bluuebunny/crossref_metadata_2025_split huggingface dataset:
Price Uncertainty and Debt Covenants: Evidence from U.S. Oil Producers
Authors: Docgne Sandrine , Duarte Diogo 
Published: September 2022

Abstract
We use an exogenous, forward-looking measure of price uncertainty to examine the effect of uncertainty on the use of covenants in private and public debt contracts. The effect of uncertainty differs significantly in loans versus bonds, suggesting that private and public lenders face different incentives when contracting under high uncertainty. In loans, uncertainty increases the use of performance-based covenants. In contrast, covenant usage decreases in bonds, but firms with low agency conflicts mainly drive this effect. However, bondholders require higher spreads to offset the lack of protection with fewer covenants. Hedging does not affect the covenant-uncertainty relationship for debt contracts. (JEL: G21, G23, G32, D82, D81)
Deciphering the Transcriptional Landscape of Human Pluripotent Stem Cell-Derived GnRH Neurons: The Role of Wnt Signaling in Patterning the Neural Fate
Authors: Wang Yafei , Madhusudan Shrinidhi , Cotellessa Ludovica , Kvist Jouni , Eskici Nazli , Yellapragada Venkatram , Pulli Kristiina , Lund Carina , Vaaralahti Kirsi , Tuuri Timo , Giacobini Paolo , Raivio Taneli 
Published: September 2022

Abstract
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lay the foundation for human development and reproduction; however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by using our established human pluripotent stem cell-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level. We found that a glutamatergic neuron population, which generated together with GnRH neurons, showed similar transcriptomic properties with olfactory sensory neuron and provided the migratory path for GnRH neurons. Through trajectory analysis, we identified a specific gene module activated along the GnRH neuron differentiation lineage, and we examined one of the transcription factors, DLX5, expression in human fetal GnRH neurons. Furthermore, we found that Wnt inhibition could increase DLX5 expression and improve the GnRH neuron differentiation efficiency through promoting neurogenesis and switching the differentiation fates of neural progenitors into glutamatergic neurons/GnRH neurons. Our research comprehensively reveals the dynamic cell population transition and gene regulatory network during GnRH neuron differentiation.
Multicountry study of SARS-CoV-2 and associated risk factors among healthcare workers in Côte d'Ivoire, Burkina Faso and South Africa
Authors: Kribi Sarah , Touré Fidèle , Mendes Adriano , Sanou Soufiane , Some Arsène , Aminou Abdoul M , Belarbi Essia , Griessel Rosemary , Hema Arsène , Kabore Firmin , Pitzinger Paul , Strydom Amy , Vietor Ann Christin , Traoré Korotimi , Zongo Arsène , Anoh Etilé A , Grossegesse Marica , Hofmann Natalie , Ouangraoua Soumeya , Poda Armel , Kagone Thérèse , Schubert Grit , Eckmanns Tim , Venter Marietjie , Leendertz Fabian , Akoua-Koffi Chantal , Tomczyk Sara 
Published: September 2022

AbstractBackgroundReports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread across Africa have varied, including among healthcare workers (HCWs). This study assessed the comparative SARS-CoV-2 burden and associated risk factors among HCWs in three African countries.MethodsA multicentre study was conducted at regional healthcare facilities in Côte d’Ivoire (CIV), Burkina Faso (BF) and South Africa (SA) from February to May 2021. HCWs provided blood samples for SARS-CoV-2 serology and nasopharyngeal/oropharyngeal swabs for testing of acute infection by polymerase chain reaction and completed a questionnaire. Factors associated with seropositivity were assessed with logistic regression.ResultsAmong 719 HCWs, SARS-CoV-2 seroprevalence was 34.6% (95% confidence interval 31.2 to 38.2), ranging from 19.2% in CIV to 45.7% in BF. A total of 20 of 523 (3.8%) were positive for acute SARS-CoV-2 infection. Female HCWs had higher odds of SARS-CoV-2 seropositivity compared with males, and nursing staff, allied health professionals, non-caregiver personnel and administration had higher odds compared with physicians. HCWs also reported infection prevention and control (IPC) gaps, including 38.7% and 29% having access to respirators and IPC training, respectively, in the last year.ConclusionsThis study was a unique comparative HCW SARS-CoV-2 investigation in Africa. Seroprevalence estimates varied, highlighting distinctive population/facility-level factors affecting COVID-19 burden and the importance of established IPC programmes to protect HCWs and patients.
LASER PROPHYLAXIS IN STICKLER SYNDROME
Authors: Linton Emma , Jalil Assad , Sergouniotis Panagiotis , Moussa George , Black Graeme , Charles Stephen , Ivanova Tsveta 
Published: September 2022

Purpose:
Patients with Stickler syndrome are at high risk of giant retinal tears (GRTs) and detachments. Vitreoretinal interventions can reduce this risk, but there is presently no consensus about the optimal prophylactic approach. The aim of our study was to determine whether 360° laser prophylaxis is a safe and effective procedure to prevent GRT detachments in patients with Stickler syndrome.

Methods:
Study subjects were recruited retrospectively through the databases of the vitreoretinal and ophthalmic genetic tertiary services in Manchester, United Kingdom. Clinical data were collected including on prophylactic intervention, the occurrence of retinal detachment, and the presence/type of retinal breaks.

Results:
One hundred thirteen eyes from 63 patients with Stickler syndrome were studied; 72.6% (82/113) of these eyes received 360° laser prophylaxis. Of these, 9% had a retinal detachment, but no GRTs occurred. Among the 27.4% (31/113) of eyes that had no prophylactic treatment, 23% suffered a retinal detachment and 42.9% of these were associated with a GRT.

Conclusion:
Patients who underwent laser prophylaxis had fewer retinal detachments and no GRTs during an average of 6.1 years of follow-up (median 5 years), suggesting that this is a safe and effective approach for individuals with Stickler syndrome.
Activation of HIF-1α/VEGF-A pathway by deferoxamine ameliorates retinal hypoxia in a rat subarachnoid hemorrhage model
Authors: Deji Qu-Zhen , Wang Xue , Zhaba Wang-Dui , Deng Hong-Ji , Han Yan-Ling , Gao Sheng-Qing , Liu Xi-Lin , Zhou Meng-Liang 
Published: September 2022

Background and purpose
Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous finding also revealed the changes in hypoxia-related elements in the retina after SAH, further lending weight to the hypothesis that retinal vasospasm and hypoxia after SAH. Deferoxamine is a high-affinity iron chelator with reported neuroprotective effects against stroke. Here, we aimed to explore the effects of deferoxamine on retinal hypoxia after SAH.

Methods
SAH was established and deferoxamine was injected intraperitoneally for 3 days in the treatment group. To detect retinal new vessels, platelet endothelial cell adhesion molecule (CD31) was labeled by immunofluorescence and immunohistochemistry. Furthermore, the effects of deferoxamine on the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were revealed by western blot analysis.

Results
The immunofluorescence and immunohistochemical staining of CD31 revealed a marked increase in new vessels in the retinal ganglion cell layer after deferoxamine treatment. By western blot analysis, HIF-1α and VEGF-A increased gradually in the first day and then rebounded to a new level on day 7. A deferoxamine-induced increase in HIF-1α/VEGF-A expression was also confirmed by western blot.

Conclusions
Our findings suggest that modulating the application of deferoxamine may offer therapeutic approaches to alleviate retinal complications after SAH.
Exploring the effect of group schema therapy and comorbidity on the treatment course of personality disorders
Authors: Koppers David , Van Henricus L. , Peen Jaap , Dekker Jack J.M. 
Published: September 2022

Purpose of review
To provide an update of outcome studies of schema group therapy for personality disorders and the effect of comorbidity in order to explore whether schema group therapy might be effective for this patient group and what dosage is required.

Recent findings
Studies of short-term schema group therapy for personality disorders with or without comorbidity show moderately effective results but the majority of patients fail to achieve full remission from global psychological symptom distress. Preliminary findings revealed that those unremitted patients might benefit from 40 to 60 sessions. Patients with severe personality disorders (such as borderline personality disorders) seem to need longer and/or more intensive treatment dosage to recover.

Summary
We advocate short-term schema therapy in groups as a valuable first step in a stepped-care programme for patients with moderate personality disorders and comorbidity.
Treatment extension or treatment intensification may be indicated in patients who do not recover. Patients with severe personality disorders seem to require long-term outpatient group treatment, with a combination of group and individual treatment being preferable. High-quality randomized controlled trials are needed in order to determine which treatment dosage is necessary for whom.
Programmed cell death-1 receptor mediated regulation of Tbet+ NK1.1− Innate Lymphoid Cells within the Tumor Microenvironment
Authors: Lim Jing Xuan , Lai Chester Y. , Mallett Grace E. , McDonald David , Hulme Gillian , Laba Stephanie , Shapanis Andrew , Payne Megan , Patterson Warren , Alexander Michael , Coxhead Jonathan , Filby Andrew , Plummer Ruth , Lovat Penny E. , Sciume Giuseppe , Healy Eugene , Amarnath Shoba 
Published: September 2022

AbstractInnate Lymphoid Cells (ILCs) play a key role in tissue mediated immunity and can be controlled by co-receptor signaling. Here we define a subset of ILCs that are Tbet+NK1.1− and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet+NK1.1−ILCs. PD-1 significantly controlled the proliferation and function of Tbet+NK1.1−ILCs in multiple murine and human tumors. We found tumor derived lactate enhanced PD-1 expression on Tbet+NK1.1−ILCs within the TME, which resulted in dampened mTOR signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1 deficient Tbet+NK1.1−ILCs expressed significantly increased IFNγ, granzyme B and K. Furthermore, PD1 deficient Tbet+NK1.1− ILCs contributed towards diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate anti-tumor responses of Tbet+NK1.1−ILCs within the tumor microenvironment.HighlightsTbet+NK1.1− ILCs are found in WT and PD1 ko micePD-1 is expressed on Tbet+NK1.1− ILC1s within multiple TMEPD-1 controls the proliferation and function of Tbet+NK1.1− ILCs within the tumor microenvironment by modulating fatty acid metabolism.PD-1 regulates the proliferation of human Tbet+ ILC1s in human cutaneous squamous cell carcinoma (cSCC) and melanoma tumor microenvironment.
Microbiome and resistome dynamics along a sewage-effluent-reservoir continuum underline the role of natural attenuation in effluent receiving reservoirs
Authors: Leão Inês , Khalifa Leron , Gallois Nicolas , Vaz-Moreira Ivone , Klümper Uli , Youdkes Daniel , Palmony Shaked , Dagai Lotan , Berendonk Thomas U. , Merlin Christophe , Manaia Célia M. , Cytryn Eddie 
Published: September 2022

AbstractThis study assessed temporal dynamics of total and antibiotic resistant fecal bacterial indicators and antibiotic resistance genes (ARG) along a sewage-effluent-reservoir continuum, in an experimental system consisting of a sewage-fed membrane-aerated bioreactor (MABR) whose effluent fed a 4500 L polypropylene basin that mimicked an effluent storage reservoir. We applied a multidisciplinary approach that coupled physicochemical analyses, cultivation of total and cefotaxime-resistant E. coli, microbiome (bacterial and eukaryotic) analysis and qPCR/ddPCR quantification of selected ARGs. Total and cefotaxime-resistant E. coli loads dropped by approximately 1.5 log units in both the MABR and the reservoir, but the relative reduction (normalized to 16S rRNA genes) in both E. coli and ARGs was higher in the reservoir. Reservoir microbiomes were significantly different from those in the MABR, and were characterized by temporal shifts and periodic algal (Chlorophyta) blooms that were coupled to oxygen and pH fluctuations. Collectively, the data indicates that the decrease in E. coli and ARGs in the MABR was primarily facilitated by sludge removal, whereas in the reservoir, it was predominantly associated with microbial community shifts. The study highlights the capacity of ecological interactions in mitigating antibiotic resistance in both engineered and natural ecosystems.ImportanceAntibiotic resistance is considered one of the most significant public health predicaments of the 21st century, and there is growing evidence that anthropogenically impacted environments such as those receiving raw and treated sewage can contribute to this phenomenon. In this study, we evaluated the dynamics of total and antibiotic resistant fecal pathogen indicators and antibiotic resistance genes along a sewage-treated wastewater-effluent reservoir continuum, concurrent to evaluation of microbial community composition and physicochemical parameters. Results indicate that both the treatment bioreactor and the effluent storage reservoir removed resistant bacteria and antibiotic resistance encoding genes. However, in the reactor removal was primarily linked to physical processes, whereas in the storage reservoir it appeared to be strongly facilitated by ecological interactions. The study highlights the capacity of aquatic ecosystems to alleviate antibiotic resistance, and suggests that ecological processes in aquatic ecosystems can be harnessed to mitigate antibiotic resistance.
Piperacillin-Tazobactam Resistance Mechanisms in Escherichia coli and Identification of a CTX-M-255 β-Lactamase Selectively Conferring Resistance to Penicillin/β-Lactamase Inhibitor Combinations
Authors: Andreasen Minna Rud , Hansen Katrine Hartung , Pedersen Martin Schou , Mollerup Sarah , Jelsbak Lotte , Schønning Kristian 
Published: September 2022

AbstractPiperacillin/tazobactam (TZP) is a widely used penicillin/β-lactamase inhibitor combination with broad antimicrobial activity. Recently, Escherichia coli strains resistant to TZP but susceptible to third generation cephalosporins (TZP-R/3GC-S isolates) have been increasingly identified. Here, we investigated resistance mechanisms underlying the TZP-R/3GC-S phenotype in clinical E. coli isolates.A total of 29 TZP-R/3GC-S E. coli isolates were retrieved from urinary cultures and subjected to whole genome sequencing. Resistance to TZP was confirmed by minimum inhibitory concentration determination. β-lactamase activity in the presence and absence of tazobactam was determined to identify hyperproduction of β-lactamase and assess susceptibility to tazobactam inhibition. A previously unrecognized β-lactamase was identified and cloned to determine its resistance profile.Four different resistance mechanisms underlying the TZP-R/3-GC phenotype were identified: 1) In 18 out of 29 isolates (62%) β-lactamase production was increased and in 16 of these either strong alternative promoters or increased gene copy numbers of blaTEM-1 or blaSHV-1 were identified, 2) seven isolates (24%) produced blaOXA-1, 3) three isolates (10%) produced inhibitor-resistant TEM-β-lactamases, and 4) a single isolate (3%) harboured a blaCTX-M gene as the only β-lactamase present. This β-lactamase, CTX-M-255, only differs from CTX-M-27 by a G239S amino acid substitution. In contrast to CTX-M-27, CTX-M-255 conferred resistance to penicillin/β-lactamase inhibitor combinations but remained susceptible to cephalosporins.In conclusion, hyperproduction of blaTEM was the most prevalent mechanism of TZP-resistance underlying the TZP-R/3GC-S phenotype followed by production of blaOXA-1 and inhibitor-resistant TEM-β-lactamases. Furthermore, we identified a previously unrecognized CTX-M-β-lactamase, CTX-M-255 that was resistant to β-lactamase inhibitors.
Genome-scale mapping of DNA damage suppressors identifies GNB1L as essential for ATM and ATR biogenesis
Authors: Zhao Yichao , Tabet Daniel , Contreras Diana Rubio , Kousholt Arne Nedergaard , Weile Jochen , Melo Henrique , Hoeg Lisa , Coté Atina G. , Lin Zhen-Yuan , Setiaputra Dheva , Jonkers Jos , Gingras Anne-Claude , Herreros Fernando Gómez , Roth Frederick P. , Durocher Daniel 
Published: September 2022

AbstractTo maintain genome integrity, cells must avoid DNA damage by ensuring the accurate duplication of the genome and by having efficient repair and signaling systems that counteract the genome-destabilizing potential of DNA lesions. To uncover genes and pathways that suppress DNA damage in human cells, we undertook genome-scale CRISPR/Cas9 screens that monitored the levels of DNA damage in the absence or presence of DNA replication stress. We identified 160 genes in RKO cells whose mutation caused high levels of DNA damage in the absence of exogenous genotoxic treatment. This list was highly enriched in essential genes, highlighting the importance of genomic integrity for cellular fitness. Furthermore, the majority of these 160 genes are involved in a limited set of biological processes related to DNA replication and repair, nucleotide biosynthesis, RNA metabolism and iron sulfur cluster biogenesis, suggesting that genome integrity may be insulated from a wide range of cellular processes. Among the many genes identified and validated in this study, we discovered that GNB1L, a schizophrenia/autism-susceptibility gene implicated in 22q11.2 syndrome, protects cells from replication catastrophe promoted by mild DNA replication stress. We show that GNB1L is involved in the biogenesis of ATR and related phosphatidylinositol 3-kinase-related kinases (PIKKs) through its interaction with the TTT co-chaperone complex. These results implicate PIKK biogenesis as a potential root cause for the neuropsychiatric phenotypes associated with 22q11.2 syndrome. The phenotypic mapping of genes that suppress DNA damage in human cells therefore provides a powerful approach to probe genome maintenance mechanisms.
Effects of microtubule length and crowding on active microtubule network organization
Authors: Chew Wei-Xiang , Henkin Gil , Nédélec François , Surrey Thomas 
Published: September 2022

SUMMARYActive filament networks can organize into various dynamic architectures driven by crosslinking motors. Densities and kinetic properties of motors and microtubules have been shown previously to determine active microtubule network self-organization, but the effects of other control parameters are less understood. Using computer simulations, we study here how microtubule lengths and crowding effects determine active network architecture and dynamics. We find that attractive interaction mimicking crowding effects or long microtubules both promote the formation of nematic networks of extensile bundles instead of contractile networks. When microtubules are very long and the network is highly percolated, a new isotropically motile network state resembling a ‘crawling mesh’ is predicted. Usingin vitroreconstitutions, we confirm the existence of this crawling mesh experimentally. These results provide a better understanding of how active microtubule network organization can be controlled, with implications for cell biology and active materials in general.
Astrocytic synapse elimination controls ocular dominance plasticity
Authors: Lee Joon-Hyuk , Kim Jinah , Kim Minjin , Shin Chi-Hong , Chung Won-Suk 
Published: September 2022

AbstractOcular dominance plasticity (ODP) is a representative form of experience-dependent synaptic plasticity observed in the primary visual cortex (V1). However, the cellular mechanisms and physiological roles of synapse elimination in ODP are largely unknown. Here, we show that astrocytic phagocytosis of thalamo-cortical synapses in V1 is a critical mediator of ODP. We found that astrocytes, but not microglia, start to engulf thalamo-cortical synapses within 24 hours after monocular deprivation and that astrocytic synapse elimination is highly selective for synapses from the deprived eye, as revealed by AAV1-mediated trans-synaptic anterograde tracing of synapse phagocytosis reporters. Importantly, mice without the Megf10 phagocytic receptor in astrocytes exhibit deficits in eliminating the synapses from the deprived eye, leading to the failure to reduce the number of thalamo-cortical synapses after monocular deprivation. Remarkably, Megf10-deficient animals show severe defects in monocular deprivation-induced cortical synapse remodeling and subsequent expansion of the thalamo-cortical circuitry from the nondeprived eye. Taken together, our data show that astrocytic synapse elimination through MEGF10 is one of the key components in ODP, revealing the physiological importance of astrocytic phagocytosis in experience-dependent synaptic plasticity.
A genetically-encoded three-colour stress biosensor reveals multimodal response at single cell level and spatiotemporal dynamics of biofilms
Authors: Zoheir Ahmed E. , Sobol Morgan S. , Ordoñez-Rueda Diana , Kaster Anne-Kristin , Niemeyer Christof M. , Rabe Kersten S. 
Published: September 2022

AbstractThe plethora of chemical, physical, and biological factors that can damage microbial cells has triggered the evolution of sophisticated stress response (SR) mechanisms. While individual SR pathways have been monitored with genetically encoded reporters, sensor concepts for the detection of multimodal effects of stressing conditions in living microorganisms are still lacking. Orthogonally detectable red, green, and blue fluorescent proteins combined in a single vector system, dubbed RGB-S reporter, enable the simultaneous, independent and real-time analysis of the stress response in Escherichia coli to physiological stress, genotoxicity, and cytotoxicity. The sensor system can be read out via conventional fluorescence microscopy or microtiter plate analysis and can also be combined with Fluorescent Activated Cell Sorting (FACS) and subsequent transcriptome analysis. Various stressors, such as the biotechnologically relevant 2-propanol, lead to the activation of one, two or all three SRs, which can have a significant impact on non-stress-related metabolic pathways. Implemented in microfluidic cultivation with confocal fluorescence microscopy imaging, the technology enabled spatiotemporal analysis of live biofilms to discover stratified subpopulations of bacteria with heterogeneous stress responses.
R2Dtool: Integration and visualization of isoform-resolved RNA features
Authors: Sethi Aditya J. , Acera Mateos Pablo , Hayashi Rippei , Shirokikh Nikolay , Eyras Eduardo 
Published: September 2022

AbstractLong-read RNA sequencing enables the mapping of RNA modifications, structures, and protein-interaction sites at the resolution of individual transcript isoforms. To understand the functions of these RNA features, it is critical to analyze them in the context of transcriptomic and genomic annotations, such as open reading frames and splice junctions. To enable this, we have developed R2Dtool, a bioinformatics tool that integrates transcript-mapped information with transcript and genome annotations, allowing for the isoform-resolved analytics and graphical representation of RNA features in their genomic context. We illustrate R2Dtool’s capability to integrate and expedite RNA feature analysis using epitranscriptomics data. R2Dtool facilitates the comprehensive analysis and interpretation of alternative transcript isoforms.R2Dtool is freely available under the MIT license at:https://github.com/comprna/R2Dtool.