Ocular Imaging.

Background: Ocular emergencies are commonly evaluated in general emergency departments (ED) where ophthalmologists are rarely available. Nonmydriatic ocular imaging combining color fundus photographs and optical coherence tomography (NMFP-OCT) can help with rapid remote triage by ophthalmologists. We evaluated the rate at which retinal detachments (RDs) can be diagnosed with NMFP-OCT in the ED. Methods: Quality improvement project with prospective collection of data on RD patients who had NMFP-OCT obtained by ED staff over 1 year. Photographs were interpreted remotely by ophthalmologists and all patients underwent an in-person ophthalmologic examination in the ED to confirm the presence of a RD. Results: A total of 63 eyes (58 patients) had a RD, among which 53 (84.1%) had strong suggestion of RD on ocular imaging (34 [54%] were seen on both color and OCT nerve/macula; 11 [17.5%] were seen on color but missed on OCT; 8 [12.7%] were missed on color but seen on OCT). Ten RDs (15.9%) were missed on both color and OCT because of peripheral location of the RD (4, 40%), vitreous hemorrhage (4, 40%), or poor image quality (2, 20%). A total of 40 out of 58 patients were not seen by an eye care provider prior to reaching our ED and 10 had an inappropriate stroke workup for acute vision loss of presumed vascular origin. Conclusion: NMFP-OCT of the posterior pole obtained by ED staff revealed the RD in 84.1% of eyes, allowing for rapid remote triage of patients with visual symptoms and avoiding unnecessary testing when the diagnosis of RD is confirmed.

Genomic analysis defines distinct pancreatic and neuronal subtypes of lung carcinoid.

Lung carcinoids (L-CDs) are rare, poorly characterised neuroendocrine tumours (NETs). L-CDs are more common in women and are not the consequence of cigarette smoking. They are classified histologically as typical carcinoids (TCs) or atypical carcinoids (ACs). ACs confer a worse survival. Histological classification is imperfect, and there is increasing interest in molecular markers. We therefore investigated global transcriptomic and epigenomic profiles of 15 L-CDs resected with curative intent at Royal Brompton Hospital. We identified underlying mutations and structural abnormalities through whole-exome sequencing (WES) and single nucleotide polymorphism (SNP) genotyping. Transcriptomic clustering algorithms identified two distinct L-CD subtypes. These showed similarities either to pancreatic or neuroendocrine tumours at other sites and so were named respectively L-CD-PanC and L-CD-NeU. L-CD-PanC tumours featured upregulation of pancreatic and metabolic pathway genes matched by promoter hypomethylation of genes for beta cells and insulin secretion (p < 1 × 10-6). These tumours were centrally located and showed mutational signatures of activation-induced deaminase/apolipoprotein B editing complex activity, together with genome-wide DNA methylation loss enriched in repetitive elements (p = 2.2 × 10-16). By contrast, the L-CD-NeU group exhibited upregulation of neuronal markers (adjusted p < 0.01) and was characterised by focal spindle cell morphology (p = 0.04), peripheral location (p = 0.01), high mutational load (p = 2.17 × 10-4), recurrent copy number alterations, and enrichment for ACs. Mutations affected chromatin remodelling and SWI/SNF complex pathways. L-CD-NeU tumours carried a mutational signature attributable to aflatoxin and aristolochic acid (p = 0.05), suggesting a possible environmental exposure in their pathogenesis. Immunologically, myeloid and T-cell markers were enriched in L-CD-PanC and B-cell markers in L-CD-NeU tumours. The substantial epigenetic and non-coding differences between L-CD-PanC and L-CD-NeU open new possibilities for biomarker selection and targeted treatment of L-CD. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Eye-movement methodology reveals a shift in attention from threat to neutral stimuli with self-reported symptoms of social anxiety across children, adolescents and adults

ABSTRACT The current study used an eye-movement remote distractor paradigm (RDP) to examine the relationship between self-reported symptoms of social anxiety in children (9–11-year-olds), young adolescents (12–14-year-olds) and adults (18–43-year-olds) on saccade latencies to identify a target and saccadic errors to task irrelevant distractor (angry, neutral and happy faces). Distractors were presented simultaneously, either at the centre of the display, or at a contralateral parafoveal or peripheral location to the target. Symptoms of social anxiety in children were associated with increased saccade latencies in the presence of angry and neutral faces suggesting avoidance of these emotion expressions in this age group. Symptoms of social anxiety in adolescents and adults were respectively linked with longer latencies for neutral faces, indicating that neutral faces represent ambiguous and potentially negative stimuli for individuals with elevated social anxiety, and fit with research that has questioned the role of neutral faces as non-emotional control stimuli in attention research and anxiety.

Geographies of race in Poland and Central and Eastern Europe

ABSTRACT This article is a discipline-defining agenda. It addresses the oversight of Geographies of race in Central and Eastern Europe (CEE) and explores geography’s potential contributions to the unfolding debates around race, decolonisation, and whiteness. Geographies of race remain unmarked and therefore unchallenged within the field of geography in CEE. Consequently, geographers typically consider CEE as peripheral to the global racial discourses and possibly post-racial. By drawing on sociological, migration, historical, and anthropological approaches, particularly in Poland, the article emphasises the importance of geography in discussions around race, decolonisation, and whiteness. It considers the appeal of geographies of race to this “peripheral location” to demonstrate a shift in racial and colonial discourses. By bridging interdisciplinary approaches and challenging prevailing discourses, the article aims to broaden the scope of the geographies of race and foster a more inclusive and global understanding of race and colonisation.

Dual-energy CT Radiomics Combined with Quantitative Parameters for Differentiating Lung Adenocarcinoma From Squamous Cell Carcinoma: A Dual-center Study

Rationale and ObjectivesTo evaluate the ability of dual-energy CT(DECT)-based quantitative parameters and radiomics features to differentiate solid lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC). MethodsThis study included 213 patients diagnosed with ADC and SCC who underwent DECT scans at two centers from November 2022 to December 2023. Patients at center 1 were randomly divided into training(n=114) and internal test set (n=50) in a 7:3 ratio, with center 2 serving as the external test set (n=49). Radiologic and clinical data were combined to establish a clinical-radiologic model. Ten types of DECT energy images including conventional images, iodine density (ID), effective atomic number (Zeff), electron density, and virtual monoenergetic images (VMI) were reconstructed in both arterial phases (AP) and venous phases (VP). Quantitative parameters were measured at the uniform enhanced solid portion of the tumor and normalized to the aorta, used to develop a quantification model and calculate the quantitative score (quantscore). Radiologists manually delineated the tumor ROI at the largest level for extracting radiomics features in these 10 energy images. These features were used to establish ten uni-energy models from which the best-performing features were selected to construct the final radiomics model and calculate a radiomics score (radscore). Then, a combined model was developed using the akaike information criterion(AIC) and compared with the clinical-radiological model to test its diagnostic validity. ResultsThe independent predictors of the clinical-radiological model included age, gender, and central or peripheral location, and the AUCs for the training set, internal test set, and external test set were 0.808, 0.837, and 0.802. The quantification model incorporated 40keV CT values, Zeff, normalized Zeff, and the slope of the spectral attenuation curve (λHU) in the AP and normalized ID, Zeff, and λHU in the VP. Uni-energy models based on AP ID maps, AP Zeff maps, and VP VMI 65keV significantly outperformed AUC = 0.5, and 11 radiomics features were selected from these three models to construct the final radiomics model. The combined model, incorporating age, gender, quantscore, and radscore, significantly outperformed the clinical-radiological model in the training set (AUC = 0.952 vs 0.808, P < 0.001), and demonstrated higher performance in both the internal and external test sets, although these differences did not reach statistical significance (AUC = 0.870 vs 0.837, for the internal test set [P = 0.542], 0.888 vs 0.802 for the external test sets [P = 0.128]). The evaluation of the combined model demonstrated good discriminative ability and potential for generalization. ConclusionsThe combined model, integrating quantitative parameters and radiomics features from DECT multi-energy images with clinical-radiological characteristics, can be used as a non-invasive tool to differentiate ADC from SCC.

Top-Down Priors Disambiguate Target and Distractor Features in Simulated Covert Visual Search.

Several models of visual search consider visual attention as part of a perceptual inference process, in which top-down priors disambiguate bottom-up sensory information. Many of these models have focused on gaze behavior, but there are relatively fewer models of covert spatial attention, in which attention is directed to a peripheral location in visual space without a shift in gaze direction. Here, we propose a biologically plausible model of covert attention during visual search that helps to bridge the gap between Bayesian modeling and neurophysiological modeling by using (1) top-down priors over target features that are acquired through Hebbian learning, and (2) spatial resampling of modeled cortical receptive fields to enhance local spatial resolution of image representations for downstream target classification. By training a simple generative model using a Hebbian update rule, top-down priors for target features naturally emerge without the need for hand-tuned or predetermined priors. Furthermore, the implementation of covert spatial attention in our model is based on a known neurobiological mechanism, providing a plausible process through which Bayesian priors could locally enhance the spatial resolution of image representations. We validate this model during simulated visual search for handwritten digits among nondigit distractors, demonstrating that top-down priors improve accuracy for estimation of target location and classification, relative to bottom-up signals alone. Our results support previous reports in the literature that demonstrated beneficial effects of top-down priors on visual search performance, while extending this literature to incorporate known neural mechanisms of covert spatial attention.

Neoproterozoic tectonic shift along the western margin of the Yangtze block, South China craton: Implications for its paleogeographic position during the Rodinia−Gondwana transition

Neoproterozoic igneous rocks in the Panxi region from the western margin of the Yangtze block, South China craton, record major changes in tectonic evolution and crustal thickness, and provide important constraints on the paleogeographic position and climate changes of the block in Rodinia and Gondwana reconstructions. Our new dating results show that the Pengguan complex from the Panxi region comprises ca. 743 Ma adakitic granodiorites and ca. 741 Ma A-type granites. The former is plagioclase-rich and has relatively low SiO2 content (65.22−67.36 wt%), high Mg# values (44.40−52.33), Sr/Y (23.22−61.94) and (La/Yb)N ratios (normalized to chondritic values; 13.41−24.00), with positive whole-rock εNd(t) values (+1.17 to +5.15), and high zircon εHf(t) (+5.53 to +8.83) and low zircon δ18O (4.21‰ to 5.51‰) values, indicating derivation from the partial melting of thickened juvenile mafic lower crust. By contrast, the granites are rich in K-feldspar and have high SiO2 contents (78.71−84.62 wt%), 10,000 × Ga/Al ratios (&amp;gt;2.6), and Fe/Mg ratios, with negative εNd(t) values (−1.47 to −0.02), high zircon εHf(t) (+2.94 to +9.77), and high saturation temperatures (828−920 °C). These features indicate fractional crystallization and partial melting of continental crust in a low-pressure, high-temperature, extensional environment. Integrated with the zircon Eu anomalies (Eu/Eu*) data and Hf-O isotopic data on pre-740 Ma magmatism in the Panxi region, we find that a rapid increase of crustal thickening (820−740 Ma) was synchronous with a gradual decrease of zircon δ18O and an increase of zircon εHf(t) values. These variations indicate an increase in the degree of hybridization between mantle sources and subducting slab-derived materials, thus generating a great number of low-δ18O melts, and continuous crustal thickening through the underplating of juvenile magmas. In addition, thinning of the crust since ca. 740 Ma, along with the gradual increase in zircon δ18O and εHf(t), suggests a shift from regional compression to extension. This documented shift, together with regional data from along the western margin of the Yangtze block, indicates a change from the well-developed and long-established Panxi convergent plate margin arc system (at least ca. 870−750 Ma) to passive-margin development and Cryogenian (720−635 Ma) glaciation. The long-lived subduction zone requires a peripheral location of South China that was linked to northern India during the Rodinia breakup. The subsequent and contemporaneous passive-margin development of the Yangtze block and India, along with the similar tectonic affinities of the Cathaysia block with India, indicate that South China lay outboard of the northern Gondwana margin during the assembly of this supercontinent.

Far-from-sight and expensive: additional costs of public services in rural areas

ABSTRACT Countries reap numerous benefits from maintaining rural communities. Those advantages, however, come at a cost. We examine the additional costs of public services in rural areas in Israel by considering sparsity, population size and density, distances, and socio-economic status of rural residents. We quantify the effect of these factors and find that the cost of providing public services in rural areas is 39% greater than in cities. Density and other structural differences contribute 20% to the added cost. Economies of scale contribute 8.2%; peripheral location 4.2%; and socio-economic status 2.6%. We show that population density moderates the relation between population size and per-resident expenditure. We also demonstrate that more rural villages in an area increases per-resident expenditure and moderates the relation between distance and expenditure. We discuss policy implications and suggest contributions to a deeper understanding of the rural public economy.

Intravascular Ultrasound during Endovascular Intervention for Peripheral Artery Disease, by Severity, Location, Device, and Procedure

There is limited evidence for the role of Intravascular Ultrasound (IVUS) in patients undergoing peripheral vascular intervention (PVI). We conducted retrospective cohort study utilizing the HCUP-AHRQ National Readmission database(NRD) to delineate outcomes in IVUS guided PVI versus non-IVUS guided PVI. The current study utilized NRD between January 1, 2016, and December 31, 2019. We identified patients undergoing endovascular intervention for peripheral artery disease using relevant ICD-10-PCS. The cohort was divided based on the use of IVUS during the procedure. The primary outcome was major amputation at 6 months after index hospitalization. Measured confounders were matched using propensity score inverse probability of treatment weighing method. We further performed a subgroup analysis based on disease severity, location of intervention, device, and procedure.A total of 434901 hospitalizations were included in the present analysis. PVI with IVUS compared with no IVUS had similar risk of amputation at 6 months (195 of 8939[2.17%] versus 10404 of 384003 [2.71%]);Hazard Ratio,0.98;CI, 0.77–1.25. Further, there was no difference in the rates of secondary outcomes. On subgroup analysis, amputation rates were significantly lower among patients with rest pain, in iliac intervention, or patients undergoing drug eluting stent implantation with the use of IVUS compared with no IVUS. This nationwide observational study showed that there was no difference in major amputation rates with the use of IVUS in patients undergoing PVI. However, in subgroup of patients with rest pain, iliac intervention or drug-eluting stent implantation IVUS use was associated with significantly lower major amputation rates.

Ultrathin Bronchoscopy Without Virtual Navigation for Diagnosis of Peripheral Lung Lesions

BackgroundThe increasing incidence of encountering lung nodules necessitates an ongoing search for improved diagnostic procedures. Various bronchoscopic technologies have been introduced or are in development, but further studies are needed to define a method that fits best in clinical practice and health care systems.Research questionHow do basic bronchoscopic tools including a combination of thin (outer diameter 4.2 mm) and ultrathin bronchoscopes (outer diameter 3.0 mm), radial endobronchial ultrasound (rEBUS) and fluoroscopy perform in peripheral pulmonary lesion diagnosis?Study Design and MethodsThis is a retrospective review of the performance of peripheral bronchoscopy using thin and ultrathin bronchoscopy with rEBUS and 2D fluoroscopy without a navigational system for evaluating peripheral lung lesions in a single academic medical center from 11/2015 to 1/2021. We used a strict definition for diagnostic yield and assessed the impact of different variables on diagnostic yield, specifically after employment of the ultrathin bronchoscope. Logistic regression models were employed to assess the independent associations of the most impactful variables.ResultsA total of 322 patients were included in this study. The median of the long axis diameter was 2.2 cm and the median distance of the center of the lesion from the visceral pleural surface was 1.9 cm. Overall diagnostic yield was 81.3% after employment of the ultrathin bronchoscope, with more detection of concentric rEBUS views (93% vs. 78%, p < 0.001). Sensitivity for detecting malignancy also increased from 60.5% to 74.7% (p = 0.033) after incorporating the ultrathin scope into practice, while bronchus sign and peripheral location of the lesion were not found to affect diagnostic yield. Concentric rEBUS view, solid appearance, upper/middle lobe location and larger size of the nodules were found to be independent predictors of successful achievement of diagnosis at bronchoscopy.Interpretation: This study demonstrates a high diagnostic yield of biopsy of lung lesions achieved by utilization of thin and ultrathin bronchoscopes. Direct visualization of small peripheral airways with simultaneous rEBUS confirmation increased localization rate of small lesions in a conventional bronchoscopy setting without virtual navigational planning.

CT Imaging Patterns in Major Histological Types of Lung Cancer.

Lung cancer ranks as the second most prevalent cancer globally and is the primary contributor to neoplastic-related deaths. The approach to its treatment relies on both tumour staging and histological type determination. Data indicate that the prognosis of lung cancer is strongly linked to its clinical stage, underscoring the importance of early diagnosis in enhancing patient outcomes. Consequently, the choice of an appropriate diagnostic method holds significant importance in elevating both the early detection rate and prognosis of lung cancer. This paper aims to assess computer tomography features specific to the most common lung cancer types (adenocarcinoma, squamous cell carcinomas and small cell lung cancer). Data were collected retrospectively from CT scans of 58 patients pathologically diagnosed with lung cancer. The following CT features were evaluated and recorded for each case: location, margins, structure, lymph node involvement, cavitation, vascular bundle-thickening, bronchial obstruction, and pleural involvement. Squamous cell carcinoma (SQCC) and small cell lung cancer (SCLC) showed a higher incidence of central location, while adenocarcinoma (ADC) showed a significant predilection for a peripheral location. Internal cavitation was mostly observed in SQCC, and a solid structure was observed in almost all cases of ADC. These features can provide information about the prognosis of the patient, considering that NSCLCs are more frequent but tend to demonstrate positive results for targetable driver mutations, such as EGFR, thereby increasing the overall survival. In addition, SCLC presents with early distant spreads, which limits the opportunity to investigate the evolution of tumorigenesis and gene alterations at early stages but can have a rapidly positively response to chemotherapy. The location of the lung cancer exhibits distinct forecasts, with several studies suggesting that peripheral lung tumours offer a more favourable prognosis. Cavity formation appears correlate with a poorer prognosis. Histopathological analysis is the gold standard for diagnosing the type of lung cancer; however, using CT scanning for the purpose of a rough, but fast, preliminary diagnosis has the potential to shorten the waiting time for treatment by helping clinicians and patients to know more about the diagnosis and prognosis.

Working memory components modulation of attentional disengagement from evaluative distractor.

It is important for people to disengage attention from a distraction, which can help them complete the task at hand as quickly as possible. Recent studies have shown that people's attention stays longer on reward-distractors than on loss-distractors, and a delay in attentional disengagement is noted when reward-distractors are present. However, few studies have examined whether attentional disengagement from an evaluative distractor relies upon working memory (WM) components. In the present study, we used an attentional disengagement paradigm in which reward- or loss-distractors were presented at a central location and the target was presented at a peripheral location, in combination with different WM tasks. The results from Experiment 1 showed that participants were slower to disengage their attention from a central reward-distractor than a loss-distractor regardless of cognitive load when the phonological loop component of WM was involved. The results from Experiment 2 revealed that people had difficulty in shifting their attention away from a reward-distractor in comparison to a loss-distractor when spatial WM was low, whereas no such difference was observed when spatial WM was high. We conclude that WM components differently modulate attentional disengagement from evaluative distractors. That is, the processing of evaluative (reward and loss) distractors may rely on the same cognitive resources as the spatial WM component, but not the phonological loop component.

SMARCA4-deficient non-small cell lung carcinoma: clinicodemographic, computed tomography, and positron emission tomography-computed tomography features.

SMARCA4-deficient non-small cell lung carcinoma (SD-NSCLC) is a relatively rare tumor, which occurs in 5-10% of NSCLC. Based on World Health Organization thoracic tumor classification system, SMARCA4-deficient undifferentiated tumor (SD-UT) is recognized as a separate entity from SD-NSCLC. Differentiation between SD-NSCLC and SD-UT is often difficult due to shared biological continuum, but often required for choosing appropriate treatment regimen. Therefore, the aim of our study was to identify the clinicopathologic, computed tomography (CT), and positron emission tomography (PET)-CT imaging features of SD-NSCLC. Nine patients of pathologically confirmed SD-NSCLC were included in our analysis. We reviewed electronic medical records for clinical information, demographic features, CT, and PET-CT imaging features were analyzed. Smoking history and male predominance are observed in all patients with SD-NSCLC (n=9). On CT, SD-NSCLC appeared as relatively well-defined masses with lobulated contour (n=8) and peripheral location (n=7). Invasion of adjacent pleura or chest wall (n=7) were frequently observed, regardless of small tumor size. Four cases showed lymph node metastases. Among nine patients, three patients showed multiple bone metastases, and one patient showed lung-to-lung metastases. In patient with SD-NSCLC, there was tendency for male smokers, peripheral location and invasion of adjacent pleural or chest wall invasion regardless of small tumor size, when compared to SD-UT.

A Phase 2 Trial of Primary Tumor Stereotactic Body Radiation Therapy Boost Before Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer

Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor before the start of CRT to improve PTC. Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1 year, and the hypothesis was that the 1-year PTC rate would be ≥90%. Secondary objectives included objective response rate, regional and distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional magnetic resonance imaging and blood-based miRNA analysis. The study enrolled 21 patients (10 men and 11 women); the median age was 62 years (range, 52-78). The median pretreatment primary tumor size was 5.0 cm (range, 1.0-8.3). The most common nonhematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 nonhematologic toxicity occurred (respiratory failure/radiation pneumonitis), and no grade 5 toxicities occurred. The objective response rate at 3 and 6 months was 72.7% and 80.0%, respectively, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control rates were 81.6% and 70.3%, respectively. Disease-free survival and overall survival at 2 years were 46.1% and 50.3%, respectively, and median survival was 37.8 months. Functional magnetic resonance imaging detected a mean relative decrease in blood oxygenation level-dependent signal of -87.1% (P = .05), and miR.142.3p was correlated with increased risk of grade ≥3 pulmonary toxicity (P = .01). Dose escalation to the primary tumor using upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. Functional magnetic resonance imaging suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p was correlated with pulmonary toxicity.

ZEISS PLEX Elite 9000 Widefield Optical Coherence Tomography Angiography as Screening Method for Early Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease.

To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting. We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated. In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA. The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy. Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.

FurC (PerR) contributes to the regulation of peptidoglycan remodeling and intercellular molecular transfer in the cyanobacterium Anabaena sp. strain PCC 7120.

Microbial extracellular proteins and metabolites provide valuable information concerning how microbes adapt to changing environments. In cyanobacteria, dynamic acclimation strategies involve a variety of regulatory mechanisms, being ferric uptake regulator proteins as key players in this process. In the nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120, FurC (PerR) is a global regulator that modulates the peroxide response and several genes involved in photosynthesis and nitrogen metabolism. To investigate the possible role of FurC in shaping the extracellular environment of Anabaena, the analysis of the extracellular metabolites and proteins of a furC-overexpressing variant was compared to that of the wild-type strain. There were 96 differentially abundant proteins, 78 of which were found for the first time in the extracellular fraction of Anabaena. While these proteins belong to different functional categories, most of them are predicted to be secreted or have a peripheral location. Several stress-related proteins, including PrxA, flavodoxin, and the Dps homolog All1173, accumulated in the exoproteome of furC-overexpressing cells, while decreased levels of FurA and a subset of membrane proteins, including several export proteins and amiC gene products, responsible for nanopore formation, were detected. Direct repression by FurC of some of those genes, including amiC1 and amiC2, could account for odd septal nanopore formation and impaired intercellular molecular transfer observed in the furC-overexpressing variant. Assessment of the exometabolome from both strains revealed the release of two peptidoglycan fragments in furC-overexpressing cells, namely 1,6-anhydro-N-acetyl-β-D-muramic acid (anhydroMurNAc) and its associated disaccharide (β-D-GlcNAc-(1-4)-anhydroMurNAc), suggesting alterations in peptidoglycan breakdown and recycling.IMPORTANCECyanobacteria are ubiquitous photosynthetic prokaryotes that can adapt to environmental stresses by modulating their extracellular contents. Measurements of the organization and composition of the extracellular milieu provide useful information about cyanobacterial adaptive processes, which can potentially lead to biomimetic approaches to stabilizing biological systems to adverse conditions. Anabaena sp. strain PCC 7120 is a multicellular, nitrogen-fixing cyanobacterium whose intercellular molecular exchange is mediated by septal junctions that traverse the septal peptidoglycan through nanopores. FurC (PerR) is an essential transcriptional regulator in Anabaena, which modulates the response to several stresses. Here, we show that furC-overexpressing cells result in a modified exoproteome and the release of peptidoglycan fragments. Phenotypically, important alterations in nanopore formation and cell-to-cell communication were observed. Our results expand the roles of FurC to the modulation of cell-wall biogenesis and recycling, as well as in intercellular molecular transfer.

Back to the suburbs? Millennial residential locations from the Great Recession to the pandemic

In the past decade, there has been a great deal of attention paid to and speculation about the residential mobility and location decisions of millennials. Academics and practitioners alike have been trying to determine where millennials are moving and why, including whether they are leading a ‘back to the city’ movement or whether they are moving to the suburbs as previous generations did at their age. Using US Census data, this article examines the geographical population distribution of young adults in the USA in recent decades. Categorising neighbourhoods by their urban or suburban character and by their central or peripheral location, we find that millennials lived in urban areas on the heels of the Great Recession at higher rates than previous generations. However, over the decade, the millennial population gradually shifted towards suburban areas: central urban and peripheral urban neighbourhoods largely lost millennial residents from 2011 to 2021, while peripheral suburban neighbourhoods experienced substantial gains. When it comes to neighbourhood amenities (e.g. restaurants and parks), millennials largely left amenity-rich areas for neighbourhoods with fewer amenities, though these amenities grew faster in the neighbourhoods that gained millennials the most. Millennial suburbanisation seems to be associated with housing affordability and demand for larger homes, as the population shift was more pronounced in the metros that have lower housing affordability and a lower share of larger homes in their central urban neighbourhoods. The results indicate the importance of affordable and right-sized housing, complemented with neighbourhood amenities, in attracting and retaining this population group.