bluuebunny/crossref_metadata_2025 huggingface dataset:
LaMiNa: A Creative Synergistic Approach to Facial Rejuvenation
Authors: Claytor Richard Brannon , Sheck Casey , Jones India , Quigley Robert
Published: March 2023

Background

Treating facial aging with CO2 lasering or microneedling are cornerstones of facial rejuvenation. Skin rejuvenation utilizing thermal and mechanical treatments have historically been considered too injurious to be combined at a single setting. Autologous nanofat has been shown to deliver wound healing properties. We investigated the safety and efficacy of co-terminus CO2 lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.

Objectives

Combination treatments may result in better results with faster recovery. We investigated the safety and efficacy of co-terminus CO2 lasering and microneedling to resolve fine lines and rhytids in facial skin with addition of autologous nanofat to aid in recovery.

Methods

Twenty-three patients underwent facial treatment with CO2 lasering followed by microneedling and application of autologous nanofat (LaMiNa). One volunteer patient had tissue biopsies of treatment areas to demonstrate histologic tissue level changes.

Results

All patients verbally reported no pain (Numerical Rating System 0–10) following procedure and had rapid recovery within an average of 5 days. Pathology results demonstrated that CO2 and microneedling had persistent epidermal disruption and perineural inflammation at 4 days, while the introduction of autologous nanofat at the time of CO2 and microneedling resulted in full recovery of epidermis and resolution of perineural inflammation.

Conclusions

Triple therapy (LaMiNa) with thermal CO2 remodeling and mechanical microneedling penetration have accelerated and pain-free recovery with the addition of autologous nanofat. Histologic analysis reveals that epidermal recovery is accelerated and perineural inflammation is reduced with the addition of autologous nanofat following skin remodeling from combined CO2 and microneedling.

Level of Evidence: 3
TLimmuno2: predicting MHC class II antigen immunogenicity through transfer learning
Authors: Wang Guangshuai , Wu Tao , Ning Wei , Diao Kaixuan , Sun Xiaoqin , Wang Jinyu , Wu Chenxu , Chen Jing , Xu Dongliang , Liu Xue-Song
Published: March 2023

Major histocompatibility complex (MHC) class II molecules play a pivotal role in antigen presentation and CD4+ T cell response. Accurate prediction of the immunogenicity of MHC class II-associated antigens is critical for vaccine design and cancer immunotherapies. However, current computational methods are limited by insufficient training data and algorithmic constraints, and the rules that govern which peptides are truly recognized by existing T cell receptors remain poorly understood. Here, we build a transfer learning-based, long short-term memory model named ‘TLimmuno2’ to predict whether epitope-MHC class II complex can elicit T cell response. Through leveraging binding affinity data, TLimmuno2 shows superior performance compared with existing models on independent validation datasets. TLimmuno2 can find real immunogenic neoantigen in real-world cancer immunotherapy data. The identification of significant MHC class II neoantigen-mediated immunoediting signal in the cancer genome atlas pan-cancer dataset further suggests the robustness of TLimmuno2 in identifying really immunogenic neoantigens that are undergoing negative selection during cancer evolution. Overall, TLimmuno2 is a powerful tool for the immunogenicity prediction of MHC class II presented epitopes and could promote the development of personalized immunotherapies.
Peak Pair Pruner: a post-processing software to MS-DIAL for peak pair validation and ratio quantification of isotopic labeling LC-MS(/MS) data
Authors: Smith Ryan A , Zhang Qibin
Published: March 2023

Motivation

Isotopic labeling is an essential relative quantification strategy in mass spectrometry-based metabolomics, ideal for studying large cohorts by minimizing common sources of variations in quantitation. MS-DIAL is a free and popular general metabolomics platform that has isotopic labeling data processing capabilities but lacks features provided by other software specialized for isotopic labeling data analysis, such as isotopic pair validation and tabular light-to-heavy peak ratio reporting.

Results

We developed Peak Pair Pruner (PPP), a standalone Python program for post-processing of MS-DIAL alignment matrixes. PPP provides these missing features and innovation including isotopic overlap subtraction based on a light-tagged pool sample as quality control. The MS-DIAL+PPP workflow for isotopic labeling-based metabolomics data processing was validated using light and heavy dansylated amino acid standard mixture and metabolite extract from human plasma.

Availability and implementation

Peak Pair Pruner is freely available on Github: https://github.com/QibinZhangLab/Peak_Pair_Pruner. Raw MS data and .ibf files analyzed are on Metabolomics Workbench with Study ID ST002427.

Contact

q_zhang2@uncg.edu

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
A framework for high-throughput sequence alignment using real processing-in-memory systems
Authors: Diab Safaa , Nassereldine Amir , Alser Mohammed , Gómez Luna Juan , Mutlu Onur , El Hajj Izzat
Published: March 2023

Motivation

Sequence alignment is a memory bound computation whose performance in modern systems is limited by the memory bandwidth bottleneck. Processing-in-memory (PIM) architectures alleviate this bottleneck by providing the memory with computing competencies. We propose Alignment-in-Memory (AIM), a framework for high-throughput sequence alignment using PIM, and evaluate it on UPMEM, the first publicly available general-purpose programmable PIM system.

Results

Our evaluation shows that a real PIM system can substantially outperform server-grade multi-threaded CPU systems running at full-scale when performing sequence alignment for a variety of algorithms, read lengths, and edit distance thresholds. We hope that our findings inspire more work on creating and accelerating bioinformatics algorithms for such real PIM systems.

Availability and implementation

Our code is available at https://github.com/safaad/aim.
Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy: nationwide, observational cohort study
Authors: Henry Anne Claire , van Dongen Jelle C , van Goor Iris W J M , Smits F Jasmijn , Nagelhout Anne , Besselink Marc G , Busch Olivier R , Bonsing Bert A , Bosscha Koop , van Dam Ronald M , Festen Sebastiaan , Groot Koerkamp Bas , van der Harst Erwin , de Hingh Ignace H , van der Kolk Marion , Liem Mike S L , de Meijer Vincent E , Patijn Gijs A , Roos Daphne , Schreinemakers Jennifer M , Wit Fennie , Daamen Lois A , van Santvoort Hjalmar C , Molenaar I Quintus , van Eijck Casper H J
Published: March 2023

Background

The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator.

Methods

This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014–2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated.

Results

In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (−1.71 (95 per cent c.i. −2.27 to −1.05) and −3.05 (95 per cent c.i. −4.03 to −1.80) respectively) and overall survival (−1.92 (95 per cent c.i. −2.60 to −1.16) and −3.49 (95 per cent c.i. −4.84 to −2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (−5.38 (95 per cent c.i. −9.27 to −1.94)) and overall survival (−6.32 (95 per cent c.i. −10.43 to −1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy.

Conclusion

Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.
Comparing the brain–behaviour relationship in acute and chronic stroke aphasia
Authors: Busby Natalie , Hillis Argye E , Bunker Lisa , Rorden Chis , Newman-Norlund Roger , Bonilha Leo , Meier Erin , Goldberg Emily , Hickok Gregory , Yourganov Grigori , Fridriksson Julius
Published: March 2023

In stroke aphasia, lesion volume is typically associated with aphasia severity. Although this relationship is likely present throughout recovery, different factors may affect lesion volume and behaviour early into recovery (acute) and in the later stages of recovery (chronic). Therefore, studies typically separate patients into two groups (acute/chronic), and this is often accompanied with arguments for and against using data from acute stroke patients over chronic. However, no comprehensive studies have provided strong evidence of whether the lesion–behaviour relationship early in recovery is comparable to later in the recovery trajectory. To that end, we investigated two aims: (i) whether lesion data from acute and chronic patients yield similar results in region-based lesion-symptom mapping analyses and (ii) if models based on one timepoint accurately predict the other. Lesions and aphasia severity scores from acute (N = 63) and chronic (N = 109) stroke survivors with aphasia were entered into separate univariate region-based lesion-symptom mapping analyses. A support vector regression model was trained on lesion data from either the acute or chronic data set to give an estimate of aphasia severity. Four model-based analyses were conducted: trained on acute/chronic using leave-one-out, tested on left-out behaviour or trained on acute/chronic to predict the other timepoint. Region-based lesion-symptom mapping analyses identified similar but not identical regions in both timepoints. All four models revealed positive correlations between actual and predicted Western Aphasia Battery-Revised aphasia-quotient scores. Lesion-to-behaviour predictions were almost equivalent when comparing within versus across stroke stage, despite differing lesion size/locations and distributions of aphasia severity between stroke timepoints. This suggests that research investigating the brain–behaviour relationship including subsets of patients from only one timepoint may also be applicable at other timepoints, although it is important to note that these comparable findings may only be seen using broad measures such as aphasia severity, rather than those aimed at identifying more specific deficits. Subtle differences found between timepoints may also be useful in understanding the nature of lesion volume and aphasia severity over time. Stronger correlations found when predicting acute behaviour (e.g. predicting acute: r = 0.6888, P < 0.001, predicting chronic r = 0.5014, P < 0.001) suggest that the acute lesion/perfusion patterns more accurately capture the critical changes in underlying vascular territories. Differences in critical brain regions between timepoints may shed light on recovery patterns. Future studies could focus on a longitudinal design to compare acute and chronic patients in a more controlled manner.
Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States
Authors: Janker Lukas , Schuster Dina , Bortel Patricia , Hagn Gerhard , Meier-Menches Samuel M , Mohr Thomas , Mader Johanna C , Slany Astrid , Bileck Andrea , Brunmair Julia , Madl Christian , Unger Lukas , Hennlich Barbara , Weitmayr Barbara , Del Favero Giorgia , Pils Dietmar , Pukrop Tobias , Pfisterer Nikolaus , Feichtenschlager Thomas , Gerner Christopher
Published: March 2023

Introduction

Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states.

Methods

UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls.

Results

Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal.

Conclusion

The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.
Epicardial connection(s) inside the pulmonary vein antrum isolation lines contribute to subsequent atrial fibrillation: a case report
Authors: Fujiwara Masaki , Takemoto Masao , Koga Tokushi , Tsuchihashi Takuya
Published: March 2023

Aims

Recent reports have demonstrated that ∼10% of patients with atrial fibrillation (AF) have epicardial connections (ECs) inside the pulmonary vein (PV) antrum isolation (AI) (PVAI) lines, which could be a possible mechanism of failure to achieve a complete PVAI, thus contributing to AF recurrence.

Case summary

We present an 80-year-old female case with consistently continuing AF associated with ECs. Epicardial connections involving the PVs were detected in the left and right superior PVs after the completion of the PVAI. The AF steadily terminated after the ablation of those ECs. She has remained well without any AF or symptoms for 2 years post-ablation.

Discussion

Those ECs might have played a possible important role in initiating and maintaining the AF. The mechanism(s) of the ECs may be a cornerstone of the failure to achieve a complete PVAI contributing to AF recurrence. Ablation of the EC(s) in addition to the PVAI may be better able to achieve the completion of the PVAI. Thus, physicians should be aware of the possibility of the presence of EC(s) when performing ablation of AF, even though complete PVAI lines have been achieved.
Effect of genetic variants in UBE2O and TPK1 on facial morphology of Koreans
Authors: Cho Hye-Won , Ban Hyo-Jeong , Jin Hyun-Seok , Cha Seongwon , Eom Yong-Bin
Published: March 2023

Human face is a highly heritable and complex trait. Many genome-wide analyses have identified genetic variants influencing facial morphology. Genome-wide association studies (GWASs) investigating facial morphologies of different populations provide a comprehensive insight into the genetic basis of the human face. Here, we report a GWAS of normal facial variation in Koreans using an array optimized for the Korean population (KoreanChip). We found that novel genetic variants encompassing four loci reached the genome-wide significance threshold. They include LOC107984547, UBE2O, TPK1, and LINC01148 loci associated with facial angle, brow ridge protrusion, nasal height, and eyelid curvature. Our results also validated previously published genetic loci, including FAT4, SOX9, and TBX3 loci. All confirmed genetic variants showed phenotypic differences involving each facial trait based on the effect of the minor allele. The present study highlights genetic signals associated with normal human facial variation and provides candidates for functional studies.

Key points
Magma transport along structural boundaries in the upper crust: insights from broad-band magnetotelluric constraints on the structure beneath Unzen volcano, Japan
Authors: Triahadini Agnis , Aizawa Koki , Hashimoto Tasuku M , Chiba Keita , Uchida Kazunari , Yamamoto Yuto , Miyano Kanta , Muramatsu Dan , Aniya Satoru , Okubo Ayumu , Kawamura Yuta
Published: March 2023

Unzen volcano, located on Shimabara Peninsula, Nagasaki, Japan, is an active volcano that has been intensively monitored since 1989, one year before the most recent eruption in 1990–1995. Previous earthquake and surface deformation studies have revealed that magma is transported obliquely from a magma reservoir beneath Tachibana Bay, to the west of Shimabara Peninsula. Here, we conduct broad-band magnetotelluric (MT) surveys at 99 sites around Shimabara Peninsula to investigate the crustal structure beneath Unzen volcano that is related to magma migration. A 3-D resistivity model that is constructed from 25 broad-band MT sites and 45 telluric sites shows a broad high-resistivity zone beneath Shimabara Peninsula and low-resistivity zones to the west and east of the peninsula. An unexpected observation is the spatial alignment of the high-resistivity zone with a seismic low-velocity zone (LVZ) at 3–15 km depth.  Quantitative analysis indicates this high-resistivity zone contains < 0.7 per cent melt under the assumption that the melt is stored in a good porosity network, while < 11 per cent melt in relatively poor pore network. We infer this high-resistivity, LVZ to be a highly crystallized mush zone (HCMZ) with low permeability. The hypocentres and pressure sources of the 1990–1995 eruption are distributed along the boundary between the high- and low-resistivity zones beneath the western part of the peninsula. We therefore conclude that the magma migrated along a structural boundary that possessed a relatively high permeability. Previous studies have suggested that eruptible magma is usually transported vertically upward through the centre of the mush zone, whereas the present results reveal that magma can be transported along the upper boundary of an HCMZ.
I think that I will just sit here and wait
Authors: Beamish Richard
Published: March 2023

Fisheries research has always been an opportunity of discovery for me and never really a job. Finding a new species of fish, discovering that fish can outlive humans, or that atmospheric transport of chemicals can profoundly affect fish survival over vast distances kept each day exciting. So many people I worked with or met remain as wonderful memories. There are now much better opportunities for discoveries of mechanisms responsible for the dynamics of fish populations than in the past. There is also an urgency for these discoveries as our changing climate affects the capacity of habitats to support fish. We need young people in spirit who can work in teams that excel in pursuing these new opportunities.
You’re Not the Boss of me, Algorithm: Increased User Control and Positive Implicit Attitudes Are Related to Greater Adherence to an Algorithmic Aid
Authors: Morrison Ben W , Kelson Joshua N , Morrison Natalie M V , Innes J Michael , Zelic Gregory , Al-Saggaf Yeslam , Paul Manoranjan
Published: March 2023

This study examined whether participants’ adherence to an algorithmic aid was related to the degree of control they were provided at decision point and their attitudes toward new technologies and algorithms. It also tested the influence of control on participants’ subjective reports of task demands whilst using the aid. A total of 159 participants completed an online experiment centred on a simulated forecasting task, which required participants to predict the performance of school students on a standardized mathematics test. For each student, participants also received an algorithm-generated forecast of their score. Participants were randomly assigned to either the ‘full control’ (adjust forecast as much as they wish), ‘moderate control’ (adjust forecast by 30%) or ‘restricted control’ (adjust forecast by 2%) group. Participants then completed an assessment of subjective task load, a measure of their explicit attitudes toward new technologies, demographic and experience items (age, gender and computer literacy) and a novel version of the Go/No-Go Association Task, which tested their implicit attitudes toward algorithms. The results revealed that participants who were provided with more control over the final forecast tended to deviate from it more greatly and reported lower levels of frustration. Furthermore, participants showing more positive implicit attitudes toward algorithms were found to deviate less from the algorithm’s forecasts, irrespective of the degree of control they were given. The findings allude to the importance of users’ control and preexisting attitudes in their acceptance of, and frustration in using a novel algorithmic aid, which may ultimately contribute to their intention to use them in the workplace. These findings can guide system developers and support workplaces implementing expert system technology.
Measuring Galactic dark matter through unsupervised machine learning
Authors: Buckley Matthew R , Lim Sung Hak , Putney Eric , Shih David
Published: March 2023

Measuring the density profile of dark matter in the Solar neighbourhood has important implications for both dark matter theory and experiment. In this work, we apply autoregressive flows to stars from a realistic simulation of a Milky Way-type galaxy to learn – in an unsupervised way – the stellar phase space density and its derivatives. With these as inputs, and under the assumption of dynamic equilibrium, the gravitational acceleration field and mass density can be calculated directly from the Boltzmann equation without the need to assume either cylindrical symmetry or specific functional forms for the galaxy’s mass density. We demonstrate our approach can accurately reconstruct the mass density and acceleration profiles of the simulated galaxy, even in the presence of Gaia-like errors in the kinematic measurements.
Evolving ONe WD+He WD systems to ultra-compact X-ray binaries
Authors: Liu D , Wang B
Published: March 2023

It has been proposed that accretion-induced collapse (AIC) of massive white-dwarfs (WDs) is an indispensable path for the formation of neutron star (NS) binaries. Although there are still no direct evidence for the existence of AIC events, several kinds of NS systems are suggested to originate from the AIC processes. One of the representative evidence is the detection of the strong magnetic field and slow spin NSs with ultra-light companions (${\le}0.1\, \rm M_{\odot }$) in close orbits. However, previous studies cannot explain the formation of AIC events with such low-mass companions. In the present work, we evolve a series of ONe WD+He WD systems to the formation of AIC events (named as the He WD donor channel), and the NS binaries behave as ultra-compact X-ray binaries when the He WDs refill their Roche lobes. We found that the ONe WD+He WD systems a possible channel for the formation of the newly formed NS+ultra-light companion systems just after the AIC event. Although there are some other inconsistent properties, the detected companion mass and orbital period of 4U 1626–67 (one of the newly formed NS binaries with ultra-light companions) can be reproduced by the He WD donor channel. In addition, combined with previous asteroseismology results, we speculate that an UCXB source (XTE J1751−305) may originate from the He WD donor channel.
Processing of hydroxylamine, NH2OH, an important prebiotic precursor, on interstellar ices
Authors: Molpeceres Germán , Rivilla Víctor M , Furuya Kenji , Kästner Johannes , Maté Belén , Aikawa Yuri
Published: March 2023

Hydroxylamine, NH2OH, is one of the already detected interstellar molecules with the highest prebiotic potential. Yet, the abundance of this molecule found by astronomical observations is rather low for a relatively simple molecule, ∼10−10 relative to H2. This seemingly low abundance can be rationalized by destruction routes operating on interstellar dust grains. In this work, we tested the viability of this hypothesis under several prisms, finding that the origin of a lower abundance of NH2OH can be explained by two chemical processes, one operating at low temperature (10 K) and the other at intermediate temperature (20 K). At low temperatures, enabling the hydrogen abstraction reaction HNO + H → NO + H2, even in small amounts, partially inhibits the formation of NH2OH through successive hydrogenation of NO, and reduces its abundance on the grains. We found that enabling a 15–30  per cent of binding sites for this reaction results in reductions of NH2OH abundance of approximately one to two orders of magnitude. At warmer temperatures (20 K, in our study), the reaction NH2OH + H → HNOH + H2, which was found to be fast (k ∼ 106 s−1) in this work, followed by further abstractions by adsorbates that are immobile at 10 K (O, N) are the main route of NH2OH destruction. Our results shed light on the abundance of hydroxylamine in space and pave the way to constraining the subsequent chemistry experienced by this molecule and its derivatives in the interstellar prebiotic chemistry canvas.
Hybrid Immunity Provides Protective Advantage Over Vaccination or Prior Remote Coronavirus Disease 2019 Alone
Authors: Virk Abinash , Johnson Matthew G , Roellinger Daniel L , Scott Christopher G , Sampathkumar Priya , Breeher Laura E , Swift Melanie
Published: March 2023

Background

The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection.

Methods

We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection.

Results

Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%–41%; P = .0065) to 36% (95% CI, 10%–54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination.

Conclusions

Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.
Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia
Authors: Tran Nikki N , Mynatt Ryan P , Kaye Keith S , Zhao Jing J , Pogue Jason M
Published: March 2023

Background

Administration of doses via an extended infusion (EI) is an important strategy to optimize beta-lactams. Available data on the impact of EI on outcomes largely focus on clinical cure or mortality in critically ill patients or those with resistant pathogens. The potential benefits of EI extend beyond these populations and outcomes, and further study is warranted.

Methods

This was a retrospective cohort study of adult patients who received cefepime, piperacillin/tazobactam, or meropenem for Gram-negative bacteremia via EI or intermittent infusion. Patients were matched 1:1 based on study drug, sepsis severity, intensive care unit (ICU) status, bacteremia source, and pathogen. Outcomes assessed included time to clinical stabilization, rates of treatment failure, mortality, recurrence, and length of stay (LOS).

Results

Two hundred sixty-eight patients were included. Baseline characteristics were similar between groups. Forty-two percent of patients were in the ICU at infection onset and the most common pathogen was Escherichia coli (41%). After adjusting for residual differences between groups, receipt of EI was independently associated with shorter time to clinical stability (adjusted odds ratio, 0.32; 95% confidence interval, .22–.47), time to defervescence, and time to white blood cell count normalization. Furthermore, EI was associated with a lower incidence of treatment failure, decreased recurrence of bacteremia, and shorter LOS. There was no difference in mortality. These findings were consistent regardless of patient location (ICU vs ward), baseline renal function, source of bacteremia, or study drug received.

Conclusions

These findings suggest that EI beta-lactams are an important stewardship strategy to improve clinical outcomes in patients with Gram-negative bacteremia.
Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January–November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data
Authors: Lutz Chelsea S , Hartman Rachel M , Vigil Deionna E , Britton Amadea , Burrage Amanda B , Campbell Angela P , Close Ryan M , Desnoyers Christine , Dobson Jennifer , Garcia Starla , Halasa Natasha , Honie Elvira , Kobayashi Miwako , McMorrow Meredith , Mostafa Heba H , Parker Dennie , Pohl Kyle , Prill Mila M , Richards Jennifer , Roessler Kristen C , Sutcliffe Catherine G , Taylor Kim , Swango-Wilson Amy , Va Puthiery , Verani Jennifer R , Singleton Rosalyn J , Hammitt Laura L
Published: March 2023

Background

Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities.

Methods

We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls.

Results

The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0–97.6) than outpatient participants (86.5%; 95% CI, 63.0–95.0), but confidence intervals overlapped.

Conclusions

Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.
Neuro-cryptococcosis in an immunocompetent individual with radiologically atypical findings: a case report and review of literature
Authors: Regmi Binit U , Pathak Bishnu D , Subedi Ram C , Dhakal Bishal , Sapkota Suhail , Joshi Sushil , Poudel Ujjawal , Poudel Raju
Published: March 2023

We present a case of a 29-year-old immunocompetent female without any known comorbidities with intermittent headache and vomiting who was ultimately diagnosed with cryptococcal meningitis (CM). Though her neuroimaging findings were atypical to those commonly found in CM, she was diagnosed with CM with a cryptococcal antigen test. However, in contrast to the good prognosis as stated in the literature, she died during her course stay at the hospital. Therefore, cryptococcosis should be taken as differentials, even in an immunocompetent individual presenting with features suggestive of meningitis, to prevent the worst clinical outcome.
Low-cost informational intervention reduced drinking water arsenic exposure in Bangladesh
Authors: Reddy Raghav R , van Velden Grace A , Abedin Md Joynul , Karim Md Rezaul , Hayes Kim F , Agrawal Arun , Raskin Lutgarde
Published: March 2023

Thirty million Bangladeshis continue to drink water with unacceptable levels of arsenic (>10 μg/L), resulting in a large public health burden. The vast majority of the Bangladeshi population relies on private wells, and less than 12% use piped water, increasing the complexity of mitigation efforts. While mass testing and informational campaigns were successful in the early 2,000 s, they have received little attention in recent years, even though the number of wells in the country has likely more than doubled. We investigated the effect of a low-cost (<USD 10/household) informational intervention on reducing arsenic exposure through a randomized control trial design. The sample size was ∼10% of the study area households, and the intervention provided exposure awareness material, the arsenic concentration of the household's drinking water, and information about alternate water sources nearby with improved water quality. The informational intervention lowered household arsenic exposure (P = 0.0002), with an average reduction in arsenic levels of ∼60%. Approximately one third of the study households requested to test an additional water source at no cost. Providing the intervention a second time led to more households changing their water source but did not further reduce exposure (P = 0.39). Our study establishes a causal relationship between the informational intervention and the observed reduction in household arsenic exposure. Our findings demonstrate that water testing and recommendations for accessing improved water provide an immediate, effective, and inexpensive means of reducing the public health burden of arsenic exposure in Bangladesh.
Diagnosis of septic arthritis in the acute care setting: the value of routine intra-operative sample culture
Authors: Shamdasani Pallavi , Liew David F L , Nohrenberg Michael , Leroi Marcel M , McMaster Christopher , Owen Claire E , Hardidge Andrew , Buchanan Russell R C
Published: March 2023

Objective

Diagnosing septic arthritis can be challenging and frequently involves clinical assessment, laboratory investigations and synovial fluid analysis. We sought to determine the utility of synovial aspiration and intra-operative synovial fluid and tissue culture for the accurate diagnosis of septic arthritis.

Methods

We carried out a retrospective review of the records of patients referred to a tertiary orthopaedic unit with possible septic arthritis between 2015 and 2019 inclusive, including clinical and laboratory data for this cohort study. Performance characteristics were determined for synovial aspiration, intra-operative synovial fluid and tissue culture in diagnosing expert review-determined true septic arthritis. Concordance between discharge diagnosis, antibiotic prescribing and true septic arthritis was determined.

Results

Of 268 patients identified with suspected septic arthritis, 143 underwent both synovial fluid aspiration and intra-operative synovial fluid and tissue biopsy culture. True septic arthritis was not differentiated significantly by laboratory parameters including serum white cell count (WCC), CRP or synovial WCC. Considering only patients with negative pre-operative synovial aspirate cultures, intra-operative samples led to diagnosis of true septic arthritis in 6 of 63 patients [number needed to treat (NNT) 10.5]. For all patients sampled in theatre, positive synovial tissue biopsy was the only evidence of true septic arthritis in six (NNT 23.9). Despite insufficient microbiological evidence, 27 of the 59 patients who did not have septic arthritis received a discharge diagnosis of septic arthritis, 26 of whom were discharged with antibiotics.

Conclusion

Intra-operative sample collection, particularly tissue biopsy, increases the likelihood of a true septic arthritis diagnosis. Such measures might help to reduce diagnostic ambiguity in clinical practice and might therefore reduce overtreatment.
Clinical phenotype in scleroderma patients based on autoantibodies
Authors: Santos Cristiana Sieiro , Morales Clara Moriano , Castro Carolina Álvarez , Álvarez Elvira Díez
Published: March 2023

Objective

We aimed to characterize the clinical phenotype of patients with SSc based on autoantibodies (topoisomerase antibody (Scl-70), ACA and ANA).

Methods

We included patients with SSc who fulfilled the 2013 ACR/EULAR criteria, with disease duration ≤15 years. Six groups of patients were defined: ACA-lcSSC, Scl-70-lcSSc, ANA-lcSSc, Scl-70-dcSSc, ANA-dcSSc and ACA-dcSSc patients. We compared the different groups of patients. In the ANA subgroup, we included patients negative for SSc-specific antibodies (Scl-70 and ACA). We assessed the following: risk of interstitial lung disease (ILD), myositis, scleroderma renal crisis, cardiac involvement, gastrointestinal involvement, pulmonary hypertension, treatment, cancer and all-cause mortality.

Results

One hundred and thirteen SSc patients were included: 72 (64%) females, 82 (73%) lcSSc and 31 (27%) dcSSc. Among patients with lcSSc, 43 (52%) were ACA+, 16 (19%) Scl-70+ and 23 (28%) ANA+, and among patients with dcSSc, 13 (42%) patients were Scl-70+, 11 (35%) ANA+ and 7 (23%) ACA+. Scl-70-lcSSc patients had a significantly shorter time from RP to SSc diagnosis (P = 0.04), higher CRP (P = 0.04), renal scleroderma crisis (P = 0.02), ILD (P = 0.03) and diastolic dysfunction (P = 0.04) than ANA-lcSSc patients. Scl-70-dcSSc patients had a higher rate of myositis (P = 0.04), renal crisis (P = 0.03), CRP elevation (P = 0.002), ILD (P = 0.04), pericardial effusion (P = 0.03) and cancer (P = 0.04) than ANA-dcSSc patients. The risk of ILD was higher in Scl-70 patients during the first 10 years than in ACA+ and ANA+ patients (P = 0.03 and P = 0.02, respectively). The risk of major organ involvement was higher in Scl-70+ patients, followed by ANA+ and ACA+ patients, throughout 15 years of follow-up. All-cause mortality was higher in dcSSc patients than in lcSSc patients, but no differences were found regarding antibody positivity.

Conclusion

We have characterized the clinical phenotype of patients based on autoantibodies: Scl-70 patients show the greatest risk of major organ involvement, followed by ANA+ patients and ACA+ patients. The risk of ILD in Scl-70+ patients suggests that these patients should be monitored closely, irrespective of skin involvement. These results might provide new ways to help with the early diagnosis and management and in assessment of the prognosis of the disease.
In vitroangiogenesis in response to biomaterial properties for bone tissue engineering: a review of the state of the art
Authors: Ellermann Else , Meyer Nima , Cameron Ruth E , Best Serena M
Published: March 2023

Bone tissue engineering (BTE) aims to improve the healing of bone fractures using scaffolds that mimic the native extracellular matrix. For successful bone regeneration, scaffolds should promote simultaneous bone tissue formation and blood vessel growth for nutrient and waste exchange. However, a significant challenge in regenerative medicine remains the development of grafts that can be vascularized successfully. Amongst other things, optimization of physicochemical conditions of scaffolds is key to achieving appropriate angiogenesis in the period immediately following implantation. Calcium phosphates and collagen scaffolds are two of the most widely studied biomaterials for BTE, due to their close resemblance to inorganic and organic components of bone, respectively, and their bioactivity, tunable biodegradability and the ability to produce tailored architectures. While various strategies exist to enhance vascularization of these scaffolds in vivo, further in vitro assessment is crucial to understand the relation between physicochemical properties of a biomaterial and its ability to induce angiogenesis. While mono-culture studies can provide evidence regarding cell–material interaction of a single cell type, a co-culture procedure is crucial for assessing the complex mechanisms involved in angiogenesis. A co-culture more closely resembles the natural tissue both physically and biologically by stimulating natural intercellular interactions and mimicking the organization of the in vivo environment. Nevertheless, a co-culture is a complex system requiring optimization of various parameters including cell types, cell ratio, culture medium and seeding logistics. Gaining fundamental knowledge of the mechanism behind the bioactivity of biomaterials and understanding the contribution of surface and architectural features to the vascularization of scaffolds, and the biological response in general, can provide an invaluable basis for future optimization studies. This review gives an overview of the available literature on scaffolds for BTE, and trends are extracted on the relationship between architectural features, biochemical properties, co-culture parameters and angiogenesis.
Feasibility of canakinumab withdrawal in colchicine-resistant familial Mediterranean fever
Authors: Sener Seher , Cam Veysel , Batu Ezgi Deniz , Kasap Cuceoglu Muserref , Balik Zeynep , Aliyev Emil , Bayindir Yagmur , Basaran Ozge , Bilginer Yelda , Ozen Seza
Published: March 2023

Objectives

There is no consensus on canakinumab treatment tapering and discontinuation strategies in colchicine-resistant FMF patients. In this study, we aimed to establish a treatment management and discontinuation protocol in paediatric FMF patients treated with canakinumab.

Methods

Fifty-eight FMF patients treated with canakinumab were included. Since 2020, we have applied a protocol based on our experience whereby canakinumab is administered monthly in the first 6 months, followed by bimonthly for 6 months, and a final period of every 3 months (for 6 months). The patients were divided into two groups: 2012–2019 (group A) and 2020–2022 (group B).

Results

In group A (n = 33), the median duration of canakinumab treatment was 2.5 years [interquartile range (IQR) 1.9–3.7]. A total of 25 of 33 patients discontinued canakinumab after a median of 2.1 years (IQR 1.8–3.4). In two patients, canakinumab was restarted because of relapse. In group B (n = 25), canakinumab was discontinued in 18 patients at the end of 18 months. After a median follow-up of 0.8 years (IQR 0.6–1.1), two patients had a relapse and canakinumab treatment was reinitiated. The remaining 16 patients still have clinically inactive disease and are receiving only colchicine. When we compared the characteristics between groups A and B, there were no significant differences regarding demographics, clinical features, and outcomes.

Conclusion

This is the largest study in the literature suggesting a protocol for discontinuing canakinumab in paediatric FMF patients. It was possible to discontinue canakinumab successfully in more than half of the patients in 18 months. Thus we suggest that this protocol can be used in paediatric FMF patients.
Distraction and cognitive control independently impact parietal and prefrontal response to pain
Authors: Silvestrini Nicolas , Corradi-Dell’Acqua Corrado
Published: March 2023

Previous studies have found that distracting someone through a challenging activity leads to hypoalgesia, an effect mediated by parietal and prefrontal processes. Other studies suggest that challenging activities affect the ability to regulate one’s aching experiences, due to the partially common neural substrate between cognitive control and pain at the level of the medial prefrontal cortex. We investigated the effects of distraction and cognitive control on pain by delivering noxious stimulations during or after a Stroop paradigm (requiring high cognitive load) or a neutral condition. We found less-intense and unpleasant subjective pain ratings during (compared to after) task execution. This hypoalgesia was associated with enhanced activity at the level of the dorsolateral prefrontal cortex and the posterior parietal cortex, which also showed negative connectivity with the insula. Furthermore, multivariate pattern analysis revealed that distraction altered the neural response to pain, by making it more similar to that associated with previous Stroop tasks. All these effects were independent of the nature of the task, which, instead, led to a localized neural modulation around the anterior cingulate cortex. Overall, our study underscores the role played by two facets of human executive functions, which exert an independent influence on the neural response to pain.
Case report: Two rare uterine cesarean scar mass cases
Authors: Zhao Xiumin , Huang Danjiang , Yan Dewen , Dai Xingxing , Wang Liping
Published: March 2023

Rationale:

Gestational trophoblastic neoplasia (GTN) located in the cesarean scar is a rare disease that has imaging appearances similar to those of an exogenous scar incision pregnancy and is often misdiagnosed due to insufficient clinical experience.

Patient concerns:

We report 2 cases of uterine cesarean scar mass. Two patients with different diagnoses had similar clinical complaints as abnormal vaginal bleeding, enlargement of uterus isthmus by physical examination, and mixed echo mass in uterine low segment by ultrasound examination; however, their magnetic resonance imaging images showed very different features.

Diagnoses:

One patient was diagnosed with cesarean scar pregnancy (CSP) and one patient was diagnosed with cesarean scar GTN.

Interventions:

The CSP patient underwent surgery by laparoscopy combined with hysteroscopy after uterine artery embolism and obtained pathological confirmation. The GTN patient received chemotherapy.

Outcomes:

For the CSP patient, her serum β-human chorionic gonadotropin (hCG) concentration returned to normal 2 weeks later, and B-ultrasound showed that the niche was completely repaired 3 months after the operation. The intrauterine lesions of the GTN patient disappeared completely 3 months after serum β-hCG normalization. And her β-hCG was normal at all follow-up visits until now.

Lessons:

Clinicians should consider GTN when identifying masses at scar incision sites. Magnetic resonance imaging images improve the understanding of the imaging features in patients suspected of having CSP/GTN.