bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Using an Acuity Score for Neonatal Nursing Research
Authors: Carey Mary G. , McMullen Sherri L.
Published: October 2020

The Score for Neonatal Acute Physiology (SNAP) is a physiological-based illness severity tool developed in 1993, and since that time, it has been revised to include SNAP-II Perinatal Extension (SNAPPE-II) for mortality risk assessment and SNAP-II to assess severity of illness. The purpose of this methodologically based article is to provide an overview of SNAP methodology and then to critically evaluate the feasibility and utility of SNAP-II in neonatal nursing research. The SNAP-II scoring measure is parsimonious and has been utilized in a variety of retrospective and prospective medical research with good results; yet, it is not often employed in nursing studies. For research purposes, the required data are readily obtainable from medical records, calculations can be performed via computer to reduce errors, and the resultant score is parsimonious and reproducible. SNAP-II has some limitations, however, and additional research is needed to further refine the scoring system. This methodological article outlines the strengths and limitations of SNAP-II and recommends the use of a severity score to better describe research samples for clinical benchmarking and comparative research. There is extensive interest in validating acuity scores for appropriate patient assignments. Rather than having established ratios, often established by law, nurses are interested in measuring patient acuity and appropriately assigning ratios based on patient needs.
Hypercoagulability in Vestibular Schwannoma Surgery
Authors: Muelleman Thomas J. , Alonso Jose , Barnard Zachary R. , Maxwell Anne K. , Mahboubi Hossein , Stefan Michael , Lekovic Gregory P. , Slattery William H. , Brackmann Derald E.
Published: October 2020

Objective:

Patients with vestibular schwannoma who harbor a genetic predisposition for venous thromboembolism require special consideration when determining optimal therapeutic management. The primary objective of the current study was to provide recommendations on treatment of hypercoagulable patients with vestibular schwannoma through a case series and review of the literature.

Patients:

Two patients who underwent resection of vestibular schwannomas.

Intervention(s):

Surgical resection and diagnostic testing.

Main Outcome Measure(s):

Postoperative venous thromboses.

Results:

One patient who underwent resection of vestibular schwannoma and suffered several postoperative thrombotic complications consistent with a clinical thrombophilia. One patient with known Factor V Leiden deficiency who underwent resection of vestibular schwannoma followed by postoperative chemoprophylaxis with a direct factor Xa inhibitor and experienced an uneventful postoperative course.

Conclusions:

In patients with a known propensity for venous thromboembolism, the skull base surgeon should consider nonsurgical management. If the patient undergoes surgical resection, we recommend careful effort to minimize trauma to the sigmoid sinus. In addition, the surgeon may consider retrosigmoid or middle fossa approaches. Best practice recommendations include the use of pneumatic compression devices, early ambulation, and consideration of postoperative prophylactic anticoagulation in patients with a known genetic predisposition.
Prediction of Vestibular Schwannoma Enlargement After Radiosurgery Using Tumor Shape and MRI Texture Features
Authors: George-Jones Nicholas A. , Wang Kai , Wang Jing , Hunter Jacob B.
Published: October 2020

Objective:

Determine if vestibular schwannoma (VS) shape and MRI texture features predict significant enlargement after stereotactic radiosurgery (SRS).

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Fifty-three patients were selected who underwent SRS and had a contrast-enhanced T1 sequence planning MRI scan and a follow-up contrast enhanced T1 MRI available for review. Median follow-up of 6.5 months (interquartile range/IQR, 5.9–7.4). Median pretreatment tumor volume was 1,006 mm3 (IQR, 465–1,794).

Intervention(s):

Stereotactic radiosurgery.

Main Outcome Measure(s):

Texture and shape features from the SRS planning scans were extracted and used to train a linear support vector machine binary classifier to predict post-SRS enlargement >20% of the pretreatment volume. Sensitivity, specificity, area under the receiver-operating-characteristic curve (AUC), and positive likelihood ratio were computed. A stratified analysis based on pretreatment tumor volume greater or less than the median volume was also performed.

Results:

The model had a sensitivity of 92%, specificity of 65%, AUC of 0.75, and a positive likelihood ratio of 2.6 (95% CI 1.4–5.0) for predicting post-SRS enlargement of >20%. In the larger tumor subgroup, the model had a sensitivity of 87%, specificity of 73%, AUC of 0.76, and a positive likelihood ratio of 3.2 (95% CI 1.2–8.5). In the smaller tumor subgroup, the model had a sensitivity of 95%, specificity of 50%, AUC of 0.65, and a positive likelihood ratio of 1.9 (95% CI 0.8–4.3).

Conclusions:

VS shape and texture features may be useful inputs for machine learning models that predict VS enlargement after SRS.
Convergence Vestibulo-ocular Reflex in Unilateral Vestibular Hypofunction: Behavioral Evidence in Support of a Novel Gaze Stability Exercise
Authors: Chang Tzu-Pu , Schubert Michael C.
Published: October 2020

Background and Purpose:

Convergence of the eyes during head rotation increases the gain (eye velocity/head velocity) of the vestibulo-ocular reflex (VOR). We sought to know whether convergence would increase the VOR gain (mean + SD) in unilateral vestibular hypofunction (UVH).

Methods:

Vestibulo-ocular reflex gain during ipsi- and contralesional horizontal head rotation at near (15 cm) and far (150 cm) targets was measured in 22 subjects with UVH and 12 healthy controls. Retinal slip was estimated (retinal slip index [RSI]) as the difference between ideal VOR gain (no retinal slip) and the actual VOR gain.

Results:

Convergence did not significantly enhance VOR gain for ipsilesional rotation (mean difference, 0.04; 95% confidence interval [CI], −0.01 to 0.09), near viewing (0.77 ± 0.34) versus far viewing (0.72 ± 0.29), yet the VOR gain during contralesional rotation was greater for near viewing (1.20 ± 0.23) than for far viewing (0.97 ± 0.21; mean difference, 0.23; 95% CI, 0.13-0.32). In the 36% of subjects with recovery of their ipsilesional VOR gain, the vergence effect trended to recover (far VOR gain: 1.06 ± 0.17 vs near VOR gain 1.16 ± 0.21; mean difference, 0.10; 95% CI, −0.02 to 0.22). Ipsilesional head rotation induced greater retinal slip for near (RSI = 0.90 ± 0.34) targets than for far targets (RSI = 0.35 ± 0.29; mean difference, 0.56; 95% CI, 0.51-0.61).

Discussion and Conclusions:

The convergence-mediated VOR gain enhancement is preserved during contralesional but impaired during ipsilesional head rotation. Recovery of ipsilesional passive VOR gain does not equate to restored convergence enhancement, although it did increase ∼10%. These data suggest head motion viewing near targets will increase retinal slip, which warrants consideration as a gaze stability exercise for subjects with UVH.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A325).
Fecal Calprotectin Is Elevated in HIV and Related to Systemic Inflammation
Authors: Eckard Allison Ross , Hughes Heather Y. , Hagood Nancy L. , O'Riordan Mary Ann , Labbato Danielle , Kosco Julia C. , Scott Sarah E. , McComsey Grace A.
Published: October 2020

Background:

Fecal calprotectin (FC), a biomarker of gastrointestinal (GI) inflammation, is used in the diagnosis and management of inflammatory bowel disease. HIV infection severely damages gut-associated lymphoid and epithelial tissues leading to GI inflammation that drives systemic inflammation and increases subsequent risk of comorbidities. For the first time, we compared FC concentrations by HIV and antiretroviral therapy (ART) status and determined the relationship to systemic inflammation.

Methods:

People with and without HIV were enrolled and underwent a comprehensive clinical and laboratory assessment. Stool samples were collected, and FC was measured by enzyme-linked immunosorbent assay ELISA. Plasma biomarkers of inflammation were also measured.

Results:

One hundred one participants with HIV (83 ART-treated and 18 ART-naive) and 89 uninfected controls were enrolled. There were no significant differences between ART-naive and ART-treated participants, but both HIV groups had significantly higher FC concentrations than controls when FC was considered as a continuous variable or by cut-offs used in inflammatory bowel disease. The highest median and largest proportion of participants with FC >100 µg/g were seen in ART-naive, followed by ART-treated and then controls. Among HIV participants, FC concentrations were positively associated with high-sensitivity C-reactive protein, soluble tumor necrosis factor receptor II, and soluble vascular cellular adhesion molecule and inversely associated with CD4 counts.

Conclusions:

FC concentrations are elevated in HIV regardless of ART status. ART and immune reconstitution seem to reduce FC but not to concentrations seen in uninfected controls. Our results suggest a role for FC as a noninvasive surrogate measurement of GI inflammation and associated systemic inflammation in HIV.
Association of Obesity With Lower Rates of Remission in a Colombian Cohort of Patients With Rheumatoid Arthritis
Authors: Flórez-Suárez Jorge Bruce , Mendez-Patarroyo Paul , Coral-Alvarado Paola , Quintana-López Gerardo
Published: October 2020

Objectives

Modifiable risk factors associated with the severity of rheumatoid arthritis have been studied, including the body mass index (BMI). The aim was to compare the evolution of disease activity during 24 months of follow-up in different initial BMI groups of patients with rheumatoid arthritis.

Method

Patients were classified based on their initial BMI (normal weight, overweight, and obese). Data were collected during 24 months of follow-up. At 24 months, they were reclassified based on their BMI. The proportion of patients in each BMI category was calculated. The mean differences between the initial and final DAS-28 (Disease Activity Score 28) were calculated using the Kruskal-Wallis test. Results were stratified based on sex and age. Survival analysis and Mantel-Cox test for the achievement of sustained remission during follow-up were calculated.

Results

A total of 269 patients were included. Most patients were at the normal weight category (n = 111). Normal weight group had the highest initial score (DAS-28, 4.01). Women present higher variability in BMI and greater disease activity compared with men. Based on age group, patients between the ages 31 and 50 years are more stable in their BMI, whereas those older than 50 years had lower BMI with time. Sustained remission was achieved by 58% of patients from the normal weight group, by 57% of patients from the overweight group, and by 42% of patients from the obese group. Survival curves of the initial normal and obese groups were significantly different (p = 0.0209).

Conclusions

Patients with initial obesity were less likely to achieve remission compared with patients with initial overweight or normal weight. Sex and age affects disease activity and BMI variation.
Bilateral Peritoneoscrotal Communication—“Chicken Leg” Appearance Demonstrated on 99mTc–Sulfur Colloid Scintigraphy
Authors: Sindhu Tanigassalam , Kavanal Anwin Joseph , Goyal Harish , Mittal Bhagwant Rai , Bhattacharya Anish
Published: October 2020

Continuous ambulatory peritoneal dialysis is a convenient alternate form of treatment in patients receiving hemodialysis for renal failure. Sometimes during the procedure, patients may develop scrotal swelling because of patent processus vaginalis. The diagnostic utility of the peritoneal scintigraphy, an infrequently performed nuclear medicine scan to identify peritoneoscrotal communication, has been reported by many authors. Most of the previous case reports in the literature demonstrated unilateral peritoneoscrotal communication. We present an interesting 99mTc–sulfur colloid peritoneal scintigraphic image finding of bilateral peritoneoscrotal communication in a 67-year-old man who developed scrotal swelling while undergoing continuous ambulatory peritoneal dialysis.
68Ga-PSMA PET/CT With Incidental Finding of COVID-19 in an Asymptomatic Patient
Authors: Morón Sarai , González Eliana , Rojas Julián
Published: October 2020

A 70-year-old man with prostate adenocarcinoma was diagnosed by transrectal biopsy, with Gleason of 4 + 5 and initial PSA of 225 ng/mL since March 2020. 68Ga-PSMA PET/CT was performed as part of initial staging. The images showed an enlarged prostate with focal PSMA uptake in both lobes. Retroperitoneal and pelvic lymph nodes with moderate uptake of PSMA were shown. Another finding was a moderate PSMA uptake in the both lung parenchymas associated with opacities in CT. The patient denied any symptoms of coronavirus disease and was referred to the emergency department for RT-PCR COVID-19, and the result was positive.
Transplant Oncology in Primary and Metastatic Liver Tumors
Authors: Sapisochin Gonzalo , Hibi Taizo , Toso Christian , Man Kwan , Berenguer Marina , Heimbach Julie , Greten Tim F. , Pugh Trevor J. , Dawson Laura A. , Mazzaferro Vincenzo
Published: October 2020

Transplant oncology defines any application of transplant medicine and surgery aimed at improving cancer patients’ survival and/or quality of life. In practice, liver transplantation for selected hepato-biliary cancers is the only solid organ transplant with demonstrated efficacy in curing cancer. Four are the proposed future contributions of transplant oncology in hepato-biliary cancer (4-e). (1) evolutionary approach to cancer care that includes liver transplantation; (2) elucidation of self and non-self recognition systems, by linking tumor and transplant immunology; (3) exploration of innovative endpoints both in clinical and experimental settings taking advantage from the access to the entire liver explant; (4) extension of surgical limitation in the multidisciplinary approach to hepato-biliary oncology. The aim of this review is to define the principles of transplant oncology that may be applied to hepato-biliary cancer treatment and research, attempting to balance current evidences with future opportunities.
A National Assessment of Trauma Systems Using the American College of Surgeons NBATS Tool: Geographic Distribution of Trauma Center Need
Authors: Dalton Michael K. , Uribe-Leitz Tarsicio , Hashmi Zain G. , Salim Ali , Haider Adil H. , Jarman Molly P.
Published: October 2020

Objective:

To compare the needs based assessment of trauma systems (NBATS) tool estimates of trauma center need to the existing trauma infrastructure using observed national trauma volume.

Summary of Background Data:

Robust trauma systems have improved outcomes for severely injured patients. The NBATS tool was created by the American College of Surgeons to align trauma resource allocation with regional needs.

Methods:

Data from the Agency for Healthcare Research and Quality Healthcare Costs and Utilization Project State Inpatient Databases, the Trauma Information Exchange Program, and US Census was used to calculate an NBATS score for each trauma service area (TSA) as defined by the Pittsburgh Atlas. This score was used to estimate the number of trauma centers allocated to each TSA and compared to the number of existing trauma centers.

Results:

NBATS predicts the need for 117 additional trauma centers across the United States to provide adequate access to trauma care nationwide. At least 1 additional trauma center is needed in 49% of TSAs.

Conclusions:

Application of the NBATS tool nationally shows the need for additional trauma infrastructure across a large segment of the United States. We identified some limitations of the NBATS tool, including preferential weighting based on current infrastructure. The NBATS tool provides a good framework to begin the national discussion around investing in the expansion of trauma systems nationally, however, in many instances lacks the granularity to drive change at the local level.
Anti-ICOS mAb Targets Pathogenic IL-17A-expressing Cells in Canine Model of Chronic GVHD
Authors: Parker Maura H. , Stone Diane , Abrams Kraig , Johnson Melissa , Granot Noa , Storb Rainer
Published: October 2020

Background.

Chronic graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality in transplant patients. We have previously shown that 3 doses of an anti-inducible costimulator (ICOS) mAb transiently ameliorated symptoms and extended survival of dogs affected by chronic GVHD over that of control dogs. The purpose of this study was to specifically correlate changes in T-cell populations in the peripheral blood with anti-ICOS treatment and chronic GVHD progression and regression to reach a better understanding of the mechanism of the disease and prioritize future studies.

Methods.

Peripheral blood cells from canines transplanted with DLA-mismatched bone marrow and peripheral blood mononuclear cells to generate chronic GVHD were analyzed by flow cytometry using a panel of antibodies specific to helper and cytolytic T cells.

Results.

Chronic GVHD was specifically associated with an increase in CD4+ICOS+ cells, ICOS+ cells expressing IL-17A, and CD8+ cells generating granzyme B. Treatment with anti-ICOS mAb at onset of chronic GVHD symptoms specifically targeted IL-17A+-expressing cells, transiently relieved symptoms, and lengthened survival but was unable to reduce the percentage of CD8+ T-cells expressing granzyme B.

Conclusions.

These studies suggested a role for both CD4+ and CD8+ T cells in pathogenesis of chronic GVHD in the canine model. We propose that future studies should focus on further extending survival by developing a treatment that would control both CD4+ and CD8+ T cells.
Do Spike Domain Analysis Interictally Correlate With the Ictal Patterns in Temporal Lobe Epilepsy?
Authors: Radhakrishnan Ashalatha , Parameswaran Sajeesh , Chandran Anuvitha , Unnithan Gopeekrishnan , Menon Ramshekhar N. , Cherian Ajith , Thomas Sanjeev V.
Published: October 2020

Purpose:

To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE).

Methods:

Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into “type A” interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed “focal” when confined to side of MTS, was “regional” when lateralized to the ipsilateral hemisphere; “diffuse” if nonlateralized/localized; and ictal onset contralateral to MTS termed as “discordant.”

Results:

A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was “diffuse” in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%).

Conclusions:

Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side.

Significance:

Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy.
Genetic Landscape of Gullah African Americans
Authors: Zimmerman Kip D. , Schurr Theodore G. , Chen Wei-Min , Nayak Uma , Mychaleckyj Josyf C. , Quet Queen , Moultrie Lee H. , Divers Jasmin , Keene Keith L. , Kamen Diane L. , Gilkeson Gary S. , Hunt Kelly J. , Spruill Ida J. , Fernandes Jyotika K. , Aldrich Melinda C. , Reich David , Garvey W. Timothy , Langefeld Carl D. , Sale Michèle M. , Ramos Paula S.
Published: October 2020

Objectives

Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West and Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah.

Materials and Methods

We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, Sierra Leone Africans, and population reference panels from Africa and Europe, to infer population structure, ancestry proportions, and global estimates of admixture.

Results

Relative to southeastern non-Gullah African Americans, the Gullah exhibit higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and stronger male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations.

Discussion

This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.

Research Highlights

Using genomic data, we show that the Gullah have lower European and higher West African genomic background compared to non-Gullah African Americans, confirming their diverse African ancestry and rejecting a model that asserts a predominant Sierra Leone origin.

Our data reveal a largely shared demographic history with southeastern non-Gullah African Americans, but also subtle differences related to high African genetic ancestry due to isolation in the Sea Islands.
Ongoing Global and Regional Adaptive Evolution of SARS-CoV-2
Authors: Rochman Nash D. , Wolf Yuri I. , Faure Guilhem , Mutz Pascal , Zhang Feng , Koonin Eugene V.
Published: October 2020

Understanding the trends in SARS-CoV-2 evolution is paramount to control the COVID- 19 pandemic. We analyzed more than 300,000 high quality genome sequences of SARS-CoV-2 variants available as of January 2021. The results show that the ongoing evolution of SARS-CoV-2 during the pandemic is characterized primarily by purifying selection, but a small set of sites appear to evolve under positive selection. The receptor-binding domain of the spike protein and the nuclear localization signal (NLS) associated region of the nucleocapsid protein are enriched with positively selected amino acid replacements. These replacements form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. Virus diversity within each geographic region has been steadily growing for the entirety of the pandemic, but analysis of the phylogenetic distances between pairs of regions reveals four distinct periods based on global partitioning of the tree and the emergence of key mutations. The initial period of rapid diversification into region- specific phylogenies that ended in February 2020 was followed by a major extinction event and global homogenization concomitant with the spread of D614G in the spike protein, ending in March 2020. The NLS associated variants across multiple partitions rose to global prominence in March-July, during a period of stasis in terms of inter- regional diversity. Finally, beginning July 2020, multiple mutations, some of which have since been demonstrated to enable antibody evasion, began to emerge associated with ongoing regional diversification, which might be indicative of speciation.

Significance

Understanding the ongoing evolution of SARS-CoV-2 is essential to control and ultimately end the pandemic. We analyzed more than 300,000 SARS-CoV-2 genomes available as of January 2021 and demonstrate adaptive evolution of the virus that affects, primarily, multiple sites in the spike and nucleocapsid protein. Selection appears to act on combinations of mutations in these and other SARS-CoV-2 genes. Evolution of the virus is accompanied by ongoing adaptive diversification within and between geographic regions. This diversification could substantially prolong the pandemic and the vaccination campaign, in which variant-specific vaccines are likely to be required.
Peto odds ratios demonstrate no advantage over classic odds ratios in meta-analysis of binary rare outcomes
Authors: Xu Chang , Furuya-Kanamori Luis , Lin Lifeng , Doi Suhail A.
Published: October 2020

In this study, we examined the discrepancy between large studies and small studies in meta-analyses of rare event outcomes and the impact of Peto versus the classic odds ratios (ORs) through empirical data from the Cochrane Database of Systematic Reviews that collected from January 2003 to May 2018. Meta-analyses of binary outcomes with rare events (event rate ≤5%), with at least 5 studies, and with at least one large study (N≥1000) were extracted. The Peto and classic ORs were used as the effect sizes in the meta-analyses, and the magnitude and direction of the ORs of the meta-analyses of large studies versus small studies were compared. The p-values of the meta-analyses of small studies were examined to assess if the Peto and the classic OR methods gave similar results. Totally, 214 meta-analyses were included. Over the total 214 pairs of pooled ORs of large studies versus pooled small studies, 66 (30.84%) had a discordant direction (kappa=0.33) when measured by Peto OR and 69 (32.24%) had a discordant direction (kappa=0.22) when measured by classic OR. The Peto ORs resulted in smaller p-values compared to classic ORs in a substantial (83.18%) number of cases. In conclusion, there is considerable discrepancy between large studies and small studies among the results of meta-analyses of sparse data. The use of Peto odds ratios does not improve this situation and is not recommended as it may result in less conservative error estimation.
High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance
Authors: Wursthorn Anne , Schwager Christian , Kurth Ina , Peitzsch Claudia , Herold-Mende Christel , Debus Jürgen , Abdollahi Amir , Nowrouzi Ali
Published: October 2020

The impact of functional heterogeneity in response to radiation therapy is poorly understood to the present. It remains elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. We applied high-resolution lentiviral cellular barcoding for quantitative clonal tracking and deconvolution of clonal dynamics in response to IR. Clonal tracking of over 400.000 HNSCC patient-derived tumor cells and the analyses of over 1500 million sequencing reads in clonogenic survival assays reveals that fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference within tumor cell lines. IR induced clonal reduction affected the majority of tumor cells ranging between 96-75% and correlated to the degree of radiation sensitivity. Survival and clonogenicity is characterized by an intensive clonal distortion and dominance of individual tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. A 2-fold increase in radiation resistance results in a 4-fold (p<0.05) higher deterministic clonal selection showing that the ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype commonly surviving IR was found at a frequency of 0.6-3.3% (p<0.001, FDR 3%). With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for tracking dynamics of clonogenic survival in response to radiation. This enables the quantification of intrinsically radiation resistant tumor cells from patient samples and reveals the contribution of stochastic and deterministic clonal selection processes in response to IR.
Enrichment for Cases of African-American Patients with Pathogenic TTR V142I Variant in the TOPCAT Trial
Authors: Papoutsidakis Nikolaos , Gandotra Neeru , Miller Edward , Murray Michael F. , Scharfe Curt , Jacoby Daniel
Published: October 2020

Transthyretin cardiac amyloidosis (ATTR-CA) is a treatable cause of heart failure with a hereditary form that disproportionally affects patients of West African ancestry. The clinical management of ATTR-CA has dramatically changed in the past five years, with rapidly evolving diagnostic approaches and life-prolonging therapies. The TTR variant c.424G>A, p.V142I (aka V122I) is pathogenic and occurs in 3-4% of individuals of West African ancestry. Despite its high frequency, V142I ATTR-CA is often unrecognized due to variable clinical penetrance, limited knowledge, and lack of inexpensive non-invasive diagnostic tests. Currently unknown is which TTR V142I carriers will progress to heart failure and at what age. Here we studied the prevalence of TTR V142I among a random cohort of African-American patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Three of the 26 HFpEF patients (11.5%) studied carried the pathogenic TTR V142I variant. While we cannot conclude at this point that TTR V142I was the underlying cause of the clinical phenotype in these patients, our results suggest that rapid TTR V142I genotyping, in combination with heart imaging, could have immediate clinical utility for identifying under-/mis-diagnosed HFpEF patients.
Microscale dynamics of electrophysiological markers of epilepsy
Authors: Yang Jimmy C. , Paulk Angelique C. , Lee Sang Heon , Ganji Mehran , Soper Daniel J. , Salami Pariya , Cleary Daniel , Simon Mirela , Maus Douglas , Lee Jong Woo , Nahed Brian , Jones Pamela , Cahill Daniel P. , Cosgrove Garth Rees , Chu Catherine J. , Williams Ziv , Halgren Eric , Dayeh Shadi , Cash Sydney S.
Published: October 2020

Objective

Interictal discharges (IIDs) and high frequency oscillations (HFOs) are neurophysiologic biomarkers of epilepsy. In this study, we use custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand their microscale dynamics.

Methods

Electrodes with spatial resolution down to 50µm were used to record intraoperatively in 30 subjects. For IIDs, putative spatiotemporal paths were generated by peak-tracking, followed by clustering. For HFOs, repeating patterns were elucidated by clustering similar time windows. Fast events, consistent with multi-unit activity (MUA), were covaried with either IIDs or HFOs.

Results

IIDs seen across the entire array were detected in 93% of subjects. Local IIDs, observed across <50% of the array, were seen in 53% of subjects. IIDs appeared to travel across the array in specific paths, and HFOs appeared in similar repeated spatial patterns. Finally, microseizure events were identified spanning 50-100µm. HFOs covaried with MUA, but not with IIDs.

Conclusions

Overall, these data suggest micro-domains of irritable cortex that form part of an underlying pathologic architecture that contributes to the seizure network.

Significance

Microelectrodes in cases of human epilepsy can reveal dynamics that are not seen by conventional electrocorticography and point to new possibilities for their use in the diagnosis and treatment of epilepsy.

Highlights

PEDOT:PSS microelectrodes with at least 50µm spatial resolution uniquely reveal spatiotemporal patterns of markers of epilepsy

High spatiotemporal resolution allows interictal discharges to be tracked and reveal cortical domains involved in microseizures

High frequency oscillations detected by microelectrodes demonstrate localized clustering on the cortical surface
ATTENTIONAL MODULATION OF NEURAL DYNAMICS IN TACTILE PERCEPTION OF COMPLEX REGIONAL PAIN SYNDROME PATIENTS
Authors: Defina Serena , Niedernhuber Maria , Shenker Nicholas , Brown Christopher , Bekinschtein Tristan A.
Published: October 2020

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of Complex Regional Pain Syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between “passive” (i.e. no task demands and equiprobable digit stimulation) and “active” tactile processing (i.e. where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28–56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier’s training, there is an unexpected increased decodability in the CRPS group compared to healthy volunteers (280–320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS.
Novel Machine-Learned Approach for COVID-19 Resource Allocation: A Tool for Evaluating Community Susceptibility
Authors: Kale Neil
Published: October 2020

Despite worldwide efforts to develop an effective COVID vaccine, it is quite evident that initial supplies will be limited. Therefore, it is important to develop methods that will ensure that the COVID vaccine is allocated to the people who are at major risk until there is a sufficient global supply. Herein, I developed a machine-learning tool that could be applied to assess the risk in communities based on social, medical, and lifestyle risk factors. As a “proof of concept,” I modeled COVID risk in the Massachusetts communities using 29 risk factors, including the prevalence of preexisting comorbid conditions like COPD and social factors such as racial composition. Of the 29 factors, 14 were found to be significant (p < 0.1) indicators: poverty, food insecurity, lack of high school education, lack of health insurance coverage, premature mortality, population, population density, recent population growth, Asian percentage, high-occupancy housing, and preexisting prevalence of cancer, COPD, overweightness, and heart attacks. The machine-learning approach finds the 9 highest risk communities in the state of Massachusetts: Lynn, Brockton, Revere, Randolph, Lowell, New Bedford, Everett, Waltham, and Fitchburg. The 5 most at-risk counties are Suffolk, Middlesex, Bristol, Norfolk, and Plymouth. With appropriate data, the tool could evaluate risk in other communities, or even enumerate individual patient susceptibility. A ranking of communities by risk may help policymakers ensure equitable allocation of limited doses of the COVID vaccine.
Physiological and psychosocial correlates of cancer related fatigue
Authors: Brownstein Callum G , Twomey Rosemary , Temesi John , Wrightson James G , Martin Tristan , Medysky Mary E. , Culos-Reed S. Nicole , Millet Guillaume Y
Published: October 2020

Cancer-related fatigue (CRF) is a common and distressing symptom of cancer and its treatments that may persist for years following treatment completion in approximately one-third of cancer survivors. Despite its high prevalence, little is known about the pathophysiology of CRF. Using a comprehensive group of physiological and psychosocial variables, the aim of the present study was to identify correlates of CRF in a heterogenous group of cancer survivors. Ninety-three cancer survivors (51 fatigued, 42 non-fatigued, with grouping based on validated cut-off scores derived from The Functional Assessment of Chronic Illness Therapy - Fatigue scale) completed assessments of performance fatigability (i.e. the change in maximal force-generating capacity, contractile function and capacity of the central nervous system to activate muscles caused by cycling exercise), cardiopulmonary exercise testing, venous blood samples for whole blood cell count and inflammatory markers and body composition. Participants also completed questionnaires measuring demographic, treatment-related, and psychosocial variables. The results showed that performance fatigability (decline in muscle strength during exercise), time-to-task-failure, peak oxygen uptake , tumor necrosis factor-α (TNF-α), body fat percentage and lean mass index were associated with CRF severity. Performance fatigability, , TNF-α and age explained 35% of the variance in CRF severity. Furthermore, those with clinically-relevant CRF reported more pain, more depressive symptoms, less social support, and were less physically active than non-fatigued cancer survivors. Given the association between CRF and numerous physical activity related measures, including performance fatigability, cardiorespiratory fitness, and anthropometric measures, the present study identifies potential biomarkers by which the mechanisms underpinning the effect of physical activity interventions on CRF can be investigated.
Leave-one-out cross-validation and linear modeling of visuospatial memory to predict long-term motor skill retention in individuals with and without chronic stroke: A short report
Authors: VanGilder Jennapher Lingo , Hooyman Andrew , Bosch Pamela R. , Schaefer Sydney Y.
Published: October 2020

Motor learning is fundamental to motor rehabilitation outcomes and has been associated with visuospatial memory function in previous studies. Current predictive models of motor recovery of individuals with stroke generally exclude cognitive measures, overlooking the connection between motor learning and visuospatial memory. Recent work has demonstrated that a clinical test of visuospatial memory (Rey-Osterrieth Complex Figure Delayed Recall) may predict one-month skill learning in older adults, but if this relationship persists in individuals with chronic stroke remains unknown. The purpose of this short report was to extend these findings by evaluating the extent these test scores impacted prediction in older adults and determine if this relationship generalized to individuals with stroke pathology. To address these questions, we trained two regression models (one including Delayed Recall scores and one without) using data from non-stroke older adults. To determine the extent to which Delayed Recall test scores impacted prediction accuracy of one-month skill learning in older adults, we used leave-one-out cross-validation to evaluate the prediction error between models. To determine if this predictive relationship persisted in individuals with chronic ischemic stroke, we then tested each trained model on an independent stroke dataset. Results indicated that in both stroke and non-stroke datasets, inclusion of Delayed Recall scores explained significantly more variance of one-month skill performance than models that included age, education, and baseline motor performance alone. This proof-of-concept suggests that the relationship between delayed visuospatial memory and one-month motor skill performance generalizes to individuals with chronic stroke and supports the idea that visuospatial testing may provide prognostic insight into motor rehabilitation outcomes.
Polygamous breeding system identified in the distylous genusPsychotria:P. manillensisin the Ryukyu archipelago, Japan
Authors: Watanabe Kenta , Shimizu Akira , Sugawara Takashi
Published: October 2020

Distyly is a genetic polymorphism composed of long- and short-styled flowers in a population. The evolutionary breakdown of distyly has been reported in many taxa, and mainly involves a shift toward monomorphism or dioecism. However, a shift toward monoecism has not been reported in distylous species.Psychotria(Rubiaceae), one of the world largest genera, consists of distylous species and their derivatives. In our preliminary study, however, we identified some monoecious individuals in a population ofPsychotria manillensis. To understand the breeding system and reproductive biology ofP. manillensis, we investigated floral traits, open fruit set, and flower visitors, and performed hand pollination and bagging experiments in five populations of Okinawa and Iriomote islands, Ryukyu Islands, Japan. The populations ofP. manillensiswere composed mainly of monoecious individuals (54%), followed by female (30%), male (14%), and hermaphroditic (2%) individuals at the time of flower collection. Of the collected flowers, 93% were functionally unisexual (male or female), whereas only 6.5% were perfect (hermaphroditic). However, some individuals changed sex mainly towards increasing femaleness during the flowering period. Moreover, 35% of the studied plants changed their sexual expression over the years.P. manillensisshowed self-compatibility and no agamospermy. The fruit set under open pollination varied among populations and years (1.8–21.9%), but it was significantly higher than that of auto-selfing (0.68–1.56%). Wasps and flies were the main flower visitors and probably the main pollinators of the species. In conclusion,P. manillensiswas revealed to be polygamous, involving monoecious, female, male, and hermaphroditic individuals. This is the first report of the polygamous breeding system not only in the genusPsychotria, but also in all heterostylous taxa.
Macroevolutionary Analyses Provide New Evidences of Phasmid Wings Evolution as a Reversible Process
Authors: Forni Giobbe , Martelossi Jacopo , Valero Pablo , Hennemann Frank H. , Conle Oskar , Luchetti Andrea , Mantovani Barbara
Published: October 2020

Abstract

The concept that complex ancestral traits can never be re-acquired after their loss has grown popular since its initial formulation and it’s often referred to as Dollo’s law. Nonetheless, several macroevolutionary evidences - along with molecular ones - suggest instances where complex phenotypes could have been lost throughout a clade evolutionary history and subsequently reverted to their former state in derived lineages. One of the first and most notable rejection of Dollo’s law is represented by wing evolution in phasmids: this polyneopteran order of insects - which comprises stick and leaf insects - has played a central role in initiating a long-standing debate on the topic. In this study, a novel and comprehensive time-tree - including over 300 Phasmatodea species - is used as a framework for investigating wing’s evolutionary patterns in the clade. Despite accounting for several possible biases and sources of uncertainty, macroevolutionary analyses consistently support a dynamic and reversible evolution of wings, with multiple transitions to ancestral states taking place after their loss. Our findings suggest that wings and flight are decoupled from Phasmatodea diversification dynamics and that brachyptery is an unstable state, unless when co-opted for non-aerodynamic adaptations. We also explored how different assumptions of wings’ reversals probability could impact their inference: we found that until reversals are assumed to be over 30 times more unlikely than losses, they are consistently retrieved despite uncertainty in tree and model parameters. Our findings demonstrate that wings evolution can be a reversible and dynamic process in phasmids and contribute to shape our understanding of how complex phenotypes evolve.
A Boolean Model of the Formation of Tumour Associated Macrophages in anin-vitroModel of Chronic Lymphocytic Leukaemia
Authors: Marku Malvina , Raynal Flavien , Verstraete Nina , Domagala Marcin , Madrid-Mencía Miguel , Poupot Mary , Fournié Jean-Jacques , Ysebaert Loïc , Pancaldi Vera
Published: October 2020

The tumour microenvironment is the collection of cells in and surrounding cancer cells in a tumour including a variety of immune cells, especially neutrophils and monocyte-derived macrophages. In a tumour setting, macrophages encompass a spectrum between a tumour-suppressive (M1) or tumour-promoting (M2) state. The biology of macrophages found in tumours (Tumour Associated Macrophages) remains unclear, but understanding their impact on tumour progression is highly important. In this paper, we perform a comprehensive analysis of a macrophage polarization network, following two lines of enquiry:(i)we reconstruct the macrophage polarization network based on literature, extending it to include important stimuli in a tumour setting, and(ii)we build a dynamical model able to reproduce macrophage polarization in the presence of different stimuli, including the contact with cancer cells. Our simulations recapitulate the documented macrophage phenotypes and their dependencies on specific receptors and transcription factors, while also elucidating the formation of a special type of tumour associated macrophages in anin-vitromodel of chronic lymphocytic leukaemia. This model constitutes the first step towards elucidating the cross-talk between immune and cancer cells inside tumours, with the ultimate goal of identifying new therapeutic targets that could control the formation of tumour associated macrophages in patients.
Immersive virtual reality interferes with default head-trunk coordination strategies in young children
Authors: Miehlbradt Jenifer C. , Cuturi Luigi F. , Zanchi Silvia , Gori Monica , Micera Silvestro
Published: October 2020

The acquisition of postural control is an elaborate process, which relies on the balanced integration of multisensory inputs. Current models suggest that young children rely on an ‘en-block’ control of their upper body before sequentially acquiring a segmental control around the age of 7, and that they resort to the former strategy under challenging conditions. While recent works suggest that a virtual sensory environment alters visuomotor integration in healthy adults, little is known about the effects on younger individuals.

Here we show that this coordination pattern is disrupted by an immersive virtual reality framework where a steering role is assigned to the trunk, which causes 6- to 8-year-olds to employ an ill-adapted segmental strategy. These results provide an alternate trajectory of motor development and emphasize the immaturity of postural control at these ages.