bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Kinesio Taping for Edema, Ecchymosis, and Pain After Liposuction: A Prospective Pilot Study
Authors: Zingaretti Nicola , Albanese Roberta , Pisano Gaetano , Isola Miriam , Giusti Alessandra , De Martino Maria , De Francesco Francesco , Riccio Michele , Parodi Pier Camillo
Published: June 2023

Background

Liposuction is a safe, simple, and effective method of body contouring. Pain, ecchymosis, and edema are often local complications at the removal site, especially in the first weeks after surgery. Several studies have shown that kinesiology (kinesio) taping improves blood and lymphatic flow, removing congestions of lymphatic fluid and alleviating hemorrhage. However, there are limited data on the effect of kinesio taping in mitigating local complications at fat grafting donor sites.

Objectives

The aim of this pilot study was to evaluate the impact of kinesio taping in reducing postoperative edema, pain, and ecchymosis in the liposuction area.

Methods

Over a period of 18 months (January 2021-June 2022), 52 patients underwent liposuction of both flanks with subsequent breast fat grafting. Immediately after the surgery, kinesio taping was used on the right abdomen flank in all patients. Degree of edema as well as ecchymosis and pain were quantified at 7, 14, and 21 days after surgery.

Results

There were statistically significant differences in the taping area for ecchymosis at 7 days after surgery, edema at 14 and 21 days after surgery, and in pain, rated on a visual analog scale, at 7, 14 and 21 days after surgery.

Conclusions

Kinesio taping, as used in this study, is beneficial in the reduction of edema and pain and the resolution of ecchymosis after liposuction.

Level of Evidence: 3
Accelerating open modification spectral library searching on tensor core in high-dimensional space
Authors: Kang Jaeyoung , Xu Weihong , Bittremieux Wout , Moshiri Niema , Rosing Tajana
Published: June 2023

Motivation

Driven by technological advances, the throughput and cost of mass spectrometry (MS) proteomics experiments have improved by orders of magnitude in recent decades. Spectral library searching is a common approach to annotating experimental mass spectra by matching them against large libraries of reference spectra corresponding to known peptides. An important disadvantage, however, is that only peptides included in the spectral library can be found, whereas novel peptides, such as those with unexpected post-translational modifications (PTMs), will remain unknown. Open modification searching (OMS) is an increasingly popular approach to annotate modified peptides based on partial matches against their unmodified counterparts. Unfortunately, this leads to very large search spaces and excessive runtimes, which is especially problematic considering the continuously increasing sizes of MS proteomics datasets.

Results

We propose an OMS algorithm, called HOMS-TC, that fully exploits parallelism in the entire pipeline of spectral library searching. We designed a new highly parallel encoding method based on the principle of hyperdimensional computing to encode mass spectral data to hypervectors while minimizing information loss. This process can be easily parallelized since each dimension is calculated independently. HOMS-TC processes two stages of existing cascade search in parallel and selects the most similar spectra while considering PTMs. We accelerate HOMS-TC on NVIDIA’s tensor core units, which is emerging and readily available in the recent graphics processing unit (GPU). Our evaluation shows that HOMS-TC is 31× faster on average than alternative search engines and provides comparable accuracy to competing search tools.

Availability and implementation

HOMS-TC is freely available under the Apache 2.0 license as an open-source software project at https://github.com/tycheyoung/homs-tc.
Plassembler: an automated bacterial plasmid assembly tool
Authors: Bouras George , Sheppard Anna E , Mallawaarachchi Vijini , Vreugde Sarah
Published: June 2023

With recent advances in sequencing technologies, it is now possible to obtain near-perfect complete bacterial chromosome assemblies cheaply and efficiently by combining a long-read-first assembly approach with short-read polishing. However, existing methods for assembling bacterial plasmids from long-read-first assemblies often misassemble or even miss bacterial plasmids entirely and accordingly require manual curation. Plassembler was developed to provide a tool that automatically assembles and outputs bacterial plasmids using a hybrid assembly approach. It achieves increased accuracy and computational efficiency compared to the existing gold standard tool Unicycler by removing chromosomal reads from the input read sets using a mapping approach.

Availability and implementation

Plassembler is implemented in Python and is installable as a bioconda package using ‘conda install -c bioconda plassembler’. The source code is available on GitHub at https://github.com/gbouras13/plassembler. The full benchmarking pipeline can be found at https://github.com/gbouras13/plassembler_simulation_benchmarking, while the benchmarking input FASTQ and output files can be found at https://doi.org/10.5281/zenodo.7996690.
Accelerating the alignment processing speed of the comprehensive end-to-end whole-genome bisulfite sequencing pipeline, wg-blimp
Authors: Lehle Jake D , McCarrey John R
Published: June 2023

Analyzing whole-genome bisulfite and related sequencing datasets is a time-intensive process due to the complexity and size of the input raw sequencing files and lengthy read alignment step requiring correction for conversion of all unmethylated Cs to Ts genome-wide. The objective of this study was to modify the read alignment algorithm associated with the whole-genome bisulfite sequencing methylation analysis pipeline (wg-blimp) to shorten the time required to complete this phase while retaining overall read alignment accuracy. Here, we report an update to the recently published pipeline wg-blimp achieved by replacing the use of the bwa-meth aligner with the faster gemBS aligner. This improvement to the wg-blimp pipeline has led to a more than ×7 acceleration in the processing speed of samples when scaled to larger publicly available FASTQ datasets containing 80–160 million reads while maintaining nearly identical accuracy of properly mapped reads when compared with data from the previous pipeline. The modifications to the wg-blimp pipeline reported here merge the speed and accuracy of the gemBS aligner with the comprehensive analysis and data visualization assets of the wg-blimp pipeline to provide a significantly accelerated workflow that can produce high-quality data much more rapidly without compromising read accuracy at the expense of increasing RAM requirements up to 48 GB.
Relational Police Work: How Police Officers Work With, On and Through ‘Personal Relationships’ in a Danish Gang Exit Programme
Authors: Johansen Mette-Louise E
Published: June 2023

This article examines how police-assisted gang desistance in Denmark is run on the backdrop of a particular kind of ‘relational work’ that focuses on relationships as the basis for change. The analysis is based on ethnographic fieldwork and interviews conducted in 2020 with police officers, social workers and gang defectors attached to the city of Aarhus Exit Unit, part of Denmark’s national gang exit programme. The Exit Unit’s relational work consisted of creating close, personal relationships with defectors, which could serve as a vehicle for interventions into the defectors’ relationships with gangs, family, friends and neighbourhoods. This relational work was highly ambiguous; it entailed dual practices of correctional control and help to reposition defectors in-between criminal and non-criminal social worlds.
Bidirectional Mendelian randomization analysis did not indicate a causal relationship between atopic dermatitis and COVID-19
Authors: Luo Min , Zhu Changhua , Lin Jinger , Lin Lihang , Han Yue
Published: June 2023

The threat of COVID-19 infection imposes an additional psychological burden on patients with AD. Whether there is an association between AD and COVID-19 remains unclear as observational studies are susceptible to confounding factors and reverse causality. This study did not indicate a causal relationship between AD and susceptibility, hospitalization and severity of COVID-19.
Use of direct microscopy to diagnose superficial mycoses: a survey of UK dermatology practice
Authors: Chandler David J , Yamamoto Reika , Hay Rod J
Published: June 2023

Direct microscopy is a useful tool in the diagnosis of superficial mycoses; however, it is a fading skill among UK dermatologists. Most dermatologists do not have access to a working microscope, and do not feel confident to perform the procedure or interpret the microscopic findings.
Coproduction with Service Users in Adult Social Work: A Study of Service Users’ and Social Workers’ Experiences in Northern Ireland
Authors: Burns Patricia , McGinn Tony , Fitzsimons Lelia
Published: June 2023

Involving service users, in the delivery of health and social care, is a focal point in social policy discourse. Coproduction has become synonymous with anti-oppressive practice and service user empowerment. This article reports on a qualitative study carried out in Northern Ireland which explored service user involvement in adult social care practice and policy development. Semi-structured interviews were completed with service users (n = 6) and social workers (n = 7); thematic analysis was applied to the resultant data. The study was coproduced with service users who informed the research design and were actively involved throughout each phase of the study. Findings suggest that service users are motivated to participate in coproduction and can feel valued in these roles, but meaningful coproduction is a challenge in the current practice environment. Close working relationships, with clear and consistent communication are difficult to maintain amid the current trend of bureaucratisation in our profession. Findings point towards the need for a service-user/social worker alliance which can challenge problematic organisational cultures. Remuneration for service users, engaged in coproduction, is encouraged, alongside organisational recognition of the time and resource necessary for effective coproduction. A procedural and ethical framework for coproduction practices would also be timely.
Are there cognitive and neuroimaging signatures in long COVID?
Authors: Matias-Guiu Jordi A , Díez-Cirarda María
Published: June 2023

This scientific commentary refers to ‘Markers of limbic system damage following SARS-CoV-2 infection’, by Thomasson et al. (https://doi.org/10.1093/braincomms/fcad177)
Coexistence of psoriasis and cutaneous T-cell lymphoma
Authors: Scott Joseph , Lai Chester , Coltart George , Bates Andrew , Bennett Luke , Sommerlad Matthew , Foria Vipul , Healy Eugene
Published: June 2023

It has been reported that individuals with psoriasis are at an increased risk of developing cutaneous T-cell lymphoma (CTCL). However, the increased risk of lymphoma in these patients has been questioned because CTCL in its early stages may be incorrectly labelled as psoriasis, thus introducing potential for misclassification bias. We retrospectively reviewed patients with a confirmed diagnosis of CTCL seen in a tertiary cutaneous lymphoma clinic (n = 115) over a 5-year period and found that 6 (5.2%) patients had clinical evidence of coexisting psoriasis. This demonstrates that there is a small cohort of individuals who develop both psoriasis and CTCL.
Age differences in neural distinctiveness during memory encoding, retrieval, and reinstatement
Authors: Pauley Claire , Kobelt Malte , Werkle-Bergner Markus , Sander Myriam C
Published: June 2023

Robust evidence points to mnemonic deficits in older adults related to dedifferentiated, i.e. less distinct, neural responses during memory encoding. However, less is known about retrieval-related dedifferentiation and its role in age-related memory decline. In this study, younger and older adults were scanned both while incidentally learning face and house stimuli and while completing a surprise recognition memory test. Using pattern similarity searchlight analyses, we looked for indicators of neural dedifferentiation during encoding, retrieval, and encoding–retrieval reinstatement. Our findings revealed age-related reductions in neural distinctiveness during all memory phases in visual processing regions. Interindividual differences in retrieval- and reinstatement-related distinctiveness were strongly associated with distinctiveness during memory encoding. Both item- and category-level distinctiveness predicted trial-wise mnemonic outcomes. We further demonstrated that the degree of neural distinctiveness during encoding tracked interindividual variability in memory performance better than both retrieval- and reinstatement-related distinctiveness. All in all, we contribute to meager existing evidence for age-related neural dedifferentiation during memory retrieval. We show that neural distinctiveness during retrieval is likely tied to recapitulation of encoding-related perceptual and mnemonic processes.
Effects of turbidity, temperature and predation cue on the stress response of juvenile delta smelt
Authors: Pasparakis Christina , Lohroff Toni , Biefel Felix , Cocherell Dennis E , Carson Evan W , Hung Tien-Chieh , Connon Richard E , Fangue Nann A , Todgham Anne E
Published: June 2023

The San Francisco Estuary (SFE) is one of the most degraded ecosystems in the United States, and organisms that inhabit it are exposed to a suite of environmental stressors. The delta smelt (Hypomesus transpacificus), a small semi-anadromous fish endemic to the SFE and considered an indicator species, is close to extinction in the wild. The goal of this study was to investigate how environmental alterations to the SFE, such as reductions in turbidities, higher temperatures and increased prevalence of invasive predators affect the physiology and stress response of juvenile delta smelt. Juvenile delta smelt were exposed to two temperatures (17 and 21°C) and two turbidities (1–2 and 10–11 NTU) for 2 weeks. After the first week of exposure, delta smelt were exposed to a largemouth bass (Micropterus salmoides) predator cue at the same time every day for 7 days. Fish were measured and sampled on the first (acute) and final (chronic) day of exposures to predator cues and later analyzed for whole-body cortisol, glucose, lactate, and protein. Length and mass measurements were used to calculate condition factor of fish in each treatment. Turbidity had the greatest effect on juvenile delta smelt and resulted in reduced cortisol, increased glucose and lactate, and greater condition factor. Elevated temperatures reduced available energy in delta smelt, indicated by lower glucose and total protein, whereas predator cue exposure had negligible effects on their stress response. This is the first study to show reduced cortisol in juvenile delta smelt held in turbid conditions and adds to the growing data that suggest this species performs best in moderate temperatures and turbidities. Multistressor experiments are necessary to understand the capacity of delta smelt to respond to the multivariate and dynamic changes in their natural environment, and results from this study should be considered for management-based conservation efforts.
Catecholamine-induced Takotsubo syndrome: a case series
Authors: Campana Nicola , Gioi Alessandra , Marchetti Maria Francesca , Giusti Martina , Angius Simone , Caggiari Ludovica , Biddau Mattia , Montisci Roberta
Published: June 2023

Background

Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department.

Case summary

Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities.

Discussion

These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications.
Multiple complications of a well-known disease: a case report of acquired Gerbode defect after bicuspid aortic valve endocarditis
Authors: Pereira Sara Couto , Antonio Pedro Silverio , Rigueira Joana , Almeida Ana G
Published: June 2023

Background

Infective endocarditis is a rare but serious disease with high morbidity and mortality due to its potential life-threatening complications. Gerbode defect is an anomalous connection between the left ventricle and the right atrium that can be either congenital or acquired, with previous rare reports following abscess formation in infective endocarditis.

Case summary

A 27-year-old woman presented in hospital with Janeway lesions, stroke, splenic and hepatic abscesses, and transient complete auriculoventricular block. Bicuspid aortic valve infective endocarditis to methicillin-sensitive Staphylococcus aureus and acquired Gerbode defect were diagnosed. After intravenous antibiotics and aortic valve replacement, the patient was discharged without sequelae.

Discussion

Bicuspid aortic valve patients have a higher risk of infective endocarditis than the general population. Infective endocarditis may present with multiple complications, including systemic embolization and local perivalvular lesions. Acquired Gerbode defect is a rare complication of infective endocarditis where transoesophageal echocardiography plays an important role for small shunt detection before surgical intervention.
EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry
Authors: Schmidt Boris , Bordignon Stefano , Neven Kars , Reichlin Tobias , Blaauw Yuri , Hansen Jim , Adelino Raquel , Ouss Alexandre , Füting Anna , Roten Laurent , Mulder Bart A , Ruwald Martin H , Mené Roberto , van der Voort Pepijn , Reinsch Nico , Kueffer Thomas , Boveda Serge , Albrecht Elizabeth M , Schneider Christopher W , Chun Kyoung Ryul Julian
Published: June 2023

Aims

Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter.

Methods and results

All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40–87) and 14 (9–21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323–386) days, the Kaplan–Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated.

Conclusion

The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.
Changes in the alcohol-specific disease burden during the COVID-19 pandemic in Germany: interrupted time series analyses
Authors: Manthey Jakob , Kilian Carolin , Schäfer Ingo , Wirth Marielle , Schulte Bernd
Published: June 2023

Background

The coronavirus disease 2019 pandemic has been linked to changes in alcohol consumption, access to healthcare services and alcohol-attributable harm. In this contribution, we quantify changes in alcohol-specific mortality and hospitalizations at the onset of the COVID-19 pandemic in March 2020 in Germany.

Methods

We obtained monthly counts of deaths and hospital discharges between January 2013 and December 2020 (n = 96 months). Alcohol-specific (International Classification of Diseases, tenth revision codes: F10.X; G31.2, G62.1, G72.1, I42.6, K29.2, K70.X, K85.2, K86.0, Q86.0, T51.X) diagnoses were further split into codes reflective of acute vs. chronic harm from alcohol consumption. To quantify the change in alcohol-specific deaths and hospital discharges, we performed sex-stratified interrupted time series analyses using generalized additive mixed models for the population aged 45–74. Immediate (step) and cumulative (slope) changes were considered.

Results

Following March 2020, we observed immediate increases in alcohol-specific mortality among women but not among men. Between the years of 2019 and 2020, we estimate that alcohol-specific mortality among women has increased by 10.8%. Hospital discharges were analyzed separately for acute and chronic conditions. The total number of hospital discharges fell by 21.4% and 25.1% for acute alcohol-specific conditions for women and men, respectively. The total number of hospital discharges for chronic alcohol-specific conditions fell by 7.4% and 8.1% for women and men, respectively.

Conclusions

Increased consumption among people with heavy drinking patterns and reduced utilization of addiction-specific healthcare services during the pandemic might explain excess mortality. During times of public health crises, access to addiction-specific services needs to be ensured.
Xylem function and leaf physiology in European beech saplings during and after moderate and severe drought stress
Authors: Hájíčková Martina , Plichta Roman , Volařík Daniel , Urban Josef , Matoušková Marie , Gebauer Roman
Published: June 2023

The extreme drought events in the last years caused high mortality amongst European beech (Fagus sylvatica L.) across Central Europe. Thus, knowledge of the response of beech to drought and its ability to recover its xylem and leaf functions after drought release is needed to better understand beech survival. In this study, changes in xylem function, leaf gas exchange, chlorophyll fluorescence and morphology of European beech saplings during drought and recovery phases were assessed. Beech saplings were exposed to three different watering intensities—well-watered (W), moderately drought stressed (M) and severely drought stressed (S) for 25 days, and then saplings were rewatered for 14 days. Reduced irrigation caused a drop in shoot water potential to −1.1 and −3.1 MPa in M and S saplings, respectively. Stomatal conductance in M and S saplings decreased to 15 and 5 per cent of that in W saplings, respectively, and it corresponded with a decrease in the photosynthesis rate and chlorophyll fluorescence parameters. Leaf water content and shoot functional xylem area were significantly affected by drought only in S saplings. Hence, these parameters could be used as sensitive indicators that distinguish plants at no risk of mortality from those at increasing risk under drought stress. In S saplings, some leaves also dried from the edges, leaving a green active central part. During the recovery phase, the leaf gas exchange and chlorophyll fluorescence parameters had recovered 4 days after rewatering in M saplings, whereas in S saplings, they were still lower after 2 weeks. Moreover, xylem function did not fully recover in S saplings till the end of the recovery phase. Hence, subsequent drought periods, even of lower intensity, could lead to tree mortality if tree functions have not fully recovered from the previous drought.
Enhancing adaptation of tropical maize to temperate environments using genomic selection
Authors: Choquette Nicole E , Weldekidan Teclemariam , Brewer Jason , Davis Scott B , Wisser Randall J , Holland James B
Published: June 2023

Tropical maize can be used to diversify the genetic base of temperate germplasm and help create climate-adapted cultivars. However, tropical maize is unadapted to temperate environments, in which sensitivities to long photoperiods and cooler temperatures result in severely delayed flowering times, developmental defects, and little to no yield. Overcoming this maladaptive syndrome can require a decade of phenotypic selection in a targeted, temperate environment. To accelerate the incorporation of tropical diversity in temperate breeding pools, we tested if an additional generation of genomic selection can be used in an off-season nursery where phenotypic selection is not very effective. Prediction models were trained using flowering time recorded on random individuals in separate lineages of a heterogenous population grown at two northern U.S. latitudes. Direct phenotypic selection and genomic prediction model training was performed within each target environment and lineage, followed by genomic prediction of random intermated progenies in the off-season nursery. Performance of genomic prediction models was evaluated on self-fertilized progenies of prediction candidates grown in both target locations in the following summer season. Prediction abilities ranged from 0.30 to 0.40 among populations and evaluation environments. Prediction models with varying marker effect distributions or spatial field effects had similar accuracies. Our results suggest that genomic selection in a single off-season generation could increase genetic gains for flowering time by more than 50% compared to direct selection in summer seasons only, reducing the time required to change the population mean to an acceptably adapted flowering time by about one-third to one-half.
New palaeoproterozoic palaeomagnetic data from Central and Northern Finland indicate a long-lived stable position for Fennoscandia
Authors: Luoto T , Salminen J , Mertanen S , Elming S-Å , Pesonen L J
Published: June 2023

The Svecofennian gabbro intrusions coincide temporally with the global 2100–1800 Ma orogens related to the amalgamation of the Mesoproterozoic supercontinent Nuna. We provide a new reliable 1891–1875 Ma palaeomagnetic pole for Fennoscandia based on rock magnetic and palaeomagnetic studies on the Svecofennian intrusions in central Finland to fill gaps in the Palaeoproterozoic palaeomagnetic record. By using the new pole together with other global high-quality data, we propose a new palaeogeographic reconstruction at 1885 Ma. This, together with previous data, supports a long-lived relatively stable position of Fennoscandia at low to moderate latitudes at 1890–1790 Ma. Similar stable pole positions have also been obtained for Kalahari at 1880–1830 Ma, Siberia at 1880–1850 Ma, and possibly India at 1980–1775 Ma. A new reconstruction at the beginning of this period indicates the convergence of several cratons at 1885 Ma in the initial stages of the amalgamation of the Nuna supercontinent at low to moderate latitudes. The close proximity of cratons at low to moderate latitudes is further supported by global and regional palaeoclimatic indicators. Stable position of several cratons could indicate a global period of minimal apparent drift at ca. 1880–1830 Ma. Before this period, the global palaeomagnetic record indicates large back-and-forth swings, most prominently seen in the high-resolution 2020–1870 Ma Coronation loops of the Slave craton. These large back-and-forth movements have been explained as resulting from an unstable geomagnetic field or basin- or local-scale vertical-axis rotations. However, the most likely explanation is inertial interchange true polar wander (IITPW) events, which is in line with the suggestion of large amplitude true polar wander events during the formation of the supercontinent.
Integrating GWAS summary statistics, individual-level genotypic and omic data to enhance the performance for large-scale trait imputation
Authors: Ren Jingchen , Lin Zhaotong , Pan Wei
Published: June 2023

Recently, a non-parametric method has been proposed to impute the genetic component of a trait for a large set of genotyped individuals based on a separate genome-wide association study (GWAS) summary dataset of the same trait (from the same population). The imputed trait may contain linear, non-linear and epistatic effects of genetic variants, thus can be used for downstream linear or non-linear association analyses and machine learning tasks. Here, we propose an extension of the method to impute both genetic and environmental components of a trait using both single nucleotide polymorphism (SNP)–trait and omics–trait association summary data. We illustrate an application to a UK Biobank subset of individuals (n ≈ 80K) with both body mass index (BMI) GWAS data and metabolomic data. We divided the whole dataset into two equally sized and non-overlapping training and test datasets; we used the training data to build SNP– and metabolite–BMI association summary data and impute BMI on the test data. We compared the performance of the original and new imputation methods. As by the original method, the imputed BMI values by the new method largely retained SNP–BMI association information; however, the latter retained more information about BMI–environment associations and were more highly correlated with the original observed BMI values.
Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes
Authors: Antwi Samuel O , Heckman Michael , White Launia , Yan Irene , Sarangi Vivekananda , Lauer Kimberly P , Reddy Joseph , Ahmed Fowsiyo , Veliginti Swathi , Mejías Febres Ellis D , Hatia Rikita I , Chang Ping , Izquierdo-Sanchez Laura , Boix Loreto , Rojas Angela , Banales Jesus M , Reig Maria , Stål Per , Gómez Manuel Romero , Singal Amit G , Li Donghui , Hassan Manal M , Roberts Lewis R , Patel Tushar
Published: June 2023

Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in the overall sample and among non-Hispanic whites. The results show that among non-Hispanic whites, presence of rare functional variants in ABCC2 was associated with 7-fold higher risk of metabolic HCC (OR = 6.92, 95% CI: 2.38–20.15, P = 0.0004), and this association remained significant when analyses were restricted to functional rare variants observed in ≥2 participants (cases 3.2% versus controls 0.0%, P = 1.02 × 10−5). In the overall multiethnic sample, presence of rare functional variants in ABCC2 was nominally associated with metabolic HCC (OR = 3.60, 95% CI: 1.52–8.58, P = 0.004), with similar nominal association when analyses were restricted to functional rare variants observed in ≥2 participants (cases 2.9% versus controls 0.2%, P = 0.006). A common variant in PNPLA3 (rs738409[G]) was associated with higher HCC risk in the overall sample (P = 6.36 × 10−6) and in non-Hispanic whites (P = 0.0002). Our findings indicate that rare functional variants in ABCC2 are associated with susceptibility to metabolic HCC in non-Hispanic whites. PNPLA3-rs738409 is also associated with metabolic HCC risk.
Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria
Authors: Lucienne Marie , Gerlini Raffaele , Rathkolb Birgit , Calzada-Wack Julia , Forny Patrick , Wueest Stephan , Kaech Andres , Traversi Florian , Forny Merima , Bürer Céline , Aguilar-Pimentel Antonio , Irmler Martin , Beckers Johannes , Sauer Sven , Kölker Stefan , Dewulf Joseph P , Bommer Guido T , Hoces Daniel , Gailus-Durner Valerie , Fuchs Helmut , Rozman Jan , Froese D Sean , Baumgartner Matthias R , de Angelis Martin Hrabě
Published: June 2023

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)–type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator–activated receptor and Fgf21-controlled pathways. Together, these shed light on the mechanisms and adaptations behind energy imbalance in methylmalonic aciduria and provide insight into metabolic responses to chronic energy shortage, which may have important implications for disease understanding and patient management.
Elevated Levels of Interleukin-1β and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus
Authors: Thudium Rebekka F , Arentoft Nicoline S , Hoel Hedda , Afzal Shoaib , von Stemann Jakob H , Forman Julie L , Wilcke Jon T , Benfield Thomas , Trøseid Marius , Borges Álvaro H , Ostrowski Sisse R , Vestbo Jørgen , Kunisaki Ken M , Jensen Jens-Ulrik S , Nielsen Susanne D
Published: June 2023

Background

People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH.

Methods

We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by >2 years. Inflammatory markers (interleukin [IL]–1β, IL-2, IL-6, IL-10, tumor necrosis factor–α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline.

Results

The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1β and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1–18.6; P = .014) and 10.0 mL/year (95% CI, 1.8–18.2; P = .017), respectively. We found no interaction between smoking and IL-1β or IL-10 on FEV1 decline.

Conclusions

Elevated IL-1β and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases.
Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study
Authors: Paulsen Grant C , Frenck Robert , Tomashek Kay M , Alarcon Rodolfo M , Hensel Elizabeth , Lowe Ashley , Brocato Rebecca L , Kwilas Steve A , Josleyn Matthew D , Hooper Jay W
Published: June 2023

Background

Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated.

Methods

Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50).

Results

While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197.

Conclusions

This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response.

Clinical Trials Registration. NCT03682107.
The Mucin-Like Domain of the Ebola Glycoprotein Does Not Impact Virulence or Pathogenicity in Ferrets
Authors: Halfmann Peter J , Borisevich Viktoriya , Levine Corri B , Mire Chad E , Fenton Karla A , Geisbert Thomas W , Kawaoka Yoshihiro , Cross Robert W
Published: June 2023

Background

Ebola virus (EBOV) is considered among the most dangerous viruses with case fatality rates approaching 90% depending on the outbreak. While several viral proteins (VPs) including VP24, VP35, and the soluble glycoprotein are understood to contribute to virulence, less is known of the contribution of the highly variable mucin-like domain (MLD) of EBOV. Early studies have defined a potential role in immune evasion of the MLD by providing a glycan shield to critical glycoprotein residues tied to viral entry. Nonetheless, little is known as to what direct role the MLD plays in acute EBOV disease (EVD).

Methods

We generated an infectious EBOV clone that lacks the MLD and assessed its virulence in ferrets compared with wild-type (WT) virus.

Results

No differences in growth kinetics were observed in vitro, nor were there any differences in time to death, viremia, or clinical picture in ferrets infected with recombinant EBOV (rEBOV)–WT or rEBOV-Δmucin.

Conclusions

The EBOV MLD does not play a critical role in acute pathogenesis of EVD in ferrets.
Orthopoxvirus-Specific T-Cell Responses in Convalescent Mpox Patients
Authors: Traut Caroline C , Jones Joyce L , Sanders Renata A , Clark Laura R , Hamill Matthew M , Stavrakis Georgia , Sop Joel , Beckey Tyler P , Keller Sara C , Gilliams Elizabeth A , Cochran Willa V , Laeyendecker Oliver , Manabe Yukari C , Mostafa Heba H , Thomas David L , Hansoti Bhakti , Gebo Kelly A , Blankson Joel N
Published: June 2023

Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2–positive participants targeted at least 1 previously described HLA-A2–restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.
Using copula graphical models to detect the impact of drought stress on maize and wheat yield
Authors: Hermes Sjoerd , van Heerwaarden Joost , Behrouzi Pariya
Published: June 2023

Improving crop yields is one of the main goals of agronomy. However, yield is determined by a complex interplay between Genotypic, Environmental and Management factors (G$\times$E$\times$M), which varies across time and space. Therefore, identifying the fundamental relations underlying yield variation is a principal aim of agricultural research. A narrow, and not necessarily appropriate, set of statistical methods tends to be used in the study of such relations, which is why we aim to introduce a diverse audience of agronomists, production ecologists, plant breeders and others interested in explaining yield variation to the use of graphical models. More specifically, we wish to demonstrate the usefulness of copula graphical models for heterogeneous mixed data. This new statistical learning technique provides a graphical representation of conditional independence relationships within data that is not necessarily normally distributed and consists of multiple groups for environments, management decisions, genotypes or abiotic stresses such as drought. This article introduces some basic graphical model terminology and theory, followed by an application on Ethiopian maize and wheat yield undergoing drought stress. The proposed method is accompanied with the R package heteromixgm https://CRAN.R-project.org/package=heteromixgm.
Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients—a population pharmacokinetic study
Authors: Tsai Danny , Zam Betty B , Tongs Carleigh , Chiong Fabian , Sajiv Cherian , Pawar Basant , Ashok Aadith , Cooper Brynley P , Tong Steven Y C , Janson Sonja , Wallis Steven C , Roberts Jason A , Parker Suzanne L
Published: June 2023

Objectives

To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis.

Methods

A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total)  ≥100 mg/L] were simulated for various dosing strategies.

Results

Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations >5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by >10-fold during dialysis.

Conclusions

A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.
Use of marine microorganisms in designing anti-infective strategies for sustainable aquaculture production
Authors: Hamza Faseela , Zinjarde Smita
Published: June 2023

Aquaculture, a noteworthy food production sector, is confronted with disease occurrences. Treatment of aquaculture pathogens with antibiotics is often rendered ineffective due to biofilm formation and the development of resistant strains. Marine ecosystems encompass unusual microorganisms that produce novel bioactive compounds, including agents that could be used as alternatives to antibiotics. Moreover, biomass and/or biomolecules associated with these microorganisms could act as feed supplements to enhance the overall health of aquaculture species’ and improve water quality parameters. The present review summarizes the contents of studies on such marine microorganisms with the potential to be developed as agents for tackling bacterial diseases in the aquaculture segment. Bioactive compounds produced by marine bacteria are known to inhibit biofilm-associated infections mediated by their bactericidal properties (produced by Bacillus, Vibrio, Photobacterium, and Pseudoalteromonas species), surfactant activity (obtained from different species of Bacillus and Staphylococcus lentus), anti-adhesive activity (derived from Bacillus sp. and Brevibacterium sp.), and quorum sensing inhibition. Several marine fungal isolates capable of producing antibacterial agents have also been effective in inhibiting aquaculture-associated pathogens. Another strategy followed by investigators to reduce the severity of infections is the use of bacterial, yeast, and microalgae biomass as feed supplements, probiotics, and immunostimulants. In some cases, marine microalgae have been employed as sustainable alternatives to fish oil and fish meal without compromising on nutritional quality. Their inclusion in aquaculture feed has enhanced growth, favored better survival of cultured species, and improved water quality parameters. Marine microorganisms (by providing effective bioactive compounds and being used as feed supplements) could enable aquaculture practices to be more sustainable in the future.