bluuebunny/crossref_metadata_2025 huggingface dataset:
The molecular profile of mucosal melanoma
Authors: Mikkelsen Lauge Hjorth , Maag Emil , Andersen Mette Klarskov , Kruhøffer Mogens , Larsen Ann-Cathrine , Melchior Linea Cecilie , Toft Peter Bjerre , von Buchwald Christian , Wadt Karin , Heegaard Steffen
Published: July 2020

Herein, we wanted to explore the molecular landscape of mucosal melanoma from different sites and identify potential molecular targets for future therapy. Mucosal melanomas (N = 40) from different sites (conjunctiva, sinonasal cavity, rectum, and vagina) were investigated. Targeted next-generation sequencing along with Nanostring gene expression profiling was performed. Genetically, conjunctival melanoma was characterized byBRAF-V600E (30%) andNF1mutations (17%). Mucosal melanomas at nonsun-exposed sites harbored alterations inNRAS,KIT,NF1, along with atypicalBRAFmutations. When comparing the gene expression profile of conjunctival melanoma and nonsun-exposed mucosal melanoma, 41 genes were found to be significantly deregulated. Programmed death-ligand 1 (PD-L1) presented a significant sixfold upregulation in conjunctival melanoma compared to the other mucosal melanomas. While melanomas of the sinonasal cavity, vagina, and rectum are molecularly similar, conjunctival melanoma is characterized by a higher frequency ofBRAF-V600E mutations and differential expression of several genes involved in the immune response.
Case of Bullous Grover Disease
Authors: Li Yumeng M. , Milikowski Clara , Galimberti Fabrizio
Published: July 2020

Grover disease is an acquired acantholytic dermatosis affecting middle-aged men, with pruritus being the most commonly associated symptom. Grover disease tends to wax and wane and can last between several months to several years. Although Grover disease is usually papular, we report here a patient who presented with mainly vesicular and bullous lesions on his back originally concerning for folliculitis, contact dermatitis, or disseminated herpes simplex viral infection. Skin biopsy demonstrated acantholysis, suprabasal blisters, and a predominantly lymphocytic dermal infiltrate. Tzanck preparation for giant cells, immunohistochemistry for viral markers, and direct immunofluorescence staining were all negative. A diagnosis of bullous Grover disease was made based on clinicopathological correlation. Minocycline was recommended based on report of its efficacy. However, patient declined treatment and his rash self-resolved within a couple of months. This case brings awareness to this atypical variant of Grover disease and encourages physician to include Grover disease in their differential of vesiculobullous disorders.
Diffuse (Generalized) Plane Xanthoma Misdiagnosed as Carotenoderma: Usefulness of Reflectance Confocal Microscopy
Authors: Cota Carlo , Pellacani Giovanni , Lora Viviana , Brancorsini Donatella
Published: July 2020

Diffuse (generalized) plane xanthoma is a rare normolipemic xanthomatosis, frequently associated with multiple myeloma and monoclonal gammopathy. Its clinical presentation is well described, and in most cases, clinical suspicion is immediate. Rarely, it can clinically present with a diffuse and uniform yellowish discoloration, and in this context, several investigations are required to identify the correct diagnosis. We describe a case characterized by progressive diffuse yellow–orange discoloration lasting about 3 years and classified as carotenoderma in which reflectance confocal microscopy addressed the diagnosis and drove the correct selection of the biopsy site. Definitive diagnosis of diffuse (generalized) plane xanthoma was confirmed later by histological examination.
Association of cytochrome P450 1B1 gene polymorphisms and environmental biomarkers with hypertension in Slovak midlife women
Authors: Falbová Darina , Vorobeľová Lenka , Čerňanová Veronika Candráková , Beňuš Radoslav , Wsólová Ladislava , Siváková Daniela
Published: July 2020

Objective:

This study investigated the association of the Leu432Val and Asn453Ser CYP1B1 polymorphisms and selected environmental biomarkers with hypertension (HT) in Slovak midlife women.

Methods:

We studied 575 women. Divided according to their blood pressure status: 255 with HT and 320 without HT. All data was obtained by using standard anthropometric, genetic methods and analyzed by regression models to adjust for HT risk factors such as age, obesity, smoking, and level of education.

Results:

Our findings revealed that CYP1B1 Leu432Val polymorphism was associated with HT, whereas no association was found between Asn453Ser polymorphism and HT. Women with at least one Val allele had significantly higher odds of HT compared to women with the Leu/Leu genotype in the total sample (Exp(B) = 1.82, CI 1.16-2.84, P = 0.009). After dividing women by menopausal status and the presence of HT environmental risk factor, the association between CYP1B1 polymorphism and HT was observed in pre/perimenopausal women (Exp(B), 2.36; 95% CI 1.13-4.92; P = 0.02), smokers (Exp(B), 3.40; 95% CI 1.48-7.82; P = 0.004), abdominal obesity (Exp(B), 2.41; 95% CI 1.23-4.75; P = 0.01) and in women with only basic education (Exp(B), 4.20, 95% CI 1.12-15.71; P = 0.03). However, general linear models did not reveal a statistically significant interactions between CYP1B1, menopausal status, and HT risk factors and their common association with HT (P > 0.05).

Conclusions:

In this pilot study, we have provided novel data that supports the significant association of CYP1B1 Leu432Val gene polymorphism with HT in Slovak midlife women.
EVALUATION OF RETINAL VESSEL DIAMETERS IN EYES WITH ACTIVE CENTRAL SEROUS CHORIORETINOPATHY
Authors: Altunel Orhan , Arifoglu Hasan Basri
Published: July 2020

Purpose:

To compare the retinal vessel diameters of healthy eyes and active central serous chorioretinopathy (CSC) eyes, and to evaluate possible effect of retinal vessel diameter alterations on the pathogenesis of CSC.

Methods:

This retrospective study included 39 patients with CSC and 34 healthy individuals. Spectralis optical coherence tomography + HRA with an infrared reflectance image were used to evaluate structure of retinal vessels in the circular region around the optic disc. For each eye, vertical inner and outer diameters of the four major arteries and veins were measured using infrared reflectance images, and vessel wall thicknesses were also calculated based on inner and outer diameters.

Results:

The 304 vessels of the 39 active CSC eyes and 266 vessels of the 34 healthy eyes were used in the analyses. The mean venous wall thickness in active CSC eyes was significantly thicker than that in healthy eyes (40.0 ± 4.9 vs. 33.5 ± 4.1 μm, P = 0.001), whereas the mean venous inner diameter in active CSC eyes was significantly narrower (52.5 ± 9.7 vs. 61.3 ± 8.1 μm, P = 0.001). Also, the mean venous outer diameter was wider in CSC eyes, albeit not significantly (131.1 ± 7.0 vs. 128.5 ± 8.4 μm, P = 0.074).

Conclusion:

Our results suggest that the alterations of retinal venous diameters may play a potential role in the pathogenesis of CSC in addition to alterations in choroidal thickness.
Comparison of Visual, Tomographic, and Biomechanical Outcomes of 360 Degrees Intracorneal Ring Implantation With and Without Corneal Crosslinking for Progressive Keratoconus: A 5-Year Follow-up
Authors: Mohammadpour Mehrdad , Khoshtinat Narges , Khorrami-Nejad Masoud
Published: July 2020

Purpose:

To evaluate the long-term (5 years) results of 360 degrees intracorneal ring (ICR) implantation with and without corneal crosslinking (CXL) in patients with progressive keratoconus (KCN).

Method:

This historical cohort study was performed on 35 eyes with progressive KCN, which was randomly divided into 2 groups. Fourteen patients were implanted only with ICR, and 21 patients with KCN were treated with ICR plus CXL simultaneously. Uncorrected distance visual acuity (UCDVA), corrected distance visual acuity (CDVA), and refractive components were collected from patients' medical records. The biomechanical properties of patients were measured using the Corvis ST (Oculus, Inc, Weltzar, Germany). Corneal topography and aberrometry parameters were also recorded from the Pentacam HR device (Oculus).

Results:

Both UCVA and CDVA increased in both groups after ICR implantation; however, this improvement was more significant in the ICR plus CXL group (P = 0.002 and P = 0.001, respectively). The mean improvement of CDVA in patients with ICR implantation with and without CXL was 0.56 ± 0.67 and 0.33 ± 0.61, respectively. A comparison of the long-term postoperative Tomographic and Biomechanical Index between 2 groups showed a better result in the ICR plus CXL group (P = 0.012). Topographic findings of the anterior corneal surface (flat-K, steep-K, mean-K, and astigmatism) after surgery were significantly better than before surgery in both groups (P < 0.05).

Conclusions:

Although ICR implantation alone might halt the KCN progression with acceptable visual, topographic, and biomechanical outcomes, the combination of ICR and CXL has an adjuvant and synergistic effect, especially in long-term follow-up.
Persistent Basal Cell Carcinoma Following Self-Treatment With a “Natural Cure,” Sanguinaria canadensis
Authors: Bozung Alison K. , Ko Audrey C. , Gallo Ryan A. , Rong Andrew J.
Published: July 2020

A 65-year-old woman presented with a 6-week history of redness, eyelid swelling, and discharge in the right eye. Slit lamp examination revealed right medial canthal erythema with cicatricial lower lid ectropion, retraction, and inferior punctal obliteration. The patient was previously diagnosed with a medial canthal basal cell carcinoma 1.5 years ago, but opted for self-treatment with black salve, a commonly used naturopathic “cure” for skin cancer. Each application resulted in increasingly severe periorbital inflammation with eventual eschar formation. Over time, this led to cicatricial band formation over the medial canthus. After biopsy confirmation of residual basal cell carcinoma within the cicatricial tissues, the patient underwent Mohs surgery followed by multistaged reconstruction. Herein, we report a case of patient whose use of an unproven naturopathic “cure” led to persistent periorbital inflammation, persistence of malignancy, and significant tissue destruction.
Management of Vulvar Cancer Precursors: A Survey of the International Society for the Study of Vulvovaginal Disease
Authors: Green Nicole , Adedipe Tolu , Dmytryshyn Julia , Preti Mario , Selk Amanda
Published: July 2020

Objective

The aim of the study was to determine how experts treat vulvar high-grade squamous intraepithelial neoplasia (VHSIL) and differentiated vulvar intraepithelial neoplasia (dVIN).

Method

A 26-question survey was designed through a literature review, reviewed by the Survey Committee of the International Society for the Study of Vulvovaginal Disease (ISSVD), and distributed to all ISSVD members via e-mail in January 2019.

Results

Overall, 90 of 441 physician members consented to participate and 78 of 90 were eligible to complete the survey. Most respondents were gynecologists (77%), followed by dermatologists (12%). Forty-five percent responded that their pathology was being reported using the 2015 ISSVD terminology of vulvar squamous intraepithelial lesions. The most common first-line treatments were as follows: unifocal VHSIL—excision (65%), multifocal VHSIL—imiquimod 5% (45%), VHSIL in a hair-bearing area—excision (69%), and clitoral disease—imiquimod 5% (47%). In the recurrent VHSIL, excision was favored (28%), followed by imiquimod 5% (26%) and laser (19%). Differentiated vulvar intraepithelial neoplasia was most often first treated with excision (82%), and more patients were referred to gynecologic oncology. Most patients were seen in follow-up at 3 months (range: 1 week–6 months). Sixty-seven respondents provided 26 different ways to follow treated patients, which were most commonly every 6 months for 2 years and then yearly (25%), followed by every 6 months indefinitely (18%).

Conclusions

Treatment of VHSIL and dVIN varies among vulvar experts with excision being the most common treatment, except in multifocal VHSIL where imiquimod is commonly used. There is wide variation in how patients are followed after treatment.
High frequency of gastric cancer precursor lesions in patients with gastric xanthelasma: a prospective case-control study
Authors: Sayar Suleyman , Ayranci Gülçiçek , Kürbüz Kemal , Ak Çağatay , Tarikçi Kiliç Ebru , Kahraman Resul , Atalay Roni , Öztürk Oğuzhan , Çalişkan Zuhal , Adali Gupse , Doganay Levent , Özdil Kamil
Published: July 2020

Objective

An association of gastric cancer and precursor lesions with gastric xanthelasma has frequently been reported. However, the incidence of both gastric xanthelasma and gastric cancer precursor lesions increases with age. The aim of this study was to evaluate the frequency and characteristics of atrophic gastritis, intestinal metaplasia and dysplasia in patients with gastric xanthelasma compared to controls.

Material and methods

Cases with gastric xanthelasma endoscopically and histopathologically were included in this prospective study. The patients included in the study were compared with age- and sex-matched controls in terms of the frequency and characteristics of atrophic gastritis, intestinal metaplasia, dysplasia and cancer.

Results

In a series of 1892 upper endoscopies, 108 patients (5.7%) were found to have gastric xanthelasma. The average age of the patients was 61.41 ± 11.43 years. Among the patients, 58 (53.7%) were male. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the xanthelasma group (n = 108) were 31.5, 68.5, 3.7 and 2.8%, respectively. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the control group (n = 183) were 11.5, 31.7, 0.5 and 0.5%, respectively. Compared to the control group, the frequency of these cancer precursor lesions and the prevalence of advanced stage based on operative link on gastritis intestinal metaplasia assessment were found to be higher in the xanthelasma group (P < 0.05).

Conclusion

Gastric xanthelasma is associated with an increased frequency of gastric precancerous lesions and should be considered an important marker.
Impact of a Follow-up Telephone Call Program on 30-Day Readmissions (FUTR-30)
Authors: Yiadom Maame Yaa A.B. , Domenico Henry J. , Byrne Daniel W. , Hasselblad Michele , Kripalani Sunil , Choma Neesha , Tucker-Marlow Sarah , Gatto Cheryl L. , Wang Li , Bhatia Monisha C. , Morrison Johnston , Harrell Frank E. , Hartert Tina V. , Lindsell Christopher J. , Bernard Gordon R.
Published: July 2020

Background:

Telephone call programs are a common intervention used to improve patients’ transition to outpatient care after hospital discharge.

Objective:

To examine the impact of a follow-up telephone call program as a readmission reduction initiative.

Research Design:

Pragmatic randomized controlled real-world effectiveness trial.

Subjects:

We enrolled and randomized all patients discharged home from a hospital general medicine service to a follow-up telephone call program or usual care discharge. Patients discharged against medical advice were excluded. The intervention was a hospital program, delivering a semistructured follow-up telephone call from a nurse within 3–7 days of discharge, designed to assess understanding and provide education, and assistance to support discharge plan implementation.

Measures:

Our primary endpoint was hospital inpatient readmission within 30 days identified by the electronic health record. Secondary endpoints included observation readmission, emergency department revisit, and mortality within 30 days, and patient experience ratings.

Results:

All 3054 patients discharged home were enrolled and randomized to the telephone call program (n=1534) or usual care discharge (n=1520). Using a prespecified intention-to-treat analysis, we found no evidence supporting differences in 30-day inpatient readmissions [14.9% vs. 15.3%; difference −0.4 (95% confidence interval, 95% CI), −2.9 to 2.1; P=0.76], observation readmissions [3.8% vs. 3.6%; difference 0.2 (95% CI, −1.1 to 1.6); P=0.74], emergency department revisits [6.1% vs. 5.4%; difference 0.7 (95% CI, −1.0 to 2.3); P=0.43], or mortality [4.4% vs. 4.9%; difference −0.5 (95% CI, −2.0 to 1.0); P=0.51] between telephone call and usual care groups.

Conclusions:

We found no evidence of an impact on 30-day readmissions or mortality due to the postdischarge telephone call program.
Direct oral anticoagulants in chronic kidney disease: an update
Authors: Mavrakanas Thomas A. , Charytan David M. , Winkelmayer Wolfgang C.
Published: July 2020

Purpose of review

Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment.

Recent findings

Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily).

DOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.
Weight loss as primary indication for FDG-PET/CT
Authors: Maliha Peter George , Singerman Julia , Probst Stephan
Published: July 2020

Purpose

Some consider fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) clinically useful in patients presenting with nonspecific symptoms of malignancy, weight loss most commonly encountered. However, the appropriateness of such FDG-PET/CT studies remains to be clarified. This study evaluated the clinical value of FDG-PET/CT in patients referred primarily for weight loss.

Methods

From 2010 to 2017 in one academic center, 252 subjects underwent 254 FDG-PET/CT studies for weight loss as primary indication and retrospectively studied. Eighteen subjects were excluded due to ongoing active malignancy, weight loss not ultimately being the main indication for the FDG-PET/CT, technically inadequate FDG-PET/CT and insufficient follow-up. The FDG-PET/CT scans were considered clinically beneficial when true positive for the cause of weight loss that other investigations missed or would have missed, clinically neutral when true negative and clinically detrimental when false positive leading to additional investigations or false negative.

Results

Ultimately 234 unique subjects (236 FDG-PET/CT studies) were included. The average subject weight loss prior to the PET was 12 kg and average follow-up time post FDG-PET/CT scan was 3.4 years. The FDG-PET/CT scans were true positive in 24 studies (10%) with 8 studies (3%) clinically beneficial; false positive in 38 studies (16%) of which 26 led to 35 additional procedures and false negative in 13 studies (6%). In total, 39 (17%) FDG-PET/CT studies were clinically detrimental. The other 149 (63%) studies were true negative, clinically neutral.

Conclusion

FDG-PET/CT appears to have limited value in assessing subjects with weight loss as the leading clinical indication, proving to be five times more often detrimental than beneficial.
99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma
Authors: Mosci Camila , Pericole Fernando V. , Oliveira Gislaine B. , Delamain Marcia T. , Takahashi Maria E.S. , Carvalheira José Barreto C. , Etchebehere Elba C.S.C. , Santos Allan O. , Miranda Eliana C. M. , Lima Mariana C.L. , Amorim Barbara J. , de Souza Carmino A. , Lorand-Metze Irene , Ramos Celso D.
Published: July 2020

Purpose

18F-fluorodeoxiglucose (18F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. 99mTc-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging.

Materials and methods

Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body 18F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded.

Results

PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive.

Conclusion

MIBI SPECT/CT performs similarly to 18F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a ‘mismatch’ pattern of FDG/MIBI uptake.
Fatal Direct Current Electrocution in a Welder
Authors: Hans Anmol , Key Phillip , Prahlow Joseph A.
Published: July 2020

Direct current (DC) electrocution is exceedingly rare, especially in the context of workplace accidents and exposure, where electrical fatality is almost exclusively associated with alternating current (AC). The DC electrocution requires a much higher voltage to cause significant injury and death, and therefore is generally considered safer than AC. Here, we present a case of DC electrocution where a welder accidentally electrocuted himself while repairing a metal plate inside a silo. The decedent had complained of feeling shocks in his arm while welding twice before being electrocuted. Autopsy revealed minimal trauma, along with a classic targetoid electrical burn and punctate lesions likely to be electrical burns. Correlation of the history obtained at the scene and the examination performed at autopsy aided the identification of this rare cause of death.
Artificial Intelligence and Machine Learning in Radiology
Authors: Wichmann Julian L. , Willemink Martin J. , De Cecco Carlo N.
Published: July 2020

Although artificial intelligence (AI) has been a focus of medical research for decades, in the last decade, the field of radiology has seen tremendous innovation and also public focus due to development and application of machine-learning techniques to develop new algorithms. Interestingly, this innovation is driven simultaneously by academia, existing global medical device vendors, and—fueled by venture capital—recently founded startups. Radiologists find themselves once again in the position to lead this innovation to improve clinical workflows and ultimately patient outcome. However, although the end of today's radiologists' profession has been proclaimed multiple times, routine clinical application of such AI algorithms in 2020 remains rare. The goal of this review article is to describe in detail the relevance of appropriate imaging data as a bottleneck for innovation, provide insights into the many obstacles for technical implementation, and give additional perspectives to radiologists who often view AI solely from their clinical role. As regulatory approval processes for such medical devices are currently under public discussion and the relevance of imaging data is transforming, radiologists need to establish themselves as the leading gatekeepers for evolution of their field and be aware of the many stakeholders and sometimes conflicting interests.
Comparison of Quality of Life and Caregiving Burden of 2- to 4-Year-Old Children Post Liver Transplant and Their Parents
Authors: Yayan Emriye Hilal , Düken Mehmet Emin
Published: July 2020

A literature search determined there are no studies on children between 2 and 4 years of age who have had a liver transplant and their parents. For this reason, this study aimed to compare the quality of life of children between 2 and 4 years of age who have had a liver transplant, and the caregiving burden of their parents. The study was carried out as a descriptive cross-sectional study on 47 children who visited Inonu University Liver Transplant Institute outpatient clinic between March 2017 and March 2018. This study found that 59.6% of the children with transplants were male and 38.3% had their organ donated by their mother. There was a positive relationship between the quality of life of the parents and the quality of life and subdimensions of the children. There was a negative relationship between parental quality of life and care burden. This study found that the quality of life of children with liver transplants and their parents was low and, as the quality of life of children was impaired, the caregiving burden of parents increased. Healthcare professionals' awareness of the effect of caregivers' care load on quality of life after liver transplantation can positively affect the healing process.
Factors favouring the evolution of multidrug resistance in bacteria
Authors: Jacopin Eliott , Lehtinen Sonja , Débarre Florence , Blanquart François
Published: July 2020

The evolution of multidrug antibiotic resistance in commensal bacteria is an important public health concern. Commensal bacteria such as
Escherichia coli
,
Streptococcus pneumoniae
or
Staphylococcus aureus
, are also opportunistic pathogens causing a large fraction of the community-acquired and hospital-acquired bacterial infections. Multidrug resistance (MDR) makes these infections harder to treat with antibiotics and may thus cause substantial additional morbidity and mortality. Here, we develop an evolutionary epidemiology model to identify the factors favouring the evolution of MDR in commensal bacteria. The model describes the evolution of antibiotic resistance in a commensal bacterial species evolving in a host population subjected to multiple antibiotic treatments. We combine statistical analysis of a large number of simulations and mathematical analysis to understand the model behaviour. We find that MDR evolves more readily when it is less costly than expected from the combinations of single resistances (positive epistasis). MDR frequently evolves when bacteria are in contact with multiple drugs prescribed in the host population, even if individual hosts are only treated with a single drug at a time. MDR is favoured when the host population is structured in different classes that vary in their rates of antibiotic treatment. However, under most circumstances, recombination between loci involved in resistance does not meaningfully affect the equilibrium frequency of MDR. Together, these results suggest that MDR is a frequent evolutionary outcome in commensal bacteria that encounter the variety of antibiotics prescribed in the host population. A better characterization of the variability in antibiotic use across the host population (e.g. across age classes or geographical location) would help predict which MDR genotypes will most readily evolve.
Spectral graph theory efficiently characterizes ventilation heterogeneity in lung airway networks
Authors: Whitfield Carl A. , Latimer Peter , Horsley Alex , Wild Jim M. , Collier Guilhem J. , Jensen Oliver E.
Published: July 2020

This paper introduces a linear operator for the purposes of quantifying the spectral properties of transport within resistive trees, such as airflow in lung airway networks. The operator, which we call the Maury matrix, acts only on the terminal nodes of the tree and is equivalent to the adjacency matrix of a complete graph summarizing the relationships between all pairs of terminal nodes. We show that the eigenmodes of the Maury operator have a direct physical interpretation as the relaxation, or resistive, modes of the network. We apply these findings to both idealized and image-based models of ventilation in lung airway trees and show that the spectral properties of the Maury matrix characterize the flow asymmetry in these networks more concisely than the Laplacian modes, and that eigenvector centrality in the Maury spectrum is closely related to the phenomenon of ventilation heterogeneity caused by airway narrowing or obstruction. This method has applications in dimensionality reduction in simulations of lung mechanics, as well as for characterization of models of the airway tree derived from medical images.
Recent increases in assemblage rarity are linked to increasing local immigration
Authors: Jones Faith A. M. , Dornelas Maria , Magurran Anne E.
Published: July 2020

As pressures on biodiversity increase, a better understanding of how assemblages are responding is needed. Because rare species, defined here as those that have locally low abundances, make up a high proportion of assemblage species lists, understanding how the number of rare species within assemblages is changing will help elucidate patterns of recent biodiversity change. Here, we show that the number of rare species within assemblages is increasing, on average, across systems. This increase could arise in two ways: species already present in the assemblage decreasing in abundance but with no increase in extinctions, or additional species entering the assemblage in low numbers associated with an increase in immigration. The positive relationship between change in rarity and change in species richness provides evidence for the second explanation, i.e. higher net immigration than extinction among the rare species. These measurable changes in the structure of assemblages in the recent past underline the need to use multiple biodiversity metrics to understand biodiversity change.
The craniomandibular anatomy of the early archosauriformEuparkeria capensisand the dawn of the archosaur skull
Authors: Sookias Roland B. , Dilkes David , Sobral Gabriela , Smith Roger M. H. , Wolvaardt Frederik P. , Arcucci Andrea B. , Bhullar Bhart-Anjan S. , Werneburg Ingmar
Published: July 2020

Archosauria (birds, crocodilians and their extinct relatives) form a major part of terrestrial ecosystems today, with over 10 000 living species, and came to dominate the land for most of the Mesozoic (over 150 Myr) after radiating following the Permian–Triassic extinction. The archosaur skull has been essential to this diversification, itself diversified into myriad forms. The archosauriformEuparkeria capensisfrom the Middle Triassic (Anisian) of South Africa has been of great interest since its initial description in 1913, because its anatomy shed light on the origins and early evolution of crown Archosauria and potentially approached that of the archosaur common ancestor.Euparkeriahas been widely used as an outgroup in phylogenetic analyses and when investigating patterns of trait evolution among archosaurs. Although described monographically in 1965, subsequent years have seen great advances in the understanding of early archosaurs and in imaging techniques. Here, the cranium and mandible ofEuparkeriaare fully redescribed and documented using all fossil material and computed tomographic data. Details previously unclear are fully described, including vomerine dentition, the epiptergoid, number of premaxillary teeth and palatal arrangement. A new diagnosis and cranial and braincase reconstruction is provided, and an anatomical network analysis is performed on the skull ofEuparkeriaand compared with other amniotes. The modular composition of the cranium suggests a flexible skull well adapted to feeding on agile food, but with a clear tendency towards more carnivorous behaviour, placing the taxon at the interface between ancestral diapsid and crown archosaur ecomorphology, corresponding to increases in brain size, visual sensitivity, upright locomotion and metabolism around this point in archosauriform evolution. The skull ofEuparkeriaepitomizes a major evolutionary transition, and places crown archosaur morphology in an evolutionary context.
Architecture and evolution of semantic networks in mathematics texts
Authors: Christianson Nicolas H. , Sizemore Blevins Ann , Bassett Danielle S.
Published: July 2020

Knowledge is a network of interconnected concepts. Yet, precisely how the topological structure of knowledge constrains its acquisition remains unknown, hampering the development of learning enhancement strategies. Here, we study the topological structure of semantic networks reflecting mathematical concepts and their relations in college-level linear algebra texts. We hypothesize that these networks will exhibit structural order, reflecting the logical sequence of topics that ensures accessibility. We find that the networks exhibit strong core–periphery architecture, where a dense core of concepts presented early is complemented with a sparse periphery presented evenly throughout the exposition; the latter is composed of many small modules each reflecting more narrow domains. Using tools from applied topology, we find that the expositional evolution of the semantic networks produces and subsequently fills knowledge gaps, and that the density of these gaps tracks negatively with community ratings of each textbook. Broadly, our study lays the groundwork for future efforts developing optimal design principles for textbook exposition and teaching in a classroom setting.
How to have more things by forgetting how to count them
Authors: Karagila Asaf , Schlicht Philipp
Published: July 2020

Cohen’s first model is a model of Zermelo–Fraenkel set theory in which there is a Dedekind-finite set of real numbers, and it is perhaps the most famous model where the Axiom of Choice fails. We force over this model to add a function from this Dedekind-finite set to some infinite ordinal
κ
. In the case that we force the function to be injective, it turns out that the resulting model is the same as adding
κ
Cohen reals to the ground model, and that we have just added an enumeration of the canonical Dedekind-finite set. In the case where the function is merely surjective it turns out that we do not add any reals, sets of ordinals, or collapse any Dedekind-finite sets. This motivates the question if there is any combinatorial condition on a Dedekind-finite set
A
which characterises when a forcing will preserve its Dedekind-finiteness or not add new sets of ordinals. We answer this question in the case of ‘Adding a Cohen subset’ by presenting a varied list of conditions each equivalent to the preservation of Dedekind-finiteness. For example, 2

A

is extremally disconnected, or [
A
]

<
ω

is Dedekind-finite.
Solving nonlinear non-local problems using positive square-root operators
Authors: Montagu E. L. , Norbury John
Published: July 2020

A non-constructive existence theory for certain operator equations

L
u
=
D
u
,

using the substitution

u
=

B

1
2

ξ

with
B
 = 
L
−1
, is developed, where
L
is a linear operator (in a suitable Banach space) and
D
is a homogeneous nonlinear operator such that
Dλu
 = 
λ

α

D u
for all
λ
 ≥ 0 and some

α
∈

R

,

 
α
 ≠ ~1. This theory is based on the positive-operator approach of Krasnosel’skii. The method has the advantage of being able to tackle the nonlinear right-hand side
D
in cases where conventional operator techniques fail. By placing the requirement that the operator
B
must have a positive square root, it is possible to avoid the usual regularity condition on either the mapping
D
or its Fréchet derivative. The technique can be applied in the case of elliptic PDE problems, and we show the existence of solitary waves for a generalization of Benjamin’s fluid dynamics problem.
Routes to global glaciation
Authors: Arnscheidt Constantin W. , Rothman Daniel H.
Published: July 2020

Theory and observation suggest that Earth and Earth-like planets can undergo runaway low-latitude glaciation when changes in solar heating or in the carbon cycle exceed a critical threshold. Here, we use a simple dynamical-system representation of the ice–albedo feedback and the carbonate–silicate cycle to show that glaciation is also triggered when solar heating changes faster than a critical rate. Such ‘rate-induced glaciations’ remain accessible far from the outer edge of the habitable zone, because the warm climate state retains long-term stability. In contrast, glaciations induced by changes in the carbon cycle require the warm climate state to become unstable, constraining the kinds of perturbations that could have caused global glaciation in Earth’s past. We show that glaciations can occur when Earth’s climate transitions between two warm stable states; this property of the Earth system could help explain why major events in the development of life have been accompanied by glaciations.
A publicly accessible database for Clostridioides difficile genome sequences supports tracing of transmission chains and epidemics
Authors: Frentrup Martinique , Zhou Zhemin , Steglich Matthias , Meier-Kolthoff Jan P. , Göker Markus , Riedel Thomas , Bunk Boyke , Spröer Cathrin , Overmann Jörg , Blaschitz Marion , Indra Alexander , von Müller Lutz , Kohl Thomas A. , Niemann Stefan , Seyboldt Christian , Klawonn Frank , Kumar Nitin , Lawley Trevor D. , García-Fernández Sergio , Cantón Rafael , del Campo Rosa , Zimmermann Ortrud , Groß Uwe , Achtman Mark , Nübel Ulrich
Published: July 2020

Clostridioides difficile

is the primary infectious cause of antibiotic-associated diarrhea. Local transmissions and international outbreaks of this pathogen have been previously elucidated by bacterial whole-genome sequencing, but comparative genomic analyses at the global scale were hampered by the lack of specific bioinformatic tools. Here we introduce a publicly accessible database within EnteroBase (http://enterobase.warwick.ac.uk) that automatically retrieves and assembles

C. difficile

short-reads from the public domain, and calls alleles for core-genome multilocus sequence typing (cgMLST). We demonstrate that comparable levels of resolution and precision are attained by EnteroBase cgMLST and single-nucleotide polymorphism analysis. EnteroBase currently contains 18 254 quality-controlled

C. difficile

genomes, which have been assigned to hierarchical sets of single-linkage clusters by cgMLST distances. This hierarchical clustering is used to identify and name populations of

C. difficile

at all epidemiological levels, from recent transmission chains through to epidemic and endemic strains. Moreover, it puts newly collected isolates into phylogenetic and epidemiological context by identifying related strains among all previously published genome data. For example, HC2 clusters (i.e. chains of genomes with pairwise distances of up to two cgMLST alleles) were statistically associated with specific hospitals (P<10−4) or single wards (P=0.01) within hospitals, indicating they represented local transmission clusters. We also detected several HC2 clusters spanning more than one hospital that by retrospective epidemiological analysis were confirmed to be associated with inter-hospital patient transfers. In contrast, clustering at level HC150 correlated with k-mer-based classification and was largely compatible with PCR ribotyping, thus enabling comparisons to earlier surveillance data. EnteroBase enables contextual interpretation of a growing collection of assembled, quality-controlled

C. difficile

genome sequences and their associated metadata. Hierarchical clustering rapidly identifies database entries that are related at multiple levels of genetic distance, facilitating communication among researchers, clinicians and public-health officials who are combatting disease caused by

C. difficile

.
“PLEXIT - Therapeutic plasma exchange (TPE) for Covid-19 cytokine release storm (CRS), a retrospective propensity matched control study”
Authors: Kamran Sultan Mehmood , Mirza Zill-e-Humayun , Naseem Arshad , Liaqat Jahanzeb , Fazal Imran , Alamgir Wasim , Saeed Farrukh , Azam Rizwan , Hussain Maryam , Yousaf Muhammad Ali , Ashraf Nadeem , Nisar Shazia , Zafar Ali Muhammad , Saleem Salman , Sajjad Kaswar , Zaman Asad , Azam Malik Nadeem , Hussain Mehmood , Iftikhar Raheel
Published: July 2020

Purpose

To evaluate the outcome of patients with COVID-19 triggered CRS treated with Therapeutic Plasma Exchange (TPE) as compared to propensity score matched (PSM)-controls not receiving TPE.

Material and methods

Using PS 1:1 matching, 90 patients were assigned 2 groups (45 receiving TPE and 45 controls). Forced matching and covariate matching was done to overcome bias between two groups.

Results

Median age was 60 years (range 32-73 in TPE and 37-75 in non-TPE group), p= 0.325. Median duration of symptoms 7 days (range 3-22 days in TPE and 3-20 days in non-TPE), p=0.266. Disease severity in both groups was 6.6% moderate, 44.4% severe and 49% critical. Twenty-eight-day survival was significantly superior in TPE group (91.1%) as compared to PS-matched controls (61.5%), HR 0.21, 95% CI for HR 0.09-0.53, log rank 0.002. Median duration of hospitalization was significantly reduced in TPE treated group as compared to non-TPE controls 10 days and 15 days respectively (p< 0.01). CRS resolution time was also significantly reduced in TPE treated group (6 days vs. 12 days) (p< 0.001).

Conclusion

Use of TPE is associated with superior overall survival, early resolution of CRS and time to discharge as compared to standard therapy for COVID-19 triggered CRS.

Highlights

□

Cytokine release syndrome (CRS) plays a pivotal role in pathophysiology and progression to severe and critical disease in patients with COVID-19.

□

Beyond supportive care, there are currently no proven effective treatment options (including Tocilizumab) for coronavirus disease (COVID-19)

□

Therapeutic plasma exchange (TPE) may dampen CRS of COVID-19 by removing circulating cytokines and toxins

□

TPE is the cheapest of all novel treatments available so far to treat severe to critical COVID-19

□

By intervening early with TPE, mortality and morbidity associated with COVID-19 triggered CRS can be reduced
Improving Hospital Readmission Prediction using Individualized Utility Analysis
Authors: Ko Michael , Chen Emma , Rajpurkar Pranav , Agrawal Ashwin , Avati Anand , Ng Andrew , Basu Sanjay , Shah Nigam H.
Published: July 2020

Structured Abstract

Importance

Machine learning (ML) models for allocating readmission-mitigating interventions are typically selected according to their discriminative ability, which may not necessarily translate into utility in allocation of resources.

Objective

To determine whether ML models for allocating readmission-mitigating interventions are ranked differently based on their overall utility and their discriminative ability.

Design

A retrospective analysis of ML models using claims data acquired from the Optum Clinformatics Data Mart.

Setting

Health plan claims from all 50 states for commercially-insured individuals.

Participants

513,495 patients who were admitted as inpatients over the period January 2016 through January 2017.

Main Outcomes and Measures

Maximum utility achieved by three machine learning models for allocating readmission-mitigating interventions, determined using cost accrued in the 90 days post-discharge of an index admission and estimated counterfactual cost. Data were analyzed between April 2019 and March 2020.

Results

The study sample consisted of 513,495 patients (mean [SD] age 69 [19] years; 294,895 [57%] Female) mean 90 day cost of $11,552 for the study period. Allocating readmission-mitigating interventions based on a LightGBM model trained to predict readmissions achieved a maximum utility of $-12,645 per patient, and an AUC of 0.74 (95% CI 0.74, 0.75); allocating interventions based on a model trained to predict cost as a proxy achieved a higher maximum utility of $-12,472 per patient, and an AUC of 0.63 (95% CI 0.62, 0.63). A hybrid model combining both intervention strategies achieved a maximum utility of $-12,472, and an AUC of 0.71 (95% CI 0.71, 0.71), comparable with the best models on either metric.

Conclusion and Relevance

We demonstrate that machine learning models may be ranked differently based on overall utility and discriminative ability. Machine learning models for allocation of limited health resources should consider directly optimizing for utility.

Key points

Question

Do machine learning models for allocating readmission-mitigating interventions rank differently based on overall utility and discriminative performance?

Finding

A machine learning model predicting a patient’s future cost of care was able to achieve higher utility than a readmission risk prediction model, even though it had a lower discriminative performance in predicting readmissions.

Meaning

Our study suggests that machine learning models guiding allocation of limited health resources may consider evaluating and optimizing on utility.