bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Rhinosinusitis: Matching the Extent of Surgery with Pathology or Does the Extent of Surgery Matter?
Authors: Blauwblomme Manon , Gevaert Philippe , Van Zele Thibaut
Published: September 2023

Purpose of Review

The purpose of this review is to summarize the current literature on the extensiveness of surgery in patients with diffuse type 2 chronic rhinosinusitis (CRS).

Recent Findings

There is currently no consensus on the role of the extent of sinus surgery in disease control and definitions of surgical terms in diffuse type 2 CRS. Several suggestions have been made to quantify the extent of surgery or standardize the description of surgical interventions.

The extent of surgery in CRS depends potentially on the severity of disease and the type of underlying inflammation. A variety of extended endoscopic procedures can be used in the management of primary diffuse bilateral type 2 chronic rhinosinusitis; however, long-term follow-up results and clear definitions of complete surgery are lacking in the current literature.
Belonging Exacerbates the Relations Between Racial Climate Stress and Physiological Dysregulation
Authors: Doan Stacey N. , Davis Alicia S. , Lazarus Molly , Poudel Akriti , Tran Phil , Clark Natalie , Fuller-Rowell Thomas E.
Published: September 2023

Objective

Belonging is often considered a buffer against the physical and emotional consequences of discrimination and racial climate stress Youth Soc. 48(5):649–72, 2016. However, recent research suggests that feelings of belonging toward an institution can be detrimental when an individual feels discriminated against by the same institution to which one feels a sense of connection J Behav Med. 44(4):571–8, 2021. Therefore, the present study aimed to investigate the moderating role of institutional belonging in the relationship between racial climate stress and health, as indexed by allostatic load (AL), a multi-system indicator of physiological dysregulation.

Methods

In a sample of Black and White college students (N = 150; White = 82; Black = 68), self-reported racial climate stress, institutional belonging, and various demographic variables were collected. An AL composite was also collected, comprised of six biological measures of the SAM system, HPA axis, cardiovascular system, and metabolic system. Multiple regression analyses were conducted to explore the relationships between these variables.

Results

Results demonstrated no main effect of racial climate stress on AL but did show a significant interaction between racial climate stress and belonging, such that the positive relationship between racial climate stress and AL was significant only for those who also felt high levels of institutional belonging (βint = .05, p = .006, 95% CI = 0.01 – 0.08).

Conclusions

Feeling a sense of belonging may have negative physiological consequences for those who experience racial climate stress in a college setting.
Neuer deutschsprachiger Fragebogen zur standardisierten Erfassung von Muskel-Skelett-Beschwerden im Betrieb
Authors: Liebers Falk , Freyer Marion , Dulon Madeleine , Freitag Sonja , Michaelis Martina , Latza Ute , Hegewald Janice
Published: September 2023

Hintergrund

Die standardisierte Erfassung von Muskel-Skelett-Beschwerden (MSB) ist wichtig für die valide Beschreibung der Auswirkungen körperlicher Belastungen im Beruf. Dazu wurde eine neue Fragebogenversion (NFB*MSB) basierend auf dem Original von Kuorinka et al. (1987) entwickelt. Das Instrument erfasst die 12-Monats- und 4‑Wochen-Prävalenz von MSB und Funktionseinschränkungen. Anliegen war die Bewertung der Praktikabilität des Fragebogens, der Antwortstabilität (Test-Retest-Reliabilität) und der Inhaltsvalidität.

Methodik

Der Fragebogen wurde zu 2 Messzeitpunkten postalisch an eine Gelegenheitsstichprobe verschickt. Die Datenauswertung der Einzelitems erfolgte deskriptiv. Die Test-Retest-Reliabilität wurde über den Intraklassenkoeffizienten (ICC) bewertet. Die inhaltliche Validierung erfolgte qualitativ über eine schriftliche Bewertung durch Expertinnen und Experten.

Ergebnisse

Es beteiligten sich 83 Personen, davon 80 an der Zweitbefragung. Die Ausfülldauer lag bei 5 bis 30 min. Die Befragten bewerteten den Fragebogen als verständlich, übersichtlich und im Umfang akzeptabel. Der ICC war je nach Körperregion moderat bis exzellent (0,67–0,89). Die Bewertung durch Expertinnen und Experten war insgesamt positiv. Die Auswahl, die Bezeichnung und Markierung der Körperregionen sowie die Items zur 12-Monats- und 4‑Wochen-Prävalenz wurden bestätigt. Die Erfassung der 7‑Tage-Prävalenz wurde empfohlen. Die Ergebnisse der Erprobung wurden in einer angepassten Version des Fragebogens (FB*MSB) berücksichtigt.

Diskussion

Der Fragebogen erfüllt die Erwartungen in Bezug auf Praktikabilität, Antwortstabilität und Inhaltsvalidität. Er steht für Erhebungen in Betrieben und die arbeitsmedizinische Vorsorge zur Verfügung. Weitere Überprüfungen des Instruments in repräsentativen Stichproben sollten folgen.
Preliminary experimental study on simultaneous polishing and shape setting of Nitinol wire
Authors: Navickaitė Kristina , Nestler Klaus , Penzel Michael , Böttger-Hiller Falko , Zeidler Henning
Published: September 2023

Separate processes for shape setting and polishing of Nitinol workpieces are well investigated in scientific literature and adopted industrially. However, a simultaneous process for shape setting and polishing of Nitinol has not yet been reported. In this study, preliminary results of such process are presented, providing insights and directions for further research on post-processing shape memory materials. For this purpose, Nitinol wire samples with phase transformation temperatures Af = 4.5 °C, Af = 31 °C and Af = 61 °C were plasma electrolytic polished (PEP) while fitted in a specially designed sample holder at three electrolyte temperatures te = 50 °C, te = 65 °C and te = 80 °C. The PEP process duration was τPEP = 60 s, τPEP = 180 s and τPEP = 300 s. After the PEP processes, the samples were investigated for the shape memory effect (SME). The training effect, known to be present in shape memory alloys (SMA), was taken into account. The surface roughness of the investigated wires was measured before and after the PEP process. The obtained results demonstrate that both a phase transformation temperature and an electrolyte temperature have a strong effect on polishing and shape setting results.
Introduction to Cancer Biology
Authors: Hesketh Robin
Published: September 2023

From basic principles to insights into pioneering research, this introductory textbook provides the fundamentals of cancer biology that will enable students of biology and medicine to enter the field with confidence. It opens with a discussion of global cancer patterns, how cancers arise, and the risk factors involved. A description of the normal signalling pathways within cells then explains how DNA mutations affect proteins and what this means for the development and behaviour of tumours. Later chapters discuss methods for tumour detection, biomarker identification and the impact of genome sequencing, before reviewing the development of anti-cancer drugs and exciting current advances in treatment. With 50% new material, including two new chapters on genetic analysis of cancer and cancer chemotherapy, improved pedagogy, examples of revolutionising technologies in drug design and delivery, and useful online resources, this textbook offers an accessible and engaging account of cancer biology for undergraduate and graduate students.
Trans (legal) parenthood and the gender of legal parenthood
Authors: Brown Alan
Published: September 2023

Trans identities are increasingly subjected to contentious public and political debate in the UK, and this has resulted in resource to the law across various contexts. Against that background, this paper considers trans legal parenthood after the decision in R (McConnell and YY) v Registrar General for England and Wales. This judgment held that a trans man who gave birth was the legal ‘mother’ of his child. The wider consequence is that trans legal parenthood will not reflect trans identities, but birth-assigned sex/gender, regardless of whether the parent holds a gender recognition certificate. Separate from this underlying social and political context concerning trans identities, the paper argues that legal parenthood is a flexible and pragmatic concept, which lacks inherent normative content, and which has previously proved capable of accommodating a variety of different familial and reproductive circumstances. The paper argues that the gendered descriptors of ‘mother’ and ‘father’, while remaining the law's default, are not inherent to legal parenthood. Thus, the paper concludes that, despite the ongoing political and cultural debates concerning trans identities, the existing concept of legal parenthood is capable of properly recognising trans parenthood, without requiring any fundamental changes to the concept itself.
Legal sex status: the attitudes of non-binary people towards reform in England and Wales
Authors: Gascoigne Mollie
Published: September 2023

The merits and means of accommodating non-binary populations into UK law is becoming an increasingly important issue for policymakers, judges, scholars and legal professionals. Following Elan-Cane's Supreme Court challenge to binary passport sex markers in 2021, the UK Government face another challenge this year concerning non-binary recognition on birth certificates. While an additional third sex option is perhaps the most well-known reform option for the current binary system, other options have been suggested, including additional multiple sex options and/or removing sex from the birth certificate. While scholars and policymakers debate the merits of these, little is known about non-binary people's own preferences towards these options. This paper therefore presents original empirical data on non-binary attitudes towards these options, demonstrating the various perceived opportunities and drawbacks of each, and reflecting on the possible consequences of reform.
Stability properties of multidimensional symmetric hyperbolic systems with damping, differential constraints and delay
Authors: Peralta Gilbert
Published: September 2023

Multidimensional linear hyperbolic systems with constraints and delay are considered. The existence and uniqueness of solutions for rough data are established using Friedrichs method. With additional regularity and compatibility on the initial data and initial history, the stability of such systems are discussed. Under suitable assumptions on the coefficient matrices, we establish standard or regularity-loss type decay estimates. For data that are integrable, better decay rates are provided. The results are applied to the wave, Timoshenko, and linearized Euler–Maxwell systems with delay.
Expression profile and function analysis of MsCSP17 and MsCSP18 in the larval development of Mythimna separata
Authors: Chen Tingting , Zhou Xue , Wu Jing , Xing Gaoliang , Cao Haiqun , Huang Yong
Published: September 2023

Chemosensory proteins (CSPs) were necessary for insect sensory system to perform important processes such as feeding, mating, spawning, and avoiding natural enemies. However, their functions in non-olfactory organs have been poorly studied. To clarify the function of CSPs in the development of Mythimna separata (Walker) larvae, two CSP genes, MsCSP17 and MsCSP18, were identified from larval integument transcriptome dataset. Both of MsCSP17 and MsCSP18 contained four conserved cysteine sites (C × (6)-C × (18)-C × (2)-C), with a signal peptide at the N-terminal. RT-qPCR analysis showed that MsCSP17 and MsCSP18 have different expression patterns among different developmental stages and tissues. MsCSP17 was highly expressed in 1st–4th instar larvae, and MsCSP18 had high expression in adults. Both genes were expressed highly in larval head, thorax, integument and mandible. Moreover, both of MsCSP17 and MsCSP18 were lowly expressed in larval integuments when larvae molted for 6 h and 9 h from 3rd to 4th instar, but highly at the beginning and end phase during molting. After injection of dsMsCSP17 and dsMsCSP18, the expression levels of two genes decreased significantly, with the body weight of larvae decreased, the mortality increased, and the eclosion rate decreased. It was suggested that MsCSP17 and MsCSP18 contributed to the development of M. separata larvae.
English in Timor–Leste
Authors: Macalister John , Akoyt Melky Costa
Published: September 2023

When Timor–Leste became the first new nation of the 21st century in 2002, one of the many decisions that needed to be made concerned language. Timor–Leste is a country of around one million people, with at least 16 indigenous languages and three foreign languages contributing to its multilingual character. For reasons related to its 400-year colonial history and the resistance to Indonesian occupation from 1975 to 1999, the new constitution declared that Portuguese would be one of two official languages, the other being the indigenous Tetun Dili. The choice of Portuguese rather than English was controversial, and criticised in some quarters, for it appeared to defy geographical location (e.g. Savage, 2012). After all, Australia lies an hour's flight south of Timor–Leste, and English has been adopted as the working language of ASEAN, an organisation which the country has aspirations of joining. English is certainly the regional lingua franca, and very often referred to as the global lingua franca. Not, however, that the constitution was ignoring this reality. As well as naming Portuguese and Tetun as official languages, it named English and Bahasa Indonesia as working languages, and all indigenous languages as national languages. Thus the decisions around language in the constitution laid claims to identity and culture, as well as remaining open to global engagement in trade, technology, education and other contributors to modernisation.
Closing cases with open-source: Facilitating the use of user-generated open-source evidence in international criminal investigations through the creation of a standing investigative mechanism
Authors: White Elizabeth
Published: September 2023

Digital open-source evidence has become ubiquitous in the context of modern conflicts, leading to an evolution in investigative practices within the context of mass atrocity crimes and international criminal law. Despite its extensive promulgation, international criminal tribunals have had few opportunities to address the admissibility of user-generated open-source evidence. Through semi-structured interviews with experts and analyses of primary and secondary sources, this article examines the current standards and practices governing the use of user-generated open-source evidence. Current practices illuminate a number of gaps in the realm of digital open-source evidence in international criminal law. This article posits the establishment of a standing international, investigative mechanism as a solution to a need for increased standardization and co-ordination within the realm of user-generated open-source evidence. By standardizing the collection and use of such evidence, investigative bodies will be prepared to more effectively serve the international justice community.
A 24-year longitudinal study of Klebsiella pneumoniae isolated from patients with bacteraemia and urinary tract infections reveals the association between capsular serotypes, antibiotic resistance, and virulence gene distribution
Authors: Kao Cheng-Yen , Zhang Yen-Zhen , Bregente Carl Jay Ballena , Kuo Pei-Yun , Chen Pek Kee , Chao Jo-Yen , Duong Tran Thi Thuy , Wang Ming-Cheng , Thuy Tran Thi Dieu , Hidrosollo Jazon Harl , Tsai Pei-Fang , Li Ying-Chi , Lin Wei-Hung
Published: September 2023

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.
Recovery from economic disasters
Authors: Ćorić Bruno , Škrabić Perić Blanka
Published: September 2023

This study uses two large datasets to explore the output dynamics following economic disasters, one including 180 economic disasters across 38 countries over the last two centuries and the other including 204 disasters in 182 countries since World War II. Our results suggest that extreme economic crises are associated with huge and remarkably persistent loss. On average, output loss surges to above 26% in the first few years after the outbreak of a disaster and remains above 20% for as long as 20 years. It is only after more than 50 years that the loss is fully recovered.
From Lifeless Numbers to the Vital Nerve of Democracy: Dolf Sternberger's Metaphorical Argumentation against Proportional Voting
Authors: Pankakoski Timo
Published: September 2023

This article analyzes Dolf Sternberger's post-World War II argumentation against proportional representation. Sternberger is central in the intellectual history of German democratization. However, he expressed his misgivings about parties and proportionality in a perplexingly antidemocratic register. Proportionality was anonymous, mechanical, dead, and purely mathematical, relying on “mere numbers” and “summing up” as opposed to living, dynamic, and organic political relations—ultimately not a form of political electing at all. Sternberger intentionally mobilized age-old topoi and metaphors which interwar antidemocratic authors had used against parliamentary democracy in its entirety, now skillfully redirecting their force against proportional representation more specifically. Sternberger's intricate metaphorical system linked his anti-proportional views to his theory of active civic engagement and ultimately served pro-democratic aspirations in the altered historical situation. His case exemplifies broader continuities between interwar and postwar discourses and highlights the need to read metaphorical argumentation in historical contexts and pragmatically rather than merely semantically.
Technological Solutions to China's Carbon Neutrality in the Steel and Cement Sectors
Authors: Chen Peipei , Zhang Shaohui , Meng Jing , Lei Tianyang , Li Boxi , Coffman D’Maris
Published: September 2023

China has set Nationally Determined Contributions (NDCs) and carbon neutrality targets without providing expected industry‐specific technological details. By focusing on the steel and cement industries in China, this study analyzes the energy consumption of different technology routes, decarbonization pathways of innovative technologies, and the synergistic impact of air pollutants. The study finds that the incumbent technology routes for steel and cement production have limited carbon reductions, and the deployment of innovative technologies (carbon capture, utilization, and storage [CCUS], electrolytic‐ and hydrogen‐based, and scrap‐based technologies) need to be accelerated to achieve carbon neutrality targets. We find that the net‐zero emissions pathway relying upon innovative technologies needs less investment than the NDCs scenario. Furthermore, electric arc furnace deployment will be mainly concentrated in Jiangsu, Guangdong, and Sichuan, while CCUS should be mainly in Hebei, Shandong, Liaoning, and Jiangsu provinces. The increased electrification of innovative technologies in steel and cement requires a shift in energy inputs from fossil energy to electricity. A combination of strict climate change mitigation and air pollution control will have higher synergistic effects.
Multiscale Spatial Patterns in Giant Dike Swarms Identified Through Objective Feature Extraction
Authors: Kubo Hutchison A. , Karlstrom L. , Mittal T.
Published: September 2023

Dike swarms are ubiquitous on terrestrial planets and represent the frozen remnants of magma transport networks. However, spatial complexity, protracted emplacement history, and uneven surface exposure typically make it difficult to quantify patterns in dike swarms on different scales. In this study, we address this challenge using the Hough transform (HT) to objectively link dissected dike segments and analyze multiscale spatial structure in dike swarms. We apply this method to swarms of three scales: the Spanish Peaks, USA; the Columbia River Flood Basalt Group (CRBG), USA; the Deccan Traps Flood Basalts, India. First, we cluster dike segments in HT space, recognizing prevalent linearly aligned structures that represent single dikes or dike packets, with lengths up to 10 −  30x the mapped mean segment length. Second, we identify colinear and radial dike segment mesoscale structures within each data set, using the HT to segment swarms into constituent spatial patterns. We show that for both the CRBG and Deccan Traps, a single radial or circumferential swarm does not well characterize the data. Instead, multiple and sometimes overlapping mesoscale linear and radial features are prevalent suggesting a complex history of crustal stresses. The HT can provide useful insights in a variety of geologic settings where many quasi‐linear features, at any scale, are superimposed spatially.
Size‐Dependent Nighttime Formation of Particulate Secondary Organic Nitrates in Urban Air
Authors: Huang Wei , Huang Ru‐Jin , Duan Jing , Lin Chunshui , Zhong Haobin , Xu Wei , Gu Yifang , Ni Haiyan , Chang Yunhua , Wang Xuan
Published: September 2023

Particulate secondary organic nitrates play a key role in understanding secondary organic aerosol production, ozone formation, and the atmospheric nitrogen cycle. However, the formation of particulate secondary organic nitrates in ambient air remains poorly understood. In this study, the nighttime formation processes of particulate secondary organic nitrates were investigated based on size‐resolved aerosols measured in urban air of China with a soot particle long‐time‐of‐flight aerosol mass spectrometer. The results show a bimodal size distribution of particulate secondary organic nitrates, peaking at ∼350 nm in condensation mode (100–400 nm) and ∼750 nm in droplet mode (400–2,500 nm), respectively. The nighttime formation processes of particulate secondary organic nitrates in the two size modes were respectively governed by temperature‐dependent condensation and aqueous‐phase processing. In particular, the mass concentration of particulate secondary organic nitrates in condensation mode was positively correlated with nitrate radical production and negatively correlated with temperature, suggesting that the formation processes were associated with the gas‐particle conversion of nitrate radical oxidation products. In contrast, the enhanced particulate secondary organic nitrates in droplet mode were predominantly contributed by aqueous‐phase processing, as indicated by the strong positive correlation with aerosol liquid water content and typical fragment ions from aqueous processing products (r = 0.52–0.59, P < 0.01). Our results highlight the potential of a size‐dependent mechanism to elucidate the formation processes of particulate secondary organic nitrates.
Observational Constraint on the Contributions of Greenhouse Gas Emission and Anthropogenic Aerosol Removal to Tibetan Plateau Future Warming
Authors: Jiang Jie , Zhou Tianjun
Published: September 2023

A decline of anthropogenic aerosol (AA) emission is expected worldwide over the coming decades. But the climate effects of aerosol removal and greenhouse gases (GHG) emission at regional scale are poorly distinguished and constrained. Taking the Tibetan Plateau (TP) as an instance, analyses of the state‐of‐the‐art climate models participating in the Detection and Attribution Model Intercomparison Project imply that while the observed warming from 1961 to 2020 is predominantly attributed to GHG emission, the future temperature rise will be influenced by the combined effects of persistent increase in GHG concentration and reduction of AA emission. Here, we develop a new constraint method considering the changed contribution of AA forcing. Constrained by detected individual external forcings, the joint contributions of GHG (1.74°C) and AA forcings (0.10°C) will lead to a warming around 1.85°C over the TP during mid‐century (2041–2060) relative to 1995–2014 under SSP2‐4.5 scenario, which is 0.44°C cooler than the raw projection.
The Effect of Seawater Carbonate Chemistry on the Stable Isotope Composition of Cibicidoides wuellerstorfi and Other Cibicidoides Species
Authors: Nederbragt Alexandra J.
Published: September 2023

The δ13C composition of Cibicidoides wuellerstorfi and other Cibicidoides spp is an important tool to reconstruct past changes in the deep ocean carbon cycle. The species are expected to match the δ13C of ambient dissolved inorganic carbon (DIC), although it has been recognized that substantial offsets can occur. Here, I present a compilation of modern δ13C and δ18O data for named Cibicidoides species in combination with fully resolved carbonate chemistry at each core location. The data show for C. wuellerstorfi that the offset from the expected value in both carbon (∆13C) and oxygen (∆18O) is correlated with seawater carbonate chemistry. The result is comparable to, but not identical with, published culture experiments in which marine organisms were grown under variable pH‐conditions. Overall, ∆13C in C. wuellerstorfi correlates positively with carbonate saturation, [DIC], and temperature. The three variables together explain 47.1% of the variation in ∆13C. The trend for ∆18O is similar, except that the effect of temperature has been removed through correction with a published δ18O‐temperature equation. Up to 35% of the remaining variation in ∆18O can be explained by ambient carbonate chemistry. Data for other named Cibicidoides species are broadly similar, but are too sparse for a detailed analysis. The results indicate that strongly negative ∆13C occurs predominantly in the deep Atlantic in response to a combination of low [DIC], low temperature, and undersaturation within the lysocline. Implications for paleoceanographic reconstructions are discussed.
Age-related cytokine imbalance in the thymus in sudden infant death syndrome (SIDS)
Authors: Qu Dong , Preuss Vanessa , Hagemeier Lars , Radomsky Lena , Beushausen Kerstin , Keil Jana , Nora Schaumann , Vennemann Benedikt , Falk Christine S. , Klintschar Michael
Published: September 2023

Background

Sudden infant death syndrome (SIDS) has been considered to be triggered by a combination of underlying immune dysregulation and infections. The thymus is a crucial lymphatic organ responsible for T cell development in infancy. We hypothesized that an altered thymic immune status may be detectable by intrathymic cytokine profiling in SIDS.

Methods

27 cytokines in protein lysates of thymus tissue and thymus weights were assessed in 26 SIDS cases and 16 infants who died of other reasons.

Results

Seventeen out of 27 cytokines were increased in thymic tissue of SIDS compared to controls without infections, and the most significant discrepancy was in infants younger than 20 weeks. The thymic cytokine profiles in SIDS cases were similar to those in controls with severe infection; however, the magnitude of the cytokine concentration elevation in SIDS was less pronounced, indicating sub-clinical infections in SIDS. In contrast to SIDS, intrathymic cytokine concentrations and thymus weight were increased with age in control children.

Conclusions

Elevated thymic cytokine expression and thymus weight, as well as impaired age-related alterations in SIDS, may be influenced by subclinical infection, which may play a role in initiating SIDS in infants with a compromised immune response.

Impact Statement

Increased thymic weight and cytokine concentration may suggest possible subclinical infection in SIDS.

Elevated thymic weight and cytokine concentration mainly in SIDS cases aged <20 weeks.

Age-related impairment in the thymic weight and cytokine expression may be impaired by subclinical infection in SIDS.
Application of next-generation imaging in biochemically recurrent prostate cancer
Authors: Moul Judd W. , Shore Neal D. , Pienta Kenneth J. , Czernin Johannes , King Martin T. , Freedland Stephen J.
Published: September 2023

Background

Biochemical recurrence (BCR) following primary interventional treatment occurs in approximately one-third of patients with prostate cancer (PCa). Next-generation imaging (NGI) can identify local and metastatic recurrence with greater sensitivity than conventional imaging, potentially allowing for more effective interventions. This narrative review examines the current clinical evidence on the utility of NGI for patients with BCR.

Methods

A search of PubMed was conducted to identify relevant publications on NGI applied to BCR. Given other relevant recent reviews on the topic, this review focused on papers published between January 2018 to May 2023.

Results

NGI technologies, including positron emission tomography (PET) radiotracers and multiparametric magnetic resonance imaging, have demonstrated increased sensitivity and selectivity for diagnosing BCR at prostate-specific antigen (PSA) concentrations <2.0 ng/ml. Detection rates range between 46% and 50%, with decreasing PSA levels for choline (1–3 ng/ml), fluciclovine (0.5–1 ng/ml), and prostate-specific membrane antigen (0.2–0.49 ng/ml) PET radiotracers. Expert working groups and European and US medical societies recommend NGI for patients with BCR.

Conclusions

Available data support the improved detection performance and selectivity of NGI modalities versus conventional imaging techniques; however, limited clinical evidence exists demonstrating the application of NGI to treatment decision-making and its impact on patient outcomes. The emergence of NGI and displacement of conventional imaging may require a reexamination of the current definitions of BCR, altering our understanding of early recurrence. Redefining the BCR disease state by formalizing the role of NGI in patient management decisions will facilitate greater alignment across research efforts and better reflect the published literature.
Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification
Authors: Shore Neal D. , Moul Judd W. , Pienta Kenneth J. , Czernin Johannes , King Martin T. , Freedland Stephen J.
Published: September 2023

Background

Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing.

Objective

This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies.

Methods

PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT).

Results

European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects.

Conclusions

Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.
Syntrophic entanglements for propionate and acetate oxidation under thermophilic and high-ammonia conditions
Authors: Singh Abhijeet , Schnürer Anna , Dolfing Jan , Westerholm Maria
Published: September 2023

Propionate is a key intermediate in anaerobic digestion processes and often accumulates in association with perturbations, such as elevated levels of ammonia. Under such conditions, syntrophic ammonia-tolerant microorganisms play a key role in propionate degradation. Despite their importance, little is known about these syntrophic microorganisms and their cross-species interactions. Here, we present metagenomes and metatranscriptomic data for novel thermophilic and ammonia-tolerant syntrophic bacteria and the partner methanogens enriched in propionate-fed reactors. A metagenome for a novel bacterium for which we propose the provisional name ‘Candidatus Thermosyntrophopropionicum ammoniitolerans’ was recovered, together with mapping of its highly expressed methylmalonyl-CoA pathway for syntrophic propionate degradation. Acetate was degraded by a novel thermophilic syntrophic acetate-oxidising candidate bacterium. Electron removal associated with syntrophic propionate and acetate oxidation was mediated by the hydrogen/formate-utilising methanogens Methanoculleus sp. and Methanothermobacter sp., with the latter observed to be critical for efficient propionate degradation. Similar dependence on Methanothermobacter was not seen for acetate degradation. Expression-based analyses indicated use of both H2 and formate for electron transfer, including cross-species reciprocation with sulphuric compounds and microbial nanotube-mediated interspecies interactions. Batch cultivation demonstrated degradation rates of up to 0.16 g propionate L−1 day−1 at hydrogen partial pressure 4–30 Pa and available energy was around −20 mol−1 propionate. These observations outline the multiple syntrophic interactions required for propionate oxidation and represent a first step in increasing knowledge of acid accumulation in high-ammonia biogas production systems.
Gasdermin D-mediated keratinocyte pyroptosis as a key step in psoriasis pathogenesis
Authors: Lian Ni , Chen Yujie , Chen Sihan , Zhang Ying , Chen Hao , Yang Yong , Gu Heng , Chen Qing , Li Min , Chen Xu
Published: September 2023

Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1β were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd−/− keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd−/− mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd−/− mice can evoke the response to imiquimod stimulation in the background of Gsdmd−/− mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.
Decoding the transcriptome of Duchenne muscular dystrophy to the single nuclei level reveals clinical-genetic correlations
Authors: Suárez-Calvet Xavier , Fernández-Simón Esther , Natera Daniel , Jou Cristina , Pinol-Jurado Patricia , Villalobos Elisa , Ortez Carlos , Monceau Alexandra , Schiava Marianela , Codina Anna , Verdu-Díaz José , Clark James , Laidler Zoe , Mehra Priyanka , Gokul-Nath Rasya , Alonso-Perez Jorge , Marini-Bettolo Chiara , Tasca Giorgio , Straub Volker , Guglieri Michela , Nascimento Andrés , Diaz-Manera Jordi
Published: September 2023

Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized by early onset muscle weakness leading to severe and irreversible disability. The cellular and molecular consequences of the lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression of the disease. Here we have analyzed quadriceps muscle biopsies of seven DMD patients aged 2 to 4 years old and five age and gender matched controls using single nuclei RNA sequencing (snRNAseq) and correlated the results obtained with clinical data. SnRNAseq identified significant differences in the proportion of cell population present in the muscle samples, including an increase in the number of regenerative fibers, satellite cells, and fibro-adipogenic progenitor cells (FAPs) and a decrease in the number of slow fibers and smooth muscle cells. Muscle samples from the younger patients with stable mild weakness were characterized by an increase in regenerative fibers, while older patients with moderate and progressive weakness were characterized by loss of muscle fibers and an increase in FAPs. An analysis of the gene expression profile in muscle fibers identified a strong regenerative signature in DMD samples characterized by the upregulation of genes involved in myogenesis and muscle hypertrophy. In the case of FAPs, we observed upregulation of genes involved in the extracellular matrix regeneration but also several signaling pathways. Indeed, further analysis of the potential intercellular communication profile showed a dysregulation of the communication profile in DMD samples identifying FAPs as a key regulator of cell signaling in DMD muscle samples. In conclusion, our study has identified significant differences at the cellular and molecular levels in the different cell populations present in skeletal muscle samples of patients with DMD compared to controls.
Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart
Authors: Gafranek Jacob T. , D’Aniello Enrico , Ravisankar Padmapriyadarshini , Thakkar Kairavee , Vagnozzi Ronald J. , Lim Hee-Woong , Salomonis Nathan , Waxman Joshua S.
Published: September 2023

How two-chambered hearts in basal vertebrates have evolved from single-chamber hearts found in ancestral chordates remains unclear. Here, we show that the teleost sinus venosus (SV) is a chamber-like vessel comprised of an outer layer of smooth muscle cells. We find that in adult zebrafish nr2f1a mutants, which lack atria, the SV comes to physically resemble the thicker bulbus arteriosus (BA) at the arterial pole of the heart through an adaptive, hypertensive response involving smooth muscle proliferation due to aberrant hemodynamic flow. Single cell transcriptomics show that smooth muscle and endothelial cell populations within the adapting SV also take on arterial signatures. Bulk transcriptomics of the blood sinuses flanking the tunicate heart reinforce a model of greater equivalency in ancestral chordate BA and SV precursors. Our data simultaneously reveal that secondary complications from congenital heart defects can develop in adult zebrafish similar to those in humans and that the foundation of equivalency between flanking auxiliary vessels may remain latent within basal vertebrate hearts.
Monolithic FAPbBr3 photoanode for photoelectrochemical water oxidation with low onset-potential and enhanced stability
Authors: Yang Hao , Liu Yawen , Ding Yunxuan , Li Fusheng , Wang Linqin , Cai Bin , Zhang Fuguo , Liu Tianqi , Boschloo Gerrit , Johansson Erik M. J. , Sun Licheng
Published: September 2023

Despite considerable research efforts on photoelectrochemical water splitting over the past decades, practical application faces challenges by the absence of efficient, stable, and scalable photoelectrodes. Herein, we report a metal-halide perovskite-based photoanode for photoelectrochemical water oxidation. With a planar structure using mesoporous carbon as a hole-conducting layer, the precious metal-free FAPbBr3 photovoltaic device achieves 9.2% solar-to-electrical power conversion efficiency and 1.4 V open-circuit voltage. The photovoltaic architecture successfully applies to build a monolithic photoanode with the FAPbBr3 absorber, carbon/graphite conductive protection layers, and NiFe catalyst layers for water oxidation. The photoanode delivers ultralow onset potential below 0 V versus the reversible hydrogen electrode and high applied bias photon-to-current efficiency of 8.5%. Stable operation exceeding 100 h under solar illumination by applying ultraviolet-filter protection. The photothermal investigation verifies the performance boost in perovskite photoanode by photothermal effect. This study is significant in guiding the development of photovoltaic material-based photoelectrodes for solar fuel applications.
Accounting for the climate benefit of temporary carbon storage in nature
Authors: Matthews H. Damon , Zickfeld Kirsten , Koch Alexander , Luers Amy
Published: September 2023

Nature-based climate solutions can contribute to climate mitigation, but the vulnerability of land carbon to disturbances means that efforts to slow or reverse land carbon loss could result in only temporary storage. The challenge of accounting for temporary storage is a key barrier to the implementation of nature-based climate mitigation strategies. Here we offer a solution to this challenge using tonne-year accounting, which integrates the amount of carbon over the time that it remains in storage. We show that tonne-years of carbon storage are proportional to degree-years of avoided warming, and that a physically based tonne-year accounting metric could effectively quantify and track the climate benefit of temporary carbon storage. If the world can sustain an increasing number of tonne-years alongside rapid fossil fuel CO2 emissions reductions, then the resulting carbon storage (even if only temporary) would have considerable and lasting climate value by lowering the global temperature peak.
Genotoxic effects of base and prime editing in human hematopoietic stem cells
Authors: Fiumara Martina , Ferrari Samuele , Omer-Javed Attya , Beretta Stefano , Albano Luisa , Canarutto Daniele , Varesi Angelica , Gaddoni Chiara , Brombin Chiara , Cugnata Federica , Zonari Erika , Naldini Matteo Maria , Barcella Matteo , Gentner Bernhard , Merelli Ivan , Naldini Luigi
Published: September 2023

Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. Here, we compared state-of-the-art BEs and PEs and Cas9 in human hematopoietic stem and progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes and on-target and genome-wide genotoxicity. BEs and PEs induced detrimental transcriptional responses that reduced editing efficiency and hematopoietic repopulation in xenotransplants and also generated DNA double-strand breaks and genotoxic byproducts, including deletions and translocations, at a lower frequency than Cas9. These effects were strongest for cytidine BEs due to suboptimal inhibition of base excision repair and were mitigated by tailoring delivery timing and editor expression through optimized mRNA design. However, BEs altered the mutational landscape of hematopoietic stem and progenitor cells across the genome by increasing the load and relative proportions of nucleotide variants. These findings raise concerns about the genotoxicity of BEs and PEs and warrant further investigation in view of their clinical application.
Integration of spatial and single-cell data across modalities with weakly linked features
Authors: Chen Shuxiao , Zhu Bokai , Huang Sijia , Hickey John W. , Lin Kevin Z. , Snyder Michael , Greenleaf William J. , Nolan Garry P. , Zhang Nancy R. , Ma Zongming
Published: September 2023

Although single-cell and spatial sequencing methods enable simultaneous measurement of more than one biological modality, no technology can capture all modalities within the same cell. For current data integration methods, the feasibility of cross-modal integration relies on the existence of highly correlated, a priori ‘linked’ features. We describe matching X-modality via fuzzy smoothed embedding (MaxFuse), a cross-modal data integration method that, through iterative coembedding, data smoothing and cell matching, uses all information in each modality to obtain high-quality integration even when features are weakly linked. MaxFuse is modality-agnostic and demonstrates high robustness and accuracy in the weak linkage scenario, achieving 20~70% relative improvement over existing methods under key evaluation metrics on benchmarking datasets. A prototypical example of weak linkage is the integration of spatial proteomic data with single-cell sequencing data. On two example analyses of this type, MaxFuse enabled the spatial consolidation of proteomic, transcriptomic and epigenomic information at single-cell resolution on the same tissue section.