bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractRapid 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

Abstract

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.
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.
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.