bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep single-cell RNA-seq data clustering with graph prototypical contrastive learning
Authors: Lee Junseok , Kim Sungwon , Hyun Dongmin , Lee Namkyeong , Kim Yejin , Park Chanyoung
Published: May 2023

Motivation

Single-cell RNA sequencing enables researchers to study cellular heterogeneity at single-cell level. To this end, identifying cell types of cells with clustering techniques becomes an important task for downstream analysis. However, challenges of scRNA-seq data such as pervasive dropout phenomena hinder obtaining robust clustering outputs. Although existing studies try to alleviate these problems, they fall short of fully leveraging the relationship information and mainly rely on reconstruction-based losses that highly depend on the data quality, which is sometimes noisy.

Results

This work proposes a graph-based prototypical contrastive learning method, named scGPCL. Specifically, scGPCL encodes the cell representations using Graph Neural Networks on cell–gene graph that captures the relational information inherent in scRNA-seq data and introduces prototypical contrastive learning to learn cell representations by pushing apart semantically dissimilar pairs and pulling together similar ones. Through extensive experiments on both simulated and real scRNA-seq data, we demonstrate the effectiveness and efficiency of scGPCL.

Availability and implementation

Code is available at https://github.com/Junseok0207/scGPCL.
Online bias-aware disease module mining with ROBUST-Web
Authors: Sarkar Suryadipto , Lucchetta Marta , Maier Andreas , Abdrabbou Mohamed M , Baumbach Jan , List Markus , Schaefer Martin H , Blumenthal David B
Published: May 2023

We present ROBUST-Web which implements our recently presented ROBUST disease module mining algorithm in a user-friendly web application. ROBUST-Web features seamless downstream disease module exploration via integrated gene set enrichment analysis, tissue expression annotation, and visualization of drug–protein and disease–gene links. Moreover, ROBUST-Web includes bias-aware edge costs for the underlying Steiner tree model as a new algorithmic feature, which allow to correct for study bias in protein–protein interaction networks and further improves the robustness of the computed modules.

Availability and implementation

Web application: https://robust-web.net. Source code of web application and Python package with new bias-aware edge costs: https://github.com/bionetslab/robust-web, https://github.com/bionetslab/robust_bias_aware.
Pygenomics: manipulating genomic intervals and data files in Python
Authors: Tamazian Gaik , Cherkasov Nikolay , Kanapin Alexander , Samsonova Anastasia
Published: May 2023

We present pygenomics, a Python package for working with genomic intervals and bioinformatic data files. The package implements interval operations, provides both API and CLI, and supports reading and writing data in widely used bioinformatic formats, including BAM, BED, GFF3, and VCF. The source code of pygenomics is provided with in-source documentation and type annotations and adheres to the functional programming paradigm. These features facilitate seamless integration of pygenomics routines into scripts and pipelines. The package is implemented in pure Python using its standard library only and contains the property-based testing framework. Comparison of pygenomics with other Python bioinformatic packages with relation to features and performance is presented. The performance comparison covers operations with genomic intervals, read alignments, and genomic variants and demonstrates that pygenomics is suitable for computationally effective analysis.

Availability and implementation

The source code is available at https://gitlab.com/gtamazian/pygenomics.
Asymmetry of sleep electrophysiological markers in patients with focal epilepsy
Authors: Sheybani Laurent , Mégevand Pierre , Roehri Nicolas , Spinelli Laurent , Kleinschmidt Andreas , van Mierlo Pieter , Seeck Margitta , Vulliémoz Serge
Published: May 2023

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17–61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5–4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak’s multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.
miR-424-3p promotes metastasis of hepatocellular carcinoma via targeting the SRF-STAT1/2 axis
Authors: Feng Lan , Chen Xi , Li Peiyao , Li Yuanfeng , Zhai Yun , Liu Xinyi , Jin Qian , Zhang Hongxing , Yu Chaohui , Xing Baocai , Cui Ying , Cao Pengbo , Zhou Gangqiao
Published: May 2023

Although emerging evidence has established the roles of miRNAs in hepatocellular carcinoma (HCC), the global functional implication of miRNAs in this malignancy remains largely uncharacterized. Here, we aim to systematically identify novel miRNAs involved in HCC and clarify the function and mechanism of specific novel candidate miRNA(s) in this malignancy. Through an integrative omics approach, we identified ten HCC-associated functional modules and a collection of candidate miRNAs. Among them, we demonstrated that miR-424-3p, exhibiting strong associations with extracellular matrix (ECM), promotes HCC cells migration and invasion in vitro and facilitates HCC metastasis in vivo. We further demonstrated that SRF is a direct functional target of miR-424-3p, and is required for the oncogenic activity of miR-424-3p. Finally, we found that miR-424-3p reduces the interferon pathway by attenuating the transactivation of SRF on STAT1/2 and IRF9 genes, which in turn enhances the matrix metalloproteinases (MMPs)-mediated ECM remodeling. This study provides comprehensive functional relevance of miRNAs in HCC by an integrative omics analysis, and further clarifies that miR-424-3p in ECM functional module plays an oncogenic role via reducing the SRF-STAT1/2 axis in this malignancy.
Rituximab in the treatment of primary FSGS: time for its use in routine clinical practice?
Authors: Morris Adam D , Floyd Lauren , Woywodt Alexander , Dhaygude Ajay
Published: May 2023

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and whilst advances have been made in the pathophysiology, diagnostics and management of other podocytopathies, primary FSGS remains the most elusive. It has been assumed for a long time that a circulatory permeability factor exists that mediates podocyte injury, and the potential for autoantibody-mediated disease therefore raises the question as to whether patients may benefit from targeted B-cell therapy with rituximab. The prospective case series of seven patients by Roccatello et al. adds to the limited but growing evidence suggesting that B-cell depletion therapy can be safe and effective in the treatment of primary FSGS. In this editorial we explore the available evidence that suggests how and in whom rituximab may play a role in the management of primary FSGS, as well as the limitations and other potential future treatments. Further research and randomized controlled trials are needed to include larger numbers of patients, feature genetic screening and incorporate data on B-cell kinetics as a potential guide for dosing and frequency of rituximab.
An Examination of School District Reopening Plans for Mental Health Supports amid COVID-19 School Reopening
Authors: Childs Tasha M , Iachini Aidyn L
Published: May 2023

The purpose of this exploratory qualitative study was to understand the types of mental health supports described in school district reopening plans in one southeastern state, and to understand school social workers’ involvement in developing these plans during the first full academic year of the COVID-19 pandemic. Publicly accessible school district reopening plans were collected from the 80 school districts in South Carolina, and 15 school social workers participated in virtual interviews. Out of the 80 school districts, 67 had reopening plans, and of those, only 43 percent mentioned mental health services and supports. Most school district reopening plans described Tier 1 universal prevention services and supports and a process for mental health assessment, identification, and referral. Fewer included Tier 2 early intervention and Tier 3 targeted and intensive services. Of the school social workers interviewed, only four were involved in helping to develop their school district reopening plans, and when involved, advocated for mental health services and supports for their students. The article concludes with a discussion of the study's implications for school social work practice.
Mid-term outcomes following the Hemi-Commando procedure for complex infective endocarditis involving the aortomitral junction
Authors: Marin-Cuartas Mateo , De La Cuesta Manuela , Davierwala Piroze M , Kang Jagdip , Stöger Guillermo , Misfeld Martin , Kiefer Philipp , Leontyev Sergey , Verevkin Alexander , Pfanmüller Bettina , Saaed Diyar , Borger Michael A , Noack Thilo
Published: May 2023

OBJECTIVES

Perivalvular abscesses with destruction of the aortomitral junction (AMJ) are a severe complication of infective endocarditis (IE) and are associated with high mortality and complex management. The Hemi-Commando procedure is a mitral valve-sparing alternative to the Commando procedure in suitable patients with complex IE and paravalvular destruction. This study reviews the mid-term outcomes in patients undergoing the Hemi-Commando procedure for treating IE with destruction of the AMJ.

METHODS

The clinical outcomes of patients with IE and AMJ involvement who underwent the Hemi-Commando procedure between 2015 and 2021 at the Leipzig Heart Center were retrospectively analysed. Primary outcomes were 30-day mortality and 1-year survival. Secondary outcome was 1-year freedom from reoperation.

RESULTS

A total of 22 patients underwent the Hemi-Commando procedure during the study period. The patients’ mean age was 59.8 ± 18.3 years. The study population was predominantly male (86.4%). Preoperative sepsis was present in 6 (27.3%) patients, and the median EuroSCORE II was 28.5%. Almost two-thirds (N = 14; 63.6%) of the patients presented with native IE. Streptococci were the most common pathogens (N = 8; 36.4%). Paravalvular abscess was found intraoperatively in 16 (72.7%) patients. The 30-day mortality was 13.6%. The estimated 1- and 3-year survival rates were 77.5% and 66.4%, respectively. The estimated freedom from reoperation at 1 and 3 years was 92.3%.

CONCLUSIONS

The Hemi-Commando procedure offers an acceptable mid-term survival chance with low reoperation rates and is, therefore, a reasonable mitral valve-sparing alternative to the Commando procedure in suitable patients with extensive IE and perivalvular involvement.
Risk factors for gingival recessions after orthodontic treatment: a systematic review
Authors: Cadenas de Llano-Pérula Maria , Castro Ana Belén , Danneels Margaux , Schelfhout Alix , Teughels Wim , Willems Guy
Published: May 2023

Background/objectives

To systematically review the available evidence concerning the risk factors for gingival recessions (GR) after orthodontic treatment (OT).

Data collection and analysis

Data was obtained and collected by systematically searching 3 data bases: Pubmed, EMBASE, and Web of Science until 20 April 2023. Controlled trials, cohort, case-control or cross-sectional studies describing GR or clinical crown height (CCH) after OT were included. The risk of bias in the selected studies was evaluated with the methodological index for non-randomized studies.

Results

Forty-eight articles were included, investigating the following six risk factors for GR: 1. OT (n = 21), 2. Type of orthodontic intervention (n = 32), 3. Patient’s baseline occlusal and skeletal characteristics (n = 14), 4. Mucogingival characteristics (n = 10), 5. Oral hygiene (n = 9), and 6. Others (n = 12). Significantly higher prevalence, severity and extent of GR were found in orthodontic patients by 10/15, 4/10, and 2/2 articles respectively. 10/16 articles reported significantly more GR and increased CCH in patients where orthodontic incisor proclination was performed. The evidence surrounding maxillary expansion and orthodontic retention was too heterogeneous to allow for? definitive conclusions. Pre-treatment angle classification, ANB, overjet, overbite, arch width and mandibular divergence were found not to be associated with GR (9/14), while pre-treatment crossbite, symphysis height and width were (5/7 studies). A thin gingival biotype, presence of previous GR, baseline width of keratinized gingiva and facial gingival margin thickness were correlated with increased risk of GR after OT by nine articles, while pocket depth was not. Oral hygiene, sex, treatment duration, and oral piercings were found not to be linked with GR in orthodontic patients, while GR was reported to increase with age in orthodontic patients by 50 per cent of the articles investigating this factor. The mean risk of bias for comparative and not comparative studies was 14.17/24 and 9.12/16.

Limitations

The selected studies were quite heterogeneous regarding study settings, variables reported and included very limited sample sizes.

Conclusion

Although studies regarding the risk factors for GR are relatively abundant, they are very heterogeneous concerning design, studied factors, methodology and reporting, which often leads to contradictory results. Uniform reporting guidelines are urgently needed for future research.

PROSPERO Registration

CRD42020181661.

Funding

This research received no funding.
Leaf litter combustion properties of Central European tree species
Authors: Ewald Michael , Labenski Pia , Westphal Erik , Metzsch-Zilligen Elke , Großhauser Michael , Fassnacht Fabian Ewald
Published: May 2023

Temperate forests of Central Europe are exposed to increasing fire risk. However, little is known about combustion properties of leaf litter, which plays an important role in the spread of surface fires. We used cone calorimetry to compare combustion properties of leaf litter samples from seven common tree species of Central European forests by reconstructing a litter layer of original depth in sample holders with a size of 10 cm × 10 cm. In addition to mono-specific leaf litter beds, combustion experiments included mixtures of different litter types, mixtures of litter and bryophytes and one mixture of litter and fine woody debris, totalling to 13 different setups (i.e. litter types). Recorded combustion properties included ignitability, flaming duration and heat release. Differences in combustion properties were analysed using analyses of variance followed by pairwise post-hoc tests. Combustion properties mainly differed between different litter types (broadleaf, pine needle, short needle). Highest total and peak heat release were observed for Scots pine (Pinus sylvestris), while peak heat release rates showed only minor differences for litter of the remaining species. Broadleaf litter was characterized by highest ignitability. For short-needle litter, we observed long flaming duration and incomplete combustion, resulting in the lowest total heat release on a sample mass basis. For litter mixtures of pine and broadleaf litter, we observed lower peak heat release rates in comparison to mono-specific pine litter. Mosses reduced peak heat release rates and increased the proportion of unburned biomass. However, the magnitude of this effect differed between bryophyte species included in the mixtures. The addition of fine woody debris strongly increased total heat release, highlighting the importance of fine woody fuels for fire behaviour. The results of this study provide valuable baseline information on combustion behaviour of leaf litter from Central European forests. Due to the limitations of laboratory combustion experiments to reproduce conditions of real forest fires, there is a need for future field studies investigating fire behaviour under natural conditions.
The Role of Repetitive Sequences in Repatterning of Major Ribosomal DNA Clusters in Lepidoptera
Authors: Dalíková Martina , Provazníková Irena , Provazník Jan , Grof-Tisza Patrick , Pepi Adam , Nguyen Petr
Published: May 2023

Genes for major ribosomal RNAs (rDNA) are present in multiple copies mainly organized in tandem arrays. The number and position of rDNA loci can change dynamically and their repatterning is presumably driven by other repetitive sequences. We explored a peculiar rDNA organization in several representatives of Lepidoptera with either extremely large or numerous rDNA clusters. We combined molecular cytogenetics with analyses of second- and third-generation sequencing data to show that rDNA spreads as a transcription unit and reveal association between rDNA and various repeats. Furthermore, we performed comparative long read analyses among the species with derived rDNA distribution and moths with a single rDNA locus, which is considered ancestral. Our results suggest that satellite arrays, rather than mobile elements, facilitate homology-mediated spread of rDNA via either integration of extrachromosomal rDNA circles or ectopic recombination. The latter arguably better explains preferential spread of rDNA into terminal regions of lepidopteran chromosomes as efficiency of ectopic recombination depends on the proximity of homologous sequences to telomeres.
Rapid Evolution of the Embryonically Expressed Homeobox GeneLEUTXwithin Primates
Authors: Lewin Thomas D , Blagrove Josephine R , Holland Peter W H
Published: May 2023

LEUTX is a homeodomain transcription factor expressed in the very early embryo with a function around embryonic genome activation. The LEUTX gene is found only in eutherian mammals including humans but, unlike the majority of homeobox genes, the encoded amino acid sequence is very different between divergent mammalian species. However, whether dynamic evolution has also occurred between closely related mammalian species remains unclear. In this work, we perform a comparative genomics study of LEUTX within the primates, revealing dramatic evolutionary sequence change between closely related species. Positive selection has acted on sites in the LEUTX protein, including six sites within the homeodomain; this suggests that selection has driven changes in the set of downstream targets. Transfection into cell culture followed by transcriptomic analysis reveals small functional differences between human and marmoset LEUTX, suggesting rapid sequence evolution has fine-tuned the role of this homeodomain protein within the primates.
Reticulons 1 and 3 are essential for axonal growth and synaptic maintenance associated with intellectual development
Authors: Zhou John , Shi Qi , Ge Ying Y , He Wanxia , Hu Xiangyou , Xia Weiming , Yan Riqiang
Published: May 2023

Reticulon (RTN) proteins are a family of proteins biochemically identified for shaping tubular endoplasmic reticulum, a subcellular structure important for vesicular transport and cell-to-cell communication. In our recent study of mice with knockout of both reticulon 1 (Rtn1) and Rtn3, we discovered that Rtn1−/−;Rtn3−/− (brief as R1R3dKO) mice exhibited neonatal lethality, despite the fact that mice deficient in either RTN1 or RTN3 alone exhibit no discernible phenotypes. This has been the first case to find early lethality in animals with deletion of partial members of RTN proteins. The complete penetrance for neonatal lethality can be attributed to multiple defects including the impaired neuromuscular junction found in the diaphragm. We also observed significantly impaired axonal growth in a regional-specific manner, detected by immunohistochemical staining with antibodies to neurofilament light chain and neurofilament medium chain. Ultrastructural examination by electron microscopy revealed a significant reduction in synaptic active zone length in the hippocampus. Mechanistic exploration by unbiased proteomic assays revealed reduction of proteins such as FMR1, Staufen2, Cyfip1, Cullin-4B and PDE2a, which are known components in the fragile X mental retardation pathway. Together, our results reveal that RTN1 and RTN3 are required to orchestrate neurofilament organization and intact synaptic structure of the central nervous system.
A Hölder-Type Inequality for the C0 Distance and Anosov–Katok Pseudo-Rotations
Authors: Joksimović Dušan , Seyfaddini Sobhan
Published: May 2023

We prove a Hölder-type inequality for Hamiltonian diffeomorphisms relating the $C^0$ norm, the $C^0$ norm of the derivative, and the Hofer/spectral norm. We obtain as a consequence that sufficiently fast convergence in Hofer/spectral metric forces $C^0$ convergence. The second theme of our paper is the study of pseudo-rotations that arise from the Anosov–Katok method. As an application of our Hölder-type inequality, we prove a $C^0$ rigidity result for such pseudo-rotations.
Spectral Gap Characterizations of Property (T) for II1 Factors
Authors: Tan Hui
Published: May 2023

For II$_1$ factors, we show that property (T) is equivalent to having weak spectral gap in any inclusion into a larger tracial von Neumann algebra. We also show that not having non-zero almost central vectors in weakly mixing bimodules characterizes property (T) for II$_1$ factors, which allows us to obtain a stronger characterization of property (T) where only weak spectral gap in any irreducible inclusion is required.
Why delegate to the IMF? Congressional preference and blame avoidance
Authors: Fujita Masafumi
Published: May 2023

Why has the United States delegated most of its crisis lending to the International Monetary Fund (IMF) in recent years, although it provided large-scale bilateral bailouts to strategically important countries until the mid-1990s? Previous research on the choice of bailout strategy has failed to explain this important change, and a major problem with such research is that it has focused on executive branch preferences, overlooking those of the legislative branch. The legislature can significantly influence the choice of bailout policies, and existing research also implies that the US Congress has steered the recent change. This article hypothesizes that, caught in a dilemma between the need for bailouts and voters’ opposition caused by widening inequality, Congress delegated bailouts to the IMF for blame avoidance. To test this hypothesis, the study conducts a statistical analysis of the IMF’s capital increase votes and case analyses of the Mexican and Asian crises.
Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients
Authors: Cowman Kelsie , Miller Alexander , Guo Yi , Chang Mei H , McSweeney Terrence , Bao Hongkai , Simpson Roxanne , Braithwaite Claire , Sunu Evans , Ros Theary , Rodriguez Maria , Laboy Eric , Bard Linda , Alsina Leslie , Cintron Angelica , Andrews Erin , Nori Priya
Published: May 2023

Objectives

To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir.

Methods

We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables.

Results

All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4–3.3, P value = 0.79).

Conclusions

These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.
HIV-1 infection in South Kivu (Democratic Republic of Congo): high genotypic resistance to antiretrovirals
Authors: Duhant Alexandra , Kusinza Byabene , Tantet Claire , Bisimwa Basimane , Gare Mathilde , Masemo Bihehe , Alloui Chakib , Ntakwinjan Mukanire , Mechai Frédéric , Le Minh Patrick , Gerber Athenaïs , Muhigirwa Balthazar , Peytavin Gilles , Gordien Emmanuel , Brichler Ségolène , Mukwege Mukengere , Le Gal Frédéric
Published: May 2023

Background

Panzi General Reference Hospital (HGR Panzi) in the Democratic Republic of Congo follows a large number of patients living with HIV-1 (PLWHIV). Although antiretrovirals (ARVs) are available, HIV-1 viral load (HIV-VL) measurement has only been implemented in the hospital since 2018. No data on ARV resistance levels and ARV dosage in plasma have yet been published for this region. We determined the prevalence of virological failure due to ARV resistance amongst patients and assessed the degree of genotypic resistance of the viral strains.

Methods

We performed an HIV-VL test and determined dosage of ARVs on samples collected from 205 PLWHIV at HGR Panzi between 2017 and 2018, including 13 ARV-naive patients. Genotypic resistance testing was performed on all samples with detectable HIV-VLs, and interpreted with the Agence Nationale de Recherches sur le Sida (ANRS) 2018 algorithm.

Results

Baseline resistance to NNRTIs was found in 2 of the 13 treatment-naive individuals (15%). ARV dosage was non-optimal for 44/192 of treated patients (22.9%), with an HIV-VL ≥1000 IU/mL for 40/192 (20.8%) of them. In particular, treatment-experienced viruses presented resistance to at least one NRTI (52.5%), to at least one NNRTIs (70%) or to at least one PIs (15%). Finally, two samples contained viruses with resistance polymorphism in the integrase gene.

Conclusions

The high level of resistance to ARVs observed during this study, mainly due to treatment compliance default, fully justifies the implementation of means for closer patient monitoring. The provision of VL tests and therapeutic education management tools in a PLWHIV follow-up remains an absolute necessity to best adapt the current treatment lines in this region.
Advances in antibacterial treatment of adults with high-risk febrile neutropenia
Authors: Contejean Adrien , Maillard Alexis , Canouï Etienne , Kernéis Solen , Fantin Bruno , Bouscary Didier , Parize Perrine , Garcia-Vidal Carolina , Charlier Caroline
Published: May 2023

Background

High-risk febrile neutropenia (HR-FN) is a life-threatening complication in patients with haematological malignancies or receiving myelosuppressive chemotherapy. Since the last international guidelines were published over 10 years ago, there have been major advances in the understanding and management of HR-FN, including on antibiotic pharmacokinetics and discontinuation/de-escalation strategies.

Objectives

Summarizing major advances in the field of antibacterial therapy in patients with HR-FN: empirical therapy, pharmacokinetics of antibiotics and antibiotic stewardship.

Sources

Narrative review based on literature review from PubMed. We focused on studies published between 2010 and 2023 about the pharmacokinetics of antimicrobials, management of antimicrobial administration, and discontinuation/de-escalation strategies. We did not address antimicrobial prophylaxis, viral or fungal infections.

Content

Several high-quality publications have highlighted important modifications of antibiotic pharmacokinetics in HR-FN, with standard dosages exposing patients to underdosing. These recent clinical and population pharmacokinetics studies help improve management protocols with optimized initial dosing and infusion rules for β-lactams, vancomycin, daptomycin and amikacin; they highlight the potential benefits of therapeutic drug monitoring. A growing body of evidence also shows that antibiotic discontinuation/de-escalation strategies are beneficial for bacterial ecology and patients’ outcome. We further discuss methods and limitations for implementation of such protocols in haematology.

Implications

We highlight recent information about the management of antibacterial therapy in HR-FN that might be considered in updated guidelines for HR-FN management.
Use of Cultured Epithelial Autograft in Conjunction with Biodegradable Temporizing Matrix in Massive Burns: A Case Series
Authors: Heard Jason , Sen Soman , Greenhalgh David , Palmieri Tina , Romanowski Kathleen
Published: May 2023

Intensive care for massively burn patients has increased survival and highlights the need for a solution to the problem of insufficient donor sites for autologous skin coverage. In this case series, we present 10 patients with average burn size of 81% TBSA and mean age of 24 years old, who underwent burn excision followed by either immediate or delayed biodegradable temporizing matrix (BTM) placement. After an integration period, the BTM was delaminated either the day before or immediately prior to placement of cultured epithelial autografts over a widely meshed (4:1 or 6:1) split thickness skin graft. One patient had cultured epithelial autografts alone, without split thickness skin graft, placed on integrated BTM and had successful take. Seven patients survived to discharge and had average 95% wound closure at 135 ± 35 days. The patients had on average 10.4 total operations and 8.7 excision and grafting operations. Five patients had complications related to the BTM requiring removal or replacement including three fungal infections, one bacterial infection and one with bleeding and a large clot burden. In conclusion, this surgical strategy is a viable option for patients with massive burns and insufficient donor for autologous skin grafting.
Impact of Alcohol and Methamphetamine Use on Burn Resuscitation
Authors: Kenney Connor L , Singh Pranav , Rizzo Julie A , Coates Elsa C , Serio-Melvin Maria L , Aden James K , Foster Kevin N , AbdelFattah Kareem R , Pham Tam N , Salinas Jose
Published: May 2023

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.
Smoking status and the association between patient-level factors and survival among lung cancer patients
Authors: Carroll Nikki M , Burnett-Hartman Andrea N , Rendle Katharine A , Neslund-Dudas Christine M , Greenlee Robert T , Honda Stacey A , Vachani Anil , Ritzwoller Debra P
Published: May 2023

Background

Declines in the prevalence of cigarette smoking, advances in targeted therapies, and implementation of lung cancer screening have changed the clinical landscape for lung cancer. The proportion of lung cancer deaths is increasing in those who have never smoked cigarettes. To better understand contemporary patterns in survival among patients with lung cancer, a comprehensive evaluation of factors associated with survival, including differential associations by smoking status, is needed.

Methods

Patients diagnosed with lung cancer between January 1, 2010, and September 30, 2019, were identified. We estimated all-cause and lung cancer-specific median, 5-year, and multivariable restricted mean survival time (RMST) to identify demographic, socioeconomic, and clinical factors associated with survival, overall and stratified by smoking status (never, former, and current).

Results

Analyses included 6813 patients with lung cancer: 13.9% never smoked, 54.2% formerly smoked, and 31.9% currently smoked. All-cause RMST through 5 years for those who never, formerly, and currently smoked was 32.1, 25.9, and 23.3 months, respectively. Lung cancer–specific RMST was 36.3 months, 30.3 months, and 26.0 months, respectively. Across most models, female sex, younger age, higher socioeconomic measures, first-course surgery, histology, and body mass index were positively associated, and higher stage was inversely associated with survival. Relative to White patients, Black patients had increased survival among those who formerly smoked.

Conclusions

We identify actionable factors associated with survival between those who never, formerly, and currently smoked cigarettes. These findings illuminate opportunities to address underlying mechanisms driving lung cancer progression, including use of first-course treatment, and enhanced implementation of tailored smoking cessation interventions for individuals diagnosed with cancer.
Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part I. Tissue-based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits
Authors: Haynes Robin L , Trachtenberg Felicia , Darnall Ryan , Haas Elisabeth A , Goldstein Richard D , Mena Othon J , Krous Henry F , Kinney Hannah C
Published: May 2023

The sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality in the United States, is typically associated with a sleep period. Previously, we showed evidence of serotonergic abnormalities in the medulla (e.g. altered serotonin (5-HT)1A receptor binding), in SIDS cases. In rodents, 5-HT2A/C receptor signaling contributes to arousal and autoresuscitation, protecting brain oxygen status during sleep. Nonetheless, the role of 5-HT2A/C receptors in the pathophysiology of SIDS is unclear. We hypothesize that in SIDS, 5-HT2A/C receptor binding is altered in medullary nuclei that are key for arousal and autoresuscitation. Here, we report altered 5-HT2A/C binding in several key medullary nuclei in SIDS cases (n = 58) compared to controls (n = 12). In some nuclei the reduced 5-HT2A/C and 5-HT1A binding overlapped, suggesting abnormal 5-HT receptor interactions. The data presented here (Part 1) suggest that a subset of SIDS is due in part to abnormal 5-HT2A/C and 5-HT1A signaling across multiple medullary nuclei vital for arousal and autoresuscitation. In Part II to follow, we highlight 8 medullary subnetworks with altered 5-HT receptor binding in SIDS. We propose the existence of an integrative brainstem network that fails to facilitate arousal and/or autoresuscitation in SIDS cases.
Motivations underlying Latino Americans’ group-based social media engagement
Authors: Saleem Muniba , Mastro Dana , Docherty Meagan
Published: May 2023

Guided by the Social Identity Model of Collective Action, the current research utilizes a three-wave longitudinal study collected pre and post the 2020 U.S. Presidential election to examine the motivations underlying Latino Americans’ group-based social media engagement (N = 1,050). Results revealed that Time 1 group (Latino) identity increased Time 2 perceptions of social media as efficacious in improving group outcomes, which in turn increased Time 3 group-based social media engagement. Although T1 Latino identification was not significantly associated with T2 perceptions of personal or group-based injustice, the former (but not the latter) increased T3 group-based social media engagement. Our findings reflect that marginalized group members engage with social media in part because they believe it is efficacious in improving their disadvantageous group status. This may be an especially attractive strategy for those who face individual experiences of unjust treatment.
Forester and Logger Response to Emerald Ash Borer in Massachusetts and Vermont: A Secondary Disturbance
Authors: Markowski-Lindsay Marla , Catanzaro Paul , Robillard Amanda , Butler Brett J , Orwig David A , D’Amato Anthony W , Thompson Jonathan R , Laflower Danelle M , MacLean Meghan Graham , Itter Malcolm
Published: May 2023

Forester and logger responses to the invasive emerald ash borer (EAB) could substantially affect regions across the United States. We analyzed forester and logger responses to EAB in Massachusetts and Vermont, exploring characteristics associated with purposeful targeting of substantial ash properties; managing forests differently because of EAB; and regeneration goals. One-third of respondents increased timber sales on ash properties, motivated by ecological, not economic, impacts of EAB. Nearly 60% said EAB changed their management activity in stands with ash; changes influenced by the ecological impact of EAB and not economic factors. Those influenced by EAB’s ecological impact to choose properties with substantial ash were more likely to have increased harvest area size, sawtimber removal, and harvest intensity. Loggers were more likely than foresters to remove small-diameter ash and low-grade trees. Both rated regenerating economically valuable species well adapted to the site as their highest essential priority.
Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-β/ Smad 2/3 signalling pathways
Authors: Vishwakarma Vishal Kumar , Shah Sadia , Kaur Tajpreet , Singh Amrit Pal , Arava Sudheer Kumar , Kumar Niraj , Yadav Raj Kanwar , Yadav Sushma , Arora Taruna , Yadav Harlokesh Narayan
Published: May 2023

Objective

Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats.

Methods

Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin–eosin and Masson’s trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-β (TGF-β) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR.

Key finding

Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-β and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril.

Conclusions

Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-β/Smad 2/3.
(No) Spillovers in reporting domestic abuse to police
Authors: Vomfell Lara , Povala Jan
Published: May 2023

Spillover effects in crime are typically studied as a result of offender behaviour. This study investigates whether spillover effects can occur in the reporting of domestic abuse by victims. Domestic abuse is a particularly interesting context because of its high prevalence but low reporting rate. Extending existing spatio-temporal Hawkes process specifications, we test for the presence of two spillover channels in all domestic abuse calls in a major English city. We find no evidence to support such effects in the reporting of domestic abuse.
Association Plots: visualizing cluster-specific associations in high-dimensional correspondence analysis biplots
Authors: Gralinska Elzbieta , Vingron Martin
Published: May 2023

In molecular biology, just as in many other fields of science, data often come in the form of matrices or contingency tables with many observations (rows) for a set of variables (columns). While projection methods like principal component analysis or correspondence analysis (CA) can be applied for obtaining an overview of such data, in cases where the matrix is very large the associated loss of information upon projection into two or three dimensions may be dramatic. However, when the set of variables can be grouped into clusters, this opens up a new angle on the data. We focus on the question of which observations are associated to a cluster and distinguish it from other clusters. CA employs a geometry geared towards answering this question. We exploit this feature in order to introduce Association Plots for visualizing cluster-specific observations in complex data. Regardless of the data matrix dimensionality Association Plots are two-dimensional and depict the observations associated to a cluster of variables. We demonstrate our method on two small data sets and then use it to study a challenging genomic data set comprising >10,000 samples. We show that Association Plots can clearly highlight those observations which characterise a cluster of variables.
Preventing thrombotic events in a case of postpartum ovarian artery aneurysm rupture: clinical challenges and management approaches
Authors: Rasti Sina , Zarean Elaheh , Jafarpisheh Mohammad S , Aria Amir
Published: May 2023

Ovarian artery aneurysm is a rare asymptomatic condition usually diagnosed when it ruptures. It causes massive bleeding, often in the peripartum period of multiparous women, who are already at an increased risk for thromboembolic events. Balancing the bleeding risk against the thrombotic complications remains unexplored in such cases. A 35-year-old woman presented with hemorrhagic shock 3 days after delivering her seventh healthy child. During the emergent exploratory laparotomy, she responded well to the blood transfusion; the stable retroperitoneal hematoma indicated no need to explore it. A subsequent episode of hemodynamic instability necessitated another laparotomy, during which the hematoma was evacuated and both ovarian arteries were ligated. Shortly thereafter, the patient suffered a pulmonary embolism (PE). In multiparous patients presenting with peripartum retroperitoneal hematoma and hemorrhagic shock, exploring the hematoma and ligating the ovarian and uterine arteries may reduce the risk of PE or the need for reoperation.
Atovaquone and Proguanil Hydrochloride for Prophylaxis of Malaria
Authors: Shanks G. Dennis , Kremsner Peter G. , Sukwa Thomas Y. , van der Berg J. Dirk , Shapiro Theresa A. , Scott Trevor R. , Chulay Jeffrey D. ,   for the Malarone Clinical Trials Study Group
Published: May 2023

Background: The spread of drug-resistant malaria and appreciation of side effects associated with existing antimalarial drugs emphasize the need for new drugs to prevent malaria. The combination of atovaquone and proguanil hydrochloride was previously shown to be safe and highly effective for treatment of malaria, including multi-drug-resistant Plasmodium falciparum.

Methods: We reviewed results of clinical trials that evaluated either a fixed-dose combination of atovaquone and proguanil hydrochloride for malaria prophylaxis or atovaquone alone for causal prophylactic activity against P. falciparum.

Results: In three placebo-controlled trials, 331 subjects received 250 mg atovaquone and 100 mg proguanil hydrochloride (or an equivalent dose based on body weight in children) once daily for 10 to 12 weeks. The overall efficacy for preventing parasitemia was 98%. Among 175 nonimmune volunteers taking the same dose of atovaquone/proguanil once daily for 10 weeks while temporarily residing in a malaria-endemic area, malaria developed in one patient who was non-compliant with therapy. Results of volunteer challenge studies indicate that both atovaquone and proguanil have causal prophylactic activity directed against the liver stages of P. falciparum. Adverse events occurred with similar or lower frequencies in subjects treated w i th atovaquone/proguanil compared to placebo. Less than 1 % of patients discontinued from these studies due to a treatment-related adverse event.

Conclusion: A fixed-dose combination of atovaquone and proguanil hydrocloride is a promising new alternative for malaria prophylaxis.