bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarization-resolved surface-enhanced infrared spectra with nanosensors based on self-organized gold nanorods
Authors: Polito Raffaella , Sotgiu S. , Sohrabi F. , Ferrando G. , Berkmann F. , Temperini M. E. , Giliberti V. , Buatier de Mongeot F. , Ortolani M. , Baldassarre L. , Giordano M.C.
Published: March 2024

Biosensors are becoming ubiquitous in the study of biomolecules, as, by modifying shape size and environment of metallic nanostructures it is now possible to engineer the field so to monitor subtle transient changes in molecular conformation at the level of a single biolayer. In this paper, we present a first step towards a polarization-resolved study of light-induced conformational changes of transmembrane proteins. We exploit a platform of self-organized gold nanorods on SiO2 substrates to enhance the infrared reflection absorption spectroscopy and to perform difference spectroscopy (i.e., spectrum under visible light ON minus spectrum under visible light OFF) on a light-sensitive transmembrane protein with simultaneous visible light illumination from the backside of the chip. The broad size distribution of nanorods allows us to probe with high sensitivity the modifications of the vibrational peaks over the entire fingerprint region. We show that it is possible to identify dissimilarities in the difference spectra, which in turn implies that we are monitoring over a broadband spectrum not only the chemical bonds with the dipole moment aligned orthogonally to our substrate/nanorod surface but also those with different orientation.
Minimal Invasive Surgical Techniques (MIST): wie relevant ist der ganze Mist?
Authors: Netsch Christopher , Gross Andreas J. , Herrmann Thomas RW , Herrmann Jonas , Becker Benedikt
Published: March 2024

Aufgrund der steigenden Lebenserwartung und der wachsenden Nachfrage nach BPH-Behandlungen wurden innovative Technologien entwickelt, die eine zügige Erholung, Symptomlinderung, geringe Komplikationsraten sowie die Durchführung des Eingriffs ambulant und teilweise unter lokaler Betäubung ermöglichen. Das Ziel dieser Übersichtsarbeit ist es, die Ergebnisse der funktionellen Miktionsparameter und der sexuellen Funktion neu entwickelter minimalinvasiver chirurgischer Therapien (MIST) zur Behandlung der BPH zu beschreiben. Diese werden in primär ablative (Aquaablation [Aquabeam]), nicht-ablative (Prostata-Harnröhren-Lifting-Verfahren [PUL, Urolift], temporär implantierbare Körbchen [iTind]), und sekundär ablative Verfahren (konvektive Wasserdampfablation, Rezum, Prostataarterienembolisation [PAE]) unterschieden. Alle MIST-Technologien haben die medizinische Versorgung der BPH mit der Erhaltung der Ejakulation vorangetrieben. Langzeitdaten, die sich speziell mit Reinterventionsraten und den Erhalt der funktionellen Miktionsparameter beschäftigen, sind derzeit jedoch noch eine Seltenheit. Trotz vielversprechender Daten aus den Zulassungsstudien sowie aus randomisierten Studien, zeigen alle MIST-Therapien auch schwerwiegende Komplikationen. Patienten, die für eine solche Methode vorstellig werden, müssen über die Unterlegenheit im Gegensatz zu den etablierten transurethralen Verfahren wie die TUR-P und die Enukleation umfassend aufgeklärt werden.
Anti-CGRP basierte Migränemedikamente – eine Übersicht der
Studienlage
Authors: Triller Paul , Raffaelli Bianca
Published: March 2024

Seit Anfang der 1990er Jahre ist bekannt, dass das Neuropeptid Calcitonin
Gene-Related Peptid (CGRP) eine Schlüsselrolle in der Pathophysiologie der
Migräne spielt. Mit dieser Entdeckung ergaben sich in der Migränetherapie neue
Angriffspunkte für Medikamente, die in den letzten Jahren unser therapeutisches
Arsenal revolutioniert haben. Während bisherige Prophylaktika relativ
unspezifisch wirkten und mit oft nicht tolerablen Nebenwirkungen einhergingen,
entstanden mit CGRP als Zielstruktur in der Migräneprophylaxe gut verträgliche
und hocheffektive neue Therapieoptionen. Die zwei Hauptklassen der
CGRP-spezifischen Migränetherapie sind monoklonale Antikörper, die CGRP oder den
CGRP-Rezeptor binden und Gepante, CGRP-Rezeptor Antagonisten, die aufgrund ihrer
molekularen Eigenschaften die intrazelluläre Signaltransmission blockieren. In
großen Zulassungsstudien konnte die Sicherheit, Verträglichkeit und Wirksamkeit
von monoklonalen CGRP-Antikörpern in der prophylaktischen Therapie der
episodischen und chronischen Migräne nachgewiesen werden. Gleiches gilt für den
Einsatz verschiedener Gepante, die sich in der Akuttherapie als Alternative zu
Triptanen und bei kontinuierlicher Einnahme als Prophylaktika in klinischen
Studien als effektiv und sicher herausstellten. In dieser Übersichtsarbeit
möchten wir den aktuellen Stand der Forschung zur CGRP-spezifischen
Migränetherapie und Erkenntnisse aus ersten Anwendungsdaten darlegen.
Dorsal Aesthetic Line (DAL) Split Maneuver in Dorsal Preservation Rhinoplasty
Authors: Neves J C. Martins
Published: March 2024

The dorsal aesthetic lines (DALs) osteotomies are a strategy to increase the plasticity of the dorsal pyramid to facilitate control of the convexity of the profile, width of the nasal dorsum, and define the eyebrow-tip aesthetic lines. It is also an alternative to lateral keystone area) disarticulation. This article discusses its advantages, indications, and the technical sequence of the DAL osteotomy procedure.
Lovers in strange places: amphibian calling and amplexus detected in tidal mangrove creeks after rainfall
Authors: Gould John , Beranek Chad , Schmahl Kate , Donelly Rachael , Matthews Lynne , Callen Alex , McHenry Colin
Published: March 2024

Temporary freshwater lenses can form in saline environments after rainfall, providing essential resources for species including drinking water and dispersal routes. However, there is limited indication that these lenses can also be used for breeding. Herein, we provide evidence of the green and golden bell frog, Litoria aurea, performing breeding activities, including calling and amplexus, in tidal mangrove creeks on Kooragang Island, NSW, Australia. Our findings suggest that these creeks intermittently phase into a low salinity state after the influx of fresh water from rainfall, forming temporary freshwater lenses that can be exploited before the creeks revert to a saline state. These lenses had salinities (1.4 ppt and 4.5 ppt) within the tolerance limit of L. aurea tadpoles, although we are unsure whether oviposition took place and offspring survival to metamorphosis was achieved. It is possible that anthropogenic disturbances to hydrology on Kooragang Island have benefited L. aurea by restricting tidal influences in mangrove creeks, prolonging the duration of freshwater lenses.
NSUN5/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion
Authors: Wu Ruixin , Sun Chunming , Chen Xi , Yang Runyue , Luan Yuxuan , Zhao Xiang , Yu Panpan , Luo Rongkui , Hou Yingyong , Tian Ruotong , Bian Shasha , Li Yuli , Dong Yinghua , Liu Qian , Dai Weiwei , Fan Zhuoyang , Yan Rucheng , Pan Binyang , Feng Siheng , Wu Jing , Chen Fangzhen , Yang Changle , Wang Hanlin , Dai Haochen , Shu Minfeng
Published: March 2024

Malignant glioma exhibits immune evasion characterized by highly expressing the immune checkpoint CD47. RNA 5-methylcytosine(m5C) modification plays a pivotal role in tumor pathogenesis. However, the mechanism underlying m5C-modified RNA metabolism remains unclear, as does the contribution of m5C-modified RNA to the glioma immune microenvironment. In this study, we demonstrate that the canonical 28SrRNA methyltransferase NSUN5 down-regulates β-catenin by promoting the degradation of its mRNA, leading to enhanced phagocytosis of tumor-associated macrophages (TAMs). Specifically, the NSUN5-induced suppression of β-catenin relies on its methyltransferase activity mediated by cysteine 359 (C359) and is not influenced by its localization in the nucleolus. Intriguingly, NSUN5 directly interacts with and deposits m5C on CTNNB1 caRNA (chromatin-associated RNA). NSUN5-induced recruitment of TET2 to chromatin is independent of its methyltransferase activity. The m5C modification on caRNA is subsequently oxidized into 5-hydroxymethylcytosine (5hmC) by TET2, which is dependent on its binding affinity for Fe
2+
and α-KG. Furthermore, NSUN5 enhances the chromatin recruitment of RBFOX2 which acts as a 5hmC-specific reader to recognize and facilitate the degradation of 5hmC caRNA. Notably, hmeRIP-seq analysis reveals numerous mRNA substrates of NSUN5 that potentially undergo this mode of metabolism. In addition, NSUN5 is epigenetically suppressed by DNA methylation and is negatively correlated with IDH1-R132H mutation in glioma patients. Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.
A half-open cavity random fiber laser based on a single-mode fiber and fiber Bragg grating
Authors: He Wei , Li Zhihan , Li Shaode , Ma Siqi , Zhang Wenduo
Published: March 2024

A random erbium-doped fiber laser based on fiber Bragg grating (FBG) and single-mode fiber (SMF) was designed and realized experimentally in this study. For the proposed random fiber laser (RFL), the 10 km long SMF was used to generate Rayleigh scattering (RS) emissions, along with FBG to provide randomly distributed feedback in the cavity. In the experiment, the RFL laser threshold is 55 mW, as the pump power is increasingly improved to 175 mW. The RS effect is gradually apparent, and 1531.59nm laser beam was formed. The signal-to-noise ratio was 38.4 dB. The FBG was stretched for sensing applications, and the lasing wavelength was adjusted from 1531.59 to 1533.83 nm when the grating was stretched from 0 to 2000 μϵ.
Enhancement of skin tumor laser hyperthermia with Ytterbium nanoparticles: numerical simulation
Authors: Othman Zamrood A , Hassan Yousif M , Karim Abdulkarim Y
Published: March 2024

Laser hyperthermia therapy (HT) has emerged as a well-established method for treating cancer, yet it poses unique challenges in comprehending heat transfer dynamics within both healthy and cancerous tissues due to their intricate nature. This study investigates laser HT therapy as a promising avenue for addressing skin cancer. Employing two distinct near-infrared (NIR) laser beams at 980 nm, we analyze temperature variations within tumors, employing Pennes’ bioheat transfer equation as our fundamental investigative framework. Furthermore, our study delves into the influence of Ytterbium nanoparticles (YbNPs) on predicting temperature distributions in healthy and cancerous skin tissues. Our findings reveal that the application of YbNPs using a Gaussian beam shape results in a notable maximum temperature increase of 5 °C within the tumor compared to nanoparticle-free heating. Similarly, utilizing a flat top beam alongside YbNPs induces a temperature rise of 3 °C. While this research provides valuable insights into utilizing YbNPs with a Gaussian laser beam configuration for skin cancer treatment, a more thorough understanding could be attained through additional details on experimental parameters such as setup, exposure duration, and specific implications for skin cancer therapy.
Replica symmetry breaking in supervised and unsupervised Hebbian networks
Authors: Albanese Linda , Alessandrelli Andrea , Annibale Alessia , Barra Adriano
Published: March 2024

Hebbian neural networks with multi-node interactions, often called Dense Associative Memories, have recently attracted considerable interest in the statistical mechanics community, as they have been shown to outperform their pairwise counterparts in a number of features, including resilience against adversarial attacks, pattern retrieval with extremely weak signals and supra-linear storage capacities. However, their analysis has so far been carried out within a replica-symmetric theory. In this manuscript, we relax the assumption of replica symmetry and analyse these systems at one step of replica-symmetry breaking, focusing on two different prescriptions for the interactions that we will refer to as supervised and unsupervised learning. We derive the phase diagram of the model using two different approaches, namely Parisi’s hierarchical ansatz for the relationship between different replicas within the replica approach, and the so-called telescope ansatz within Guerra’s interpolation method: our results show that replica-symmetry breaking does not alter the threshold for learning and slightly increases the maximal storage capacity. Further, we also derive analytically the instability line of the replica-symmetric theory, using a generalization of the De Almeida and Thouless approach.
Optimization of volatile organic compounds sampling from dairy cow exhaled breath using polymer-based solid-phase extraction cartridges for gas chromatographic analysis
Authors: Eichinger Julia , Reiche Anna-Maria , Dohme-Meier Frigga , Fuchsmann Pascal
Published: March 2024

We explored appropriate technical setups for the detection of volatile organic compounds (VOCs) from exhaled cow breath by comparing six different polymer-based solid-phase extraction (SPE) cartridges currently on the market for gas chromatography/mass spectrometry (GC-MS) screening. Exhaled breath was sampled at a single timepoint from five lactating dairy cows using six different SPE cartridges (Bond Elut ENV (ENV); Chromabond HRX (HRX); Chromabond HRP (HRP); Chromabond HLB (HLB); Chromabond HR-XCW (XCW) and Chromabond HR-XAW (XAW)). The trapped VOCs were analyzed by dynamic headspace vacuum in-tube extraction GC-MS (DHS-V-ITEX-GC-MS). Depending on the SPE cartridge, we detected 1174–1312 VOCs per cartridge. Most VOCs were alkenes, alkanes, esters, ketones, alcohols, aldehydes, amines, nitriles, ethers, amides, carboxylic acids, alkynes, azoles, terpenes, pyridines, or sulfur-containing compounds. The six SPE cartridges differed in their specificity for the chemical compounds, with the XAW cartridge showing the best specificity for ketones. The greatest differences between the tested SPE cartridges appeared in the detection of specific VOCs. In total, 176 different VOCs were detected with a match factor >80%. The greatest number of specific VOCs was captured by XAW (149), followed by ENV (118), HLB (117), HRP (115), HRX (114), and XCW (114). We conclude that the tested SPE cartridges are suitable for VOC sampling from exhaled cow breath, but the SPE cartridge choice enormously affects the detected chemical groups and the number of detected VOCs. Therefore, an appropriate SPE adsorbent cartridge should be selected according to our proposed inclusion criteria. For targeted metabolomics approaches, the SPE cartridge choice depends on the VOCs or chemical compound groups of interest based on our provided VOC list. For untargeted approaches without information on the animals’ metabolic condition, we suggest using multi-sorbent SPE cartridges or multiple cartridges per animal.
Proto-Indo-European
Authors: Ringe Don
Published: March 2024

This chapter outlines the grammar of Proto-Indo-European (PIE), the earliest reconstructable ancestor of Ancient Greek, and of Core IE, the most solidly reconstructable stage in the prehistoric development of Greek. The language’s complex phonology, phonological rules, and inflectional morphology are all discussed in detail; so is the development of inflectional morphology in the immediate daughters of PIE, in which inflection seems to have become more complex. Complete sample paradigms of verbs, nouns, adjectives, pronouns, determiners, and quantifiers are included. Derivational morphology and syntax are treated more briefly. The chapter is essentially an updated version of the corresponding chapter in the 2nd edition of From Proto-Indo-European to Proto-Germanic.
Comparison of β-blocker agents and mortality in maintenance hemodialysis patients: an international cohort study
Authors: Toye Corey , Sood Manish M , Mallick Ranjeeta , Akbari Ayub , Bieber Brian , Karaboyas Angelo , Guedes Murilo , Hundemer Gregory L
Published: March 2024

Background

Despite a lack of clinical trial data, β-blockers are widely prescribed to dialysis patients. Whether specific β-blocker agents are associated with improved long-term outcomes compared with alternative β-blocker agents in the dialysis population remains uncertain.

Methods

We analyzed data from an international cohort study of 10 125 patients on maintenance hemodialysis across 18 countries that were newly prescribed a β-blocker medication within the Dialysis Outcomes and Practice Patterns Study (DOPPS). The following β-blocker agents were compared: metoprolol, atenolol, bisoprolol and carvedilol. Multivariable Cox proportional hazards models were used to estimate the association between the newly prescribed β-blocker agent and all-cause mortality. Stratified analyses were performed on patients with and without a prior history of cardiovascular disease.

Results

The mean (standard deviation) age in the cohort was 63 (15) years and 57% of participants were male. The most commonly prescribed β-blocker agent was metoprolol (49%), followed by carvedilol (29%), atenolol (11%) and bisoprolol (11%). Compared with metoprolol, atenolol {adjusted hazard ratio (HR) 0.77 [95% confidence interval (CI) 0.65–0.90]} was associated with a lower mortality risk. There was no difference in mortality risk with bisoprolol [adjusted HR 0.99 (95% CI 0.82–1.20)] or carvedilol [adjusted HR 0.95 (95% CI 0.82–1.09)] compared with metoprolol. These results were consistent upon stratification of patients by presence or absence of a prior history of cardiovascular disease.

Conclusions

Among patients on maintenance hemodialysis who were newly prescribed β-blocker medications, atenolol was associated with the lowest mortality risk compared with alternative agents.
Neoadjuvant chemoimmunotherapy confers survival advantage for patients undergoing sleeve lobectomy
Authors: Chen Tao , Wen Jialiang , He Yiming , Zhong Yifan , Deng Jiajun , Chen Qiankun , She Yunlang , Jiang Lei , Xie Dong , Zhao Deping , Chen Chang
Published: March 2024

OBJECTIVES

It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes.

METHODS

Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort.

RESULTS

A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16–0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06–0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15–0.86, P = 0.020, adjusted for clinical TNM stage).

CONCLUSIONS

Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.
Impact on nurse workload and patient satisfaction of atrioventricular junction ablation performed simultaneously with conduction system pacing using a superior approach from the pocket compared with the conventional femoral approach
Authors: Palmisano Pietro , Sergi Cesario , Panico Vincenzo , Chiarillo Marco Valerio , Chiuri Maria Domenica , Martella Maria Lucia , Stefanelli Gianluca , Martella Deborah , Mauro Raffaele , Ponzetta Maria Antonietta , Parlavecchio Antonio , Accogli Michele , Coluccia Giovanni
Published: March 2024

Aims

Conduction system pacing (CSP) and atrioventricular junction ablation (AVJA) improve outcomes in patients with symptomatic, refractory atrial fibrillation (AF). Superior approach (SA) from the pocket, via the axillary or subclavian vein, has been recently proposed as an alternative to the conventional femoral access (FA) to perform AVJA. In this study, we compare the impact of these alternative approaches on nurse workload (NWL) and patient satisfaction.

Methods and results

This was a prospective, observational study enrolling consecutive patients undergoing simultaneous CSP and AVJA. Electrophysiology laboratory (EP Lab) NWL was calculated by using a self-developed model. Ward NWL was calculated using the MIDENF® validated scale. Patient satisfaction was collected using the Hospital Consumer Assessment of Healthcare Provider Systems questionnaire. A total of 119 patients were enrolled: in 50, AVJA was primarily attempted with SA, and in 69 with FA. Compared with FA, SA was associated with a lower EP Lab NWL (169.8 ± 26.7 vs. 202.7 ± 38.9 min; P < 0.001) and a lower Ward NWL (474.5 ± 184.8 vs. 808.6 ± 289.9 min; P < 0.001). Multivariate analysis identified SA as an independent predictor of lower EP Lab NWL [hazard ratio (HR) 4.60; P = 0.001] and of lower Ward NWL (HR 45.13; P < 0.001). Compared with FA, SA was associated with a higher patient-reported rating regarding their experience during hospital stay (P = 0.035) and the overall hospital evaluation (P = 0.026).

Conclusion

In patients undergoing simultaneous CSP and AVJA, the use of an SA for ablation is a valid alternative to conventional FA. Compared with FA, this approach significantly reduces NWL and is associated with greater patient satisfaction.

Registration

ClinicalTrials.gov: NCT03612635
Unraveling the role of tumor sidedness in prognosis of stage II colon cancer
Authors: Yang Yun , Yang Xiaobao , Bai Zhigang , Gu Xiaozhe , Shah Saloni Rameshchandra , Salewala Kenish Sirajbhai , Kevadiya Mansi Pankajbhai , Zhang Zhongtao
Published: March 2024

Background

Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies.

Methods

We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004–2017). Patients were divided into a primary study cohort (2010–2017) and a validation cohort (2004–2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis.

Results

The study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC.

Conclusions

RCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.
Phylogeny and Expansion of Serine/Threonine Kinases in Phagocytotic Bacteria in the Phylum Planctomycetota
Authors: Odelgard Anna , Hägglund Emil , Guy Lionel , Andersson Siv G E
Published: March 2024

The recently isolated bacterium “Candidatus Uabimicrobium amorphum” is the only known prokaryote that can engulf other bacterial cells. Its proteome contains a high fraction of proteins involved in signal transduction systems, which is a feature normally associated with multicellularity in eukaryotes. Here, we present a protein-based phylogeny which shows that “Ca. Uabimicrobium amorphum” represents an early diverging lineage that clusters with the Saltatorellus clade within the phylum Planctomycetota. A gene flux analysis indicated a gain of 126 protein families for signal transduction functions in “Ca. Uabimicrobium amorphum”, of which 66 families contained eukaryotic-like Serine/Threonine kinases with Pkinase domains. In total, we predicted 525 functional Serine/Threonine kinases in “Ca. Uabimicrobium amorphum”, which represent 8% of the proteome and is the highest fraction of Serine/Threonine kinases in a bacterial proteome. The majority of Serine/Threonine kinases in this species are membrane proteins and 30% contain long, tandem arrays of WD40 or TPR domains. The pKinase domain was predicted to be located in the cytoplasm, while the WD40 and TPR domains were predicted to be located in the periplasm. Such domain combinations were also identified in the Serine/Threonine kinases of other species in the Planctomycetota, although in much lower abundances. A phylogenetic analysis of the Serine/Threonine kinases in the Planctomycetota inferred from the Pkinase domain alone provided support for lineage-specific expansions of the Serine/Threonine kinases in “Ca. Uabimicrobium amorphum”. The results imply that expansions of eukaryotic-like signal transduction systems are not restricted to multicellular organisms, but have occurred in parallel in prokaryotes with predatory lifestyles and phagocytotic-like behaviors.
The genome of the rayed Mediterranean limpet Patella caerulea (Linnaeus, 1758)
Authors: Halstead-Nussloch Gwyneth , Signorini Silvia Giorgia , Giulio Marco , Crocetta Fabio , Munari Marco , Della Torre Camilla , Weber Alexandra Anh-Thu
Published: March 2024

Patella caerulea (Linnaeus, 1758) is a mollusc limpet species of the class Gastropoda. Endemic to the Mediterranean Sea, it is considered a keystone species due to its primary role in structuring and regulating the ecological balance of tidal and subtidal habitats. It is currently being used as a bioindicator to assess the environmental quality of coastal marine waters and as a model species to understand adaptation to ocean acidification. Here, we provide a high-quality reference genome assembly and annotation for P. caerulea. We generated ∼30 Gb of Pacific Biosciences high-fidelity data from a single individual and provide a final 749.8 Mb assembly containing 62 contigs, including the mitochondrial genome (14,938 bp). With an N50 of 48.8 Mb and 98% of the assembly contained in the 18 largest contigs, this assembly is near chromosome-scale. Benchmarking Universal Single-Copy Orthologs scores were high (Mollusca, 87.8% complete; Metazoa, 97.2% complete) and similar to metrics observed for other chromosome-level Patella genomes, highlighting a possible bias in the Mollusca database for Patellids. We generated transcriptomic Illumina data from a second individual collected at the same locality and used it together with protein evidence to annotate the genome. A total of 23,938 protein-coding gene models were found. By comparing this annotation with other published Patella annotations, we found that the distribution and median values of exon and gene lengths was comparable with other Patella species despite different annotation approaches. The present high-quality P. caerulea reference genome, available on GenBank (BioProject: PRJNA1045377; assembly: GCA_036850965.1), is an important resource for future ecological and evolutionary studies.
Everyday Discrimination Is Associated With Higher Odds of Hospitalizations Among Older African Americans
Authors: Lange-Maia Brittney S , James Bryan D , Capuano Ana W , Grodstein Francine , Chen Yi , Barnes Lisa L
Published: March 2024

Background

Everyday discrimination—experiences of being treated unfairly based on background characteristics like race—is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored.

Methods

Community-dwelling participants from 3 longitudinal cohort studies (N = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included. Hospitalizations were identified using Medicare fee-for-service claims, available for an average of 6.2 (SD: 3.7) years of follow-up after baseline.

Results

In mixed-effects ordinal logistic regression models (outcomes of 0, 1, or 2+ hospitalizations per year) adjusted for age, sex, education, and income, higher discrimination was associated with higher odds of total annual hospitalizations (odds ratio [OR] per point higher = 1.09, 95% confidence intervals [95% CI]: 1.02–1.17). Results were similar when accounting for depressive symptoms.

Conclusions

Higher exposure to everyday discrimination is associated with higher odds of hospitalization among older African Americans. Mechanisms underlying associations should be explored further to understand how hospitalizations may be reduced in older African Americans.
Reflecting on Race, Racism and Transitional Justice
Authors: Sirleaf Matiangai , Achiume E. Tendayi
Published: March 2024

ABSTRACT∞

Following the racial justice uprisings of 2020, our world order continues to reel from the consequences of the systemic racism that is the product of colonial projects past and present. In this introduction to the International Journal for Transitional Justice’s (IJTJ) Special Issue on Race, Racism and Transitional Justice, we ruminate on key disciplinary critiques of the bounds of transitional justice. We analyze the IJTJ’s record of addressing race and racism, relying on data from a coding project of almost all its publications. We find that the explicit discussion and engagement with race and racism has been wanting in the Journal. This volume helps us to consider what it would mean for the field to begin to take race, racism and racial justice seriously. Our hope is that it will help catalyze the remembering, exposing and reimagining of the role of race and racism in transitional justice and beyond.
Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions
Authors: Bergmann Felix , Wölfl-Duchek Michael , Jorda Anselm , Al Jalali Valentin , Leutzendorff Amelie , Sanz-Codina Maria , Gompelmann Daniela , Trimmel Karin , Weber Maria , Eberl Sabine , Van Os Wisse , Minichmayr Iris K , Reiter Birgit , Stimpfl Thomas , Idzko Marco , Zeitlinger Markus
Published: March 2024

Background

Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited.

Materials and methods

We conducted a prospective single-centre pharmacokinetic (PK) study in 12 healthy volunteers. Subjects received seven doses of 200 mg isavuconazole to achieve an assumed steady-state. After the first and final infusion, plasma sampling was conducted over 8 and 12 h, respectively. All subjects underwent one lumbar puncture and bronchoalveolar lavage, at either 2, 6 or 12 h post-infusion of the final dose. PBMCs were collected in six subjects from blood to determine intracellular isavuconazole concentrations at 6, 8 or 12 h. The AUC/MIC was calculated for an MIC value of 1 mg/L, which marks the EUCAST susceptibility breakpoint for Aspergillus fumigatus and Aspergillus flavus.

Results

C max and AUC0-24h of isavuconazole in plasma under assumed steady-state conditions were 6.57 ± 1.68 mg/L (mean ± SD) and 106 ± 32.1 h·mg/L, respectively. The average concentrations measured in CSF, ELF and in PBMCs were 0.07 ± 0.03, 0.94 ± 0.46 and 27.1 ± 17.8 mg/L, respectively. The AUC/MIC in plasma, CSF, ELF and in PBMCs under steady-state conditions were 106 ± 32.1, 1.68 ± 0.72, 22.6 ± 11.0 and 650 ± 426 mg·h/L, respectively.

Conclusion

Isavuconazole demonstrated moderate penetration into ELF, low penetrability into CSF and high accumulation in PBMCs. Current dosing regimens resulted in sufficient plasma exposure in all subjects to treat isolates with MICs ≤ 1 mg/L.
Ceftazidime/avibactam serum concentration in patients on ECMO
Authors: Curtiaud Anaïs , Petit Matthieu , Chommeloux Juliette , Pineton de Chambrun Marc , Hekimian Guillaume , Schmidt Matthieu , Combes Alain , Luyt Charles-Edouard
Published: March 2024

Objectives

The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing.

Methods

Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing.

Results

Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition.

Conclusions

In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing.
Expanding the Use of Continuous Sedation Until Death and Physician-Assisted Suicide
Authors: LiPuma Samuel H , Demarco Joseph P
Published: March 2024

The controversy over the equivalence of continuous sedation until death (CSD) and physician-assisted suicide/euthanasia (PAS/E) provides an opportunity to focus on a significant extended use of CSD. This extension, suggested by the equivalence of PAS/E and CSD, is designed to promote additional patient autonomy at the end-of-life. Samuel LiPuma, in his article, “Continuous Sedation Until Death as Physician-Assisted Suicide/Euthanasia: A Conceptual Analysis” claims equivalence between CSD and death; his paper is seminal in the equivalency debate. Critics contend that sedation follows proportionality protocols for which LiPuma’s thesis does not adequately account. Furthermore, sedation may not eliminate consciousness, and as such LiPuma’s contention that CSD is equivalent to neocortical death is suspect. We not only defend the equivalence thesis, but also expand it to include additional moral considerations. First, we explain the equivalence thesis. This is followed by a defense of the thesis against five criticisms. The third section critiques the current use of CSD. Finally, we offer two proposals that, if adopted, would broaden the use of PAS/E and CSD and thereby expand options at the end-of-life.
Molecular and genetic regulation of petal number variation
Authors: Wang Dan , Dong Xue , Zhong Mi-Cai , Jiang Xiao-Dong , Cui Wei-Hua , Bendahmane Mohammed , Hu Jin-Yong
Published: March 2024

Floral forms with an increased number of petals, also known as double-flower phenotypes, have been selected and conserved in many domesticated plants, particularly in ornamentals, because of their great economic value. The molecular and genetic mechanisms that control this trait are therefore of great interest, not only for scientists, but also for breeders. In this review, we summarize current knowledge of the gene regulatory networks of flower initiation and development and known mutations that lead to variation of petal number in many species. In addition to the well-accepted miR172/AP2-like module, for which many questions remain unanswered, we also discuss other pathways in which mutations also lead to the formation of extra petals, such as those involved in meristem maintenance, hormone signalling, epigenetic regulation, and responses to environmental signals. We discuss how the concept of ‘natural mutants’ and recent advances in genomics and genome editing make it possible to explore the molecular mechanisms underlying double-flower formation, and how such knowledge could contribute to the future breeding and selection of this trait in more crops.
Commentary: Special Issue - Current Understanding of Colorectal and Pancreatic Cancers
Authors: Vodicka Pavel , Vodickova Ludmila
Published: March 2024

The Commentary on Special Issue- Current Understanding of Colorectal and Pancreatic Cancers provides the reasoning for the selection of the contributions on pancreatic and colorectal cancer, and summarizes in brief the individual topics and comments upon the main outcomes. The current knowledge, contribution of the individual articles within this Special Issue, and arising priorities in the research on pancreatic ductal adenocarcinoma and colorectal cancer are highlighted.
Reconstructing human history from ancient genomes: an interview with Nobel laureate Svante Pääbo
Authors: Zhao Weijie
Published: March 2024

Professor Svante Pääbo, Director of the Max Planck Institute for Evolutionary Anthropology, won the Nobel Prize in Physiology or Medicine in 2022 for his discoveries in ancient hominine genomes and human evolution. His pioneering work in sequencing and interpreting the paleo genomes of Neanderthals and Denisovans, as well as their relationship with the modern human genome, was groundbreaking in terms of our understanding of human origins. Nowadays, we can even use commercial kits to easily detect the proportion of Neanderthal genes in our own genomes.

Recently, NSR conducted an interview with Professor Pääbo to learn about his interesting work chasing the ancient genomes and reconstructing human evolutionary and migration history from the DNA evidence, as well as his perspective on paleo genome studies and his advice to young researchers: follow your interests and be ready to try some crazy things.
Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System
Authors: Mitro Susanna D. , Xu Fei , Lee Catherine , Zaritsky Eve , Waetjen L. Elaine , Wise Lauren A. , Hedderson Monique M.
Published: March 2024

OBJECTIVE:

To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system.

METHODS:

We studied a cohort of 10,324 patients aged 18–50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009–2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan–Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics.

RESULTS:

Median follow-up was 3.8 years (interquartile range 1.8–7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients.

CONCLUSION:

Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.
Obstetric Racial Disparities in the Era of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) Trial and the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Wheeler Sarahn M. , Truong Tracy , Unnithan Shakthi , Hong Hwanhee , Myers Evan , Swamy Geeta K.
Published: March 2024

OBJECTIVE:

To evaluate the influence of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial and the coronavirus disease 2019 (COVID-19) pandemic on racial and ethnic differences in labor induction, pregnancy-associated hypertension, and cesarean delivery among non-Hispanic Black and non-Hispanic White low-risk, first-time pregnancies.

METHODS:

We conducted an interrupted time series analysis of U.S. birth certificate data from maternal non-Hispanic Black and non-Hispanic White race and ethnicity, first pregnancy, 39 or more weeks of gestation, with no documented contraindication to vaginal delivery or expectant management beyond 39 weeks. We compared the rate of labor induction (primary outcome), pregnancy-associated hypertension, and cesarean delivery during three time periods: pre-ARRIVE (January 1, 2015–July 31, 2018), post-ARRIVE (November 1, 2018–February 29, 2020), and post-COVID-19 (March 1, 2020–December 31, 2021).

RESULTS:

In the post-ARRIVE period, the rate of labor induction increased in both non-Hispanic White and non-Hispanic Black patients, with no statistically significant difference in the magnitude of increase between the two groups (rate ratio for race [RRrace] 0.98, 95% CI, 0.95–1.02, P=.289). Post-COVID-19, the rate of labor induction increased in non-Hispanic White but not non-Hispanic Black patients. The magnitude of the rate change between non-Hispanic White and non-Hispanic Black patients was significant (RRrace 0.95, 95% CI, 0.92–0.99, P=.009). Non-Hispanic Black pregnant people were more likely to have pregnancy-associated hypertension and more often delivered by cesarean at all time periods.

CONCLUSION:

Changes in obstetric practice after both the ARRIVE trial and the COVID-19 pandemic were not associated with changes in Black–White racial differences in labor induction, cesarean delivery, and pregnancy-associated hypertension.
Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence
Authors: Laue Hannah E. , Lanphear Bruce P. , Calafat Antonia M. , Cecil Kim M. , Chen Aimin , Xu Yingying , Kalkwarf Heidi J. , Madan Juliette C. , Karagas Margaret R. , Yolton Kimberly , Fleisch Abby F. , Braun Joseph M.
Published: March 2024

Background:

Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage.

Methods:

We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003–2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]—dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males—testosterone; females—estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche.

Results:

For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (−29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: −18%, −2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1–3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months.

Conclusion:

Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.