Peripheral Zone Research Articles

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.

Влияние ортокератологических контактных линз на анатомо-функциональное состояние роговицы

Aim: To analyze the potential impact of orthokeratological lenses when correcting myopia on the anatomical and functional state of the cornea. 160 eyes (80 patients) were examined – 60 eyes (30 patients) with mild myopia, 100 eyes (50 patients) with moderate myopia, average age 12.0 ± 0.38 years. Control group – 40 eyes (20 patients), with emmetropia, average age – 13.0 ± 0.45 years. All patients used reverse geometry orthokeratological lenses «Moonlens» from «Sky Optix» in night mode. Research methods. Special research methods were carried out: keratotopography, OCT of the anterior segment of the eye, autorefractometry, ophthalmometry, biometry, skiascopy against the background of cycloplegia, ultrasound of the eye, biomicroscopy, ophthalmoscopy. Results. After the use of orthokeratological lenses, flattening of the cornea from the center to the periphery was revealed with the formation of a negative value of the asphericity index «Q» – exactly (-) 0.57±0.054 (p &lt;0.01); an increase in refraction in the middle and peripheral zones of the cornea with an increase in the asymmetry index «l-S» is 3.0±0.12D (p &lt;0.01). According to the SimK1 and SimK2 meridians, the degree of weakening of refraction in the center of the cornea was revealed (-) 2.32±0.19D and the degree of enhancement of refraction of the cornea in the middle and peripheral zones – (+) 61±0.53D and (+) 0.97 0, 11D. Conclusion. Thus, the identified changes in the anatomical and functional state of the cornea during the treatment of myopia with orthokeratological lenses in the night mode indicate a transformation of the induced myopic defocus.

Investigating anxiolytic effect of intranasal micro emulsion in experimental animal models

This investigation aimed to assess the anxiolytic potential of an intranasal micro emulsion formulation in an experimental model utilizing Swiss Albino Mice. The evaluation of anti-anxiety activity was conducted through the Elevated plus Maze and Open Field tests. In the Elevated plus Maze, parameters such as the total count of arm entries and the duration spent in both open and enclosed arms were meticulously recorded. Similarly, the Open Field tests involved the documentation of entries in the central region, the time spent in the central region, entries into the peripheral zone, and time spent in the peripheral zone. The experimental subjects received treatment with the intranasal micro emulsion formulation at a dosage of 50mg/kg. The results from the Elevated plus Maze exhibited a noteworthy (p&lt;0.01**) augmentation in the quantity of entries and the duration of sojourn within the open arm. Parallelly, the Open Field tests revealed a significant (p&lt;0.01**) escalation in the count of squares traversed and the frequency of crossings. This investigation unequivocally indicated that the intranasal micro emulsion formulation elicited a pronounced anti-anxiety effect in the experimental animal model. This research contributes to the expanding body of knowledge on the potential therapeutic efficacy of intranasal micro emulsion formulations in addressing anxiety-related behaviors, thereby paving the way for further investigations and potential clinical applications.

Giant honeybees (Apis dorsata) trade off defensiveness against periodic mass flight activity.

The giant honeybee Apis dorsata (Fabricius, 1793) is an evolutionarily ancient species that builds its nests in the open. The nest consists of a single honeycomb covered with the bee curtain which are several layers of worker bees that remain almost motionless with their heads up and abdomens down on the nest surface, except for the mouth area, the hub between inner- and outer-nest activities. A colony may change this semi-quiescence several times a day, depending on its reproductive state and ambient temperature, to enter the state of mass flight activity (MFA), in which nest organisation is restructured and defense ability is likely to be suppressed (predicted by the mass-flight-suspend-defensiveness hypothesis). For this study, three episode of MFA (mfa1-3) of a selected experimental nest were analysed in a case study with sequences of >60 000 images at 50 Hz, each comprise a short pre-MFA session, the MFA and the post-MFA phase of further 10 min. To test colony defensiveness under normative conditions, a dummy wasp was cyclically presented with a standardised motion programme (Pd) with intervening sessions without such a presentation (nPd). Motion activity at five selected surveillance zones (sz1-5) on the nest were analysed. In contrast to mfa1,2, in mfa3 the experimental regime started with the cyclic presentation of the dummy wasp only after the MFA had subsided. As a result, the MFA intensity in mfa3 was significantly lower than in mfa1-2, suggesting that a colony is able to perceive external threats during the MFA. Characteristic ripples appear in the motion profiles, which can be interpreted as a start signal for the transition to MFA. Because they are strongest in the mouth zone and shift to higher frequencies on their way to the nest periphery, it can be concluded that MFA starts earlier in the mouth zone than in the peripheral zones, also suggesting that the mouth zone is a control centre for the scheduling of MFA. In Pd phases of pre- and postMFA, the histogram-based motion spectra are biphasic, suggesting two cohorts in the process, one remaining at quiescence and the other involved in shimmering. Under MFA, nPd and Pd spectra were typically Gaussian, suggesting that the nest mates with a uniform workload shifted to higher motion activity. At the end of the MFA, the spectra shift back to the lower motion activities and the Pd spectra form a biphasic again. This happens a few minutes earlier in the peripheral zones than in the mouth zone. Using time profiles of the skewness of the Pd motion spectra, the mass-flight-suspend-defensiveness hypothesis is confirmed, whereby the inhibition of defense ability was found to increase progressively during the MFA. These sawtooth-like time profiles of skewness during MFA show that defense capability is recovered again quite quickly at the end of MFA. Finally, with the help of the Pd motion spectra, clear indications can be obtained that the giant honeybees engage in a decision in the sense of a tradeoff between MFA and collective defensiveness, especially in the regions in the periphery to the mouth zone.

Conceptual Dichotomy “Word of God – Human Word” in the Biblical Discourse

The article deals with the study of the concept “word” as a basic one in the Holy Scripture. The Bible as a precedent text has always attracted researchers’ attention and still remains topical. It provokes interest as it renders sacral conceptual paradigm to the fullest. The article deals with cognitive linguistic modeling of the mentioned concept in the Biblical discourse, considering binary opposition “word of God – human word”. Cognitive meanings of the nuclear and peripheral concept zones, which are represented in the forms of notional, figurative and evaluative information, have been revealed in the course of study. Its nucleus contains factual and conceptual information, within which two components are characterized: linguistic and theological. The nomens “group of sounds”, “a language unit”, “speech”, “language”,”talk” and “conversation” represent the linguistic nature of a word. The lexemes “Logos”, “Gospel”, “the expressed or manifested mind and will of God”, “Jesus Christ” and “Holy Scripture” verbalize the theological component. A range of senses of the concept “word” has been singled out and analyzed, which often constitute whole microcontexts in the Biblical discourse. The peripheral zone of the concept “word” has been analyzed, that is represented as imagery and value information. The value information has been constructed on the opposition of the positive and negative connotations of the concept “word”. The imagery information naturally complements the notional one mostly by using the conceptual metaphor. The concept “word” in the Biblical discourse has been interpreted through comparison of dichotomies “sacral – profane”, “eternal – temporary”, “ideal – real”, “transcendental – immanent”, which manifest the extreme opposition “Word of God – human word”.

Birds&amp;amp;#8217; Diversity in Kalfou Forest Reserve and Its Peripheral Zone, Far North, Cameroon

Birds&amp;amp;#8217; Diversity in Kalfou Forest Reserve and Its Peripheral Zone, Far North, Cameroon

LITHIUM IN THE SUBSOIL OF UKRAINE Part 5. Mineralogy of lithium-bearing objects: lithium minerals

The fifth part of the publication "Lithium in the depths of Ukraine" is devoted to the mineralogy of lithium — silicates and phosphates, but without lithium micas, which, together with other micas, are described in Part 4. Here, the following lithium minerals are characterized in varying detail (the Li2O content of the mineral (mas. %) is given in parentheses after the formula): eucryptite — LiAl[SiO4] (11.80), elbaite Na(Al,Li)3Al6(BO3)3(F,OH)4[Si6O18] (1.1—1.4); spodumene — LiAl[Si2O6] (5.9—7.6); holmquistite Li3Mg3Al2(OH)2[Si8O22] (2.1—3.5); petalite — Li[AlSi4O10] (2.0—4.1); margarite — CaAl2(OH)2[Si2Al2O10]-(Li,Be) (1.82); donbasite — Al2[(Si3Al)O10](OH)2·Al2.33(OH)6 (0.1—3.0); cukeite (Al,Li)3Al2[(Si,,Al)4O10](OH)8 (0.8—4.3); triphillite — Li(Fe2+,Mn2+)[PO4] (5.51—8.62); lithiophyllite — Li(Mn2+,Fe2+)[PO4] (5.50—8.60); amblygonite LiAl(F)[PO4] (6.4—9.0); montebrasite — LiAl(OH)[PO4] (10.7—11.1); simferite — Li(Mg,Fe3+,Mn3+)2.0[PO4] (5.35—5.45). The description of these minerals is supplemented by a summary table of the mineral composition of rare metal pegmatites, selected according to the quantitative ratio of the main ore minerals — spodumene and petalite. The latter are not the first phases of crystallization of the pegmatite melt, so their distribution in space is close to the following pattern: the highest content of ore minerals is concentrated between the peripheral zones and cores of pegmatites. Spodumene and petalite of Ukrainian pegmatites, in comparison with similar minerals of large global lithium deposits, differ in the following features: 1) smaller sizes of mineral individuals; 2) greater xenomorphism of mineral individuals; 3) a weaker manifestation of isomorphic substitutions of atoms.

КУЛЬТУРНОЕ ПРОСТРАНСТВО СОВРЕМЕННОГО ГОРОДА КАК ОБЪЕКТ ПСИХОЛОГИЧЕСКОГО ИССЛЕДОВАНИЯ

The paper examines the phenomenon of urban identity within the context of an individual’s sense of belonging to the urban cultural space. The urban cultural milieu represents a significant factor in shaping an individual’s attachment to their place of residence and an emotional connection with the city. This is an essential aspect of the subjective well-being of the residents. The objective of this study is to provide theoretical justification for the concept of “urban cultural space” and to empirically examine the respondents’ perceptions of urban cultural space. The research methods employed were an associative experiment and a prototypical analysis, as proposed by P. Vergès. The empirical base of the study comprised 354 respondents permanently residing in Krasnodar. The concept of the “cultural space of the city” as a semantic sphere embodied in the urban landscape is substantiated from the perspective of the subjective approach. The core of social ideas of Krasnodar residents about urban culture and the culture of their city is characterized by consistency. This is evidenced by common elements, including city cultural institutions, parks, city customs and traditions, and the culture of everyday. The social representations of urban culture are distinguished by an expanded core, encompassing both material cultural objects and the activity aspect of urban culture. The peripheral zone of social perceptions (SP) of Krasnodar residents about urban culture includes categories that distinguish the urban environment from the rural one (specifically in terms of the visible signs of urbanization.). The same zone of SP about Krasnodar culture encompasses specific urban locations, urban cultural practices, distinctive behaviors, and the everyday culture of citizens. The common element of the peripheral zone of SP is the category “city residents” (“Krasnodar residents”). The social perceptions of a given city, such as Krasnodar, imbue these elements with a specific content that is determined by the specifics of the urban environment.

African urban peripheries and informal development: A review of challenges and sustainable approaches to inclusive cities

ABSTRACT The aim of the study is to provide a comprehensive understanding of the complex relationship between African urban peripheries and informal development that also aligns with the broader goal of creating inclusive and sustainable urban environments. The authors employed a literature review approach and examined the complexities of informal settlements. In the presentation of their findings, the authors focus on conceptualizing of informality beyond slum areas, unravelling urbanization complexities in African urban peripheries, analysing the emergence of informal development in urban peripheral zones, and addressing informal settlements in the context of SDG 11. The findings reveal the embeddedness of informal practices in African urban peripheries, and the emphasis on adaptability, hybridity, and the role of informal entities in shaping complex urban fabrics. Additionally, inclusivity, safety, resilience, and sustainability are emphasized within the context of SDG 11. The authors conclude that a holistic and collaborative approach is important for shaping inclusive and sustainable urban futures in African urban peripheries. Additionally, they propose strategies for upgrading and formalizing informal settlements, the provision of essential social services, creation of economic opportunities, enhancement of safety, and to foster resilience through adaptive strategies.

The category of emotivity in modern Russian literature

The article discusses issues related to the qualifying modus category of emotivity and the ways of its expression in contemporary Russian literature of the second and third decades of the 21st century. The category of emotivity closely interacts with the categories of modality and evaluation, while explicating the qualifying subject, which makes it possible to analyze the degree of emotionality and the level of emotive evaluation. A decrease in emotionality and a shift towards a negative assessment of emotives is noted in modern literary texts as well as the predominance of primary, sensual emotions over cultured ones. Examples are given of the texts written by the most readable modern authors. In some stories, the category of emotivity is analyzed in dynamics, that is, a decrease or increase in the emotionality of the characters can be traced. In other works, emotionality is considered either in connection with the author’s attitude to what is being reported, or in interaction with life values, which form the emotional state of the characters. It was important to focus on what family and moral values are expressed through emotions. As a means of expressing emotionality, we highlight the vocabulary of emotions with nuclear and central emotive meanings, as well as syntactic and artistic means of their expression, which are often characterized by a peripheral zone of emotivity.

Additions to the composition of the ural beryls and inclusions of syngenetic minerals in them

In addition to the data of predecessors, the chemical composition of zoned or zoned-sectorial beryl crystals from pegmatites of the Mariinsky and Kvartalny deposits of the Urals emerald mines in the Central Urals, granitic pegmatite of mine no. 242 of the Ilmeny State Reserve and Svetlinsky pegmatite quarry in the South Urals is characterized using scanning electron microscopy and energy-dispersive analysis. The light peripheral zones of prism and pinacoid in crystal sections differ in variations in Al, Fe and Mg contents from the inner zones or areas. The presence of fractures and regenerated fragments of early beryl indicates synmineralization tectonics. In beryl from the Mariinsky deposit, the previously unknown syntactic ingrowths of bavenite and zones of parallel columnar aggregates of co-crystallization of beryl and bavenite, as well as late pyrite, fuorite, gismondine-Ca and tobermorite, are identifed. Beryls from mine no. 242 of the Ilmeny State Reserve are yellowish-greenish and bluish with a peripheral white zone and syntactic microingrowths of annite and syngenetic inclusions of columbite and Ta-Nb rutile. Muddy bluish-white beryl regenerated by colorless beryl from the Svetlinsky quarry hosts numerous syntactic inclusions of muscovite, gahnite, calcite, quartz and quartz-muscovite microaggregates with pyrite, chalcopyrite, sphalerite, galena, siderite, calcite, and micropores. The syntaxy of mica, quartz and gahnite with beryl is revealed for the frst time.

Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation.

Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of >45,000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+ T cells with circulating cells identified CX3CR1high and CX3CR1int CD8+ T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8+ T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.

Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation

Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of &gt;45,000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+ T cells with circulating cells identified CX3CR1high and CX3CR1int CD8+ T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8+ T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.

Predictors of prostate cancer detection in MRI PI-RADS 3 lesions - Reality of a tertiary center.

The Prostate Imaging Reporting and Data System (PI-RADS) score reports the likelihood of a clinically significant prostate cancer (CsPCa) based on various multiparametric prostate magnetic resonance imaging (mpMRI) characteristics. The PI-RADS category 3 is an intermediate status, with an equivocal risk of malignancy. The PSA density (PSAD) has been proposed as a tool to facilitate biopsy decisions on PI-RADS category 3 lesions. The objective of this study is to determine the frequency of CsPCa, assess the diagnostic value of targeted biopsy and identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. Between 1st January 2017 and 31st December 2022, a total of 1661 men underwent a prostate biopsy at our institution. Clinical and mpMRI data of men with PI-RADS 3 lesions was reviewed. The study population was divided into two groups: target group, including those submitted to systematic plus targeted biopsy versus non-target group when only systematic or saturation biopsy were performed. Patients with PI-RADS 3 lesions were divided into three categories based on pathological biopsy results: benign, clinically insignificant disease (score Gleason = 6 or International Society of Urologic Pathologic (ISUP) 1) and clinically significant cancer (score Gleason ≥ 7 (3+4) or ISUP ≥ 2) according to target and non-target group. Univariate and multivariate analyses were performed to identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. A total of 130 men with PIRADS 3 index lesions were identified. Pathologic results were benign in 77 lesions (59.2%), 19 (14.6%) were clinically insignificant (Gleason score 6) and 34 (26.2%) were clinically significant (Gleason score 7 or higher). Eighty-seven of the patients were included in the target group (66.9%) and 43 in the non-target group (33.1%). The CsPCa detection was higher in the non-target group (32.6%, n = 14 vs 23.0%, n = 20 respectively). When systematic and target biopsies were jointly performed, if the results of systematic biopsies are not considered and only the results of target biopsies are taken into account, a CsPCa diagnosis would be missed on 9 patients. The differences of insignificant cancer and CsPCa rates among the target or non-target group were not statistically significant (p = 0.50 and p = 0.24, respectively). on multivariate analysis, the abnormal DRE and lesions localized in Peripheral zone (PZ) were significantly associated with a presence of CsPCa in PI-RADS 3 lesions (oR = 3.61, 95% CI [1.22,10.72], p = 0.02 and oR = 3.31, 95% CI [1.35, 8.11], p = 0.01, respectively). A higher median PSAD significantly predisposed for CsPCa on univariate analyses (p = 0.05), however, was not significant in the multivariate analysis (p = 0.76). In our population, using 0.10 ng/ml/ml as a cut-off to perform biopsy, 41 patients would have avoided biopsy (31.5%), but 5 cases of CsPCa would not have been detected (3.4%). We could not identify any statistical significance between other clinical and imagiological variables and CsPCa detection. PI-RADS 3 lesions were associated with a low likelihood of CsPCa detection. A systematic biopsy associated or not with target biopsy is essential in PI-RADS 3 lesions, and targeted biopsy did not demonstrate to be superior in the detection of CsPCa. The presence of abnormal DRE and lesions localized in PZ potentially predict the presence of CsPCa in biopsied PI-RADS 3 lesions.

Mechanical epilation exerts complex biological effects on human hair follicles and perifollicular skin: An exvivo study approach.

Electrical epilation of unwanted hair is a widely used hair removal method, but it is largely unknown how this affects the biology of human hair follicles (HF) and perifollicular skin. Here, we have begun to explore how mechanical epilation changes selected key biological read-out parameters exvivo within and around the pilosebaceous unit. Human full-thickness scalp skin samples were epilated exvivo using an electro-mechanical device, organ-cultured for up to 6 days in serum-free, supplemented medium, and assessed at different time points by quantitative (immuno-)histomorphometry for selected relevant read-out parameters in epilated and sham-epilated control samples. Epilation removed most of the hair shafts, often together with fragments of the outer and inner root sheath and hair matrix. This was associated with persistent focal thinning of the HF basal membrane, decreased melanin content of the residual HF epithelium, and increased HF keratinocyte apoptosis, including in the bulge, yet without affecting the number of cytokeratin 15+ HF epithelial stem cells. Sebocyte apoptosis in the peripheral zone was increased, albeit without visibly altering sebum production. Epilation transiently perturbed HF immune privilege, and increased the expression of ICAM-1 in the bulge and bulb mesenchyme, and the number of perifollicular MHC class II+ cells as well as mast cells around the distal epithelium and promoted mast cell degranulation around the suprabulbar and bulbar area. Moreover, compared to controls, several key players of neurogenic skin inflammation, itch, and/or thermosensation (TRPV1, TRPA1, NGF, and NKR1) were differentially expressed in post-epilation skin. These data generated in denervated, organ-cultured human scalp skin demonstrate that epilation-induced mechanical HF trauma elicits surprisingly complex biological responses. These may contribute to the delayed re-growth of thinner and lighter hair shafts post-epilation and temporary post-epilation discomfort. Our findings also provide pointers regarding the development of topically applicable agents that minimize undesirable sequelae of epilation.

Radiomics from multisite MRI and clinical data to predict clinically significant prostate cancer.

Magnetic resonance imaging (MRI) is useful in the diagnosis of clinically significant prostate cancer (csPCa). MRI-derived radiomics may support the diagnosis of csPCa. To investigate whether adding radiomics from biparametric MRI to predictive models based on clinical and MRI parameters improves the prediction of csPCa in a multisite-multivendor setting. Clinical information (PSA, PSA density, prostate volume, and age), MRI reviews (PI-RADS 2.1), and radiomics (histogram and texture features) were retrieved from prospectively included patients examined at different radiology departments and with different MRI systems, followed by MRI-ultrasound fusion guided biopsies of lesions PI-RADS 3-5. Predictive logistic regression models of csPCa (Gleason score ≥7) for the peripheral (PZ) and transition zone (TZ), including clinical data and PI-RADS only, and combined with radiomics, were built and compared using receiver operating characteristic (ROC) curves. In total, 456 lesions in 350 patients were analyzed. In PZ and TZ, PI-RADS 4-5 and PSA density, and age in PZ, were independent predictors of csPCa in models without radiomics. In models including radiomics, PI-RADS 4-5, PSA density, age, and ADC energy were independent predictors in PZ, and PI-RADS 5, PSA density and ADC mean in TZ. Comparison of areas under the ROC curve (AUC) for the models without radiomics (PZ: AUC = 0.82, TZ: AUC = 0.80) versus with radiomics (PZ: AUC = 0.82, TZ: AUC = 0.82) showed no significant differences (PZ: P = 0.366; TZ: P = 0.171). PSA density and PI-RADS are potent predictors of csPCa. Radiomics do not add significant information to our multisite-multivendor dataset.

Speculations on the Paleozoic legacy of Gondwana amalgamation

Using Gondwana as an example, we show how the geological record can be interrogated to detect significant changes in mantle convection patterns at critical junctures in Earth’s evolution. Evidence of major changes in mantle circulation in the aftermath of late Neoproterozoic-early Paleozoic Gondwana assembly is provided by widespread (i) plume-related magmatism around Gondwana’s periphery, (ii) ironstone deposits related to mantle plume-ocean ridge interaction and enhanced hydrothermal activity, and (iii) super-mature clastic deposits that reflect epeirogenic uplift triggered by mantle upwelling beneath Gondwana combined with deep tropical weathering.In our model, Gondwana assembled above a region of mantle downwelling in which subducted slabs between the converging Gondwanan continents descended to the core-mantle boundary. Renewed subduction along Gondwana’s periphery yielded early arc magmas. But as downwelling beneath Gondwana evolved into upwelling as a result of the ponding of subducted slabs at the base of the mantle, mantle plumes rose from the margins of the nascent upwelling to interact with the edges of Gondwana, where they penetrated the peripheral subduction zones via slab windows, tears and transform faults to generate voluminous calc-alkalic crustal melts in hydrated arc regions and A-type magmas in dry back-arc regions. The plumes also underplated oceanic lithosphere and interacted with adjacent ocean ridges, thereby enhancing hydrothermal activity and the flux of bioessential nutrients, leading to the recurrence of marine iron-rich sedimentary rocks in the geological record. At the same time, upwelling beneath a tropical to equatorial Gondwana led to epeirogenic uplift, deep weathering and erosion, resulting in the production of widespread super-mature clastic deposits. We contend that major changes in mantle convection patterns were encoded into the geological record of Gondwana assembly, influenced global-scale mantle convection patterns, and should be incorporated into geodynamic models for the assembly of Pangea.

Role of non-contrast CT component of prostate-specific membrane antigen PET/CT scan in the detection of peripheral zone prostate cancer.

The aim of this study was to look for feasibility of non-contrast CT (NCCT) in detecting peripheral zone prostate cancer (PCa). A retrospective analysis included 50 biopsy-proven PCa patients between April 2019 and March 2022 who underwent staging whole body prostate-specific membrane antigen (PSMA)/CT prior to treatment. The control subjects were 50 randomly selected adult male patients who underwent PET/CT for non-prostate malignancy during the same time period. Two readers independently calculated the Hounsfield unit (HU) of normal peripheral zone, central zone, and corresponding PSMA avid focus in cases. No significant difference was seen in the mean HU value of normal peripheral zone between cases and controls. Significant difference in the mean HU was seen between the PSMA avid focus in cases (40.1 ± 6.2) and normal peripheral zone of cases (28.2 ± 7.0) and controls (27.7 ± 5.8). No significant difference was found between the mean HU values of high-grade PCa and non-high-grade PCa. Receiver operating characteristic (ROC) curve analysis revealed a mean HU cut-off of ≥35 for detecting PCa with a sensitivity and specificity of 86% and 90%, respectively, between cases and controls (AUC 0.88). Detection of clinically significant PCa is possible on routinely performed NCCT scans. Radiologists should routinely look for and convey these findings to facilitate further work-up and early detection of PCa. Our study adds to the knowledge that NCCT scans performed for unrelated indications can serve as a screening tool for clinically significant PCa.

How ASEAN and Western media covers China’s Belt and Road Initiative: a case study of representation of the Laos-China railway under international news flows framework

The research uses the coverage of the Laos-China railway as a case to compare how media in ASEAN versus Western countries represents China’s Belt and Road Initiative. Under the framework of international news flows, through investigating the agenda-setting, news source distribution and frames of 137 stories by 42 news outlets in seven ASEAN and seven Western countries, the study finds that the long-existing imbalances in volume, direction and content of information in international news flows have seen continuities and changes. On the one hand, the international news flows remain unidirectional from the center toward semi-peripheral and peripheral zones in the world system, rather than the other way around. On the other hand, the dominance of Western media in the flows as major news suppliers providing the master narratives of most international events has been disrupted due to the emergence of counter-narratives offered by alternative news providers such as China’s Xinhua and Asian News Network. Such continuities and changes in international communication flows exemplified by the media coverage of a China’s BRI project serve as both empirical evidence of a broader global power shift and a thermometer measuring the Global North’s and Global South’s reactions to such a shift.