bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of height on ED95 of intrathecal 2-chloroprocaine for knee arthroscopy
Authors: Guntz Emmanuel , Jeanne Gaelle , Gouwy Jonathan , M’rini Mehdi , Saxena Sarah , Fils Jean-François , Kapessidou Yota
Published: June 2022

BACKGROUND

Plain 2-chloroprocaine , a rapid acting amino-ester-type local anaesthetic, is used in short ambulatory procedures under spinal anaesthesia. The ED95 of 2-chloroprocaine for lower limb surgery has not yet been defined. Moreover, patients’ body height could influence the effects of the administered dose.

OBJECTIVES

The aim of this study was to determine the ED95 of plain 2-chloroprocaine based on the height of patients undergoing ambulatory knee arthroscopy under spinal anaesthesia using the continual reassessment statistical method (CRM).

DESIGN

Prospective, dose-response, double blind, controlled, bi-center, clinical trial.

SETTING

One university teaching hospital in Brussels and one general teaching hospital, Braine l’Alleud, Belgium. Université libre de Bruxelles,

PATIENTS

ASA I-III (120 patients) scheduled for day-case knee arthroscopy under spinal anaesthesia

INTERVENTIONS

Patients were divided into three groups of 40, each comprising 10 cohorts of 4 patients, according to their respective heights (Group 1: 150–165 cm, Group 2: 166–180 cm, Group 3: 181–195 cm). Each patient enrolled into one of the 3 groups received an intrathecal dose of plain 2-chloroprocaine determined by the CRM. The starting doses for the first cohorts of four were 40 mg in group 1, 45 mg in group 2 and 50 mg in group 3. The doses for subsequent cohorts were determined by CRM of outcomes in all patients in the previous competed cohorts. Anaesthesia was considered successful when there was a lack of pinprick or cold sensation up to T12, the visual analogue scale score for tourniquet pain was < 2 and no pain during surgery.

MAIN OUTCOMES

The primary outcome was the success or failure of the block. Side effects were also recorded.

RESULTS

ED95 of 2-chloroprocaine is 40 mg in group 1, 35 mg in group 2, 45 mg in group 3. Groups were different in terms of height and gender (P < 0.05) and similar in terms of body mass index and age (P > 0.05).

CONCLUSION

The ED95 of intrathecal 2-chloroprocaine for patients undergoing ambulatory knee arthroscopy is between 35 and 45 mg. Height could be a factor involved in the calculation, and patient sex could partly explain the nonlinear relation between height and dose.

TRIAL REGISTRY NUMBER

Clinicaltrials.gov NCT03882489.
Systematic detection of keratoconus in OCT: corneal and epithelial thickness maps
Authors: Yücekul Burcu , Dick H. Burkhard , Taneri Suphi
Published: June 2022

Purpose:

To detect keratoconus (KC) only by analyzing the corneal and epithelial map parameters and patterns in optical coherence tomography (OCT).

Setting:

Tertiary care refractive surgery center.

Design:

Retrospective data collection.

Methods:

Corneal and epithelial thickness maps of normal, manifest, and subclinical keratoconic eyes (according to the Belin-Ambrosio display, Pentacam) were evaluated using spectral-domain OCT (Zeiss Cirrus 5000 HD). A new 2-step decision tree was developed based on previous studies with another OCT device. In the first step, if at least 1 of the 4 independent parameters (pachymetry minimum, pachymetry minimum-median, pachymetry superonasal-inferotemporal, and epithelial superonasal-inferotemporal) overruns the cutoff values, the eye was suspicious for KC. In the second step, if the epithelial map showed concentric thinning and the thinnest point of the cornea and epithelium is coincident, the eye was classified as keratoconic.

Results:

172 manifest keratoconic eyes (108 patients), 21 subclinical keratoconic eyes (20 patients), and 172 normal eyes (90 age-matched participants) were included in this study. Step 1 captured 100% of manifest and subclinical keratoconic eyes. Step 2 ruled out all suspicious but normal cases and, falsely, 2 subclinical keratoconic eyes. Our 2-step decision tree reached 100% specificity, 100% sensitivity in manifest KC, and 90.4% sensitivity in subclinical KC.

Conclusions:

Pachymetric and epithelial map parameters and patterns in OCT can be used in the diagnosis of KC, including subclinical cases, yielding a high level of agreement with the commonly used diagnostic reference, the Belin-Ambrosio display. Further improvements by refining our algorithm and including an automated evaluation in the software are desirable.
An Injustice to the Justice-Involved
Authors: Nguyen Monica , Mead Julia , St. Ivany Amanda
Published: June 2022

Traumatic brain injury (TBI) is one of the leading causes of death and long-term disability among young adults worldwide and in the United States. TBIs are often associated with a high prevalence of morbidity, mortality, and other behavioral and cognitive problems. Several studies have shown that women living with TBIs have significantly higher odds of committing criminal acts, yet the impact of TBI on incarcerated women remains an underresearched area. By contrast, the effect of TBI on men is more prevalent in current literature, particularly relating to sports-related injuries. Given that an estimate of 80% of incarcerated women are mothers, we conducted a literature review in two phases focused on TBI in incarcerated mothers. The initial search of TBI in incarcerated mothers returned no results, so we proceeded in two phases. Phase 1 searched maternal outcomes of TBI, using the terms “maternal health” and “traumatic brain injury,” whereas Phase 2 searched “traumatic brain injury” and “incarcerated women.” Because so little information is available regarding TBI in incarcerated mothers, we used what we could find in these two phases to highlight the scarcity of knowledge about this population. This brief report addresses the knowledge gap that exists for incarcerated mothers living with TBI to encourage regular TBI screening to raise awareness and advocate for accommodated care. Correctional forensic nurses are perfectly placed to do TBI screening and to provide continuous rehabilitation after release to prevent reoffending.
Proprotein convertase subtilisin/kexin type 9 inhibition after acute coronary syndrome or prior myocardial infarction
Authors: Schwartz Gregory G. , Giugliano Robert P.
Published: June 2022

Purpose of review

Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe reduces major adverse cardiovascular events (MACE) in patients with coronary heart disease. Additional treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may lower LDL-C to levels not achievable with conventional lipid-lowering agents. This review summarizes findings from two large, placebo-controlled trials that evaluated the cardiovascular efficacy of monoclonal antibodies directed against PCSK9, added to background statin therapy, in patients with established atherosclerotic cardiovascular disease (ASCVD) or recent acute coronary syndrome (ACS) and persistent elevation of atherogenic lipoproteins despite statin treatment.

Recent findings

The FOURIER trial with evolocumab and the ODYSSEY OUTCOMES trial with alirocumab demonstrated 15% overall reductions in MACE compared to placebo, associated with average achieved LDL-C levels as low as 30–40 mg/dl. Alirocumab treatment was associated with fewer deaths after ACS. Subgroups with large absolute treatment benefit included those with baseline LDL-C ≥100 mg/dl, diabetes, polyvascular or peripheral artery disease, prior coronary bypass surgery, statin intolerance, or elevated lipoprotein(a) levels. No safety concerns arose with use of PCSK9 monoclonal antibodies, even in patients who achieved LDL-C levels below 20 mg/dl.

In selected patients with established ASCVD or recent ACS, PCSK9 inhibitors can play an important role in reducing the risk of MACE, and may also reduce the risk of death after ACS.
Practicing What We Preach: An Effort to Improve Safe Sleep of Hospitalized Infants
Authors: Salada Katherine O. , Arzu Jennifer , Unti Sharon M. , Tanz Robert R. , Badke Colleen M.
Published: June 2022

Introduction:

To prevent sudden unexpected infant death, pediatric providers recommend the ABCs of infant sleep: Alone, on the Back, and in an empty Crib. This study’s objective was to document sleep practices of infants admitted to a large children’s hospital, examine adherence to American Academy of Pediatrics safe sleep guidelines, and develop interventions to improve guideline adherence.

Methods:

We conducted a pre/post quality improvement study at a single quaternary care medical center from 2015 to 2019. Infants 0 to younger than 12 months were observed in their sleeping environment pre- and post-implementation of multiple hospital-wide interventions to improve the sleep safety of hospitalized infants.

Results:

Only 1.3% of 221 infants observed preintervention met all ABCs of safe sleep; 10.6% of 237 infants met the ABCs of safe sleep postintervention. Significant improvements in the post-intervention cohort included sleeping in a crib (94% versus 80% preintervention; P < 0.001), avoidance of co-sleeping (3% versus 15% preintervention; P < 0.001), absence of supplies in the crib (58% versus 15% preintervention; P < 0.001), and presence of an empty crib (13% versus 2% preintervention; P < 0.001).

Conclusions:

Most infants hospitalized at our institution do not sleep in a safe environment. However, the implementation of a care bundle led to improvements in the sleep environment in the hospital. Further research is necessary to continue improving in-hospital safe sleep and to assess whether these practices impact the home sleep environment.
Improving Follow-Up Skeletal Survey Completion in Children with Suspected Nonaccidental Trauma
Authors: Ashraf Iram J. , Faivus Ackley Danielle , Razawich Kristin , Botash Ann , Schafer Melissa , Pekarsky Alicia
Published: June 2022

Introduction:

The skeletal survey (SS) is used to evaluate and diagnose bone abnormalities, including fractures caused by child abuse. The American Academy of Pediatrics recommends initial SS for all children younger than 24 months old who are suspected victims of abuse and a follow-up skeletal survey (FUSS) 2 weeks later. The latter can further characterize abnormal or equivocal findings, detect ongoing trauma, or fractures too acute for visualization upon initial assessment.

Methods:

Preintervention review at our hospital for FUSS completion of children younger than 36 months old yielded a low 40% average monthly completion rate. We reviewed charts of children who underwent SS during the study period for FUSS completion. There were several barriers to FUSS completion, including lack of provider knowledge regarding FUSS importance, lack of an order for FUSS before hospital discharge, absent chart documentation regarding FUSS decision, loss to follow-up, and parental refusal. Interventions targeting the barriers included provider education, protocolizing FUSS scheduling, standardizing documentation, and community pediatrician outreach. The goal was to increase the average monthly FUSS completion rate from 40% to 90% over 1 year.

Results:

After interventions implementation, the average monthly FUSS completion rate rapidly increased from 40% to 80%. There was sustained improvement over the subsequent 12 months.

Conclusions:

Interventions were implemented sequentially, targeting barriers at various levels of workflow. Provider education was key and helped increase the reliability of intervention implementation. The most effective intervention was protocol change. This approach led to significant improvement in FUSS completion and sustained improvement.
Predictive Value of Different Computed Tomography Perfusion Software Regarding 90-Day Outcome of Acute Ischemic Stroke Patients After Endovascular Treatment: A Comparison With Magnetic Resonance Imaging
Authors: Li Ling , Jiang Yun , Wang Junjie , Chen Yuhui , Cao Ruoyao , Lu Yao , Wang Guoxuan , Chen Juan
Published: June 2022

Objective

This study compared ischemic core and penumbra volumes obtained using different computed tomography perfusion (CTP) software and evaluated the predictive value of CTP and magnetic resonance imaging (MRI) results for 90-day outcomes.

Methods

In total, 105 acute ischemic stroke patients who underwent endovascular treatment from January 2016 to December 2020 were included. Patients were divided into good and poor outcome groups by a modified Rankin Scale score. Computed tomography perfusion core and penumbra volumes were obtained using OleaSphere and Vitrea software to assess the volumetric relationship with MRI using the Spearman correlation test, intraclass correlation coefficient (ICC), and Bland-Altman plot. Three multivariable models were developed: baseline variables with MRI infarct volume, baseline variables with OleaSphere core volume, and baseline variables with Vitrea core volume. The area under the receiver operating characteristic curve of the 3 models was compared using the DeLong test.

Results

Median core volumes were 27.5, 26.9, and 31.1 mL for OleaSphere, Vitrea, and MRI, respectively. There was substantial correlation and excellent agreement between OleaSphere and MRI core volume (ρ = 0.84, P < 0.001; ICC = 0.84) and Vitrea and MRI core volume (ρ = 0.80, P < 0.001; ICC = 0.83). The areas under curve for MRI volume, OleaSphere, and Vitrea were 0.86, 0.84, and 0.83, respectively. There were no significant differences (P = 0.18) between the predictive value of the 3 models.

Conclusions

Computed tomography perfusion core volumes showed substantial correlation and excellent agreement with MRI. There was no significant difference in the predictive value of the 3 models, suggesting that core volumes measured using CTP software can predict patient prognosis.
A Case of Infective Endocarditis Associated With Patent Ductus Arteriosus in Which PET/CT Was Useful for Diagnosis
Authors: Miyagami Taiju , Kushiro Seiko , Arikawa Mari , Murakami Koji , Naito Toshio
Published: June 2022

A 33-year-old woman presented to our hospital with a 4-month history of fever of unknown origin. Physical examination revealed a vascular murmur in the left subclavian region. Blood culture revealed bacteria and PET/CT revealed tracer accumulation in the patent ductus arteriosus area, leading to the diagnosis of infective endocarditis in this area. This case report may aid in diagnosing this disease in the future, as infective endocarditis in a patent ductus arteriosus is rare and difficult to diagnose.
Delayed [18F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis
Authors: Otman Hosameldin , Farce Julien , Meneret Pierre , Palard-Novello Xavier , Le Reste Pierre-Jean , Lecouillard Isabelle , Vauleon Elodie , Chanchou Marion , Carsin Nicol Beatrice , Bertaux Marc , Devillers Anne , Mariano-Goulart Denis , Cachin Florent , Girard Antoine , Le Jeune Florence
Published: June 2022

Purpose

Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [18F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [18F]-FDG PET with delayed images (4–5 hours postinjection) with the ones provided by standard and dual-time-point imaging.

Methods

Consecutive patients referred for brain [18F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared.

Results

Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75–0.95) than both standard (0.69; 95% CI, 0.54–0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63–0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images (κ = 0.83), whereas it was moderate with both standard (κ = 0.48) and dual-time-point images (κ = 0.61).

Conclusions

[18F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.
Potential Utility of SPECT/CT for Early Detection of Spontaneous Osteonecrosis of the Knee
Authors: Yoo Min Young , Shin Young-Soo , Song Ok Kyu , Kim Bom Sahn , Kang Seo Young , Moon Byung Seok , Yoon Hai-Jeon
Published: June 2022

Spontaneous osteonecrosis of the knee (SONK) is the most common phenotype of osteonecrosis of knee joints in older adults. Early diagnosis with appropriate management is crucial for improving the prognosis of the SONK. We present SONK in bone scintigraphy and SPECT/CT in 65-year-old man with sudden worsening knee pain and normal radiographs. SPECT/CT revealed intense uptake in subchondral area of left femoral medial condyle, which can be differed from progressed osteoarthritic change of the knee joints suspected on planar scintigraphy. Subsequently performed MRI showed characteristic finding of SONK. Total knee replacement arthroplasty was performed with final histological diagnosis of SONK.
Differentiation of Reversible Hemichorea Due to Vitamin B12 Deficiency From Huntington Disease Via FDG PET
Authors: Schroeter Tabea , Gühne Falk , Schwab Matthias , Drescher Robert , Axer Hubertus
Published: June 2022

Vitamin B12 deficiency may present with diverse symptoms, complicating the differential diagnosis. Extrapyramidal movement disorders, for instance, are a rare manifestation of vitamin B12 deficiency. MRI of the brain frequently remains without conclusive findings. However, 18F-FDG PET/CT may reveal characteristic changes in the metabolism of the basal ganglia and thus contribute to an accurate diagnosis. We demonstrate the case of a woman with left-sided hemichoreatic movements due to vitamin B12 deficiency showing a contralateral putaminal hypermetabolism, which normalized after vitamin B12 supplementation, ruling out other deviating causes, particularly Huntington disease.
Suicidality and psychotic episodes after starting aripiprazole: two case reports
Authors: Meyer Guillaume , Gitahy Falcao Faria Clara , Beck Marine , Riutort Marielle , Michel Bruno , Javelot Hervé
Published: June 2022

Switching antipsychotic medication must be done carefully to ensure patient safety and a successful response. Here, we present two major psychotic decompensations that occurred following a switch to aripiprazole in two patients with schizophrenia. Mr. X was treated with paliperidone and experienced residual anxiety. Thus, a switch to aripiprazole was planned with risperidone and a gradual decrease in paliperidone. Initially, an increase in aripiprazole resulted in remission of his residual symptoms. However, two weeks later, he presented an anxiety relapse with persecutory ideas which required hospitalization. Mr. Y, who was treated for many years with risperidone, presented with a treatment resistant psychotic episode. A switch to aripiprazole enhanced his clinical condition. Despite the initial improvement, soon after discharge from the hospital, the patient presented psychotic symptoms requiring home intervention. Ultimately, the patient in the midst of a delusional recrudescence, had killed himself when the health care team arrived. A strong dopamine antagonist may lead to the development of dopaminergic upregulation. The addition of a partial agonist to these hypersensitive neurotransmitter pathways could explain these episodes. We agree with previous reports and recommend careful management when switching from strong dopamine antagonists to aripiprazole.
Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series
Authors: Tham Joseph C.W. , Do André , Fridfinnson Jason , Rafizadeh Reza , Siu Jacky T.P. , Budd George P. , Lam Raymond W.
Published: June 2022

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures. Results from the first 10 consecutive patients demonstrated the effectiveness of SC racemic ketamine in relieving symptoms of TRD as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16). Response (≥50% reduction in scores from baseline to endpoint) was achieved in 8/10 cases on the MADRS and 6/10 on the QIDS-SR16. Remission was achieved in 8/10 (based on MADRS ≤10) and 5/10 (based on QIDS-SR16 ≤6). Patients tolerated the treatments well with only transient blood pressure changes and dissociative side effects. Repeated SC ketamine treatments could be a safe, feasible, and effective alternative to IV ketamine infusions for patients with TRD.
Persian translation and validation of community attitudes toward the mentally ill scale: a tool for assessing social stigma about mental illness
Authors: Kafami Zahra , Farhoudi Fatemeh , Alimoradi Mohammad , Sangsefidi Zahra , Delshad Navid , Khadem-Rezaiyan Majid
Published: June 2022

No study, best of our knowledge, has been conducted on assessing the validity and reliability of community attitudes toward the mentally ill (CAMI) inventory in Iran. The questionnaire was translated into Persian and then returned to English. Content validity ratio (CVR), content validity index (CVI), impact score (IS) to assess content validity, Cronbach’s alpha, and test–retest reliability was used to prove the internal and external reliabilities, respectively. The questionnaires were distributed to 130 people from different levels of society. Some were in contact with at least one patient with mental illness and some others had no connection. After 2 weeks, the questionnaires were resent to 50 participants to evaluate the reliability using the test–retest method. All questions had CVI (>0.79) and CVR (>0.49) except for three questions (Q 10, 24, and 30), which were excluded from the questionnaire. The questions were relevant, clear, simple, and valid. The IS was more than 1.5. The Cronbach’s alpha values of four subscales including authoritarianism, benevolence, social restrictiveness, and community mental health ideology were recorded as 0.61, 0.49, 0.64, and 0.76, respectively. The CAMI scale is a valid and sustainable tool over time to assess the negative attitude toward mental illness.
Iterative evolution of supergene-based social polymorphism in ants
Authors: Kay Tomas , Helleu Quentin , Keller Laurent
Published: June 2022

Species commonly exhibit alternative morphs, with individual fate being determined during development by either genetic factors, environmental cues or a combination thereof. Ants offer an interesting case study because many species are polymorphic in their social structure. Some colonies contain one queen while others contain many queens. This variation in queen number is generally associated with a suite of phenotypic and life-history traits, including mode of colony founding, queen lifespan, queen–worker dimorphism and colony size. The basis of this social polymorphism has been studied in five ant lineages, and remarkably social morph seems to be determined by a supergene in all cases. These ‘social supergenes’ tend to be large, having formed through serial inversions, and to comprise hundreds of linked genes. They have persisted over long evolutionary timescales, in multiple lineages following speciation events, and have spread between closely related species via introgression. Their evolutionary dynamics are unusually complex, combining recessive lethality, spatially variable selection, selfish genetic elements and non-random mating. Here, we synthesize the five cases of supergene-based social polymorphism in ants, highlighting interesting commonalities, idiosyncrasies and implications for the evolution of polymorphisms in general.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
The relevance of chromatin architecture to genome rearrangements in
Drosophila
Authors: Wright Dynisty , Schaeffer Stephen W.
Published: June 2022

DNA within chromosomes in the nucleus is non-randomly organized into chromosome territories, compartments and topologically associated domains (TADs). Chromosomal rearrangements have the potential to alter chromatin organization and modify gene expression leading to selection against these structural variants.
Drosophila pseudoobscura
has a wealth of naturally occurring gene arrangements that were generated by overlapping inversion mutations caused by two chromosomal breaks that rejoin the central region in reverse order. Unlike humans,
Drosophila
inversion heterozygotes do not have negative effects associated with crossing over during meiosis because males use achiasmate mechanisms for proper segregation, and aberrant recombinant meiotic products generated in females are lost in polar bodies. As a result,
Drosophila
populations are found to harbour extensive inversion polymorphisms. It is not clear, however, whether chromatin architecture constrains which inversions breakpoints persist in populations. We mapped the breakpoints of seven inversions in
D. pseudoobscura
to the TAD map to determine if persisting inversion breakpoints are more likely to occur at boundaries between TADs. Our results show that breakpoints occur at TAD boundaries more than expected by chance. Some breakpoints may alter gene expression within TADs supporting the hypothesis that position effects contribute to inversion establishment.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Stepwise evolution of a butterfly supergene via duplication and inversion
Authors: Kim Kang-Wook , De-Kayne Rishi , Gordon Ian J. , Omufwoko Kennedy Saitoti , Martins Dino J. , ffrench-Constant Richard , Martin Simon H.
Published: June 2022

Supergenes maintain adaptive clusters of alleles in the face of genetic mixing. Although usually attributed to inversions, supergenes can be complex, and reconstructing the precise processes that led to recombination suppression and their timing is challenging. We investigated the origin of the BC supergene, which controls variation in warning coloration in the African monarch butterfly,
Danaus chrysippus
. By generating chromosome-scale assemblies for all three alleles, we identified multiple structural differences. Most strikingly, we find that a region of more than 1 million bp underwent several segmental duplications at least 7.5 Ma. The resulting duplicated fragments appear to have triggered four inversions in surrounding parts of the chromosome, resulting in stepwise growth of the region of suppressed recombination. Phylogenies for the inversions are incongruent with the species tree and suggest that structural polymorphisms have persisted for at least 4.1 Myr. In addition to the role of duplications in triggering inversions, our results suggest a previously undescribed mechanism of recombination suppression through independent losses of divergent duplicated tracts. Overall, our findings add support for a stepwise model of supergene evolution involving a variety of structural changes.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
International Committee on Systematics of Prokaryotes, Subcommittee on the taxonomy of Rhizobia and Agrobacteria, minutes of the annual meeting by videoconference, 5 July 2021, followed by online discussion until 31 December 2021
Authors: Mousavi Seyed Abdollah , Young J. Peter W.
Published: June 2022

Minutes of the closed meeting of the International Committee on Systematics of Prokaryotes Subcommittee on the Taxonomy of Rhizobia and Agrobacteria held by videoconference, 5 July 2021, followed by online discussion until 31 December 2021, and list of recent species.
Genomic Benchmarks: A Collection of Datasets for Genomic Sequence Classification
Authors: Gresova Katarina , Martinek Vlastimil , Cechak David , Simecek Petr , Alexiou Panagiotis
Published: June 2022

In this paper, we propose a collection of curated and easily accessible sequence classification datasets in the field of genomics. The proposed collection is based on a combination of novel datasets constructed from the mining of publicly available databases and existing datasets obtained from published articles. The main aim of this effort is to create a repository for shared datasets that will make machine learning for genomics more comparable and reproducible while reducing the over-head of researchers that want to enter the field. The collection currently contains eight datasets that focus on regulatory elements (promoters, enhancers, open chromatin region) from three model organisms: human, mouse, and roundworm. A simple convolution neural network is also included in a repository and can be used as a baseline model. Benchmarks and the baseline model are distributed as the Python package ‘genomic-benchmarks’, and the code is available at https://github.com/ML-Bioinfo-CEITEC/genomic_benchmarks.
Performance of digital Early Warning Score (NEWS2) in a cardiac specialist setting: retrospective cohort study
Authors: Alhmoud Baneen , Bonnici Timothy , Melley Daniel , Patel Riyaz , Banerjee Amitava
Published: June 2022

Introduction

Patients with Cardiovascular diseases (CVD) are at significant risk of developing critical events. Early warning scores are recommended for early recognition and rapid response to deteriorating patients, yet their performance has been poorly studied in cardiac care settings. Standardisation and integrated National early warning score (NEWS2) in EHRs are recommended but their evaluation in specialist settings is limited.

Objective

To investigate the performance of digital NEWS2 in predicting critical events: death, ICU admission, Cardiac arrest, and medical emergencies.

Methods

Retrospective cohort analysis

Study cohort

Individuals admitted with cardiovascular disease diagnoses in 2020 and patients with positive COVID-19.

Measures

We tested the ability of NEWS2 in predicting death, ICU admission, cardiac arrest, and medical emergency from admission and within 24 hours before the event. NEWS2 was supplemented with age and cardiac rhythm and investigated. We used logistic regression analysis with the area under the receiver operating curve (AUC) to measure discrimination.

Results

In 6143 patients admitted under cardiac speciality, NEWS2 showed moderate to low predictive accuracy (AUC: 0.63, 0.56, 0.7& 0.63; 95% CI). Supplemented NEWS2 with age showed no improvement while age and cardiac rhythm improved discrimination (AUC: 0.75, 0.84, 0.95 & 0.94; 95%CI). Improved Performance was found of NEWS2 for COVID-19 cases with age (AUC: 0.96, 0.7, 0.87& 0.88; 95% CI).

Conclusion

The performance of NEWS2 in patients with CVD is suboptimal, and fair for patients with COVID-19 to predict deterioration early. Adjustment with variables that strongly correlate with critical cardiovascular outcomes, i.e. cardiac rhythm, can improve the early scoring models. There is a need to define critical endpoints, engagement with clinical experts in development of models and further validation and implementation studies of EHR-integrated EWS in cardiac specialist settings.
Addition of losartan to FOLFORINOX and chemoradiation downregulates pro-invasion and immunosuppression-associated genes in locally advanced pancreatic cancer
Authors: Boucher Yves , Posada Jessica M. , Subudhi Sonu , Rosario Spencer R. , Gu Liqun , Kumar Ashwin S. , Kumra Heena , Mino-Kenudson Mari , Talele Nilesh P. , Duda Dan G. , Fukumura Dai , Wo Jennifer Y. , Clark Jeffrey W. , Ryan David P. , Castillo Carlos Fernandez-Del , Hong Theodore S. , Pittet Mikael J. , Jain Rakesh K.
Published: June 2022

Purpose

Adding losartan to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) resulted in 61% R0 surgical resection in our phase II trial in patients with locally advanced pancreatic cancer (LAPC). Here we identify potential mechanisms of benefit by assessing the effects of neoadjuvant losartan+FFX+CRT versus FFX+CRT on the stromal tumor microenvironment.

Experimental Design

We performed a gene expression analysis of RNA extracted from pancreatic cancer tissue sections and immunofluorescence for cancer cells and immune cells using archived surgical samples from patients treated with losartan+FFX+CRT (NCT01591733), FFX+CRT (NCT01591733) or surgery upfront, without any neoadjuvant therapy. We then assessed whether certain gene sets could stratify the overall survival (OS) of patients.

Results

Neoadjuvant losartan+FFX+CRT and FFX+CRT increased the expression of genes linked to vascular normalization, transendothelial migration of leukocytes, T cell activation and cytolytic activity, and dendritic cell (DC) related genes versus no neoadjuvant treatment. In comparison to FFX+CRT, losartan+FFX+CRT downregulated pro-invasion, immunosuppression, and M2 macrophages related genes, and upregulated genes associated with tumor suppression, including the p53 pathway. Furthermore, immunostaining revealed significantly less residual disease in lesions treated with losartan+FFX+CRT versus FFX+CRT. Losartan+FFX+CRT also reduced CD4+FOXP3+regulatory T cells in PDAC lesions with a complete/near complete response. OS was associated with DC and antigen presentation genes for patients treated with FFX+CRT, and with immunosuppression and invasion genes or DC- and blood vessel-related genes for those treated with losartan+FFX+CRT.

Conclusions

Adding losartan to FFX+CRT reduced pro-invasion and immunosuppression related genes, which were associated with improved treatment outcomes in patients with LAPC.
High overexploitation risk due to management shortfall in highly traded requiem sharks
Authors: Sherman C. Samantha , Digel Eric D. , Zubick Patrick , Eged Jonathan , Haque Alifa B. , Matsushiba Jay H. , Simpfendorfer Colin A. , Sant Glenn , Dulvy Nicholas K.
Published: June 2022

Most of the international trade in fins (and likely meat too) is derived from requiem sharks (family Carcharhinidae), yet trade in only two of the 56 species is currently regulated. Here, we quantify catch, trade, and the shortfall in national and regional fisheries management (M-Risk) for all 56 requiem shark species based on 831 assessments across 30 countries and four Regional Fisheries Management Organisations (RFMOs). Requiem sharks comprise over half (60%) of the annual reported global chondrichthyan catch with most species (86%) identified in the international fin trade. Requiem sharks are inadequately managed by fisheries, with an average M-Risk of half (50%) of an ideal score, consequently 70% of species are threatened globally. The high catch and trade volume and shortfall in management of these iconic species requires a global integrated improvement in fisheries management, supported by regulating international trade to sustainable levels.
β-catenin obstructs γδ T cell immunosurveillance in colon cancer through loss of BTNL expression
Authors: Suzuki Toshiyasu , Kilbey Anna , Ridgway Rachel A. , Hayman Hannah , Bryne Ryan , Rodríguez Nuria Casa , Georgakopoulou Anastasia , Chen Lei , Verzi Michael , Gay David , Vázquez Ester G. , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte , Wiesheu Robert , Jandke Anett , Roberts Natalie , Blyth Karen , Roseweir Antonia , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: June 2022

WNT/β-catenin signaling endows cancer cells with proliferative capacity and immune-evasive functions that impair anti-cancer immunosurveillance by conventional, cytoxtoic T cells. However, the impact of dysregulated WNT signalling on unconventional, tissue-resident T cells, specifically in colon cancer is unknown. Here, we show that cancer cells in Apc-mutant mouse models escape immunosurveillance from gut-resident intraepithelial lymphocytes (IELs) expressing γδ T cell receptors (γδTCRs). Analysis of late-stage tumors from mice and humans revealed that γδIELs are largely absent from the tumor microenvironment, and that butyrophilin-like (BTNL) molecules, which can critically regulate γδIEL through direct γδTCR-interactions, are also downregulated. We could attribute this to β-catenin stabilization, which rapidly decreased expression of the transcription factors, HNF4A and HNF4G, that we found to bind promoter regions of Btnl genes, thereby driving their expression in normal gut epithelial cells. Indeed, inhibition of β-catenin signaling restored Btnl1 gene expression and γδ T cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts γδIEL immunosurveillance and furthers cancer progression.
Bento: A toolkit for subcellular analysis of spatial transcriptomics data
Authors: Mah Clarence K. , Ahmed Noorsher , Lopez Nicole , Lam Dylan , Monell Alexander , Kern Colin , Han Yuanyuan , Prasad Gino , Cesnik Anthony J. , Lundberg Emma , Zhu Quan , Carter Hannah , Yeo Gene W.
Published: June 2022

The spatial organization of molecules in a cell is essential for performing their functions. Spatial transcriptomics technologies have opened the door to characterization of cellular and subcellular organization. While current computational methods focus on discerning tissue architecture, cell-cell interactions and spatial expression patterns, these approaches are limited to investigating spatial variation at the multicellular scale. We present Bento, a Python toolkit that fully takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three fundamental analyses: defining subcellular domains, annotating localization patterns, and quantifying gene-gene colocalization. To demonstrate the toolkit, we apply these methods to a variety of datasets including U2-OS cells (MERFISH), 3T3 cells (seqFISH+), and treated cardiomyocytes (Molecular Cartography). We quantify RNA localization changes in cardiomyocytes identifying mRNA depletion of critical cardiac disease-associated genes RBM20 and CACNB2 from the endoplasmic reticulum upon doxorubicin treatment. The Bento package is a member of the open-source Scverse ecosystem, enabling integration with other single-cell omics analysis tools.
Sodium ion regulates liquidity of biomolecular condensates in hyperosmotic stress response
Authors: Morishita Kazuhiro , Watanabe Kengo , Naguro Isao , Ichijo Hidenori
Published: June 2022

Biomolecular condensates are membraneless structures formed through phase separation. Recent studies have demonstrated that the material properties of biomolecular condensates are crucial for their biological functions and pathogenicity. However, the phase maintenance of biomolecular condensates in cells remains elusive. Here, we show that sodium ion (Na+) influx regulates the condensate liquidity under hyperosmotic stress. The fluidity of ASK3 condensates increases at the high intracellular Na+ concentration derived from extracellular hyperosmotic solution. Moreover, we identified TRPM4 as a cation channel that allows Na+ influx under hyperosmotic stress. TRPM4 inhibition causes the liquid-to-solid phase transition of ASK3 condensates, leading to impairment of the ASK3 osmoresponse. In addition to ASK3 condensates, intracellular Na+ widely regulates the condensate liquidity and aggregate formation of biomolecules, including DCP1A, TAZ and polyQ-protein, under hyperosmotic stress. Our findings demonstrate that changes in Na+ contribute to the cellular stress response via liquidity maintenance of biomolecular condensates.
SonoMyoNet: A Convolutional Neural Network for Predicting Isometric Force From Highly Sparse Ultrasound Images
Authors: Kamatham Anne Tryphosa , Alzamani Meena , Dockum Allison , Sikdar Siddhartha , Mukherjee Biswarup
Published: June 2022

Ultrasound imaging or sonomyography has been found to be a robust modality for sensing muscle activity due to its ability to directly image deep-seated muscles while providing superior spatiotemporal specificity compared to surface electromyography-based techniques. Quantifying the morphological changes during muscle activity involves computationally expensive approaches to track muscle anatomical structures or extracting features from B-mode images and A-mode signals. In this paper an offline regression convolutional neural network (CNN) called SonoMyoNet for estimating continuous isometric force from sparse ultrasound scanlines has been presented. SonoMyoNet learns features from a few equispaced scanlines selected from B-mode images and utilizes the learned features to accurately estimate continuous isometric force. The performance of SonoMyoNet was evaluated by varying the number of scanlines to simulate the placement of multiple single element ultrasound transducers in a wearable system. Results showed that SonoMyoNet could accurately predict isometric force with just four scanlines and is immune to speckle noise and shifts in the scanline location. Thus, the proposed network reduces the computational load involved in feature tracking algorithms and estimates muscle force from global features of sparse ultrasound images.
Microglia and meningeal macrophages depletion delay the onset of experimental autoimmune encephalomyelitis
Authors: Montilla Alejandro , Zabala Alazne , Er-Lukowiak Marco , Rissiek Björn , Magnus Tim , Rodriguez-Iglesias Noelia , Sierra Amanda , Matute Carlos , Domercq María
Published: June 2022

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population andCcr2RFP/+fmsEGFP/+mice, to distinguish peripheral macrophages and microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+macrophages into demyelinating lesions and spinal cord parenchyma. PLX5622 treatment did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of CD80 co-stimulatory molecule in dendritic and myeloid cells and reduced T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data points to a specific role of CNS microglia meningeal macrophages in antigen presentation and T cell reactivation at initial stages of the EAE model.
Determination of secretion type associated motifs from pathogenic protein sequences
Authors: Özcan Orhan , Çelik Gökalp , Sert Seren , Özcengiz Gülay , Sezerman O. Uğur
Published: June 2022

Currently, potential vaccine candidates are determined using protein localization predictors to identify surface or secreted protein sequences. The pathogenic bacterial sequences constitute only a tiny percentage of this database. They search for general motifs found in bacteria and miss out on pathogen-specific motifs, which is crucial for identifying vaccine candidates. We developed a motif search algorithm derived from pathogenic bacterial sequences in this work. Using this method, we identified secretion motifs of pathogenic bacteria for six different secretion pathways and non-specific secretion motifs. To this end, we established a database of immunogenic sequences from patented vaccine sequences, AntigenDb, and PUB-MED. The motifs are filtered out according to their presence in a cytoplasmic dataset to keep motifs that are present only in secreted sequences. These sequences are validated on newly identified novel vaccine candidates from 20 pathogenic bacterial immunoproteomics data.
Pinpointing the distinctive impacts of ten cover crop species on the resident and active fractions of the soil microbiome
Authors: Cazzaniga Sara Giulia , Braat Lize , van den Elsen Sven , Lombaers Carin , Visser Johnny , Maciá-Vicente Jose G. , Postma Joeke , Mommer Liesje , Helder Johannes
Published: June 2022

Cover crops are used in agriculture to minimise soil erosion, prevent nutrient leaching and increase soil organic matter content. Cover crops can also be grown to stimulate the soil microbial community to improve soil biological conditions. Despite their widespread use, little is known about the impact of different cover crop species on the composition and activity of the soil microbiome. Here we investigate the effect of distinct cover crop species on the rhizosphere microbiome and to characterise both the resident (DNA-based) and the active (RNA-based) fractions of the bacterial, fungal, protist and metazoan communities in the cover crops rhizosphere. We conducted a field experiment using 70-litre bottomless containers in which we grew ten monocultures of commonly used cover crop species belonging to five plant families, and an unplanted control treatment (fallow). The total DNA and RNA were extracted from soil and the bacterial, fungal, protistan and metazoan communities were characterized using Illumina MiSeq sequencing. We found that all cover crop species significantly impacted the resident and active microbial community composition. Moreover, cover crops showed distinct selection strengths on their rhizospheres. Together with borage (Boraginaceae), oilseed radish (Brassicaceae) was shown to provoke the strongest microbial shifts, in part attributable to a promotion of the bacterial family Pseudomonadaceae and a repression of Microascaceae in the rhizosphere. Lentil (Fabaceae) showed enrichment in fungal taxa, including Trichocomaceae and fungal members of the Glomerales order, whereas black oat, hybrid ryegrass (both Poaceae) and marigold (Asteraceae) induced relatively mild changes in the soil microbial communities. Predominantly, differences in selection strengths were consistent among the four organismal groups under investigation and were observed in both the active and resident communities. Our work provides a broad baseline for the effects of cover crops on four organismal groups, which may facilitate future cover crop selection to advance soil health.