bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUBRETINAL DRUSENOID DEPOSIT IN AGE-RELATED MACULAR DEGENERATION
Authors: Chen Ling , Messinger Jeffrey D. , Zhang Yuhua , Spaide Richard F. , Freund K. Bailey , Curcio Christine A. 
Published: October 2019

Purpose:
To clarify the role of subretinal drusenoid deposits (SDD; pseudodrusen) in the progression of age-related macular degeneration through high-resolution histology.

Methods:
In 33 eyes of 32 donors (early age-related macular degeneration, n = 15; geographic atrophy, n = 9; neovascular age-related macular degeneration, n = 7; unremarkable, n = 2), and 2 eyes of 2 donors with in vivo multimodal imaging including optical coherence tomography, examples of SDD contacting photoreceptors were assessed.

Results:
Subretinal drusenoid deposits were granular extracellular deposits at the apical retinal pigment epithelium (RPE); the smallest were 4-µm wide. Outer segment (OS) fragments and RPE organelles appeared in some larger deposits. A continuum of photoreceptor degeneration included OS disruption, intrusion into inner segments, and disturbance of neurosensory retina. In a transition to outer retinal atrophy, SDD appeared to shrink, OS disappeared, inner segment shortened, and the outer nuclear layer thinned and became gliotic. Stage 1 SDD on optical coherence tomography correlated with displaced OS. Confluent and disintegrating Stage 2 to 3 SDD on optical coherence tomography and dot pseudodrusen by color fundus photography correlated with confluent deposits and ectopic RPE.

Conclusion:
Subretinal drusenoid deposits may start at the RPE as granular, extracellular deposits. Photoreceptor OS, RPE organelles, and cell bodies may appear in some advanced deposits. A progression to atrophy associated with deposit diminution was confirmed. Findings support a biogenesis hypothesis of outer retinal lipid cycling.
VITAMIN A DEFICIENCY MONITORED BY QUANTITATIVE SHORT WAVELENGTH FUNDUS AUTOFLUORESCENCE IN A CASE OF BARIATRIC SURGERY
Authors: Lima de Carvalho Jose Ronaldo , Tsang Stephen H. , Sparrow Janet R. 
Published: October 2019

Background/Purpose:
Bariatric surgery is recognized as a treatment option for obesity. However, the cost-efficiency of screening for serum vitamin A and the effectiveness of its oral supplementation in these patients remain unclear. Here, we report a case in which vitamin A and carotenoid deficiency after bariatric surgery were monitored by noninvasive quantitative fundus autofluorescence imaging.

Methods:
Case report.

Results:
A 62-year-old man presented with a history of progressive night blindness. He had duodenal switch surgery 13 years earlier. One year before the initial visit, he had begun oral supplements of vitamins A. Short wavelength fundus autofluorescence images acquired for quantitative fundus autofluorescence revealed an intensity that was lower than the healthy-eye range. Scotopic rod-specific full-field electroretinograms were extinguished. These findings were consistent with vitamin A deficiency. The patient was given intramuscular vitamin A injections. At follow-up, quantitative fundus autofluorescence improved, ERG increased to normal, but macular pigment was unchanged.

Conclusion:
Oral vitamin A supplementation may not be sufficient after mal-absorptive surgery and a quantitative and noninvasive short wavelength fundus autofluorescence imaging technique may be useful to monitor the status of vitamin A and the carotenoids comprising macular pigment in the retina.
Genitourinary vascularized composite allotransplantation: a review of penile transplantation
Authors: Jonczyk Michael M. , Tratnig-Frankl Philipp , Cetrulo Curtis L. 
Published: October 2019

Purpose of review
Vascularized composite allotransplantation (VCA) has developed over the past 20 years, resulting in promising new reconstructive prospects for extensive soft tissue defects. More than 200 VCAs have been performed worldwide, including five genitourinary (GU)VCAs and here we review the most recent literature in this field.

Recent findings
Developments in GUVCA are continuously evolving to improve patient outcomes and suggest ethical equivalency to solid organ transplant. Recent treatment options have focused on preventing GUVCA complications by acknowledging the immunogenic tissue composition of the penis to treat rejection episodes and implementing stem cell transplant to recognized the GUVCA as self. Utilizing modern, postoperative, treatments can minimize complications and although the ethical dilemma remains, the morality of performing a GUVCA has diminished. The ethical focus relic's on standardization of patient safety.

Summary
GUVCA has become an established reconstructive surgical option. The prospect of VCA's future insinuates systemization between multidisciplinary VCA programs and the United Network for Organ Sharing in efforts to endorse ethical standardization. Over the last five years, the unprecedented outcomes have shown purpose to GUVCA that initiates an obligation to help those with severe genitourinary tissue defects. Progress in immunobiology continues to evolve optimal immunosuppression drug regimens and tolerance induction protocols, highlighting potential new immunologic pathways for graft acceptance.
Neoadjuvant Radiotherapy Versus Surgery Alone for Stage II/III Mid-low Rectal Cancer With or Without High-risk Factors
Authors: Deng Xiangbing , Liu Ping , Jiang Dan , Wei Mingtian , Wang Xin , Yang Xuyang , Zhang Yuanchuan , Wu Bing , Liu Yanjun , Qiu Meng , Zhuang Hua , Zhou Zongguang , Li Yunfeng , Xu Feng , Wang Ziqiang 
Published: October 2019

Objective:
The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts.

Background:
NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients.

Methods:
According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514).

Results:
In total, 401 patients were analyzed. With a median 54 months’ follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483).

Conclusions and Relevance:
Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.
Withdrawing noninvasive ventilation at end-of-life care: is there a right time?
Authors: Tripodoro Vilma A. , Rabec Claudio A. , De Vito Eduardo L. 
Published: October 2019

Purpose of review
The purpose of this review is the ‘when’ and ‘how’ of the matter of withdrawing noninvasive ventilation (NIV) at end-of-life (EoL) setting, having in mind the implications for patients, families and healthcare team.

Recent findings
Several recent publications raised the place and potential applications of NIV at EoL setting. However, there are no clear guidelines about when and how to withdraw NIV in these patients. Continuing NIV in a failing clinical condition may unnecessarily prolong the dying process. This is particularly relevant as frequently, EoL discussions are started only when patients are in severe distress, and they have little time to discuss their preferences and decisions.

Summary
Better advanced chronic disease and EoL condition definitions, as well as identification of possible scenarios, should help to decision-making and find the appropriate time to initiate, withhold and withdraw NIV. This review emphasized the relevance of an integrated approach across illness’ trajectories and key transitions of patients who will need EoL care and such sustaining support measure.
Meaningful measures in cancer cachexia: implications for practice and research
Authors: McDonald James J. , Fallon Marie T. , Laird Barry J.A. 
Published: October 2019

Purpose of review
Cancer cachexia is a complex inflammatory syndrome, which presents with a variety of discrete symptoms and signs. This creates a challenge for both clinicians and researchers in recognizing and assessing the syndrome. This review explores the evidence for various measures used in the assessment of cachexia.

Recent findings
Objectively, cachexia may be assessed using CT-derived measures of skeletal muscle [skeletal muscle index (SMI) and skeletal muscle density (SMD)]. Evidence suggests that SMD may be of equal or greater value than SMI in assessing cachexia. Inflammatory markers are also used, and include interleukin(IL)-1α; IL-1β; IL-6 and Interferon Gamma (IFNγ). Other robust measures include performance status and the modified Glasgow prognostic score (mGPS). These measures, however, are more commonly used in academia. By comparison, clinical assessment is limited to individual measures of patient function, such as hand grip strength (HGS), calf circumference, gait speed, and the ‘timed up and go test’ (TUG). These have each been linked with components of cachexia but are less well evidenced. Evidence also exists for patient-reported quality-of-life measures, based upon the EORTC- QLQ-C30 questionnaire, in assessing cachexia.

Summary
Further assessment is required to compare clinical measures of cachexia and determine their utility.
Development and Validation of a Socioeconomic Kidney Transplant Derailers Index
Authors: Peipert John D. , Beaumont Jennifer L. , Robbins Mark L. , Paiva Andrea L. , Anderson Crystal , Cui Yujie , Waterman Amy D. 
Published: October 2019

Background.
Socioeconomic barriers can prevent successful kidney transplant (KT) but are difficult to measure efficiently in clinical settings. We created and validated an individual-level, single score Kidney Transplant Derailers Index (KTDI) and assessed its association with waitlisting and living donor KT (LDKT) rates.

Methods.
The dataset included 733 patients presenting for KT evaluation in a transplant center in California. Exploratory factor analysis was used to identify socioeconomic barriers to KT (derailers) to include in the index. Potential KT derailers included health insurance, employment, financial insecurity, educational attainment, perception of neighborhood safety, access to a vehicle, having a washer/dryer, and quality of social support. Validity was tested with associations between KTDI scores and the following: (1) the Area Deprivation Index (ADI) and (2) time to KT waitlisting and LDKT.

Results.
Nine derailers were retained, omitting only social support level from the original set. The KTDI was scored by summing the number of derailers endorsed (mean: 3.0; range: 0–9). Black patients had higher estimated KTDI scores than other patient groups (versus White patients, 3.8 versus 2.1; P < 0.001, effect size = 0.81). In addition, the KTDI was associated with the ADI (γ = 0.70, SE = 0.07; P < 0.001). Finally, in comparison to the lower tertile, patients in the upper and middle KTDI tertiles had lower hazard of waitlisting (upper tertile hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.25-0.45; middle tertile HR: 0.54, 95% CI: 0.40-0.72) and receiving an LDKT (upper tertile HR: 0.15, 95% CI: 0.08-0.30; middle tertile HR: 0.35, 95% CI: 0.20-0.62). These associations remained significant when adjusting for the ADI and other patient characteristics.

Conclusions.
The KTDI is a valid indicator of socioeconomic barriers to KT for individual patients that can be used to identify patients at risk for not receiving a KT.
Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys
Authors: Hameed Ahmer M. , Lu David B. , Patrick Ellis , Xu Bo , Hu Min , Chew Yi Vee , Keung Karen , P’ng Chow H. , Gaspi Renan , Zhang Chris , Robertson Paul , Alexander Stephen , Thomas Gordon , Laurence Jerome , De Roo Ronald , Wong Germaine , Miraziz Ray , O’Grady Greg , Yuen Lawrence , Hawthorne Wayne J. , Rogers Natasha M. , Pleass Henry C. 
Published: October 2019

Background.
Normothermic machine perfusion (NMP) may allow resuscitation and improved assessment of kidneys before transplantation. Using discarded human kidneys, we investigated the mechanistic basis and translational potential of NMP compared with cold static storage (CS).

Methods.
Discarded deceased donor kidneys (n = 15) underwent 1-hour NMP following CS. Renal perfusion, biochemical, and histologic parameters were recorded. NMP was directly compared with CS in paired donor kidneys using simulated transplantation with allogeneic whole blood, followed by assessment of the aforementioned parameters, in addition to RNA sequencing.

Results.
Kidneys were successfully perfused, with improved renal blood flows and resistance over the course of perfusion, and evidence of urine output (median 21 mL), in all but one kidney. NMP completely resolved nonperfused regions in discarded donation after circulatory death kidneys. In paired kidneys (n = 4 pairs), transcriptomic analyses showed induction of stress and inflammatory pathways in NMP kidneys, with upregulation of pathways promoting cell survival and proliferation. Furthermore, the NMP pairs had significantly better renal perfusion (1.5–2 fold improvement) and functional parameters, and amelioration of cell death, oxidative stress, and complement activation.

Conclusions.
In this pilot preclinical study using simulated transplantation of paired kidneys, NMP of discarded marginal kidneys demonstrated some significant mechanistic benefits in comparison to CS alone. NMP may have potential to reduce organ discards and enhance early graft function in such kidneys.
Conscious perception of flickering stimuli in binocular rivalry and continuous flash suppression is not affected by tACS-induced SSR modulation
Authors: Schauer Georg , Ogawa Carolina Yuri , Tsuchiya Naotsugu , Bartels Andreas 
Published: October 2019

AbstractThe content of conscious perception is known to correlate with steady-state responses (SSRs), yet their causal relationship remains unclear. Can we manipulate conscious perception by directly interfering with SSRs through transcranial alternating current stimulation (tACS)? Here, we directly addressed this question in three experiments involving binocular rivalry and continuous flash suppression (CFS). Specifically, while participants (N=24) viewed either binocular rivalry or tried to detect stimuli masked by CFS, we applied sham or real tACS across parieto-occipital cortex at either the same or a different frequency and phase as an SSR eliciting flicker stimulus. We found that tACS did not differentially affect conscious perception in the forms of predominance, CFS detection accuracy, reaction time, or metacognitive sensitivity, confirmed by Bayesian statistics. We conclude that tACS application at frequencies of stimulus-induced SSRs does not have perceptual effects and that SSRs may be epiphenomenal to conscious perception.
RRP7A links primary microcephaly to radial glial cells and dysfunction of ribosomal biogenesis, neurogenesis and ciliary resorption
Authors: Farooq Muhammad , Lindbæk Louise , Krogh Nicolai , Doganli Canan , Keller Cecilie , Mönnich Maren , Sakthivel Srinivasan , Mang Yuan , Fatima Ambrin , Andersen Vivi Søgaard , Hussain Muhammad. S. , Eiberg Hans , Hansen Lars , Kjaer Klaus Wilbrandt , Gopalakrishnan Jay , Pedersen Lotte Bang , Møllgård Kjeld , Nielsen Henrik , Baig Shahid. M. , Tommerup Niels , Christensen Søren Tvorup , Larsen Lars Allan 
Published: October 2019

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.
Measuring anesthetic resistance in Drosophila by VAAPR
Authors: Petersen E. Nicholas , Clowes Katherine R. , Hansen Scott B. 
Published: October 2019

AbstractVolatile anesthetics are compounds which are commonly used to induce a reversable loss of consciousness (LOC) in animals. The molecular mechanism of how anesthetics induce LOC is largely unknown. However, observations have been made which show that there are genetically-encoded traits which influence the effective concentration of anesthetics in the inducement of LOC. Despite this long-term observation, little progress has been made in identifying genes involved in anesthetic sensitivity. One reason for this is that many techniques to test anesthetic sensitivity are technically challenging and are inhibitory for high-throughput studies. Here we introduce a technique for testing volatiles and aerosols with positional recording (VAAPR), a method which allows for high-throughput testing of the effect of anesthetics and other aerosolized drugs using Drosophila. Using VAAPR we show that the enzyme phospholipase D (PLD) significantly shifts the concentration of diethyl ether, chloroform, and isoflurane needed to induce LOC in Drosophila. We also show that PLD is required for a paradoxical hyperactivity phenotype. We expect that this technique will allow for additional genes to be found which control anesthetic sensitivity as well as other behavioral phenotypes.
Gene-environment interactions using a Bayesian whole genome regression model
Authors: Kerin Matthew , Marchini Jonathan 
Published: October 2019

AbstractThe contribution of gene-environment (GxE) interactions for many human traits and diseases is poorly characterised. We propose a Bayesian whole genome regression model, LEMMA, for joint modeling of main genetic effects and gene-environment interactions in large scale datasets such as the UK Biobank, where many environmental variables have been measured. The method estimates a linear combination of environmental variables, called an environmental score (ES), that interacts with genetic markers throughout the genome, and provides a readily interpretable way to examine the combined effect of many environmental variables. The ES can be used both to estimate the proportion of phenotypic variance attributable to GxE effects, and also to test for GxE effects at genetic variants across the genome. GxE effects can induce heteroscedasticity in quantitative traits and LEMMA accounts for this using robust standard error estimates when testing for GxE effects. When applied to body mass index, systolic, diastolic and pulse pressure in the UK Biobank we estimate that 9.3%, 3.9%, 1.6% and 12.5% of phenotypic variance is explained by GxE interactions, and that low frequency variants explain most of this variance. We also identify 3 loci that interact with the estimated environmental scores (− log10p > 7.3).
Robust blind spectral unmixing for fluorescence microscopy using unsupervised learning
Authors: McRae Tristan D. , Oleksyn David , Miller Jim , Gao Yu-Rong 
Published: October 2019

AbstractDue to the overlapping emission spectra of fluorophores, fluorescence microscopy images often have bleed-through problems, leading to a false positive detection. This problem is almost unavoidable when the samples are labeled with three or more fluorophores, and the situation is complicated even further when imaged under a multiphoton microscope. Several methods have been developed and commonly used by biologists for fluorescence microscopy spectral unmixing, such as linear unmixing, non-negative matrix factorization, deconvolution, and principal component analysis. However, they either require pre-knowledge of emission spectra or restrict the number of fluorophores to be the same as detection channels, which highly limits the real-world applications of those spectral unmixing methods. In this paper, we developed a robust and flexible spectral unmixing method: Learning Unsupervised Means of Spectra (LUMoS), which uses an unsupervised machine learning clustering method to learn individual fluorophores’ spectral signatures from mixed images, and blindly separate channels without restrictions on the number of fluorophores that can be imaged. This method highly expands the hardware capability of two-photon microscopy to simultaneously image more fluorophores than is possible with instrumentation alone. Experimental and simulated results demonstrated the robustness of LUMoS in multi-channel separations of two-photon microscopy images. We also extended the application of this method to background/autofluorescence removal and colocalization analysis. Lastly, we integrated this tool into ImageJ to offer an easy to use spectral unmixing tool for fluorescence imaging. LUMoS allows us to gain a higher spectral resolution and obtain a cleaner image without the need to upgrade the imaging hardware capabilities.