bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Diffusion Basis Spectrum Imaging in Quantifying Baseline Disease Severity and Prognosis of Cervical Spondylotic Myelopathy
Authors: Zhang Justin K. , Sun Peng , Jayasekera Dinal , Greenberg Jacob K. , Javeed Saad , Dibble Christopher F. , Blum Jacob , Song Chunyu , Song Sheng-Kwei , Ray Wilson Z.
Published: August 2022

Study Design.

Prospective cohort study

Objective.

To assess the association between diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) measures and cervical spondylotic myelopathy (CSM) clinical assessments at baseline and two-year follow-up.

Summary of Background Data.

Despite advancements in diffusion-weighted imaging, few studies have examined associations between diffusion MRI markers and CSM-specific clinical domains at baseline and long-term follow-up.

Methods.

A single-center prospective cohort study enrolled fifty CSM patients who underwent surgical decompression and twenty controls from 2018-2020. At initial evaluation, all patients underwent diffusion-weighted MRI acquisition, followed by DTI and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. To improve estimations of intra-axonal anisotropic diffusion, DBSI measures intra-/extra-axonal fraction, and intra-axonal axial diffusivity. DBSI also evaluates extra-axonal isotropic diffusion by restricted and non-restricted fraction. Clinical assessments were performed at baseline and two-year follow-up and included the mJOA, SF-36 PCS, SF-36 MCS, NDI, MDI, and DASH. Pearson’s correlation coefficients were computed to compare associations between DTI/DBSI and clinical measures. A False Discovery Rate correction was applied for multiple comparisons testing.

Results.

At baseline presentation, of 36 correlations analyzed between DTI metrics and CSM clinical measures, only DTI fractional anisotropy showed a positive correlation with SF-36 PCS (r=0.36, P=0.02). In comparison, there were 30/81 (37%) significant correlations among DBSI and clinical measures. Increased DBSI axial diffusivity, intra-axonal axial diffusivity, intra-axonal fraction, restricted fraction, and extra-axonal anisotropic fraction were associated with worse clinical presentation (decreased mJOA, SF-36 PCS/MCS, and increased NDI, MDI, DASH). At latest follow-up, increased preoperative DBSI intra-axonal axial diffusivity and extra-axonal anisotropic fraction were significantly correlated with improved mJOA.

Conclusions.

Our findings demonstrate that DBSI measures may reflect baseline disease burden and long-term prognosis of CSM as compared to DTI. With further validation, DBSI may serve as a non-invasive biomarker following decompressive surgery.

Level of Evidence.

III
Investigating treatment response and immune profile in association with pattern identification in NSCLC patients scheduled for immune checkpoint inhibitor monotherapy (HARMONY study)
Authors: Jang Jung-Hee , Jun Hyeong Joon , Choi Yujin , Kim Jin Chul , Jang Ho , Park Sang-Min , Kwon Ojin , Choi Chang-Min , Kim Seung Joon , Choi Jong Gwon , Son Ji Woong , Lee Seung Hyeun , Jang Tae-Won , Yoon Seong Hoon , Ryu Jeong-Seon , Lim Jun Hyeok , Jang Seung-Hun , Oh In-Jae , Lee Sung Yong , Jeong Mi-Kyung
Published: August 2022

Immune checkpoint inhibitors (ICI) considerably improve overall survival of advanced nonsmall cell lung cancer (NSCLC) patients. However, it has certain limitations, such as low response rates. Although programmed death-ligand 1 (PD-L1) expression is currently used as a representative predictive biomarker, it cannot robustly predict response; thus, identifying other dynamic biomarkers to ensure better selection of patients susceptible for ICI therapy is required. Pattern identification is a diagnostic system used in oriental medicine and is performed through collecting and analyzing a series of symptoms and characteristic signs. We intended to analyze the association between survival, treatment response, and immune profile evaluated on every visit according to different pattern identifications and determine how pattern identification changes during the course of NSCLC treated with ICI.

Across 10 academic hospitals, 200 patients diagnosed with stage Ⅲb-Ⅳ NSCLC and scheduled for ICI monotherapy (pembrolizumab or atezolizumab) as second-line or more treatment following platinum-based first-line treatment for NSCLC will be recruited. Throughout the study, participants are expected to exhibit different immune profiles according to pattern identification in association with treatment response and survival. The primary endpoint is progression-free survival (PFS), while secondary endpoints are overall survival (OS), objective response rate (ORR), and immune profile, all of which will be analyzed in association with pattern identification. Approximately 10 mL blood samples will be obtained from each patient.

Results from the analysis of immune cells and cytokines will be analyzed together with pattern identification. Results from the analysis of differences in survival, treatment response, and immune profile, together with pattern identification for NSCLC patients during ICI therapy, will have significant scientific and medical contributions, and will provide comprehensive data to identify pattern identification-based immune biomarkers for predicting survival and treatment response of ICI therapy for NSCLC patients. Ethical approval has been obtained from the medical ethics committees of 10 academic hospitals. All amendments to the research protocol were submitted and approved.

This trial is registered in Clinical Research Information Service (CRIS) of the Republic of Korea with the number KCT0005173. Registration date: July 22, 2020 (version 3.0).
Burden of Pediatric Functional Gastrointestinal Disorder in an Emergency Department—A Single-Center Experience
Authors: Yousaf Afroze , Mutalib Mohamed
Published: August 2022

Objectives

Functional gastrointestinal disorders (FGIDs) are recurrent or chronic gastrointestinal signs and symptoms in the absence of anatomical or biochemical alterations. They are commonly treated in outpatient setting but often present to emergency departments. We aimed to estimate the burden of pediatric FGID on a busy accident and emergency (A&E) department.

Methods

Electronic patient records were used to retrospectively analyze the A&E attendances of 3866 patients presenting with either constipation or abdominal pain. Those found not to have a surgical/organic cause were assessed in terms of various parameters, that is, arrival times, wait times, and investigations performed.

Results

A total of 91.31% of the attendances relating to constipation or nonsurgical, nonorganic causes of abdominal pain were self-referred with only 3.64% arriving via ambulance, an average wait time ranging between 138 and 156 minutes, and a total of 1008 investigations carried out on patients presenting with these symptoms. A total of 63.65% of the patients were discharged without follow-up.

Conclusions

Functional gastrointestinal disorders place considerable burden on the A&E, in terms of resource usage, time of clinicians, and financial strain. More education should be provided to families of those experiencing FGID in an outpatient setting to minimize A&E resource utilization. More research is needed to ascertain the true burden of FGIDs, both financially and in terms of time and resource.
Higher prevalence of QTc interval prolongation among virologically suppressed older people with HIV
Authors: Theerasuwipakorn Nonthikorn , Rungpradubvong Voravut , Chattranukulchai Pairoj , Siwamogsatham Sarawut , Satitthummanid Sudarat , Apornpong Tanakorn , Ohata Pirapon J. , Han Win Min , Kerr Stephen J. , Boonyaratavej Smonporn , Avihingsanon Anchalee
Published: August 2022

Objective:

To assess the prevalence, and factors associated with QTc interval prolongation, among 383 virologically suppressed people with HIV (PWH), without evidence of cardiovascular disease and active opportunistic infections in Thailand.

Design:

Cross-sectional study.

Methods:

Resting 12-lead digital ECGs were performed in 2019. QT interval corrected for heart rate (QTc) >450 ms in males and >460 ms in females was defined as QTc interval prolongation. We used multivariable logistic regression to investigate factors associated with QTc interval prolongation.

Results:

Mean (standard deviation) age was 56 (5.5) years and 42% were female. The median current CD4+ was 619 (interquartile range [IQR] 487, 769) cells/mm3. The median duration of antiretroviral therapy (ART) was 11.9 (IQR 7.1–16.1) years. Commonly used ART were rilpivirine (37.9%), efavirenz (20.1%), atazanavir/ritonavir (15.7%), lopinavir/ritonavir (12.3%) and dolutegravir (5%). The prevalence of QTc interval prolongation was 22.7%. In multivariable analysis, older age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.12, P = 0.005), female sex (OR 1.69, 95% CI 1.01–2.82, P = 0.046) and increasing BMI (OR 1.08, 95% CI 1.01–1.15, P = 0.03) were associated with QTc interval prolongation. With every 1-year increase in age, the odds of QTc interval prolongation increased by 7%.

Conclusions:

In this well-suppressed aging Asian HIV cohort, the prevalence of QTc interval prolongation was relatively high, and associated with increasing age, female sex, and higher BMI. For PLWH with these characteristics, QTc interval should be monitored before and after initiating any medications known to prolong QTc intervals, to prevent fatal cardiac arrhythmias.
An algebraic framework for structured epidemic modelling
Authors: Libkind Sophie , Baas Andrew , Halter Micah , Patterson Evan , Fairbanks James P.
Published: August 2022

Pandemic management requires that scientists rapidly formulate and analyse epidemiological models in order to forecast the spread of disease and the effects of mitigation strategies. Scientists must modify existing models and create novel ones in light of new biological data and policy changes such as social distancing and vaccination. Traditional scientific modelling workflows detach the structure of a model—its submodels and their interactions—from its implementation in software. Consequently, incorporating local changes to model components may require global edits to the code base through a manual, time-intensive and error-prone process. We propose a compositional modelling framework that uses high-level algebraic structures to capture domain-specific scientific knowledge and bridge the gap between how scientists think about models and the code that implements them. These algebraic structures, grounded in applied category theory, simplify and expedite modelling tasks such as model specification, stratification, analysis and calibration. With their structure made explicit, models also become easier to communicate, criticize and refine in light of stakeholder feedback.

This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
Vote-processing rules for combining control recommendations from multiple models
Authors: Probert William J. M. , Nicol Sam , Ferrari Matthew J. , Li Shou-Li , Shea Katriona , Tildesley Michael J. , Runge Michael C.
Published: August 2022

Mathematical modelling is used during disease outbreaks to compare control interventions. Using multiple models, the best method to combine model recommendations is unclear. Existing methods weight model projections, then rank control interventions using the combined projections, presuming model outputs are directly comparable. However, the way each model represents the epidemiological system will vary. We apply electoral vote-processing rules to combine model-generated rankings of interventions. Combining rankings of interventions, instead of combining model projections, avoids assuming that projections are comparable as all comparisons of projections are made within each model. We investigate four rules: First-past-the-post, Alternative Vote (AV), Coombs Method and Borda Count. We investigate rule sensitivity by including models that favour only one action or including those that rank interventions randomly. We investigate two case studies: the 2014 Ebola outbreak in West Africa (37 compartmental models) and a hypothetical foot-and-mouth disease outbreak in UK (four individual-based models). The Coombs Method was least susceptible to adding models that favoured a single action, Borda Count and AV were most susceptible to adding models that ranked interventions randomly. Each rule chose the same intervention as when ranking interventions by mean projections, suggesting that combining rankings provides similar recommendations with fewer assumptions about model comparability.

This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
Technical challenges of modelling real-life epidemics and examples of overcoming these
Authors: Panovska-Griffiths J. , Waites W. , Ackland G. J.
Published: August 2022

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of mathematical modelling in informing and advising policy decision-making. Effective practice of mathematical modelling has challenges. These can be around the technical modelling framework and how different techniques are combined, the appropriate use of mathematical formalisms or computational languages to accurately capture the intended mechanism or process being studied, in transparency and robustness of models and numerical code, in simulating the appropriate scenarios via explicitly identifying underlying assumptions about the process in nature and simplifying approximations to facilitate modelling, in correctly quantifying the uncertainty of the model parameters and projections, in taking into account the variable quality of data sources, and applying established software engineering practices to avoid duplication of effort and ensure reproducibility of numerical results. Via a collection of 16 technical papers, this special issue aims to address some of these challenges alongside showcasing the usefulness of modelling as applied in this pandemic.

This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
The cognitive basis of intracranial self-stimulation of midbrain dopamine neurons
Authors: Millard Samuel J. , Hoang Ivy B. , Greer Zara , O’Connor Shayna L. , Wassum Kate M. , James Morgan H. , Barker David J. , Sharpe Melissa J.
Published: August 2022

Recently there has been a reckoning in the dopamine field. This has suggested that the dopamine prediction error may function as a teaching signal, without endowing preceding events with value. We studied the cognitive basis of intracranial self-stimulation (ICSS), a setting where dopamine appears to be valuable. Physiological frequencies seen during reinforcement learning did not support robust ICSS or promote behavior that would indicate the stimulation was represented as a meaningful reward in a specific or general sense. This was despite demonstrating that this same physiologically-relevant signal could function as a teaching signal. However, supraphysiological frequencies supported robust ICSS where the stimulation was represented as a specific sensory event, which acted as a goal to motivate behavior. This demonstrates that dopamine neurons only support ICSS at supraphysiological frequencies, and in a manner that does not reflect our subjective experience with endogenous firing of dopamine neurons during reinforcement learning.

One sentence summary

Dopamine neurons only support ICSS at supraphysiological frequencies and in a manner not reflecting dopamine’s role in learning.
Remote sensing-based forest modeling reveals positive effects of functional diversity on productivity at local spatial scale
Authors: Schneider Fabian D , Longo Marcos , Paul-Limoges Eugénie , Scholl Victoria M , Schmid Bernhard , Morsdorf Felix , Pavlick Ryan P , Schimel David S , Schaepman Michael E , Moorcroft Paul R
Published: August 2022

Forest biodiversity is critical for many ecosystem functions and services at plot scale, but it is uncertain how biodiversity influences ecosystem functioning across environmental gradients and contiguous larger areas. We used remote sensing and process-based terrestrial biosphere modeling to explore functional diversity–productivity relationships at multiple scales for a heterogeneous forest site in Switzerland.

We ran the biosphere model with empirical data about forest structure and composition derived from ground-based surveys, airborne laser scanning and imaging spectroscopy for the years 2006–2015 at 10×10-m spatial resolution. We then related the model outputs forest productivity to functional diversity under observed and experimental model conditions.

Functional diversity increased productivity significantly (p<0.001) across all simulations at 20×20-m to 30×30-m scale, but at 100×100-m scale positive relationships disappeared under homogeneous soil conditions.

Whereas local functional diversity was an important driver of productivity, environmental context (especially soil depth, texture and water availability) underpinned the variation of productivity (and functional diversity) at larger spatial scales. Integration of remotely-sensed information on canopy composition and structure into terrestrial biosphere models helps fill the knowledge gap about how plant biodiversity affects carbon cycling and biosphere feedbacks onto climate over large contiguous areas.
The post-translational modification SUMO affects TDP-43 phase separation, compartmentalization, and aggregation in a zebrafish model
Authors: Maurel Cindy , Scherer Natalie M. , Hogan Alison , Vidal-Itriago Andres , Don Emily K. , Radford Rowan , Chapman Tyler , Cull Stephen , Vourc’h Patrick , Chung Roger , Lee Albert , Morsch Marco
Published: August 2022

TDP-43 is a nuclear RNA-binding protein that can undergo liquid-liquid phase separation (LLPS) and forms pathological insoluble aggregates in frontotemporal dementia and amyotrophic lateral sclerosis (ALS). Perturbations of TDP-43 function are linked to mislocalization and neurodegeneration. By studying TDP-43 in vivo, we confirmed for the first time that TDP-43 undergoes LLPS and forms biomolecular condensates in spinal motor neurons (MNs). Importantly, we discovered that interfering with the K136 SUMOylation site of TDP-43 altered its phase separation behavior, reducing cytoplasmic mislocalization and aggregation. Introduction of the ALS-linked mutation G294V did not alter these LLPS characteristics, indicating that posttranslational modifications such as lysine-specific alterations can modulate TDP-43 pathogenesis through regulating phase separation. Altogether, our in vivo characterization of TDP-43 confirms the formation of dynamic nuclear TDP-43 condensates in zebrafish spinal neurons and establishes a critical platform to validate the molecular grammar of phase separation that underpins TDP-43 aggregation in ALS and other proteinopathies.
An evolutionarily conserved pacemaker role for HCN ion channels in smooth muscle
Authors: Yang Lei , Ricart Arbona Rodolfo J. , Smith Carl , Banks Kelly M. , Thomas V. Kaye , Palmer Lawrence , Evans Todd , Hurtado Romulo
Published: August 2022

Although HCN ion channels are well established to underlie cardiac pacemaker activity, their role in smooth muscle organs remains controversial. HCN expressing cells are localized to renal pelvic smooth muscle (RPSM) pacemaker tissues of the murine upper urinary tract and HCN channel conductance is required for peristalsis. To date, however, the Ih pacemaker current conducted by HCN channels has never been detected in these cells, raising questions on the identity of RPSM pacemakers. Indeed, the RPSM pacemaker mechanisms of the unique multicalyceal upper urinary tract exhibited by humans remains unknown. Here, we developed immunopanning purification protocols and demonstrate that 96% of isolated HCN+ cells exhibit Ih. Single molecule STORM to whole-tissue imaging showed HCN+ cells express single HCN channels on their plasma membrane and integrate into the muscular syncytium. By contrast, PDGFR-α+ cells exhibiting the morphology of ICC gut pacemakers were shown to be vascular mural cells. Translational studies in the homologous human and porcine multicalyceal upper urinary tracts showed that contractions and pacemaker depolarizations originate in proximal calyceal RPSM. Critically, HCN+ cells were shown to integrate into calyceal RPSM pacemaker tissues, and HCN channel block abolished electrical pacemaker activity and peristalsis of the multicalyceal upper urinary tract. Cumulatively, these studies demonstrate that HCN ion channels play a broad, evolutionarily conserved pacemaker role in both cardiac and smooth muscle organs and have implications for channelopathies as putative etiologies of smooth muscle disorders.
Morphological Differences in Isolated Brook Trout Populations in the Desolation Wilderness of the Sierra Nevada
Authors: Luby-Prikot Lukas , Bock Oliver , Martin Joseph
Published: August 2022

abstract

Brook trout (Salvelinus fontinalis) is an invasive species in the Desolation Wilderness of California. But it is unknown to what extent this species is evolving to adapt to isolated high altitude lakes. We quantified morphological differences between three brook trout populations in Desolation Wilderness that are in isolation and of common origin. We took standardized photos of fish, created geometric nets of each specimen using points located at known morphological features, and performed a Procrustes superimposition and principal component analysis to examine and cluster morphological variation between individuals. Together, our results show morphological differences between three Salvelinus fontinalis populations in independent environments. Our results suggest that invasive species introduced from one source can show physical variation generations after introduction, and thus deserve attention for adapting to and perhaps becoming an increasingly complex part of their ecosystem.
IgG derived dendritic cells can induce production of IL-17 by T cells in multiple sclerosis
Authors: Pournasrolla Nazanin , Ahmadi Ehsan , Siroos Seyedbahaadin , Nourizadeh Maryam , Harirchian Mohammad Hossein , Izad Maryam
Published: August 2022

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Myelin-autoreactive T cells have been implicated in the initiation of an inflammatory cascade. Dendritic cells (DC) are key modulators of this immuno-pathological cascade. The interaction between immune complexes (IC) and FcγRs results in activation of the immune system and induction of host inflammatory responses. Otherwise, monocytes differentiate into DCs after ligation of their FcγRs to IgG. We investigated circulating immune complexes levels (CIC) and differentiation of monocytes onto immature dendritic cell (iDC) via FcγR by Plate-bound human IgG in MS patients compared to healthy individuals. Our results showed that the concentration of CIC in patients with MS was significantly higher than healthy controls. Human IgG alone differentiate monocytes into DCs with a phenotype, including up-regulation of CD1b, CD86 and down-regulation of CD14. Also, the ability of LPS/MBP matured DCs in activation and cytokine production of autologous T cells was evaluated by MLR assay and ELISA. The level of IL-17 was significantly higher in MS patients when IgG derived DCs cocultured with T cells. Also, a correlation between IL-17 levels and circulating immune complexes level was observed in MS patients. Therefore, activation of FcγR on monocytes triggers differentiation into specialized iDC with the capacity to induce auto-reactive T cells that may contribute to the pathogenesis of MS.
Development and validation of glycolysis-cholesterol synthesis genes in lung adenocarcinoma
Authors: Qian Bao , Guo Yangjie , Jiang Jiuzhou
Published: August 2022

Background

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer which is one of the most dangerous malignant tumors affecting human health. The pathways of glycolysis and cholesterol production play an essential role in the metabolism of cancer. The mitochondrial pyruvate carrier (MPC) consists of MPC1 and MPC2, and impaired MPC function may induce a solid capacity for tumor proliferation, migration, and invasion.

Methods

Genes positively and negatively correlated with MPC1/2 expression were identified by calculating Spearman correlation, then gene ontology (GO) analysis was conducted. Univariate cox regression, lasso regression, and multivariate cox regression analyses were performed to model predictive outcome events using differentially expressed genes. Thirteen prognostic genes were selected to construct a prognostic model.

Results

1359 and 2026 genes were positively and negatively associated with MPC1/2, respectively. The expression of MPC1 and MPC2 was significantly different. The prognostic model had great predictive performance in the test set.

Conclusions

MPC1/2 genes were involved in a cellular network associated with the malignant development of LUAD. The prognostic model can provide an essential basis for physicians to predict the clinical outcomes of LUAD patients.
Minimal alveolar concentration of sevoflurane in combination with dexmedetomidine in patients with hysteroscopy: An up‐down sequential allocation study
Authors: Guo Yan‐Xia , Luo Kai , Jiang Ping‐Ping , Wang Dan , Wang Yi‐Zheng , Yang Xiao‐Lin
Published: August 2022

Background

Dexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end‐tidal concentration of sevoflurane when it is co‐administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery.

Methods

One‐hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, D1, D2, D3) and received a loading dose of dexmedetomidine (0, 0.6, 0.8 and 1.0 μg/kg) over 10 min before anaesthesia induction, respectively. Anaesthesia was induced in each patient with 5% sevoflurane in 100% oxygen via a facemask. A laryngeal mask (LMA) was inserted when the patient had lost consciousness and the BIS value decreased below 40. The response to cervical dilatation stimulus (movement vs non‐movement) by the insert of hysteroscope was recorded. The MAC of sevoflurane was measured by up and down sequential method of Dixon and Mood and centred isotonic regression analysis.

Results

The calculated MAC of sevoflurane using up‐and‐down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, D1, D2 and D3, respectively.

Conclusions

The administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 μg/kg.
Inductive research in last‐mile delivery routing: Introducing the Re‐Gifting heuristic
Authors: Rose William J. , Bell John E. , Griffis Stanley E.
Published: August 2022

The last‐mile problem presents a daunting challenge for many logistics service providers, especially some 7000 small, localized operations for whom the cost of complex software solutions is often prohibitive. As a result, last‐mile dispatchers rely on simple heuristics to ensure adequate customer service at an acceptable cost. This research effort extends prior qualitative work by developing and testing a simple vehicle routing heuristic, based on behaviors observed in practice, that prioritizes customer service over cost against other simple vehicle routing heuristics across a variety of environments using simulation. The results support the inclusion of a customer service focus in vehicle routing and the addition of such heuristics to existing algorithm portfolios, specifically in urban areas with well‐developed highway systems.
Case‐only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD‐2353F22.1 implying the importance of periodontal wound healing for disease aetiology
Authors: Müller Ricarda , Freitag‐Wolf Sandra , Weiner January , Chopra Avneesh , Top Tugba , Dommisch Henrik , Schaefer Arne S.
Published: August 2022

Aim

The basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles.

Materials and Methods

We used the case‐only design and investigated single‐nucleotide polymorphism (SNPs) that showed associations in our recent genome‐wide association study (GWAS) and GWAS meta‐analysis with p < 5 × 10−6. CRISPR‐dCas9 gene activation followed by RNA‐sequencing and gene‐set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele‐specific effects on transcription factor binding.

Results

SNPs at the genes sialic acid binding Ig‐like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non‐coding RNA (lncRNA) CTD‐2353F22. Associated chromatin cis‐activated CTD‐2353F22.1 6.5‐fold (p = .003), indicating CTD‐2353F22.1 as target gene of this interaction. CTD‐2353F22.1 regulated GADD45A (padj < 4.9 × 10−11, log2 fold change (FC) = −0.55), THBS1, SERPINE1 and Tissue Factor F3 (padj < 5 × 10−7, log2 FC ≥ −0.35) and the gene set “angiogenesis” (area under the curve = 0.71, padj = 8.2 × 10−5). rs1122900 effect C‐allele decreased reporter gene activity (5.5‐fold, p = .0003) and PRDM14 binding (76%).

Conclusions

CTD‐2353F22.1 mediates interaction of SIGLEC5 and PLG, together with genes that function in periodontal wound healing.
(Un)conditional consumer protections in high‐cost lending regulation: Impacts on local lending geographies
Authors: Bea Megan Doherty , Bley K.
Published: August 2022

Regulation of small‐dollar lending in the United States is heterogeneous, leaving open the question about what policy designs work best for protecting consumers. We compare the effectiveness of regulations that include a consumer eligibility component and regulations that apply to all consumers, centering our analyses on communities with disproportionate exposure to high‐interest lending storefronts. Specifically, we compare how the Military Lending Act (MLA), which provided military‐specific protections, and statewide policies affected high‐cost lender activity in military communities in three states. We find that statewide regulations were effective in reducing the number of high‐cost lenders within local communities across states, including military communities, while the MLA had no impact on the number of lenders around military bases. Our findings have implications for how to regulate small‐dollar lending and protect consumers at increased risk of exposure to high‐cost lending, with specific attention to product alternatives and access to low‐cost financial services.
MRI of a middle ear cholesteatoma in a cat
Authors: Herberger Arielle , Hammond James , Miller Andrew , Olson Benjamin
Published: August 2022

A 9‐year‐old Maine coon cat presented with right‐sided Horner and facial nerve paralysis. Magnetic resonance imaging (MRI) showed a heterogeneously contrast‐enhancing mass occupying the right dorsolateral compartment of the tympanic cavity and extending into the ventromedial compartment, which was expanded and fluid filled. A ventral bulla osteotomy was performed to debulk the soft tissue mass. Histopathology revealed a cholesteatoma. The cat showed slow improvement of clinical signs and was euthanized eleven months postoperatively for unrelated causes. The MRI characteristics of middle ear cholesteatoma in the present case varied from those described in humans and dogs.
Auditory grouping is necessary to understand interrupted mosaic speech stimuli
Authors: Ueda Kazuo , Takeichi Hiroshige , Wakamiya Kohei
Published: August 2022

The intelligibility of interrupted speech stimuli has been known to be almost perfect when segment duration is shorter than 80 ms, which means that the interrupted segments are perceptually organized into a coherent stream under this condition. However, why listeners can successfully group the interrupted segments into a coherent stream has been largely unknown. Here, we show that the intelligibility for mosaic speech in which original speech was segmented in frequency and time and noise-vocoded with the average power in each unit was largely reduced by periodical interruption. At the same time, the intelligibility could be recovered by promoting auditory grouping of the interrupted segments by stretching the segments up to 40 ms and reducing the gaps, provided that the number of frequency bands was enough (≥4) and the original segment duration was equal to or less than 40 ms. The interruption was devastating for mosaic speech stimuli, very likely because the deprivation of periodicity and temporal fine structure with mosaicking prevented successful auditory grouping for the interrupted segments.
Many tasks, same outcome: Role of training task on learning and maintenance of noise-vocoded speech
Authors: Drouin Julia R. , Theodore Rachel M.
Published: August 2022

Listeners who use cochlear implants show variability in speech recognition. Research suggests that structured auditory training can improve speech recognition outcomes in cochlear implant users, and a central goal in the rehabilitation literature is to identify factors that maximize training. Here, we examined factors that may influence perceptual learning for noise-vocoded speech in normal hearing listeners as a foundational step towards clinical recommendations. Three groups of listeners were exposed to anomalous noise-vocoded sentences and completed one of three training tasks: transcription with feedback, transcription without feedback, or talker identification. Listeners completed a word transcription test at three time points: immediately before training, immediately after training, and one week following training. Accuracy at test was indexed by keyword accuracy at the sentence-initial and sentence-final position for high and low predictability noise-vocoded sentences. Following training, listeners showed improved transcription for both sentence-initial and sentence-final items, and for both low and high predictability sentences. The training groups showed robust and equivalent learning of noise-vocoded sentences immediately after training. Critically, gains were largely maintained equivalently among training groups one week later. These results converge with evidence pointing towards the utility of non-traditional training tasks to maximize perceptual learning of noise-vocoded speech.
A Novel Leucyl-tRNA Synthetase Inhibitor, MRX-6038, Expresses Anti-Mycobacterium abscessus Activity
In Vitro
and
In Vivo
Authors: Wu Wenye , He Siyuan , Li Anqi , Guo Qi , Tan Zhili , Liu Shicong , Wang Xinghai , Zhang Zhemin , Li Bing , Chu Haiqing
Published: August 2022

Therapeutic options for
Mycobacterium abscessus
infections are extremely limited, and new drugs are needed. The anti-
M. abscessus
activity of MRX-6038,
Cell Cycle-Dependent Recruitment of FtsN to the Divisome in Escherichia coli
Authors: Männik Jaana , Pichoff Sebastien , Lutkenhaus Joe , Männik Jaan
Published: August 2022

Cell division in most bacteria starts with the formation of an FtsZ protofilament network at midcell, the Z ring. However, cells only start to constrict after a considerable lag.
Deciphering the Tissue Tropism of the RNA Viromes Harbored by Field-Collected Anopheles sinensis and Culex quinquefasciatus
Authors: Kang Yan-Jun , Zhu Guoding , Cheng Yang , Yang Haitao , Cao Jun
Published: August 2022

ISVs are considered to be ancestral to arboviruses. Because of their medical importance, arboviruses have been well studied from the aspects of their transmission mode, evolution of dual-host tropism, and genetic dynamics within mosquito vectors.
Molecular Epidemiology of Plasmid-Mediated Types 1 and 3 Fimbriae Associated with Biofilm Formation in Multidrug Resistant Escherichia coli from Diseased Food Animals in Guangdong, China
Authors: Guo Wen-Ying , Zhang Hui , Cheng Ming , Huang Min-Rui , Li Qian , Jiang Yu-Wei , Zhang Ji-Xing , Sun Ruan-Yang , Wang Min-Ge , Liao Xiao-Ping , Liu Ya-Hong , Sun Jian , Fang Liang-Xing
Published: August 2022

Biofilms allow bacteria to tolerate disinfectants and antimicrobials, as well as mammalian host defenses, and are therefore difficult to treat clinically. Most research concerning biofilm-related infections is typically focused on chromosomal biofilm-associated factors, including types 1 and 3 fimbriae of biofilm-forming Enterobacterium.
Tobacco industry ownership of pharmaceutical companies: an international survey of people with respiratory disease
Authors: Tal-Singer Ruth , Walsh Linda , Deuby Tim , Shaughnessy Angela , Hoth Karin F , Gascon Victor , Hintringer Susanne , Hass Nicole , Winders Tonya , Morgan Lucy , Thomashow Byron , Mannino David M
Published: August 2022

The 2021 purchase of the respiratory pharmaceutical company Vectura by Phillip Morris International has been criticised by the public health and medical community, as a conflict of interest, with little input to date, from the patient community or the public. To address this gap, the COPD Foundation, along with global partners, surveyed 1196 people with chronic respiratory disease. 70% were bothered by a tobacco company making an inhaler to treat lung conditions and 48% reported that they would want to switch inhalers if they knew that a tobacco company made or sold their inhaler devices. Patients care about who makes the therapies used to treat their diseases.
Weather aerodynamic adaptation for autonomous vehicles: a tentative framework
Authors: Hangan H. , Agelin-Chaab M. , Gultepe I. , Elfstrom G. , Komar J.
Published: August 2022

While autonomous vehicles (AVs) are potentially the future of transportation, one of the main issues that need to be addressed is their behaviour and response to adverse weather conditions. Herein, we proposed a research frame to understand and mitigate the impact of weather stressors (wind, rain, snow, ice, and fog) on AVs. A recently launched initiative to design and engineer an indigenous Canadian road vehicle served as a background for this intended framework. The proposed frame consists of ( i) on-road testing and numerical computational fluid dynamics (CFD) simulations to derive statistically significant critical weather conditions (weather design cases, WDCs) and ( ii) simulation of these weather conditions in the ACE climatic wind tunnel at Ontario Tech University, Canada, to ( iii) identify adaptive controls to minimize the effects of the WDCs on vehicles improving their aerodynamics, safety, and sensor functionality. This framework is intended to ( i) provoke discussions among the AV industry and research stakeholders in Canada and elsewhere and ( ii) provide a context for future research in related areas such as AV aerodynamics, maneuverability, weather impacts (e.g., wind, rain, snow, ice, and fog), sensors, and soiling.
Does the Use of Gelled Platelet-Rich Plasma during Fixation of Subacute Proximal Pole Scaphoid Fractures Help? – A Single Centre Experience
Authors: DE VITIS Rocco , PASSIATORE Marco , PERNA Andrea , CILLI Vitale , PONZO Ida , TACCARDO Giuseppe
Published: August 2022

Background: Subacute proximal pole scaphoid fractures (1 month to 6 months) have a higher risk of non-union. The aim of the present retrospective analysis is to evaluate the efficacy of gelled platelet-rich plasma (GPRP) as additional treatment to antegrade headless screw fixation of proximal pole scaphoid fractures.

Methods: Forty-one patients were divided into two groups based on surgical treatment received: screw fixation alone (group A) and screw fixation and GPRP application at the fracture site (group B). A short cast was maintained for 4 weeks after surgery. Outcome measures included time to union, need for additional procedures, time to return to work, disabilities of the arm, shoulder, and hand (DASH) questionnaire, Michigan Hand Questionnaire (MHQ) and Mayo wrist score (MWS).Time to union was determined by monthly radiographs and confirmed by a computerized tomographic (CT) scan done at 4 months.

Results: Union was achieved in 85.7% of patients in group A and in 100% of patients in group B. Patients in group B showed a faster time to healing (2.3 ± 0.4 months vs 3.1 ± 0.7 months, p = 0.0001) and earlier return to work (10.4 ± 2.2 vs 15.1 ± 2.9, p = 0.0001). There were no significant differences in patient-rated outcomes scores between the two groups at final follow-up.

Conclusions: Internal fixation alone is effective in treating subacute proximal pole scaphoid fractures. GPRP application improves bone healing and functional recovery.

Level of Evidence: Level III (Therapeutic)
Treatment of Recurrent Carpal Tunnel Syndrome with the Abductor Digiti Minimi Flap: A Case Series
Authors: de ROO Saskia F , van LEEUWEN Wouter F. , COERT Jan H. , van der HEIJDEN Brigitte
Published: August 2022

Background: Approximately 5% of patients experience recurrent symptoms after carpal tunnel release (CTR) and need revision surgery. Several surgical techniques have been described for recurrent carpal tunnel syndrome (CTS) and the abductor digiti minimi (ADM) flap is one of them. Literature concerning clinical results of the ADM flap for recurrent CTS is lacking. The aim of this study is to evaluate the outcomes of the ADM flap for recurrent CTS.

Methods: We treated seven patients with the ADM flap (eight hands) between July 2016 and February 2019. Patient characteristics were assessed, and patients were asked about their symptoms (pain, sensation and paresthesia) before and after surgery. Postoperatively, we administered CTS symptoms, satisfaction with the surgery, patient-reported outcome measurements (BCTQ and QuickDASH) and whether they would undergo the same surgery again. Complications were also recorded

Results: The median follow-up was 14 months. The success rate measured by CTS symptoms was 88%. Seven out of eight patients were satisfied with the results and two patients would not elect to undergo the same procedure again. Two patients reported having a weaker grip at the donor site. The median BCTQ symptom and function scores were 2.9 (1.7–3.5) and 2.6 (1.8–3.0) respectively. The median QuickDASH score was 41 (IQR 22–52). Complications reported were wound dehiscence (n = 1) and hypertrophic scar (n = 1).

Conclusions: The outcomes of the ADM flap in patients with recurrent CTS were like other commonly used procedures in recurrent CTS.

Level of Evidence: Level IV (Therapeutic)
Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression
Authors: Koumangoye Rainelli , Penny Parker , Delpire Eric
Published: August 2022

Conditions that cause the loss of epithelial barrier integrity are often accompanied by dysregulation of tight junction protein expression and/or localization. Recently, we have reported that patients with mutations in SLC12A2, the gene encoding the basolateral Na+-K+-2Cl− cotransporter (NKCC1), suffer from severe gastrointestinal deficits, including chronic gastrointestinal inflammation, gastrointestinal hemorrhage, intestinal obstruction, and constipation. Although the intestinal inflammation observed in patients with loss of NKCC1 function may or may not be due to tight junction dysfunction, we investigated whether the loss of NKCC1 function affects paracellular ion transport and epithelial barrier function. Wild-type HT29-MTX-E12 and CRISPR/Cas9-mediated NKCC1 knockout (KO) HT29 clones were tested for tight junction protein expression and localization. Tightness of epithelial cell monolayer was assessed by measurement of transepithelial electrical resistance and permeability of molecular tracers in transwell filters. Tight junction protein localization was assessed by immunofluorescence. Loss of NKCC1 expression strongly increases the expression of claudin-2 and occludin in epithelial cell monolayers. Loss of NKCC1 significantly reduces the transepithelial electrical resistance (TER) indicating an increase in paracellular ions flux, consistent with upregulation of the cation-selective and channel-forming claudin-2. In addition, NKCC1-KO monolayers showed a significant increase in the paracellular flux of small molecules like fluorescein (0.33 kDa), whereas the permeability of higher molecular weight TRITC-Dextran (4 kDa and 70 kDa) remained unchanged. Thus, NKCC1 regulates tight junction protein expression and loss of NKCC1 function affects epithelial barrier integrity.
Seven days of ischemic preconditioning augments hypoxic exercise ventilation and muscle oxygenation in recreationally trained males
Authors: Seeley Afton D. , Caldwell Aaron R. , Cahalin Lawrence P. , Ahn Soyeon , Perry Arlette C. , Arwari Brian , Jacobs Kevin A.
Published: August 2022

This investigation sought to assess whether single or repeated bouts of ischemic preconditioning (IPC) could improve oxyhemoglobin saturation ([Formula: see text]) and/or attenuate reductions in muscle tissue saturation index (TSI) during submaximal hypoxic exercise. Fifteen healthy young men completed submaximal graded exercise under four experimental conditions: 1) normoxia (NORM), 2) hypoxia (HYP) [oxygen fraction of inspired air ([Formula: see text]) = 0.14, ∼3,200 m], 3) hypoxia preceded by a single session of IPC (IPC1-HYP), and 4) hypoxia preceded by seven sessions of IPC, one a day for 7 consecutive days (IPC7-HYP). IPC7-HYP heightened minute ventilation (V̇e) at 80% HYP peak cycling power output ( Wpeak) (+10.47 ± 3.35 L·min−1, P = 0.006), compared with HYP, as a function of increased breathing frequency. Both IPC1-HYP (+0.17 ± 0.04 L·min−1, P < 0.001) and IPC7-HYP (+0.16 ± 0.04 L·min−1, P < 0.001) elicited greater oxygen consumption (V̇o2) across exercise intensities compared with NORM, whereas V̇o2 was unchanged with HYP alone. [Formula: see text] was unchanged by either IPC condition at any exercise intensity, yet the reduction of muscle TSI during resting hypoxic exposure was attenuated by IPC7-HYP (+9.9 ± 3.6%, P = 0.040) compared with HYP, likely as a function of reduced local oxygen extraction. Considering all exercise intensities, IPC7-HYP attenuated reductions of TSI with HYP (+6.4 ± 1.8%, P = 0.001). Seven days of IPC heightens ventilation, posing a threat to ventilatory efficiency, during high-intensity submaximal hypoxic exercise and attenuates reductions in hypoxic resting and exercise muscle oxygenation in healthy young men. A single session of IPC may be capable of modulating hypoxic ventilation; however, our present population was unable to demonstrate this with certainty.