bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods of In Ovo and Ex Ovo Ostrich Embryo Culture with Observations on the Development and Maturation of the Chorioallantoic Membrane
Authors: Makanya Andrew N , Jimoh Sikiru A , Maina John N
Published: June 2023

Culture of shell-free and windowed eggs for drug testing and other experiments has been perfected for smaller eggs such as those of chickens, where the developing blood vessels of the chorioallantoic membrane (CAM) become accessible for manipulative studies. However, due to the thickness and hardness of the ostrich egg shell, such techniques are not applicable. Using a tork craft mini rotary and a drill bit, we established windowed egg, in-shell-membrane windowed egg, and in-shell-membrane shell–free methods in the ostrich egg, depending on whether the shell membranes were retained or not. Concomitant study of the developing CAM revealed that at embryonic day 16 (E16), the three layers of the CAM were clearly delineated and at E25, the chorionic capillaries had fused with the epithelium while the CAM at E37 had reached maturity and the chorion and the allantois were both 3–4 times thicker and villous cavity (VC) and capillary-covering cells were well delineated. Both intussusceptive and sprouting angiogenesis were found to be the predominant modes of vascular growth in the ostrich CAM. Development and maturation of the ostrich CAM are similar to those of the well-studied chicken egg, albeit its incubation time being twice in duration.
Progesterone signaling in the regulation of luteal steroidogenesis
Authors: Yakin Kayhan , Hela Francesko , Oktem Ozgur
Published: June 2023

The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of non-canonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering these mechanisms has significant implications in the management of luteal phase disorders and early pregnancy complications. The purpose of this review is to highlight the complex mechanisms through which progesterone-induced signaling mediates luteal granulosa cell activity in the corpus luteum. Here, we review the literature and discuss the up-to-date evidence on how paracrine and autocrine effects of progesterone regulate luteal steroidogenic activity. We also review the limitations of the published data and highlight future research priorities.
IFI16 phase separation via multi-phosphorylation drives innate immune signaling
Authors: Liu Dawei , Lum Krystal K , Treen Nicholas , Núñez Corazón T , Yang Jinhang , Howard Timothy R , Levine Michael , Cristea Ileana M
Published: June 2023

The interferon inducible protein 16 (IFI16) is a prominent sensor of nuclear pathogenic DNA, initiating innate immune signaling and suppressing viral transcription. However, little is known about mechanisms that initiate IFI16 antiviral functions or its regulation within the host DNA-filled nucleus. Here, we provide in vitro and in vivo evidence to establish that IFI16 undergoes liquid–liquid phase separation (LLPS) nucleated by DNA. IFI16 binding to viral DNA initiates LLPS and induction of cytokines during herpes simplex virus type 1 (HSV-1) infection. Multiple phosphorylation sites within an intrinsically disordered region (IDR) function combinatorially to activate IFI16 LLPS, facilitating filamentation. Regulated by CDK2 and GSK3β, IDR phosphorylation provides a toggle between active and inactive IFI16 and the decoupling of IFI16-mediated cytokine expression from repression of viral transcription. These findings show how IFI16 switch-like phase transitions are achieved with temporal resolution for immune signaling and, more broadly, the multi-layered regulation of nuclear DNA sensors.
Efficient and sensitive profiling of RNA–protein interactions using TLC-CLIP
Authors: Ernst Christina , Duc Julien , Trono Didier
Published: June 2023

RNA-binding proteins are instrumental for post-transcriptional gene regulation, controlling all aspects throughout the lifecycle of RNA molecules. However, transcriptome-wide methods to profile RNA–protein interactions in vivo remain technically challenging and require large amounts of starting material. Herein, we present an improved library preparation strategy for crosslinking and immunoprecipitation (CLIP) that is based on tailing and ligation of cDNA molecules (TLC). TLC involves the generation of solid-phase cDNA, followed by ribotailing to significantly enhance the efficiency of subsequent adapter ligation. These modifications result in a streamlined, fully bead-based library preparation strategy, which eliminates time-consuming purification procedures and drastically reduces sample loss. As a result, TLC-CLIP displays unparalleled sensitivity, enabling the profiling of RNA–protein interactions from as few as 1000 cells. To demonstrate the effectiveness of TLC-CLIP, we profiled four endogenous RNA-binding proteins, showcasing its reproducibility and improved precision resulting from a higher occurrence of crosslinking-induced deletions. These deletions serve as an intrinsic quality metric and increase both specificity and nucleotide-resolution.
Single-molecule characterization of target search dynamics of DNA-binding proteins in DNA-condensed droplets
Authors: Kamagata Kiyoto , Kusano Ryo , Kanbayashi Saori , Banerjee Trishit , Takahashi Hiroto
Published: June 2023

Target search models of DNA-binding proteins in cells typically consider search mechanisms that include 3D diffusion and 1D sliding, which can be characterized by single-molecule tracking on DNA. However, the finding of liquid droplets of DNA and nuclear components in cells cast doubt on extrapolation from the behavior in ideal non-condensed DNA conditions to those in cells. In this study, we investigate the target search behavior of DNA-binding proteins in reconstituted DNA-condensed droplets using single-molecule fluorescence microscopy. To mimic nuclear condensates, we reconstituted DNA-condensed droplets using dextran and PEG polymers. In the DNA-condensed droplets, we measured the translational movement of four DNA-binding proteins (p53, Nhp6A, Fis and Cas9) and p53 mutants possessing different structures, sizes, and oligomeric states. Our results demonstrate the presence of fast and slow mobility modes in DNA-condensed droplets for the four DNA-binding proteins. The slow mobility mode capability is correlated strongly to the molecular size and the number of DNA-binding domains on DNA-binding proteins, but only moderately to the affinity to single DNA segments in non-condensed conditions. The slow mobility mode in DNA-condensed droplets is interpreted as a multivalent interaction mode of the DNA-binding protein to multiple DNA segments.
Mutational and structural analyses of UdgX: insights into the active site pocket architecture and its evolution
Authors: Aroli Shashanka , Woo Eui-Jeon , Gopal Balasubramanian , Varshney Umesh
Published: June 2023

UdgX excises uracil from uracil-containing DNA to concurrently form a covalent bond with the resulting AP-DNA. Structurally, UdgX is highly similar to family-4 UDGs (F4-UDGs). However, UdgX is unique in possessing a flexible R-loop (105KRRIH109). Among the class-defining motifs, while its motif A (51GEQPG55) diverged to possess Q53 in place of A53/G53 in F4-UDGs, motif B [178HPS(S/A)(L/V)(L/V)R184] has remained unchanged. Previously, we proposed an SN1 mechanism resulting in a covalent bond between H109 and AP-DNA. In this study, we investigated several single/double mutants of UdgX. The H109A, H109S, H109G, H109Q, H109C and H109K mutants gain conventional UDG activity to varying levels. The crystal structures of UdgX mutants show topological changes in their active sites, rationalizing their UDG activities. The E52Q, E52N and E52A mutants reveal that E52 forms a catalytic dyad with H109 to enhance its nucleophilicity. The Q53A mutant supports that UdgX specific evolution of Q53 occurred essentially to stabilize the R-loop conformation. The R184A mutation (motif B) supports the role of R184 in substrate-binding. Taken together, the structural, bioinformatics, and mutational studies suggest that UdgX diverged from F4-UDGs, and the emergence of the characteristic R-loop in UdgX is functionally assisted by A53/G53 to Q53 changes in motif A.
N
2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing
Authors: Wang Can , Ulryck Nathalie , Herzel Lydia , Pythoud Nicolas , Kleiber Nicole , Guérineau Vincent , Jactel Vincent , Moritz Chloé , Bohnsack Markus T , Carapito Christine , Touboul David , Bohnsack Katherine E , Graille Marc
Published: June 2023

Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation and translation. Dysregulation of such modifications and the enzymes installing them have been linked to various human pathologies including neurodevelopmental disorders and cancers. Several methyltransferases (MTases) are regulated allosterically by human TRMT112 (Trm112 in Saccharomyces cerevisiae), but the interactome of this regulator and targets of its interacting MTases remain incompletely characterized. Here, we have investigated the interaction network of human TRMT112 in intact cells and identify three poorly characterized putative MTases (TRMT11, THUMPD3 and THUMPD2) as direct partners. We demonstrate that these three proteins are active N2-methylguanosine (m2G) MTases and that TRMT11 and THUMPD3 methylate positions 10 and 6 of tRNAs, respectively. For THUMPD2, we discovered that it directly associates with the U6 snRNA, a core component of the catalytic spliceosome, and is required for the formation of m2G, the last ‘orphan’ modification in U6 snRNA. Furthermore, our data reveal the combined importance of TRMT11 and THUMPD3 for optimal protein synthesis and cell proliferation as well as a role for THUMPD2 in fine-tuning pre-mRNA splicing.
A meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production
Authors: Fu Yu , Dong Yu-Qi , Shen Jin-Long , Yin Bin-Cheng , Ye Bang-Ce , You Di
Published: June 2023

Actinobacteria are ubiquitous bacteria undergoing complex developmental transitions coinciding with antibiotic production in response to stress or nutrient starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate these intriguing cell biological processes remain unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA and disrupted the signal transduction of c-di-GMP, thus governing both developmental transition and antibiotic production. Additionally, practical mutation of BldDK11R bypassing acetylation regulation could enhance the positive effect of BldD on antibiotic production. The study of AcP-dependent acetylation is usually confined to the control of enzyme activity. Our finding represents an entirely different role of the covalent modification caused by AcP, which integrated with c-di-GMP signal in modulating the activity of BldD for development and antibiotic production, coping with environmental stress. This coherent regulatory network might be widespread across actinobacteria, thus has broad implications.
Widespread CRISPR-derived RNA regulatory elements in CRISPR-Cas systems
Authors: Shmakov Sergey A , Barth Zachary K , Makarova Kira S , Wolf Yuri I , Brover Vyacheslav , Peters Joseph E , Koonin Eugene V
Published: June 2023

CRISPR-cas loci typically contain CRISPR arrays with unique spacers separating direct repeats. Spacers along with portions of adjacent repeats are transcribed and processed into CRISPR(cr) RNAs that target complementary sequences (protospacers) in mobile genetic elements, resulting in cleavage of the target DNA or RNA. Additional, standalone repeats in some CRISPR-cas loci produce distinct cr-like RNAs implicated in regulatory or other functions. We developed a computational pipeline to systematically predict crRNA-like elements by scanning for standalone repeat sequences that are conserved in closely related CRISPR-cas loci. Numerous crRNA-like elements were detected in diverse CRISPR-Cas systems, mostly, of type I, but also subtype V-A. Standalone repeats often form mini-arrays containing two repeat-like sequence separated by a spacer that is partially complementary to promoter regions of cas genes, in particular cas8, or cargo genes located within CRISPR-Cas loci, such as toxins-antitoxins. We show experimentally that a mini-array from a type I-F1 CRISPR-Cas system functions as a regulatory guide. We also identified mini-arrays in bacteriophages that could abrogate CRISPR immunity by inhibiting effector expression. Thus, recruitment of CRISPR effectors for regulatory functions via spacers with partial complementarity to the target is a common feature of diverse CRISPR-Cas systems.
Global transmission of broad-host-range plasmids derived from the human gut microbiome
Authors: Yang Lili , Mai Guoqin , Hu Zheng , Zhou Haokui , Dai Lei , Deng Ziqing , Ma Yingfei
Published: June 2023

Broad-host-range (BHR) plasmids in human gut bacteria are of considerable interest for their ability to mediate horizontal gene transfer (HGT) across large phylogenetic distance. However, the human gut plasmids, especially the BHR plasmids, remain largely unknown. Here, we identified the plasmids in the draft genomes of gut bacterial isolates from Chinese and American donors, resulting in 5372 plasmid-like clusters (PLCs), of which, 820 PLCs (comPLCs) were estimated with > 60% completeness genomes and only 155 (18.9%) were classified to known replicon types (n = 37). We observed that 175 comPLCs had a broad host range across distinct bacterial genera, of which, 71 were detected in at least two human populations of Chinese, American, Spanish, and Danish, and 13 were highly prevalent (>10%) in at least one human population. Haplotype analyses of two widespread PLCs demonstrated their spreading and evolutionary trajectory, suggesting frequent and recent exchanges of the BHR plasmids in environments. In conclusion, we obtained a large collection of plasmid sequences in human gut bacteria and demonstrated that a subset of the BHR plasmids can be transmitted globally, thus facilitating extensive HGT (e.g. antibiotic resistance genes) events. This study highlights the potential implications of the plasmids for global human health.
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis
Authors: Whitlock Reid , Leon Silvia J , Manacsa Hazel , Askin Nicole , Rigatto Claudio , Fatoba Samuel T , Farag Youssef M K , Tangri Navdeep
Published: June 2023

Background and Objectives

Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.

Design, setting, participants, and measurements

This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.

Results

There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23–1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32–2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81–1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84–2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15–13.67).

Conclusion

Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Oldhamite: a new link in upper mantle for C–O–S–Ca cycles and an indicator for planetary habitability
Authors: Liu Yuegao , Chou I-Ming , Chen Jiangzhi , Wu Nanping , Li Wenyuan , Bagas Leon , Ren Minghua , Liu Zairong , Mei Shenghua , Wang Liping
Published: June 2023

In the solar system, oldhamite (CaS) is generally considered to be formed by the condensation of solar nebula gas. Enstatite chondrites, one of the most important repositories of oldhamite, are believed to be representative of the material that formed Earth. Thus, the formation mechanism and the evolution process of oldhamite are of great significance to the deep understanding of the solar nebula, meteorites, the origin of Earth, and the C–O–S–Ca cycles of Earth. Until now, oldhamite has not been reported to occur in mantle rock. However, here we show the formation of oldhamite through the reaction between sulfide-bearing orthopyroxenite and molten CaCO3 at 1.5 GPa/1510 K, 0.5 GPa/1320 K, and 0.3 GPa/1273 K. Importantly, this reaction occurs at oxygen fugacities within the range of upper-mantle conditions, six orders of magnitude higher than that of the solar nebula mechanism. Oldhamite is easily oxidized to CaSO4 or hydrolysed to produce calcium hydroxide. Low oxygen fugacity of magma, extremely low oxygen content of the atmosphere, and the lack of a large amount of liquid water on the celestial body's surface are necessary for the widespread existence of oldhamite on the surface of a celestial body otherwise, anhydrite or gypsum will exist in large quantities. Oldhamites may exist in the upper mantle beneath mid-ocean ridges. Additionally, oldhamites may have been a contributing factor to the early Earth's atmospheric hypoxia environment, and the transient existence of oldhamites during the interaction between reducing sulfur-bearing magma and carbonate could have had an impact on the changes in atmospheric composition during the Permian–Triassic Boundary.
Visualizing the role of applied voltage in non-metal electrocatalysts
Authors: Wang Ziyuan , Chen Jun , Ni Chenwei , Nie Wei , Li Dongfeng , Ta Na , Zhang Deyun , Sun Yimeng , Sun Fusai , Li Qian , Li Yuran , Chen Ruotian , Bu Tiankai , Fan Fengtao , Li Can
Published: June 2023

Understanding how applied voltage drives the electrocatalytic reaction at the nanoscale is a fundamental scientific problem, particularly in non-metallic electrocatalysts, due to their low intrinsic carrier concentration. Herein, using monolayer molybdenum disulfide (MoS2) as a model system of non-metallic catalyst, the potential drops across the basal plane of MoS2 (ΔVsem) and the electric double layer (ΔVedl) are decoupled quantitatively as a function of applied voltage through in-situ surface potential microscopy. We visualize the evolution of the band structure under liquid conditions and clarify the process of EF keeping moving deep into Ec, revealing the formation process of the electrolyte gating effect. Additionally, electron transfer (ET) imaging reveals that the basal plane exhibits high ET activity, consistent with the results of surface potential measurements. The potential-dependent behavior of kf and ns in the ET reaction are further decoupled based on the measurements of ΔVsem and ΔVedl. Comparing the ET and hydrogen evolution reaction imaging results suggests that the low electrocatalytic activity of the basal plane is mainly due to the absence of active sites, rather than its electron transfer ability. This study fills an experimental gap in exploring driving forces for electrocatalysis at the nanoscale and addresses the long-standing issue of the inability to decouple charge transfer from catalytic processes.
Exploring Young Adults’ Beliefs About Cigar Smoking by Susceptibility: A Belief Elicitation Study
Authors: Phan Lilianna , Seyl Christen , Chen-Sankey Julia , Niederdeppe Jeff , Guy Mignonne C , Sterling Kymberle L , Choi Kelvin
Published: June 2023

Introduction

Young adults are at risk for cigar smoking, which is associated with cancers and pulmonary and cardiovascular diseases. Little is known about young adults’ beliefs about smoking cigarillos, little filtered cigars, and large cigars, and how these beliefs may vary across cigar types and by cigar susceptibility.

Aims and Methods

The larger study surveyed a U.S. sample of young adults (18–30 years old) who never used tobacco products (n = 948) through Qualtrics online panel services in August 2021–January 2022. We assessed participants’ susceptibility to using different cigar types. Participants were randomly assigned to open-ended questions about one of the three cigar types to elicit behavioral, normative, and control beliefs. We conducted thematic analysis to code emergent themes within each belief and examined the frequency of reported themes at the intersection of cigar type and cigar susceptibility.

Results

Cigar susceptible participants reported positive behavioral beliefs (eg, anticipated relaxation, mood regulation, being cool), friends as supportive referents, and easy-to-smoke control beliefs (eg, high accessibility, low cost) more frequently than non-susceptible participants. Varied frequency by cigar type also emerged. For example, cigarillo and little filtered cigar features were mentioned more frequently as easy-to-smoke control beliefs, while low accessibility was reported more frequently as a hard-to-smoke control belief for large cigars.

Conclusions

Findings identify salient beliefs about cigarillo, little filtered cigar, and large cigar smoking among young adult tobacco never-users. Future research should investigate the potential importance of these beliefs in cigar smoking susceptibility and initiation among young adults, and their potential utility in prevention research.

Implications

This thematic analysis identified salient beliefs about cigarillos, little filtered cigars, and large cigars among a U.S. young adult sample, and differentiated emergent beliefs by cigar susceptibility status and by cigar type. Given the lack of cigar smoking prevention media campaigns, identifying these beliefs is the one of the first steps in developing effective cigar smoking prevention strategies. Future quantitative studies are needed to confirm the relationships between these beliefs and smoking initiation of each cigar type to further inform the types of beliefs to be targeted in strategic communication and help prevent cigar smoking initiation among susceptible young adults.
A systematic review and meta-analysis of randomized controlled trials to evaluate plant-based omega-3 polyunsaturated fatty acids in nonalcoholic fatty liver disease patient biomarkers and parameters
Authors: Moore Ella , Patanwala Imran , Jafari Alireza , Davies Ian G , Kirwan Richard P , Newson Lisa , Mazidi Mohsen , Lane Katie E
Published: June 2023

Context

Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25–30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis.

Objective

The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters.

Data Sources

Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980).

Data Extraction

A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD.

Results

The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: –76.93, –12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05).

Conclusion

Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations.

Systematic Review Registration

PROSPERO registration no. CRD42021251980.
Treatment of Piperacillin-Tazobactam–Nonsusceptible/Ceftriaxone-Susceptible Infections With Carbapenem Versus Carbapenem-Sparing Antimicrobials
Authors: Cao John , Dubrovskaya Yanina , Siegfried Justin , Decano Arnold , Mazo Dana , Hochman Sarah , Zacharioudakis Ioannis M , So Jonathan , Solomon Sadie , Papadopoulos John , Marsh Kassandra
Published: June 2023

Background

Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies.

Methods

This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy.

Results

Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3–9] vs 6 [4–9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074–1.340]; P = .001), while treatment with carbapenem-sparing therapy was not.

Conclusions

Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.
Maternal Breast Milk Secretor Phenotype Does Not Affect Infant Susceptibility to Rotavirus Diarrhea
Authors: Williams Frank B , Kader Md Abdul , Dickson Dorothy M , Colgate E Ross , Alam Masud , Haque Rashidul , Petri William A , Kirkpatrick Beth D , Lee Benjamin
Published: June 2023

Breast milk secretor status is associated with antibody seroconversion to oral rotavirus vaccination. Here, we were unable to detect a similar impact on risk of infant rotavirus diarrhea or vaccine efficacy through 2 years of life, underscoring limitations of immunogenicity assessment alone in evaluation of oral rotavirus vaccine response.
Eradicating Pulmonary Mycobacterium abscessus: The Promise of Dual β-Lactam Therapy
Authors: Alahmdi Bayan , Dousa Khalid M , Kurz Sebastian G , Kaufman Andrew , Bonomo Robert A , Taimur Sarah
Published: June 2023

Macrolide resistance has rendered the treatment of Mycobacterium abscessus extremely difficult and is fueling a crisis. Recently, there has been dramatically increased incidence of infections by M abscessus. Select dual β-lactam combinations have shown promising in vitro results. Herein, we present a patient whose M abscessus infection cured using dual β-lactams as part of multidrug regimen.
Detection of six massive contact binaries with tertiary component candidates in the Small Magellanic Cloud
Authors: Wu Chu-Qi , Qian Sheng-Bang , Li Fu-Xing , Zhu Li-Ying , Zhao Er-Gang , Liao Wen-Ping
Published: June 2023

To study massive binaries in different evolution stages or environments, we use the Small Magellanic Cloud (SMC) as our target because the metallicity in the SMC is much lower than that in our Milky Way. The period change of early-type close binary systems in the SMC was studied based on OGLE collections. Six of these systems are found to have periodic period changes. Since all of them are of early type, the light-traveltime effect probably created by these massive binaries with third bodies is used to explain such a phenomenon. We use the Wilson–Devinney code (WD method) to analyze their I-band photometric light curves. The results show the six third bodies as having orbital periods from 6.41–24.65 yr and minimum masses from 0.31–4.11 M⊙. Among all six systems, three have a negative $\dot{P}$, which means that their periods keep decreasing. In addition, from the WD result, we find there are three deep-contact binaries, one intermediate-contact binary, and two shallow-contact binaries. The fraction of companions in massive contact binaries is quite high based on this sample, which may demonstrate the notion of high multiplicity in massive binary stars. This might mean that additional components may play an important role in the evolution of massive close binaries.
Les commotions cérébrales liées au sport et les mises en échec chez les enfants et les adolescents : l’évaluation, la prise en charge et les répercussions sur les politiques
Authors: Goulet Kristian , Beno Suzanne
Published: June 2023

Les commotions cérébrales sont des lésions courantes tant dans un contexte sportif et de loisirs qu’ailleurs, et elles demeurent une grave préoccupation chez les enfants et les adolescents. Toute jeune personne chez qui on soupçonne une commotion cérébrale devrait être soumise à une évaluation médicale le plus rapidement possible, et lorsque la commotion est subie pendant une activité sportive, la victime doit être immédiatement retirée du jeu afin d’éviter des lésions secondaires. Une brève période initiale de repos physique et cognitif est suivie d’un protocole graduel et supervisé de retour à l’apprentissage et de retour au jeu. Tous les intervenants qui participent aux sports et aux loisirs chez les enfants et les adolescents doivent être en mesure de reconnaître les risques de commotion cérébrale, de même que les signes et symptômes s’y rattachant. Ils doivent également s’assurer que toute personne chez qui on soupçonne une commotion est évaluée et prise en charge de manière appropriée par du personnel médical qualifié. L’évolution des données et des publications scientifiques a renforcé à la fois la compréhension de la physiopathologie des commotions cérébrales et les conseils de prise en charge clinique, particulièrement en matière de soins aigus, de symptômes persistants et de prévention. Le présent document de principes revient également sur la relation entre les mises en échec au hockey et le taux de blessures et préconise de changer les politiques au hockey mineur.
Career adaptability to prevent unexpected careers and burnout for woman employees in the remote work era
Authors: Aminah Siti , Hidayah Nur , Hanurawan Fattah , Indreswari Henny , Rangka Itsar Bolo
Published: June 2023

Since the coronavirus disease 2019 pandemic, female remote workers need career adaptability. The main reason is that women are susceptible to mental health issues like burnout and unexpected career. To balance public and domestic roles, women need access to new skills and professional networks.
Quantitative results of the Romanov type representation functions
Authors: Chen Yong-Gao , Ding Yuchen
Published: June 2023

For α > 0, let$$\mathscr{A}=\{a_1 \lt a_2 \lt a_3\lt\cdots\}$$and$$\mathscr{L}=\{\ell_1, \ell_2, \ell_3,\cdots\} \quad \text{(not\ necessarily\ different)}$$be two sequences of positive integers with $\mathscr{A}(m)\gt(\log m)^\alpha $ for infinitely many positive integers m and $\ell_m\lt0.9\log\log m$ for sufficiently large integers m. Suppose further that $(\ell_i,a_i)=1$ for all i. For any n, let $f_{\mathscr{A},\mathscr{L}}(n)$ be the number of the available representations listed below$$\ell_in=p+a_i \quad \left(1\le i\le \mathscr{A}(n)\right),$$where p is a prime number. It is proved that$$\limsup_{n\to \infty } \frac{f_{\mathscr{A},\mathscr{L}}(n)}{\log\log n}\gt0,$$which covers an old result of Erdős in 1950 by taking $a_i=2^i$ and $\ell_i=1$. One key ingredient in the argument is a technical lemma established here, which illustrates how to pick out the admissible parts of an arbitrarily given set of distinct linear functions. The proof then reduces to the verifications of a hypothesis involving well-distributed sets introduced by Maynard, which of course would be the other key ingredient in the argument.
FinTech, Investor Sophistication, and Financial Portfolio Choices
Authors: Gambacorta Leonardo , Gambacorta Romina , Mihet Roxana
Published: June 2023

This paper analyzes the links between advances in financial technology, investors’ sophistication, and the composition and returns of their financial portfolios. We develop a simple portfolio choice model under asymmetric information and derive some theoretical predictions. Using detailed microdata from Banca d’Italia, we test these predictions for Italian households over the period 2004-2020. In general, heterogeneity in portfolio composition and in returns between sophisticated and unsophisticated investors grows with improvements in financial technology. This heterogeneity is reduced only if financial technology is accessible to everyone and if investors have a similar capacity to use it. (JEL: G1, G5, G4, D83, L8, O3)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Arterial stiffness tested by pulse wave velocity and augmentation index for cardiovascular risk stratification in antiphospholipid syndrome
Authors: Evangelatos Gerasimos , Konstantonis George , Tentolouris Nikolaos , Sfikakis Petros P , Tektonidou Maria G
Published: June 2023

Objectives

Cardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS.

Methods

ArS was evaluated by carotid–femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group.

Results

We included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [β = −0.142 (95% CI −0.514, 0.230), p = 0.454] but increased AIx@75 [β = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [β = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [β = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [β = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-β2-glycoprotein I IgM positivity [β = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [β = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [β = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [β = 0.425 (95% CI 0.187, 0.663), p = 0.001].

Conclusion

APS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.
Cardiorespiratory fitness assessed with cardiopulmonary exercise testing in patients with juvenile idiopathic arthritis: a systematic review and meta-analysis
Authors: Pella Eva , Sgouropoulou Vasiliki , Theodorakopoulou Marieta , Iatridi Fotini , Boutou Afroditi , Karpetas Antonios , Papagianni Aikaterini , Sarafidis Pantelis , Dimitroulas Theodoros
Published: June 2023

Objectives

JIA is the most common type of arthritis in children and adolescents, causing joint damage, chronic pain and disability. Deconditioning is also prevalent in patients with JIA due to both inactivity and the disease progression, resulting in reduced cardiorespiratory fitness (CRF). We aimed to evaluate CRF of patients with JIA compared with healthy controls.

Methods

This is a systematic review and meta-analysis of studies using cardiopulmonary exercise testing (CPET) to examine differences in determinants of CRF between patients with JIA vs healthy controls. The primary outcome was peak oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and Scopus databases, manual search of article references and grey literature. Quality assessment was undertaken with Newcastle–Ottawa Scale.

Results

From 480 literature records initially retrieved, eight studies (538 participants) were included in final meta-analysis. VO2peak was significantly lower in patients with JIA compared with controls [weighted mean difference (WMD): −5.95 ml/kg/min (95% CI −9.26, −2.65)]. Exercise duration and VO2peak (% predicted) were found to be significantly impaired in patients with JIA compared with controls [standardized mean difference: −0.67 (95% CI −1.04, −0.29) and WMD: −11.31% (95% CI −20.09, −2.53), respectively], while no significant differences were found in maximum heart rate.

Conclusion

VO2peak and other CPET variables were lower in patients with JIA compared with controls, indicating reduced CRF in the former. Overall, exercise programs for patients with JIA should be promoted as part of their treatment to improve physical fitness and reduce muscle atrophy.

PROSPERO Registration

CRD42022380833.
Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders
Authors: Slapø Nora Berz , Nerland Stener , Jørgensen Kjetil Nordbø , Mørch-Johnsen Lynn , Pettersen Johanne Hagen , Roelfs Daniel , Parker Nadine , Valstad Mathias , Pentz Atle , Timpe Clara M F , Richard Geneviève , Beck Dani , Frogner Werner Maren C , Lagerberg Trine Vik , Melle Ingrid , Agartz Ingrid , Westlye Lars T , Steen Nils Eiel , Andreassen Ole A , Moberget Torgeir , Elvsåshagen Torbjørn , Jönsson Erik G
Published: June 2023

Background and Hypothesis

The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood.

Study Design

Patients with a schizophrenia spectrum disorder (SCZspect), including patients with a lifetime experience of AH (AH+), without (AH−), and healthy controls underwent magnetic resonance imaging (39 SCZspect, 22 AH+, 17 AH−, and 146 HC) and electroencephalography (33 SCZspect, 17 AH+, 16 AH−, and 144 HC). Cortical thickness of the primary (AC1, Heschl’s gyrus) and secondary (AC2, Heschl’s sulcus, and the planum temporale) AC was compared between SCZspect and controls and between AH+, AH−, and controls. To examine if the association between AC thickness and N100 amplitude differed between groups, we used regression models with interaction terms.

Study Results

N100 amplitude was nominally smaller in SCZspect (P = .03, d = 0.42) and in AH− (P = .020, d = 0.61), while AC2 was nominally thinner in AH+ (P = .02, d = 0.53) compared with controls. AC1 thickness was positively associated with N100 amplitude in SCZspect (t = 2.56, P = .016) and AH− (t = 3.18, P = .008), while AC2 thickness was positively associated with N100 amplitude in SCZspect (t = 2.37, P = .024) and in AH+ (t = 2.68, P = .019).

Conclusions

The novel findings of positive associations between AC thickness and N100 amplitude in SCZspect, suggest that a common neural substrate may underlie AC thickness and N100 amplitude alterations.
Automatic sleep spindles identification and classification with multitapers and convolution
Authors: Zapata Ignacio A , Wen Peng , Jones Evan , Fjaagesund Shauna , Li Yan
Published: June 2023

Sleep spindles are isolated transient surges of oscillatory neural activity present during sleep stages 2 and 3 in the nonrapid eye movement (NREM). They can indicate the mechanisms of memory consolidation and plasticity in the brain. Spindles can be identified across cortical areas and classified as either slow or fast. There are spindle transients across different frequencies and power, yet most of their functions remain a mystery. Using several electroencephalogram (EEG) databases, this study presents a new method, called the “spindles across multiple channels” (SAMC) method, for identifying and categorizing sleep spindles in EEGs during the NREM sleep. The SAMC method uses a multitapers and convolution (MT&C) approach to extract the spectral estimation of different frequencies present in sleep EEGs and graphically identify spindles across multiple channels. The characteristics of spindles, such as duration, power, and event areas, are also extracted by the SAMC method. Comparison with other state-of-the-art spindle identification methods demonstrated the superiority of the proposed method with an agreement rate, average positive predictive value, and sensitivity of over 90% for spindle classification across the three databases used in this paper. The computing cost was found to be, on average, 0.004 seconds per epoch. The proposed method can potentially improve the understanding of the behavior of spindles across the scalp and accurately identify and categories sleep spindles.
Development and pilot testing of a clinic implementation program delivering physical activity electronic referrals to cancer survivors
Authors: Faro Jamie M , Yue Kai-Lou , Leach Heather J , Crisafio Mary E , Lemon Stephenie C , Wang Bo , McManus David D , Sadasivam Rajani S
Published: June 2023

Provider physical activity referrals are recommended for cancer survivors, though barriers exist to clinical system integration.

To develop and test ActivityChoice, an electronic referral (eReferral) clinic implementation program referring cancer survivors to physical activity programs of their choice. In Phase 1, we conducted semi-structured interviews with Cancer Center clinicians (n = 4) and cancer-focused physical activity program leaders (n = 3) assessing adaptations needed to implement an eReferral previously designed for another context. In Phase 2, we pilot-tested clinician-delivered referrals to survivors in two 12-week Plan, Do, Study, Act (PDSA) cycles. We examined feasibility using descriptive statistics (clinicians’ adoption and engagement, patient referrals, and physical activity program enrollment) and acceptability through semi-structured interviews with enrolled clinicians (n = 4) and referred patients (n = 9). ActivityChoice included a secure referral webform, text message/email referral confirmations, clinician training/booster sessions, visual reminders, and referrals to in-person or virtual group physical activity programs. Results for each PDSA cycle respectively included: 41% (n = 7) and 53% (n = 8) of clinicians adopted ActivityChoice; 18 and 36 patients were referred; 39% (n = 7) and 33% (n = 12) of patients enrolled in programs, and 30% (n = 4) and 14% (n = 5) of patients deferred enrollment. Patients and clinicians appreciated the referrals and choices. A printed handout describing both programs was added to the clinic workflow for Cycle 2, which yielded more referrals, but lower program enrollment rates. Clinic-based eReferrals to choices of physical activity programs were feasible and acceptable by clinicians and patients. Added clinic workflow support may facilitate referrals.
An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation
Authors: Günay Büşra , Matthews Elizabeth , Morgan Jack , Tryfonidou Marianna A. , Saldova Radka , Pandit Abhay
Published: June 2023

Degeneration of the intervertebral disc is an age‐related condition. It also accompanies the disappearance of the notochordal cells, which are remnants of the developmental stages of the nucleus pulposus (NP). Molecular changes such as extracellular matrix catabolism, cellular phenotype, and glycosaminoglycan loss in the NP have been extensively studied. However, as one of the most significant co‐ and posttranslational modifications, glycosylation has been overlooked in cells in degeneration. Here, we aim to characterize the N‐glycome of young and mature NP and identify patterns related to aging. Accordingly, we isolated N‐glycans from notochordal cell‐rich NP from porcine discs, characterized them using a combined approach of exoglycosidase digestions and analysis with hydrophilic interaction ultra‐performance liquid chromatography and mass spectrometry. We have assigned over 300 individual N‐glycans for each age group. Moreover, we observed a notable abundance of antennary structures, galactosylation, fucosylation, and sialylation in both age groups. In addition, as indicated from our results, increasing outer arm fucosylation and decreasing α(2,3)‐linked sialylation with aging suggest that these traits are age‐dependent. Lastly, we have focused on an extensive characterization of the N‐glycome of the notochordal cell‐rich NP in aging without inferred degeneration, describing glycosylation changes specific for aging only. Our findings in combination with those of other studies, suggest that the degeneration of the NP does not involve identical processes as aging.