bluuebunny/crossref_metadata_2025 huggingface dataset:
Long tidal tails in merging galaxies and their implications
Authors: Ren Jian , Zheng X Z , Valls-Gabaud David , Duc Pierre-Alain , Bell Eric F , Pan Zhizheng , Qin Jianbo , Shi D D , Qiao Man , He Yongqiang , Wen Run
Published: September 2020

We investigate the properties of long tidal tails using the largest to date sample of 461 merging galaxies with $\log (M_\ast /\rm M_\odot)\ge 9.5$ within 0.2 ≤ z ≤ 1 from the COSMOS survey in combination with Hubble Space Telescope imaging data. Long tidal tails can be briefly divided into three shape types: straight (41 per cent), curved (47 per cent), and plume (12 per cent). Their host galaxies are mostly at late stages of merging, although 31 per cent are galaxy pairs with projected separations d > 20 kpc. The high formation rate of straight tidal tails needs to be understood as the projection of curved tidal tails accounts for only a small fraction of the straight tails. We identify 165 tidal dwarf galaxies (TDGs), yielding a TDG production rate of 0.36 per merger. Combined with a galaxy merger fraction and a TDG survival rate from the literature, we estimate that ∼5 per cent of local dwarf galaxies (DGs) are of tidal origin, suggesting the tidal formation is not an important formation channel for the DGs. About half of TDGs are located at the tip of their host tails. These TDGs have stellar masses in the range of $7.5\le \log (M_\ast /\rm M_\odot)\le 9.5$ and appear compact with half-light radii following the M*–Re relation of low-mass elliptical galaxies. However, their surface brightness profiles are generally flatter than those of local disc galaxies. Only 10 out of 165 TDGs have effective radii larger than 1.5 kpc and would qualify as unusually bright ultradiffuse galaxies.
Gene-Level, but Not Chromosome-Wide, Divergence between a Very Young House Fly Proto-Y Chromosome and Its Homologous Proto-X Chromosome
Authors: Son Jae Hak , Meisel Richard P
Published: September 2020

X and Y chromosomes are usually derived from a pair of homologous autosomes, which then diverge from each other over time. Although Y-specific features have been characterized in sex chromosomes of various ages, the earliest stages of Y chromosome evolution remain elusive. In particular, we do not know whether early stages of Y chromosome evolution consist of changes to individual genes or happen via chromosome-scale divergence from the X. To address this question, we quantified divergence between young proto-X and proto-Y chromosomes in the house fly, Musca domestica. We compared proto-sex chromosome sequence and gene expression between genotypic (XY) and sex-reversed (XX) males. We find evidence for sequence divergence between genes on the proto-X and proto-Y, including five genes with mitochondrial functions. There is also an excess of genes with divergent expression between the proto-X and proto-Y, but the number of genes is small. This suggests that individual proto-Y genes, but not the entire proto-Y chromosome, have diverged from the proto-X. We identified one gene, encoding an axonemal dynein assembly factor (which functions in sperm motility), that has higher expression in XY males than XX males because of a disproportionate contribution of the proto-Y allele to gene expression. The upregulation of the proto-Y allele may be favored in males because of this gene’s function in spermatogenesis. The evolutionary divergence between proto-X and proto-Y copies of this gene, as well as the mitochondrial genes, is consistent with selection in males affecting the evolution of individual genes during early Y chromosome evolution.
Microchromosomes Exhibit Distinct Features of Vertebrate Chromosome Structure and Function with Underappreciated Ramifications for Genome Evolution
Authors: Perry Blair W , Schield Drew R , Adams Richard H , Castoe Todd A
Published: September 2020

Microchromosomes are common yet poorly understood components of many vertebrate genomes. Recent studies have revealed that microchromosomes contain a high density of genes and possess other distinct characteristics compared with macrochromosomes. Whether distinctive characteristics of microchromosomes extend to features of genome structure and organization, however, remains an open question. Here, we analyze Hi-C sequencing data from multiple vertebrate lineages and show that microchromosomes exhibit consistently high degrees of interchromosomal interaction (particularly with other microchromosomes), appear to be colocalized to a common central nuclear territory, and are comprised of a higher proportion of open chromatin than macrochromosomes. These findings highlight an unappreciated level of diversity in vertebrate genome structure and function, and raise important questions regarding the evolutionary origins and ramifications of microchromosomes and the genes that they house.
FACT and Ash1 promote long-range and bidirectional nucleosome eviction at the HO promoter
Authors: Yu Yaxin , Yarrington Robert M , Stillman David J
Published: September 2020

The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.
Low-Profile Visualized Intraluminal Support Jr Braided Stent Versus Atlas Self-Expandable Stent for Treatment of Intracranial Aneurysms: A Single Center Experience
Authors: Monteiro Andre , Cortez Gustavo M , Aghaebrahim Amin , Sauvageau Eric , Hanel Ricardo A
Published: September 2020

BACKGROUND

The Neuroform Atlas Stent and Low-profile Visualized Intraluminal Support (LVIS) and LVIS Jr stents are used to treat intracranial aneurysms (IAs), but their safety, performance, and outcomes have not been directly compared.

OBJECTIVE

To compare the technical performance and outcomes of Atlas and LVIS Jr stents for treatment of IAs.

METHODS

IAs treated by stent-assisted coiling using an Atlas (Stryker, Kalamazoo, Michigan) or LVIS Jr (MicroVention, Aliso Viejo, California) device between January 2014 to November 2019 were retrospectively evaluated. Patient demographics, aneurysm size and location, technical difficulties, and clinical and angiographic follow-up were analyzed.

RESULTS

A total of 116 patients, (mean age 64.2 ± 11.8 yr, 72.7% female) with 121 aneurysms underwent stent-assisted coiling with deployment of Atlas (n = 64) or LVIS Jr (n = 57) stents. Mean aneurysm size was 6.2 ± 2.7 mm. Immediate rates of Raymond-Roy (RR) 1/2 were 89.0% (57/64) and 80.7% (46/57) for the Atlas and LVIS Jr groups, respectively. Neither group had major postoperative thromboembolic complications; however, 15.8% (9/57) of the LVIS Jr procedures had technical issues. Additionally, 88.5% (46/52) and 91.2% (33/36) of patients in the Atlas and LVIS Jr groups had RR 1/2 at a mean follow-up of 13.6 and 18.7 mo, respectively.

CONCLUSION

Treatment of IAs with Atlas and LVIS Jr stents results in favorable clinical outcomes and angiographic results at follow-up, with low rates of recurrence and retreatment, suggesting both devices are safe and effective. Notably, LVIS Jr had more technical problems than Atlas.
Predicting the Extent of Resection in Low-Grade Glioma by Using Intratumoral Tractography to Detect Eloquent Fascicles Within the Tumor
Authors: Mato David , Velasquez Carlos , Gómez Elsa , Marco de Lucas Enrique , Martino Juan
Published: September 2020

BACKGROUND

An early maximal safe surgical resection is the current treatment paradigm for low-grade glioma (LGG). Nevertheless, there are no reliable methods to accurately predict the axonal intratumoral eloquent areas and, consequently, to predict the extent of resection.

OBJECTIVE

To describe the functional predictive value of eloquent white matter tracts within the tumor by using a pre- and postoperative intratumoral diffusion tensor imaging (DTI) tractography protocol in patients with LGG.

METHODS

A preoperative intratumoral DTI-based tractography protocol, using the tumor segmented volume as the only seed region, was used to assess the tracts within the tumor boundaries in 22 consecutive patients with LGG. The reconstructed tracts were correlated with intraoperative electrical stimulation (IES)-based language and motor subcortical mapping findings and the extent of resection was assessed by tumor volumetrics.

RESULTS

Identification of intratumoral language and motor tracts significantly predicted eloquent areas within the tumor during the IES mapping: the positive predictive value for the pyramidal tract, the inferior fronto-occipital fasciculus, the arcuate fasciculus and the inferior longitudinal fasciculus positive was 100%, 100%, 33%, and 80%, respectively, whereas negative predictive value was 100% for all of them. The reconstruction of at least one of these tracts within the tumor was significantly associated with a lower extent of resection (67%) as opposed to the extent of resection in the cases with a negative intratumoral tractography (100%) (P < .0001).

CONCLUSION

Intratumoral DTI-based tractography is a simple and reliable method, useful in assessing glioma resectability based on the analysis of intratumoral eloquent areas associated with motor and language tracts within the tumor.
Occurrence, Risk Factors, and Time Trends for Late Reoperations due to Degenerative Cervical Spine Disease: A Finnish National Register Study of 19 377 Patients Operated on Between 1999 and 2015
Authors: Kotkansalo Anna , Leinonen Ville , Korajoki Merja , Korhonen Katariina , Rinne Jaakko , Malmivaara Antti
Published: September 2020

BACKGROUND

Surgery for degenerative cervical spine disease has escalated since the 1990s. Fusion has become the mainstay of surgery despite concerns regarding adjacent segment degeneration. The patient-specific trends in reoperations have not been studied previously.

OBJECTIVE

To analyze the occurrence, risk factors, and trends in reoperations in a long-term follow-up of all the patients operated for degenerative cervical spine disease in Finland between 1999 and 2015.

METHODS

The patients were retrospectively identified from the Hospital Discharge Registry. Reoperations were traced individually; only reoperations occurring >365 d after the primary operation were included. Time trends in reoperations and the risk factors were analyzed by regression analysis.

RESULTS

Of the 19 377 identified patients, 9.2% underwent a late reoperation at a median of 3.6 yr after the primary operation. The annual risk of reoperation was 2.4% at 2 yr, 6.6% at 5 yr, 11.1% at 10 yr, and 14.2% at 15 yr. Seventy-five percent of the late reoperations occurred within 6.5 yr of the primary operation. Foraminal stenosis, the anterior cervical decompression and fusion (ACDF) technique, male gender, weak opiate use, and young age were the most important risk factors for reoperation. There was no increase in the risk of reoperations over the follow-up period.

CONCLUSION

The risk of reoperation was stable between 1999 and 2015. The reoperation risk was highest during the first 6 postoperative years and then declined. Patients with foraminal stenosis had the highest risk of reoperation, especially when ACDF was performed.
Impact of Frailty on Outcomes Following Spine Surgery: A Prospective Cohort Analysis of 668 Patients
Authors: Agarwal Nitin , Goldschmidt Ezequiel , Taylor Tavis , Roy Souvik , Dunn Stefanie C Altieri , Bilderback Andrew , Friedlander Robert M , Kanter Adam S , Okonkwo David O , Gerszten Peter C , Hamilton D Kojo , Hall Daniel E
Published: September 2020

BACKGROUND

With an aging population, elderly patients with multiple comorbidities are more frequently undergoing spine surgery and may be at increased risk for complications. Objective measurement of frailty may predict the incidence of postoperative adverse events.

OBJECTIVE

To investigate the associations between preoperative frailty and postoperative spine surgery outcomes including mortality, length of stay, readmission, surgical site infection, and venous thromboembolic disease.

METHODS

As part of a system-wide quality improvement initiative, frailty assessment was added to the routine assessment of patients considering spine surgery beginning in July 2016. Frailty was assessed with the Risk Analysis Index (RAI), and patients were categorized as nonfrail (RAI 0-29) or prefrail/frail (RAI ≥ 30). Comparisons between nonfrail and prefrail/frail patients were analyzed using Fisher's exact test for categorical data or by Wilcoxon rank sum tests for continuous data.

RESULTS

From August 2016 through September 2018, 668 patients (age of 59.5 ± 13.3 yr) had a preoperative RAI score recorded and underwent scheduled spine surgery. Prefrail and frail patients suffered comparatively higher rates of mortality at 90 d (1.9% vs 0.2%, P < .05) and 1 yr (5.1% vs 1.2%, P < .01) from the procedure date. They also had longer in-hospital length of stay (LOS) (3.9 d ± 3.6 vs 3.1 d ± 2.8, P < .001) and higher rates of 60 d (14.6% vs 8.2%, P < .05) and 90 d (15.8% vs 9.8%, P < .05) readmissions.

CONCLUSION

Preoperative frailty, as measured by the RAI, was associated with an increased risk of readmission and 90-d and 1-yr mortality following spine surgery. The RAI can be used to stratify spine patients and inform preoperative surgical decision making.
Acute Hepatitis B Infection After a Switch to Long-Acting Cabotegravir and Rilpivirine
Authors: Pintado Claire , Delaugerre Constance , Molina Jean-Michel
Published: September 2020

Maintenance antiretroviral therapy with combination of two injectable long-acting drugs, cabotegravir and rilpivirine, is a new strategy addressing the challenges of daily adherence to oral pills that has shown non-inferior efficacy to standard of care therapy in patients with suppressed HIV-infection. Patients co-infected with hepatitis B virus (HBV) are not eligible for this dual therapy since it has no activity against HBV, but this strategy should also be restricted to patients with anti-HBs antibodies since people with HIV are still at risk of HBV acquisition due to high risk behavior and since HBV vaccination does not always elicit anti-HBs antibodies, as highlighted in the case report below.
Political Cycles in Bank Lending to the Government
Authors: Koetter Michael , Popov Alexander
Published: September 2020

We study how political party turnover after German state elections affects banks’ lending to the regional government. We find that between 1992 and 2018, party turnover at the state level leads to a sharp and substantial increase in lending by local savings banks to their home-state government. This effect is accompanied by an equivalent reduction in private lending. A statistical association between political party turnover and government lending is absent for comparable cooperative banks that exhibit a similar regional organization and business model. Our results suggest that political frictions may interfere with government-owned banks’ local development objectives.
Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986
Authors: Ramsay Hugh , Surcel Heljä-Marja , Björnholm Lassi , Kerkelä Martta , Khandaker Golam M , Veijola Juha
Published: September 2020

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.
Distinguishing Oneself From Others: Spontaneous Perspective-Taking in First-Episode Schizophrenia and its relation to Mentalizing and Psychotic Symptoms
Authors: Simonsen Arndis , Mahnkeke Mia Ilsø , Fusaroli Riccardo , Wolf Thomas , Roepstorff Andreas , Michael John , Frith Chris D , Bliksted Vibeke
Published: September 2020

Characteristic symptoms of schizophrenia, such as thought broadcasting, verbal hallucinations, and delusions of being controlled, suggest a failure in distinguishing between oneself and others. In addition, patients frequently experience mentalizing deficits, which could be related to such a failure. Here we investigated the tendency to distinguish self and other with a visual perspective-taking task that measures to what extent individuals spontaneously take another’s perspective when having to process their own (altercentric intrusion) or vice versa (egocentric intrusion). This was done in 22 patients with first-episode schizophrenia and 23 matched healthy controls. We assessed whether patients displayed altered altercentric or egocentric intrusion and whether such alterations are related to mentalizing deficits—as measured with the Animated Triangles Task (ATT) and The Awareness of Social Inference Task (TASIT) —and/or specific psychotic symptoms, suggestive of problems with self-other distinction. The results showed that patients display similar egocentric intrusion and increased altercentric intrusion compared to controls. Degree of altercentric intrusion was associated with severity of delusions and hallucinations that have been tied to problems with self-other distinction but not with unrelated delusions and hallucinations or negative symptom severity. Higher altercentric intrusion was also associated with better TASIT performance in both patients and controls; suggesting that it may also be beneficial. In conclusion, patients display difficulties inhibiting representations of the other when having to process self-relevant information. A failure to control or distinguish the 2 representations could give rise to the experience that others have access to and control of your thoughts and actions.
Convergent patterns of structural brain changes in rapid eye movement sleep behavior disorder and Parkinson’s disease on behalf of the German rapid eye movement sleep behavior disorder study group
Authors: Holtbernd Florian , Romanzetti Sandro , Oertel Wolfgang Hermann , Knake Susanne , Sittig Elisabeth , Heidbreder Anna , Maier Andrea , Krahe Janna , Wojtala Jennifer , Dogan Imis , Schulz Jörg Bernhard , Schiefer Johannes , Janzen Annette , Reetz Kathrin
Published: September 2020

Study Objectives

Rapid eye movement sleep behavior disorder (RBD) is considered a prodromal state of Parkinson’s disease (PD). We aimed to characterize patterns of structural brain changes in RBD and PD patients using multimodal MRI.

Methods

A total of 30 patients with isolated RBD, 29 patients with PD, and 56 age-matched healthy controls (HC) underwent MRI at 3T, including tensor-based morphometry, diffusion tensor imaging, and assessment of cortical thickness.

Results

RBD individuals showed increased volume of the right caudate nucleus compared with HC, and higher cerebellar volume compared with both PD subjects and HC. Similar to PD subjects, RBD patients displayed increased fractional anisotropy (FA) in the corticospinal tracts, several tracts mainly related to non-motor function, and reduced FA of the corpus callosum compared with HC. Further, RBD subjects showed higher FA in the cerebellar peduncles and brainstem compared with both, PD patients and HC. PD individuals exhibited lower than normal volume in the basal ganglia, midbrain, pedunculopontine nuclei, and cerebellum. In contrast, volume in PD subjects was increased in the thalamus compared with both HC and RBD subjects.

Conclusions

We found convergent patterns of structural brain alterations in RBD and PD patients compared with HC. The changes observed suggest a co-occurrence of neurodegeneration and compensatory mechanisms that fail with emerging PD pathology. Our findings strengthen the hypothesis of RBD and PD constituting a continuous disease spectrum.
Parallel ddRAD and Genome Skimming Analyses Reveal a Radiative and Reticulate Evolutionary History of the Temperate Bamboos
Authors: Guo Cen , Ma Peng-Fei , Yang Guo-Qian , Ye Xia-Ying , Guo Ying , Liu Jing-Xia , Liu Yun-Long , Eaton Deren A R , Guo Zhen-Hua , Li De-Zhu
Published: September 2020

Rapid evolutionary radiations are among the most challenging phylogenetic problems, wherein different types of data (e.g., morphology and molecular) or genetic markers (e.g., nuclear and organelle) often yield inconsistent results. The tribe Arundinarieae, that is, the temperate bamboos, is a clade of tetraploid originated 22 Ma and subsequently radiated in East Asia. Previous studies of Arundinarieae have found conflicting relationships and/or low support. Here, we obtain nuclear markers from ddRAD data for 213 Arundinarieae taxa and parallel sampling of chloroplast genomes from genome skimming for 147 taxa. We first assess the feasibility of using ddRAD-seq data for phylogenetic estimates of paleopolyploid and rapidly radiated lineages, optimize clustering thresholds, and analysis workflow for orthology identification. Reference-based ddRAD data assembly approaches perform well and yield strongly supported relationships that are generally concordant with morphology-based taxonomy. We recover five major lineages, two of which are notable (the pachymorph and leptomorph lineages), in that they correspond with distinct rhizome morphologies. By contrast, the phylogeny from chloroplast genomes differed significantly. Based on multiple lines of evidence, the ddRAD tree is favored as the best species tree estimation for temperate bamboos. Using a time-calibrated ddRAD tree, we find that Arundinarieae diversified rapidly around the mid-Miocene corresponding with intensification of the East Asian monsoon and the evolution of key innovations including the leptomorph rhizomes. Our results provide a highly resolved phylogeny of Arundinarieae, shed new light on the radiation and reticulate evolutionary history of this tribe, and provide an empirical example for the study of recalcitrant plant radiations. [Arundinarieae; ddRAD; paleopolyploid; genome skimming; rapid diversification; incongruence.]
Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis
Authors: Alcantara Diana R , Jones Christopher I , Altmann Daniel M , Boyton Rosemary J , Haniffa Muzlifah , Newport Melanie J
Published: September 2020

Background

Podoconiosis is a tropical lymphoedema of the leg resulting from barefoot exposure to irritant volcanic soils. Approximately 4 million people are affected, mainly in African highland regions. The pathogenesis of this neglected tropical disease is still largely unknown, although HLA class II (HLAII) polymorphisms are associated with the disease.

Methods

NanoString technology was used to assess expression of 579 immune-related genes in formalin-fixed and paraffin-embedded lymph node archival samples from podoconiosis patients and unaffected controls.

Results

Forty-eight genes were upregulated and 21 downregulated in podoconiosis samples compared with controls. Gene ontology analysis showed differentially expressed genes to be closely related to major histocompatibility complex protein, cytokine and TNF receptor binding genes. Pathway enrichment analysis revealed involvement of lymphocyte activation, adaptive immunity, cytokine signalling, antigen processing and the IL-12 pathways.

Conclusions

This exploratory study reports a multiplex gene expression analysis in podoconiosis and shows upregulation of pro-inflammatory transcripts compatible with the notion of local, chronic immune activation in this HLAII-associated disease. Implicated pathways will inform future research into podoconiosis immunopathogenesis.
Assessing the Quality of Low-Frequency Acoustic Hearing: Implications for Combined Electroacoustic Stimulation With Cochlear Implants
Authors: Spitzer Emily R. , Landsberger David M. , Friedmann David R.
Published: September 2020

Objectives:

There are many potential advantages to combined electric and acoustic stimulation (EAS) with a cochlear implant (CI), including benefits for hearing in noise, localization, frequency selectivity, and music enjoyment. However, performance on these outcome measures is variable, and the residual acoustic hearing may not be beneficial for all patients. As such, we propose a measure of spectral resolution that might be more predictive of the usefulness of the residual hearing than the audiogram alone. In the following experiments, we measured performance on spectral resolution and speech perception tasks in individuals with normal hearing (NH) using low-pass filters to simulate steeply sloping audiograms of typical EAS candidates and compared it with performance on these tasks for individuals with sensorineural hearing loss with similar audiometric configurations. Because listeners with NH had similar levels of audibility and bandwidth to listeners with hearing loss, differences between the groups could be attributed to distortions due to hearing loss.

Design:

Listeners with NH (n = 12) and those with hearing loss (n = 23) with steeply sloping audiograms participated in this study. The group with hearing loss consisted of 7 EAS users, 14 hearing aid users, and 3 who did not use amplification in the test ear. Spectral resolution was measured with the spectral-temporal modulated ripple test (SMRT), and speech perception was measured with AzBio sentences in quiet and noise. Listeners with NH listened to stimuli through low-pass filters and at two levels (40 and 60 dBA) to simulate low and high audibility. Listeners with hearing loss listened to SMRT stimuli unaided at their most comfortable listening level and speech stimuli at 60 dBA.

Results:

Results suggest that performance with SMRT is significantly worse for listeners with hearing loss than for listeners with NH and is not related to audibility. Performance on the speech perception task declined with decreasing frequency information for both listeners with NH and hearing loss. Significant correlations were observed between speech perception, SMRT scores, and mid-frequency audiometric thresholds for listeners with hearing loss.

Conclusions:

NH simulations describe a “best case scenario” for hearing loss where audibility is the only deficit. For listeners with hearing loss, the likely broadening of auditory filters, loss of cochlear nonlinearities, and possible cochlear dead regions may have contributed to distorted spectral resolution and thus deviations from the NH simulations. Measures of spectral resolution may capture an aspect of hearing loss not evident from the audiogram and be a useful tool for assessing the contributions of residual hearing post–cochlear implantation.
Patients’ Experiences of Deciding Whether or Not to Accept Bone Conduction Hearing Implants: A Qualitative Investigation
Authors: McFarland Sophie M. , Powell Rachael , Green Kevin , Andrew Rachel , Coppack Kathryn , Hill-Feltham Penny , Wearden Alison
Published: September 2020

Objectives:

Bone conduction hearing implants (BCHIs) are an effective option to rehabilitate hearing for people who cannot use conventional, air conduction hearing aids. However, the uptake of such devices in the United Kingdom is lower than might be expected, and the reasons for this are not fully understood. The present study used qualitative methods to explore decision-making about whether to accept or reject BCHIs.

Design:

Semistructured telephone interviews were conducted with 17 BCHI candidates who had recently accepted or rejected BCHIs.

Results:

A thematic analysis identified four overarching themes: participants wanted to look and feel normal; potential risks were weighed against rewards; participants felt that there was a “right time” to have a BCHI; and information from clinicians and BCHI users was treated differently. Participants’ perceptions of normality were influential in the final decision, and the BHCI was seen either as a barrier or facilitator of this. Participants consistently weighed up potential advantages and disadvantages of BCHIs, with potential for hearing improvement typically used as a benchmark against which other factors were measured. Some participants who rejected BCHIs felt that they could reconsider having a BCHI when they felt the time was right for them. Participants highly valued advice from clinicians, but felt that their expertise lacked validity as clinicians typically did not have experience of using BCHIs themselves.

Conclusions:

The decision to accept or reject a BCHI was highly individual. Each participant considered a range of factors; the influence of each factor depended on the individual’s perceptions and experiences. This work highlights the importance of clinical staff being able to explore the individual priorities and concerns of each patient to ensure that patients feel happy and confident with the decision that they make.
Improved Sensitivity of Digits-in-Noise Test to High-Frequency Hearing Loss
Authors: Motlagh Zadeh Lina , Silbert Noah H. , Swanepoel De Wet , Moore David R.
Published: September 2020

Objectives:

Hearing loss is most commonly observed at high frequencies. High-frequency hearing loss (HFHL) precedes and predicts hearing loss at lower frequencies. It was previously shown that an automated, self-administered digits-in-noise (DIN) test can be sensitized for detection of HFHL by low-pass filtering the speech-shaped masking noise at 1.5 kHz. This study was designed to investigate whether sensitivity of the DIN to HFHL can be enhanced further using low-pass noise filters with higher cutoff frequencies.

Design:

The US-English digits 0 to 9, homogenized for audibility, were binaurally presented in different noise maskers including one broadband and three low-pass (cutoff at 2, 4, and 8 kHz) filtered speech-shaped noises. DIN-speech reception thresholds (SRTs) were obtained from 60 normal hearing (NH), and 40 mildly hearing impaired listeners with bilateral symmetric sensorineural hearing loss. Standard and extended high-frequency audiometric pure-tone averages (PTAs) were compared with the DIN-SRTs.

Results:

Narrower masking noise bandwidth generally produced better (more sensitive) mean DIN-SRTs. There were strong and significant correlations between SRT and PTA in the hearing impaired group. Lower frequency PTALF 0.5,1, 2, 4 kHz had the highest correlation and the steepest slope with SRTs obtained from the 2-kHz filter. Higher frequency PTAHF 4,8,10,12.5 kHz correlated best with SRTs obtained from 4- and 8-kHz filtered noise. The 4-kHz low-pass filter also had the highest sensitivity (92%) and equally highest (with the 8-kHz filter) specificity (90%) for detecting an average PTAHF of 20 dB or more.

Conclusions:

Of the filters used, DIN sensitivity to higher frequency hearing loss was greatest using the 4-kHz low-pass filter. These results suggest that low-pass filtered noise may be usefully substituted for broadband noise to improve earlier detection of HFHL using DIN.
Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells
Authors: Jin Hongyong , Gao Sujie , Song Defeng , Liu Yiting , Chen Xuebo
Published: September 2020

Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and suppress the colon cancer liver metastasis has not been evaluated. In this study, we report CNT enhances CpG uptake in mouse colon cancer cells. Results demonstrated only CpG with CNT conjugation showed significant activation of NF-κB signal. Moreover, intratumorally delivery of CNT-CpG successfully suppressed local xenograft tumor growth and liver metastasis. CNT-CpG treatments cured 75% of mice and inhibited local tumor growth, significantly prolonged survival outcomes and limited liver metastatic tumor nodules from colon cancer cells. Using human colon cancer cell line, HCT116, we observed significantly inhibitory effects of CNT-CpG on cell growth, invasion and migration. Importantly, CNT-CpG treatment blocked the epithelial to mesenchymal transition (EMT). We compared the mRNA levels of EMT markers of colon cancer cells without or with CNT-CpG treatment from in-vitro and in-vivo models. Consistent results demonstrated expression of epithelial marker, E-cadherin was upregulated by CNT-CpG. In contrast, three mesenchymal markers, snail, fibronectin and vimentin were significantly suppressed by CNT-CpG treatment compared with control or free CpG. In summary, our data suggest CNT-CpG is an effective therapeutic approach against local colon tumor and their liver metastasis. This study presents the CNT-CpG complex as a promising therapeutic target for developing novel therapies against both local colon tumors and liver metastatic tumors.
Discovery and Validation of Urinary Molecular Signature of Early Sepsis
Authors: Bandyopadhyay Sabyasachi , Lysak Nicholas , Adhikari Lasith , Velez Laura M. , Sautina Larysa , Mohandas Rajesh , Lopez Maria-Cecilia , Ungaro Ricardo , Peng Ying-Chih , Kadri Ferdous , Efron Philip , Brakenridge Scott , Moldawer Lyle , Moore Frederick , Baker Henry V. , Segal Mark S. , Ozrazgat-Baslanti Tezcan , Rashidi Parisa , Bihorac Azra
Published: September 2020

Objectives:

Identify alterations in gene expression unique to systemic and kidney-specific pathophysiologic processes using whole-genome analyses of RNA isolated from the urinary cells of sepsis patients.

Design:

Prospective cohort study.

Setting:

Quaternary care academic hospital.

Patients:

A total of 266 sepsis and 82 control patients enrolled between January 2015 and February 2018.

Interventions:

Whole-genome transcriptomic analysis of messenger RNA isolated from the urinary cells of sepsis patients within 12 hours of sepsis onset and from control subjects.

Measurements and Main Results:

The differentially expressed probes that map to known genes were subjected to feature selection using multiple machine learning techniques to find the best subset of probes that differentiates sepsis from control subjects. Using differential expression augmented with machine learning ensembles, we identified a set of 239 genes in urine, which show excellent effectiveness in classifying septic patients from those with chronic systemic disease in both internal and independent external validation cohorts. Functional analysis indexes disrupted biological pathways in early sepsis and reveal key molecular networks driving its pathogenesis.

Conclusions:

We identified unique urinary gene expression profile in early sepsis. Future studies need to confirm whether this approach can complement blood transcriptomic approaches for sepsis diagnosis and prognostication.
Impact of Geographical Cohorting in the ICU: An Academic Tertiary Care Center Experience
Authors: Kapoor Rajat , Gupta Nupur , Roberts Scott D. , Naum Chris , Perkins Anthony J. , Khan Babar A.
Published: September 2020

Objectives:

ICU is a multifaceted organization where multiple teams care for critically ill patients. In the current era, collaboration between teams and efficient workflows form the backbone of value-based care. Geographical cohorting is a widespread model for hospitalist rounding, but its role in ICUs is unclear. This study evaluates the outcomes of geographical cohorting in a large ICU of an Academic Health Center.

Design:

This is a retrospective analysis of quality metrics collected 12 months pre- and post-implementation of geographical cohorting.

Setting:

A total of 130 bedded ICU at tertiary academic health center in Midwest.

Patients:

All patients admitted to the ICU.

Interventions:

Our institution piloted the geographical cohorting model for critical care physician rounding on September 1, 2018.

Measurements:

The quality metrics were categorized as ICU harm events and ICU hospital metrics. Team of critical care providers were surveyed 12 months after implementation.

Main Results:

The critical care utilization in the pre- and post-implementation numbers were similar for patient days (pre = 34,839, post = 35,155), central-line days (pre = 17,648, post = 19,224), and Foley catheter days (pre = 18,292, post = 17,364). The ICU length of stay was similar (4.9 d) in both pre- and post-intervention periods. Significant reduction in the incidence of Clostridium difficile infection (relative risk, –0.50; 95% CI, 0.25–0.96; p = 0.039), hospital-acquired pressure injury (relative risk, –0.60; 95% CI, 0.39–0.92; p = 0.020), central line-associated bloodstream infection incidence (relative risk, –0.19; 95% CI, 0.05–0.52; p = 0.008), and catheter-associated urinary tract infection (relative risk, –0.52; 95% CI, 0.29–0.93; p = 0.027). Healthcare providers perceived optimal utilization of their time, reduced interruptions, and improved coordination of care with geographical rounding.

Conclusions:

Geographical cohorting improves coordination of care, physician workflow, and critical care quality metrics in very large ICUs.
A Higher Fluid Balance in the Days After Septic Shock Reversal Is Associated With Increased Mortality: An Observational Cohort Study
Authors: van Mourik Niels , Geerts Bart F. , Binnekade Jan M. , Veelo Denise P. , Bos Lieuwe D. J. , Wiersinga W. Joost , van der Poll Tom , Cremer Olaf L. , Schultz Marcus J. , Vlaar Alexander P. J.
Published: September 2020

Objectives:

Previous studies demonstrated that extensive fluid loading and consequently positive fluid balances during sepsis resuscitation are associated with adverse outcome. Yet, the association between fluid balance and mortality after reversal of shock, that is, during deresuscitation, is largely unappreciated. Our objective was to investigate the effects of fluid balance on mortality in the days after septic shock reversal.

Design:

Retrospective observational cohort study.

Setting:

ICUs of two university-affiliated hospitals in The Netherlands.

Patients:

Adult patients admitted with septic shock followed by shock reversal. Reversal of septic shock was defined based on Sepsis-3 criteria as the first day that serum lactate was less than or equal to 2 mmol/L without vasopressor requirement.

Interventions:

None.

Measurements and Main Results:

Reversal of septic shock occurred in 636 patients, of whom 20% died in the ICU. Mixed-effects logistic regression modeling, adjusted for possible confounders, showed that fluid balance in the days after reversal of septic shock (until discharge or death) was an independent predictor of ICU mortality: odds ratio 3.18 (1.90–5.32) per 10 mL/kg increase in daily fluid balance. Similar results were found for 30-day, 90-day, hospital, and 1-year mortality: odds ratios 2.09 (1.64–2.67); 1.79 (1.38–2.32); 1.70 (1.40–2.07); and 1.53 (1.17–2.01), respectively. Positive cumulative fluid balances vs. neutral or negative fluid balances on the final day in the ICU were associated with increased ICU, hospital, 30-day, and 90-day mortality: odds ratios 3.46 (2.29–5.23); 3.39 (2.35–4.9); 5.33 (3.51–8.08); and 3.57 (2.49–5.12), respectively. Using restricted cubic splines, we found a dose-response relationship between cumulative fluid balance after shock reversal and ICU mortality.

Conclusions:

A higher fluid balance in the days after septic shock reversal was associated with increased mortality. This stresses the importance of implementing restrictive and deresuscitative fluid management strategies after initial hemodynamic resuscitation. Prospective interventional studies are needed to confirm our results.
Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population
Authors: Malińska Karolina , Deptuła Jakub , Rogoża-Janiszewska Emilia , Górski Bohdan , Scott Rodney , Rudnicka Helena , Kashyap Aniruddh , Domagała Paweł , Hybiak Jolanta , Masojć Bartłomiej , Cybulski Cezary , Kram Andrzej , Boer Magdalena , Kiedrowicz Magdalena , Lubiński Jan , Dębniak Tadeusz
Published: September 2020

Evaluation of the prevalence of POT1, ACD, and TERF2IP mutations among Polish melanoma patients. A cohort of 60 patients from melanoma-prone families, 1500 unselected cases and 1500 controls were genotyped. Methodology included Sanger sequencing, in-silico software predilection, and TaqMan assays. We identified three nonsynonymous variants: POT1 c.903 G>T; TERF2IP c.970 A>G; and ACD c.1544 T>C and a splice site variant ACD c.645 G>A. The c.903 G>T was predicted to be pathogenic according to PolyPhen-2, benign according to Mutation Taster, PROVEAN, AGVGD, and SIFT. The c.645 G>A was defined as disease caused by Mutation Taster and Human Splicing Finder and as variant of unknown significance by ClinVar. The other detected variants were described as benign. The c.903 G>T variant was present in two unselected cases and one control [P = 0.57, odds ratio (OR) = 2.00]; the c.645 G>A variant was not detected among the unselected cases and the controls; the c.970 A>G variant was present in 110 cases and 133 controls (P = 0.14, OR = 0.81); the c.1544 T>C variant was present in 687 cases and 642 controls (P = 0.11, OR = 1.07). We found no loss of heterozygosity of the c.903 G>T, c.970 A>G, and c.645 G>A variants. C.645 G>A variant had no effect on splicing or expression. The changes in POT1 c.903 G>T and ACD c.645 G>A can be classified as rare variants of unknown significance, the other variants appear to be polymorphisms. Germline mutations in POT1, ACD, and TERF2IP are infrequent among Polish melanoma patients.
Adjuvant FOLFOX+Nab-Paclitaxel (FOLFOX-A) for Pancreatic Cancer
Authors: Raufi Alexander G. , Breakstone Rimini , Leonard Kara , Charpentier Kevin , Beard Rachel , Renaud Jennifer , Cavanaugh Lindsey , Sturtevant Ashlee , MacKinnon Kelsey , Almhanna Khaldoun , Olszewski Adam , Safran Howard P.
Published: September 2020

Objectives:

Multiple clinical trials have established a role for adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma. Adjuvant FOLFIRINOX increases survival as compared with gemcitabine but with increased toxicity. FOLFOX+nab-paclitaxel (FOLFOX-A) was developed by the Brown University Oncology Research Group (BrUOG) as an alternative to FOLFIRINOX. This phase II trial explored the feasibility and toxicity of adjuvant FOLFOX-A in patients who have completed resection for pancreatic ductal adenocarcinoma.

Patients and Methods:

Patients with resected pancreatic ductal adenocarcinoma were eligible. The primary objective was to determine the feasibility of adjuvant FOLFOX-A. Patients experiencing grade 2 neuropathy received a 20% reduction of oxaliplatin. Secondary end points were disease-free survival, and overall survival.

Results:

Between June 2014 and October 2018, 25 patients were enrolled following surgical resection. The median number of cycles completed was 9.5. Median disease-free survival was 19.7 months (95% confidence interval, 10.3 to not reached) and median overall survival was 53.5 months (95% confidence interval, 24.2 to not reached). The most common treatment-related grade 3 or greater adverse events were fatigue (58%), nausea (13%), and neutropenia (26%). Fourteen patients had grade 2 neuropathy (58%) and 1 patient (4%) had grade 3 neuropathy. Only 2 patients (8%) had grade 3 diarrhea.

Conclusions:

Adjuvant FOLFOX-A is a feasible multi-agent adjuvant treatment regimen and, with further validation, could be an alternative to FOLFIRINOX.
Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016
Authors: Sanford Nina N. , Folkert Michael R. , Aguilera Todd A. , Beg Muhammad S. , Kazmi Syed A. , Sanjeevaiah Aravind , Zeh Herbert J. , Farkas Linda
Published: September 2020

Background:

When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC.

Methods:

Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression.

Results:

Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001).

Conclusions:

From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.