bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Health Workers as Patient-Site Facilitators in Adult Hearing Aid Services via Synchronous Teleaudiology: Feasibility Results from the Conexiones Randomized Controlled Trial
Authors: Coco Laura , Carvajal Scott , Navarro Cecilia , Piper Rosie , Marrone Nicole
Published: October 2022

Objectives:

The purpose of this study was to investigate the feasibility of Community Health Workers (CHWs) as patient-site facilitators in teleaudiology-facilitated hearing aid services to improve hearing aid rehabilitation outcomes for older Hispanic/Latino adults in a medically underserved, rural, US-Mexico border community.

Design:

A total of 28 adults (aged 55 to 89) with bilateral hearing loss participated in this study. Individuals were randomized to one of two teleaudiology intervention arms that differed at the level of the patient-site facilitator. Participants in the experimental group were assisted locally by trained CHW facilitators. Participants in the control group were assisted locally by trained university student facilitators. Synchronous (real-time) teleaudiology hearing aid services took place with participants located at a rural community health center and the clinician located a university 70 miles away. The results of this feasibility study are presented within the reach, effectiveness, adoption, implementation fidelity, and maintenance implementation framework.

Results:

Regarding reach, the participants in this study population are historically under-represented in research (primarily low-income Hispanic/Latino older adults). A total of 57 individuals were recruited, 47 were consented and assessed for eligibility and 28 individuals met inclusion criteria and were randomized. The average age of participants was 73.9 years, (range: 55 to 89 years) and most individuals were female (75%). Most participants (86%) reported having incomes less than $20,000 annually. Effectiveness results (via the Self Efficacy for Situational Communication Management Questionnaire) showed that both groups (CHW and control) significantly improved listening self-efficacy from pre-fitting baseline and no difference between groups was observed. Regarding datalogging, at the short-term follow-up, participants in the CHW group wore their hearing aids for more hours/day on average compared with participants in the control group. Implementation fidelity was high for both groups. Long-term maintenance of CHW-supported teleaudiology appears feasible given that training and institutional support is in place.

Conclusions:

Teleaudiology-delivered hearing aid services were feasible when facilitated locally by trained CHWs. Future efficacy and effectiveness research is warranted with CHWs and teleaudiology, potentially leading to a significant reduction in barriers for rural and medically under-resourced communities.
MRI-based Score for Assessment of Bone Mineral Density in Operative Spine Patients
Authors: Kim Ashley Yeo Eun , Lyons Keith , Sarmiento Manuel , Lafage Virginie , Iyer Sravisht
Published: October 2022

Study Design.

Retrospective comparison.

Objective.

To determine whether a previously developed MRI-derived BMD scoring system can differentiate between healthy and osteoporotic vertebrae and to validate this scoring system against quantitative computed tomography measurements.

Summary of Background Data.

Bone mineral density is an important pre-operative consideration in spine surgery. Techniques to measure BMD are subject to falsely elevated values in the setting of spondylosis (DEXA) or require significant exposure to radiation (QCT). Previous studies have shown that MRI may be utilized to measure bone quality using changes in the bone marrow signal observed on T1-weighted MRIs.

Methods.

Retrospective study of patients who underwent operative lumbar procedures at a single tertiary institution between 2016 and 2021 (n=61). Vertebral bone quality (VBQ) scores were measured by dividing the median signal intensities of L1-L4 by the SI of CSF on noncontrast T1W MRI. Demographic data, comorbidities, VBQ scores, and QCT-derived T-scores and BMD of the lumbar spine were compared between healthy (T-score ≥−1; n=21), osteopenic (−2.5 < T-score < −1; n=21), and osteoporotic (T-score ≤−2.5; n=19) cohorts using ANOVA with post-hoc Tukey test. Linear regression and receiver operating characteristic curve analyses were performed to assess the predictive value of VBQ scores. Pearson correlation test was used to evaluate the association between VBQ scores and QCT-derived measurements.

Results.

VBQ differentiated between healthy and osteoporotic groups (P=0.009). ROC curve analysis revealed that a greater VBQ score was associated with presence of osteoporosis (AUC=0.754, P=0.006). Cutoff VBQ for osteoporosis was 2.6 (Youden index 0.484; sensitivity: 58%; specificity: 90%). VBQ scores weakly correlated with QCT-derived BMD (P=0.03, r=−0.27) and T-scores (P=0.04, r=−0.26).

Conclusion.

This study attempted to further validate a previously developed MRI-based BMD scoring system against QCT-derived measurements. VBQ score was found to be a significant predictor of osteoporosis and could differentiate between healthy and osteoporotic vertebrae.
Proton Pump Inhibitors and Cancer Risk
Authors: Zhang Man-Li , Fan Yu-Xin , Meng Rui , Cai Wen-Ke , Yin Sun-Jun , Zhou Tao , Huang Yan-Hua , Wang Ping , Jiang Fang-Fang , Yang Mei , He Gong-Hao
Published: October 2022

Objectives:

Increasing evidence suggested that proton pump inhibitors (PPIs) use might affect the development of cancers, but previous conclusions remain controversial. Therefore, an umbrella review was performed to clarify the associations between PPIs and various types of cancer by summarizing the existing meta-analyses and systematic reviews.

Methods:

We searched PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP database up to June 2022 for eligible meta-analyses or systematic reviews. The summary effect size, 95% CI, heterogeneity, small study effect, and 95% prediction interval were considered in the present study. A Measurement Tool to Assess Systematic Review 2 and grading of recommendation, assessment, development, and evaluation were used to assess methodological quality and evidence.

Results:

The umbrella review included 21 meta-analyses containing 65 studies and 10 cancer types with 6.8 million subjects. The results showed that PPI use was significantly associated with increased risks of certain types of cancer, including gastric cancer (odds ratio [OR]: 2.07; 95% CI, 1.30 to 3.29), pancreatic cancer (OR: 1.73; 95% CI, 1.23 to 2.44), colorectal cancer (OR: 1.84; 95% CI, 1.26 to 2.67), and liver cancer (OR: 1.80; 95% CI, 1.27 to 2.54), but was not associated with esophageal cancer. In addition, PPI use was associated with decreased risk of breast cancer (OR: 0.69; 95% CI, 0.50 to 0.96).

Conclusions:

These findings suggested that clinicians should pay more attention to the occurrence of gastric cancer, pancreatic cancer, colorectal cancer, and liver cancer in patients who used PPIs, and PPI prescription should be written only when an accurate specific diagnosis has been made. Furthermore, additional PPIs to the treatment regimen may be benefit for women with a higher-than-average risk of breast cancer.
Double-Scroll Formation by Fluid Column Manipulation in Preloaded DMEK Grafts Prepared From Younger and Older Donor Tissue
Authors: Straiko Megan M. W. , Odell Kelly , Blitzer Andrea L. , Tran Khoa D. , Veldman Peter B.
Published: October 2022

Purpose:

The purpose of this study was to determine whether manipulation of preloaded single-scroll Descemet membrane endothelial keratoplasty (DMEK) grafts within the fluid column of an injector can safely and reliably result in formation of double-scroll DMEK grafts and whether there are differential effects on younger versus older donor tissue.

Methods:

Pairs of DMEK grafts prepared from older (65–80 years) and younger (48–64 years) donors were preloaded into a Straiko modified Jones tube. One member of the pair was manipulated within the fluid column to form a double-scroll graft, and the other remained unmanipulated. Outcomes measured include success rate for double-scroll formation, endothelial cell loss (ECL), and relative scroll width.

Results:

Older donor grafts formed double scrolls with a 100% success rate. ECL of older donor manipulated grafts was statistically higher than that of unmanipulated mate grafts (17.4% ± 3.5% vs. 13.0% ± 4.2%, P = 0.03), but was still within the acceptable range for transplant. Younger donor grafts were successfully manipulated into double scrolls with a 67% success rate, and there was no difference in the ECL of manipulated and unmanipulated grafts (15.5% ± 4.4% vs. 13.0% ± 4.5%, P = 0.24). For all grafts and conformations, there was a significant relationship between relative scroll width and ECL (P < 0.01).

Conclusions:

Fluid column manipulation can be used reliably to form double-scroll DMEK grafts. For younger donor grafts, manipulation yields a double scroll without increasing ECL. For older donor grafts, manipulation results in a minimal, acceptable increase in ECL. Surgeons should weigh the advantage of an easily opened graft against the risk of increased ECL when considering this technique.
Quantifying Clinicians’ Diagnostic Uncertainty When Making Initial Treatment Decisions for Microbial Keratitis
Authors: Hicks Patrice M. , Singh Karandeep , Prajna N. Venkatesh , Lu Ming-Chen , Niziol Leslie M. , Greenwald Miles F. , Verkade Angela , Amescua Guillermo , Farsiu Sina , Woodward Maria A.
Published: October 2022

Purpose:

There is a need to understand physicians' diagnostic uncertainty in the initial management of microbial keratitis (MK). This study aimed to understand corneal specialists’ diagnostic uncertainty by establishing risk thresholds for treatment of MK that could be used to inform a decision curve analysis for prediction modeling.

Methods:

A cross-sectional survey of corneal specialists with at least 2 years clinical experience was conducted. Clinicians provided the percentage risk at which they would always or never treat MK types (bacterial, fungal, herpetic, and amoebic) based on initial ulcer sizes and locations (<2 mm2 central, <2 mm2 peripheral, and >8 mm2 central).

Results:

Seventy-two of 99 ophthalmologists participated who were 50% female with an average of 14.7 (SD = 10.1) years of experience, 60% in academic practices, and 38% outside the United States. Clinicians reported they would “never” and “always” treat a <2 mm2 central MK infection if the median risk was 0% and 20% for bacterial (interquartile range, IQR = 0–5 and 5–50), 4.5% and 27.5% for herpetic (IQR = 0–10 and 10–50), 5% and 50% for fungal (IQR = 0–10 and 20–75), and 5% and 50.5% for amoebic (IQR = 0–20 and 32–80), respectively. Mixed-effects models showed lower thresholds to treat larger and central infections (P < 0.001, respectively), and thresholds to always treat differed between MK types for the United States (P < 0.001) but not international clinicians.

Conclusions:

Risk thresholds to treat differed by practice locations and MK types, location, and size. Researchers can use these thresholds to understand when a clinician is uncertain and to create decision support tools to guide clinicians’ treatment decisions.
Molecular Classification of Extrapulmonary Neuroendocrine Carcinomas With Emphasis on POU2F3-positive Tuft Cell Carcinoma
Authors: Koh Jiwon , Kim Haeryoung , Moon Kyung Chul , Lee Cheol , Lee Kyoungbun , Ryu Han Suk , Jung Kyeong Cheon , Jeon Yoon Kyung
Published: October 2022

Extrapulmonary neuroendocrine carcinomas (EP-NECs) are associated with a poor clinical outcome, and limited information is available on the biology and treatment of EP-NECs. We studied EP-NECs by applying the recent novel findings from studies of pulmonary neuroendocrine carcinomas, including POU2F3, the master regulator of tuft cell variant of small cell lung carcinomas. A cohort of 190 patients with surgically resected EP-NECs or poorly differentiated carcinomas (PDCs) were established. Immunohistochemistry (IHC) for POU2F3 along with ASCL1, NEUROD1, YAP1, and conventional neuroendocrine markers was performed on tissue microarrays. Selected cases with or without POU2F3 expression were subjected to targeted gene expression profiling using nCounter PanCancer Pathway panel. POU2F3-positive tuft cell carcinomas were present in 12.6% of EP-NEC/PDCs, with variable proportions according to organ systems. POU2F3 expression was negatively correlated with the expression levels of ASCL1, NEUROD1, and conventional neuroendocrine markers (P<0.001), enabling IHC-based molecular classification into ASCL1-dominant, NEUROD1-dominant, POU2F3-dominant, YAP1-dominant, and not otherwise specified subtypes. Compared wih POU2F3-negative cases, POU2F3-positive tuft cell carcinomas showed markedly higher expression levels of PLCG2 and BCL2, which was also validated in the entire cohort by IHC. In addition to POU2F3, YAP1-positive tumors were a distinct subtype among EP-NEC/PDCs, characterized by unique T-cell inflamed microenvironment. We found rare extrapulmonary POU2F3-positive tumors arising from previously unappreciated cells of origin. Our data show novel molecular pathologic features of EP-NEC/PDCs including potential therapeutic vulnerabilities, thereby emphasizing the need for focusing on unique features of EP-NEC/PDCs.
Variability in Serious Safety Event Classification among Children’s Hospitals: A Measure for Comparison?
Authors: Poppy Amy , Ziniel Sonja I , Hyman Daniel
Published: October 2022

Introduction:

Hospitals have no standard for measuring comparative rates of serious safety events (SSE). A pediatric hospital safety collaborative has used a common definition and measurement system to classify SSE and calculate a serious safety event rate. An opportunity exists to evaluate the use of this measurement system.

Methods:

A web-based survey utilizing 7 case vignettes was sent to 132 network hospitals to assess agreement in classifying the vignettes as SSEs. Respondents classified the vignettes according to the taxonomy used at their respective organizations for deviations and SSE classification.

Results:

Of the 82 respondents, 67 (82%) utilized the same SSE classification system. Respondents did not assess deviations for 2 of the 7 vignettes, which had clear deviations. Of the remaining 5 vignettes, 3 had a substantial agreement of deviation (>85%, Gwet’s AC ≥ 0.68), and 2 had fair agreement (<70%, Gwet’s AC ≤ 0.39). Four of the 7 vignettes had a substantial agreement on SSE classification (>80%; Gwet’s AC ≥ 0.80), and 3 had slight to moderate agreement (<70%, Gwet’s AC ≤ 0.78).

Conclusions:

Results demonstrated agreement and variability in determining deviation and SSE classification in the 7 vignettes. Although the SSE methodology and metric used by participant pediatric hospitals yields generally similar review results, one must be cautious in using the SSE rate to compare patient safety outcomes across different hospitals.
Risk factors and outcome of concurrent and sequential multiviral cytomegalovirus, Epstein–Barr virus, BK virus, adenovirus and other viral reactivations in transplantation
Authors: Sim Beatrice Z. , Yong Kar Yee , Slavin Monica A. , Yong Michelle K.
Published: October 2022

Purpose of review

Reactivation of viral infections occurs frequently in immunosuppressed populations, particularly in solid organ (SOT) or allogeneic haematopoietic cell (HCT) transplant patients. Concurrent and sequential multivirus infections are common, yet risk factors and outcomes remain unclear. This review aims to identify the patients vulnerable to multivirus infections and characterize the impact of increased viral burden to formulate prevention and treatment strategies.

Recent findings

Incidences of up to 89% in SOT and 36% in HCT have been reported for two viruses, and 32% in SOT and 28% in HCT for at least three viruses. Risk factors appear related to an increased burden of immunosuppression, with most viral coinfections occurring within 12 months of transplantation. Direct viral complications such as cytomegalovirus disease are more frequent in coinfected patients, with documented prolonged duration of viraemia, higher viral load and increased end-organ disease. Graft dysfunction, acute rejection and graft-vs.-host disease (GVHD) have also been associated. Increased mortality is reported in the HCT population.

Multivirus infections occur in a significant proportion of transplant patients and is linked to immunosuppressive burden. There is increasing evidence that this leads to worse graft and patient outcomes. Further prospective studies are required to further comprehensively characterise viral epidemiology, mechanisms and treatment strategies to ameliorate this risk.
Similar Findings on 68Ga-Pentixafor PET/CT and 18F-FDG PET/CT in a Patient With Widespread Metastatic Hepatic Neuroendocrine Carcinoma
Authors: Deng Maoxue , Shu Qiaoqiao , Hu Mei , Chen Yue , Cai Liang
Published: October 2022

A patient with suspected malignant tumor underwent 18F-FDG PET/CT. Based on the findings, the patient was suspected of having multiple myeloma. Then the patient underwent 68Ga-pentixafor PET/CT, which showed similar results to 18F-FDG PET/CT. Finally, the patient was eventually diagnosed with neuroendocrine carcinoma.
203Pb-VMT-α-NET Scintigraphy of a Patient With Neuroendocrine Tumor
Authors: Müller Dirk , Herrmann Hendrik , Schultz Michael K. , Solbach Christoph , Ettrich Thomas , Prasad Vikas
Published: October 2022

In an end-stage midgut neuroendocrine tumor patient with carcinoid heart disease, right ventricular dysfunction, mildly reduced renal function, and refractory to 6 cycles of 177Lu-HA-DOTATATE therapy, planar, and 22 hours SPECT/CT images were acquired after injection of 224 MBq of 203Pb-VMT-α-NET to assess the feasibility of performing 212Pb-VMT-α-NET therapy. A comparison of the 1.5 and 22 hours SPECT/CT images with 68Ga-HA-DOTATATE PET/CT showed high uptake of 203Pb-VMT-α-NET in liver metastases matching with the results of the PET/CT investigation.
Incorporation of Genetic Studies in the Kidney Transplant Evaluation Clinic: The Value of a Multidisciplinary Approach
Authors: El Ters Mireille , Pinto e Vairo Filippo , Prochnow Carri , Schinstock Carrie , Dean Patrick , Kemppainen Jennifer , Lazaridis Konstantinos , Cosio Fernando , Fervenza Fernando C. , Cornell Lynn , Amer Hatem , Hogan Marie C.
Published: October 2022

Background.

Recent studies identified underlying genetic causes in a proportion of patients with various forms of kidney disease. In particular, genetic testing reclassified some focal segmental glomerulosclerosis (FSGS) cases into collagen type 4 (COL4)-related nephropathy. This knowledge has major implications for counseling prospective transplant recipients about recurrence risk and screening biologically related donors. We describe our experience incorporating genetic testing in our kidney transplant multidisciplinary practice.

Methods.

Patients’ DNA was analyzed using whole exome sequencing for a comprehensive kidney gene panel encompassing 344 genes associated with kidney diseases and candidate genes highly expressed in the kidney. Results were correlated with phenotype by a multidisciplinary committee of nephrologists, renal pathologists, geneticists, and genetic counselors. Between October 2018 and July 2020, 30 recipient and 5 donor candidates completed testing.

Results.

Among recipient candidates, 24 (80%) carried the diagnosis of FSGS, 2 (6.7%) tubulointerstitial nephritis, and 1 (3.3%) nephrolithiasis, and 3 (10%) had an unknown cause of kidney disease. The yield for pathogenic/likely pathogenic variants was 43.3%, with majority being COL4 variants (53.8%). Among those with FSGS diagnosis, the yield was 10 of 24 (41.6%), with 29% reclassified into a COL4-related nephropathy. Family history of kidney disease was the only clinical characteristic difference between recipients with positive and negative results (76.9 versus 29.4%; P = 0.025). One of 5 donors tested positive for a pathogenic/likely pathogenic variant and was excluded from donation.

Conclusions.

We conclude that thoughtful use of genetic testing can be valuable for kidney donor selection and transplant recipient management.
Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review
Authors: Carazo-Barrios Lina , Cabrera-Maestre Andrés , Alba-Linero Carmen , Gutiérrez-Bedmar Mario , Garzón-Maldonado Francisco J. , Serrano Vicente , de la Cruz-Cosme Carlos , García-Casares Natalia
Published: October 2022

Background:

Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD.

Methods:

This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies.

Results:

Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders.

Conclusions:

More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.
Cancer incidence and mortality estimates in Arab countries in 2018: A GLOBOCAN data analysis
Authors: Al-Muftah Mariam , Al-Ejeh Fares
Published: October 2022

Arab countries are projecting continuing growth in cancer incidence and mortality which require improvements in cancer policies and management. However, there are limited studies that investigate and compare the epidemiology of cancer incidence in Arab countries with only few studies addressing the age-specific rates across cancers. Based on the 2018 estimates from the Global Cancer Observatory, this study provides a comprehensive perspective of cancer burden in 2018 in Arab-speaking countries compared to the rest of the world. The age standardized rates for incidence and mortality for all cancers combined in Arab countries were lower than the global rates but the incidence rates of non-Hodgkin and Hodgkin lymphoma, bladder, breast, and liver cancers were higher. The top-most common cancers and incidence rates, even in age-specific groups, varied between sub-regions of Arab countries (the Levant, Arabian Gulf and Arab African sub-regions), and Iraq and Egypt, suggesting some common and unique environmental factors and possible ethnic or genetic heritages. Arab countries generally had higher mortality-to-incidence ratio than the world’s ratio. This study data is essential reference parameter to evaluate and monitor progress of national initiatives for surveillance programs and clinical management improvements tailored towards reducing cancer incidence and mortality in Arab countries.
MSFragger-Labile: A Flexible Method to Improve Labile PTM Analysis in Proteomics
Authors: Polasky Daniel A. , Geiszler Daniel J. , Yu Fengchao , Li Kai , Ci Teo Guo , Nesvizhskii Alexey I.
Published: October 2022

Post-translational modifications of proteins play essential roles in defining and regulating the functions of the proteins they decorate, making identification of these modifications critical to understanding biology and disease. Methods for enriching and analyzing a wide variety of biological and chemical modifications of proteins have been developed using mass spectrometry (MS)-based proteomics, largely relying on traditional database search methods to annotate resulting mass spectra of modified peptides. These database search methods treat modifications as static attachments of a mass to particular position in the peptide sequence, but many modifications undergo fragmentation in tandem MS experiments alongside, or instead of, the peptide backbone. While this fragmentation can confound traditional search methods, it also offers unique opportunities for improved searches that incorporate modification-specific fragment ions. Here, we present a new Labile Mode in the MSFragger search engine that can tailor modification-centric searches to the fragmentation observed. We show that labile mode can dramatically improve spectrum annotation rates of phosphopeptides, RNA-crosslinked peptides, and ADP-ribosylated peptides. Each of these modifications presents distinct fragmentation characteristics, showcasing the flexibility of MSFragger labile mode to improve search for a wide variety of biological and chemical modifications.
Selection of the Early Genetic Code by Ultraviolet Light
Authors: Kufner Corinna L. , Krebs Stefan , Fischaleck Marlis , Philippou-Massier Julia , Blum Helmut , Bucher Dominik B. , Braun Dieter , Zinth Wolfgang , Mast Christof B.
Published: October 2022

The DNA sequences available in the prebiotic era were the genomic building blocks of the first life forms on Earth and have therefore been a matter of intense debate.1,2On the surface of the Early Earth, ultraviolet (UV) light is a key energy source3, which is known to damage nucleic acids4. However, a systematic study of the sequence selectivity upon UV exposure under Early Earth conditions is still missing. In this work, we quantify the UV stability of all possible canonical DNA sequences and derive information on codon appearance under UV irradiation as selection pressure. We irradiate a model system of random 8mers at 266 nm and determine its UV stability via next-generation sequencing. As a result, we obtain the formation rates of the dominant dimer lesions as a function of their neighboring sequences and find a strong sequence selectivity. On the basis of our experimental results, we simulate the photodamage of short proto-genomes of 150 bases length by a Monte Carlo approach. Our results strongly argue for UV compatibility of early life and allow the ranking of codon evolutionary models with respect to their UV resistance.
Physics-informed Deep Learning Approach to Quantification of Human Brain Metabolites from Magnetic Resonance Spectroscopy Data
Authors: Shamaei Amir M , Starcukova Jana , Starcuk Zenon
Published: October 2022

Purpose:

While the recommended analysis method for magnetic resonance spectroscopy data is linear combination model (LCM) fitting, the supervised deep learning (DL) approach for quantification of MR spectroscopy (MRS) and MR spectroscopic imaging (MRSI) data recently showed encouraging results; however, supervised learning requires ground truth fitted spectra, which is not practical. Moreover, this work investigates the feasibility and efficiency of the LCM-based self-supervised DL method for the analysis of MRS data.

Method:

We present a novel DL-based method for the quantification of relative metabolite concentrations, using quantum-mechanics simulated metabolite responses and neural networks. We trained, validated, and evaluated the proposed networks with simulated and publicly accessible in-vivo human brain MRS data and compared the performance with traditional methods. A novel adaptive macromolecule fitting algorithm is included. We investigated the performance of the proposed methods in a Monte Carlo (MC) study.

Result:

The validation using low-SNR simulated data demonstrated that the proposed methods could perform quantification comparably to other methods. The applicability of the proposed method for the quantification of in-vivo MRS data was demonstrated. Our proposed networks have the potential to reduce computation time significantly.

Conclusion:

The proposed model-constrained deep neural networks trained in a self-supervised manner can offer fast and efficient quantification of MRS and MRSI data. Our proposed method has the potential to facilitate clinical practice by enabling faster processing of large datasets such as high-resolution MRSI datasets, which may have thousands of spectra.

Highlights

A novel self-supervised deep learning method for quantifying metabolite concentrations in MR spectroscopy signals.

Providing a unique opportunity to quantify complex-valued MRS data in the time domain.

Faster MR spectroscopy quantification with comparable accuracy to traditional methods.

Investigating the impacts of the dataset size and neural network design on our proposed model
Representations in human primary visual cortex drift over time
Authors: Roth Zvi N. , Merriam Elisha P.
Published: October 2022

Primary sensory regions are believed to instantiate stable neural representations, yet a number of recent rodent studies suggest instead that representations drift over time. We analyzed a massive fMRI dataset using an image-computable encoding model and found systematic changes in model fits that exhibited cumulative drift over many months. Convergent analyses pinpoint changes in neural responsivity as the source of the drift, while population-level representational dissimilarities between visual stimuli were unchanged, suggesting that downstream cortical areas may read-out a stable representation, even as representations within V1 drift.
Masking effects onIso-valeric Acid Recognition by Sub-threshold Odor Mixture
Authors: Huang J. , Lin J. , Yueng R. , Wu S. , Solla L. , Acree T.
Published: October 2022

Masking unpleasant odors with high levels of pleasant-smelling odorants is an ancient practice that has evolved into many enterprises, from perfumery to consumer products. However, effective odor masking turns out to be idiosyncratic and impermanent. Here, we used Sniff Olfactometry (SO)(Rochelle et al., 2017; Wyckoff & Acree, 2017) to investigate the psychophysics of masking during 70ms-stimulations with mixtures of the mal-odorantiso-valeric Acid (IVA) and different masking agents. IVA is a component of human sweat that can dominate its smell, and is often described in unpleasant terms, e.g., “gym locker”, “smelly feet”, “dirty clothes”, etc. Conventionally, high concentrations of positive smelling odorants are used to reduce the unpleasantness of IVA in clothing or environments contaminated with IVA. To investigate the masking effects of sub-threshold levels of masking agents (neohivernal, geraniol, florhydral, decanal,iso-longifolanone, methyliso-eugenol, ands-limonene) on IVA, we used SO to measure the probability of recognizing IVA after 70ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA-suppressors for 9 subjects. On average, the single masking agent could decrease IVA-recognition probability by 14% to 72%, and a subthreshold odor mixture consisting of 6 masking agents decreased IVA recognition by 96%.
The Physiological Response of Salt and Drought-Stressed Plant to Exogenous Application of Salicylic Acid
Authors: Adebanjo Oluwatosin , Setordjie Elikplim Aku , Almat Anelya
Published: October 2022

Salinity and osmotic stress affect crop growth and yield. To meet the food demand of the increasing global population, there is a need to continually study the plant-stress factor relationship. This experiment studies the physiological response of salt and drought-stressed plant to exogenous application of salicylic acid. Tomato plants were grown in medium, under controlled conditions. The six treatments (T1 - control, T2 - MgSO4for salinity stress, T3 - 5% PEG 8000 for osmotic stress, T4 - control + salicylic acid, T5 - MgSO4+ salicylic acid, T6 - 5% PEG 8000 + salicylic acid) were replicated six times to make a total of 36 plants. The treatments were assessed for parameters associated with photosynthetic parameters and yield: chlorophyll content, net photosynthetic rate, leaf water potential, fresh arial weight, leaf ion content, intercellular carbon dioxide concentration, transpiration rate and gaseous exchange. The result showed that the exogenous application of salicylic acid increased the leaf water potential of both the stressed and non-stressed plants. However, for other parameters, the role of MgSO4 and %PEG in inducing salinity stress and drought stress. Respectively, was not clearly observed. Likewise, the exogenous application of salicylic acid showed no clear effect in stressed plants, relative to unstressed plants. Hence, the observations from this experiment showed a high variation in physiological responses and a repeat of the experiment can be considered to further investigate the validation of the role of salicylic acid in plants under salt and osmotic stress conditions.
rBahadur: Efficient simulation of high-dimensional genotype data with global dependence structures
Authors: Border Richard , Malik Osman Asif
Published: October 2022

Existing methods for generating synthetic genotype data are ill-suited for replicating the effects of assortative mating (AM). We proposerb_dplr, a novel and computationally efficient algorithm for generating high-dimensional binary random variates that effectively recapitulates AM-induced genetic architectures using the Bahadur order-2 approximation of the multivariate Bernoulli distribution.

Availability and implementation

TherBahadurR library is available athttps://github.com/rborder/rBahadur.
Widespread coding of navigational variables in prefrontal cortex
Authors: Maisson David J-N. , Voloh Benjamin , Cervera Roberto Lopez , Conover Indirah , Zambre Mrunal , Zimmermann Jan , Hayden Benjamin Y.
Published: October 2022

To navigate, we must represent information about our place in the environment. Traditional research highlights the role of the hippocampal complex in this process. Spurred by recent research highlighting the widespread cortical encoding of cognitive and motor variables previously thought to have localized function, we hypothesized that navigational variables would be likewise encoded widely, especially in the prefrontal cortex, which is often associated with control of volitional behavior. We recorded neural activity from six prefrontal structures while macaques performed a foraging task in an open enclosure. In all six regions, we found strong encoding of allocentric position, head direction, egocentric boundary distance, and linear and angular velocity. These encodings were not accounted for by distance or time to reward. Strength of coding of all variables increase along a ventral-to-dorsal gradient. Together these results argue that encoding of navigational variables is not localized to the hippocampal complex and support the hypothesis that navigation is continuous with other forms of flexible cognition in the service of action.
A Local Hebbian Rule Based Neural Network Model of Invariant Object Representation and Classification
Authors: Raj Rishabh , Yu C. Ron
Published: October 2022

Our recognition of an object is consistent across conditions, unaffected by motion, perspective, rotation, and corruption. This robustness is thought to be enabled by invariant object representations, but how the brain achieves it remains unknown1. In artificial neural networks, learning to represent objects is simulated as an optimization process2. The system reduces discrepancies between actual and desired outputs by updating specific connections through mechanisms such as error backpropagation3. These operations are biologically implausible primarily because they require individual connections at all levels to be sensitive to errors found at the late stages of the network4,5. On the other hand, learning in the nervous system occurs locally, and synaptic changes depend only on pre- and post-synaptic activities6,7. It is unclear how local updates translate into coordinated changes across large populations of neurons and lead to sophisticated cognitive functions. Here we demonstrate that it is possible to achieve robust and invariant object representations in naturally observed network architectures using only biologically realistic local learning rules. Adopting operations fundamentally different from current ANN models, unsupervised recurrent networks can learn to represent and categorize objects through sensory experiences without propagating or detecting errors. This white box, fully interpretable networks can extract clean images from their corrupted forms and produce representations prospectively robust against unfamiliar perturbations. Continuous learning does not cause catastrophic forgetting commonly observed in ANNs. Without explicit instructions, the networks can classify objects and represent the identity of 3D objects regardless of perspective, size, or position. These findings have substantial implications for understanding how biological brains achieve invariant object representation and for developing biologically realistic intelligent networks that are efficient and robust.
Cyclosporin A delays the terminal disease stage inTfamKO mice without improving mitochondrial energy production
Authors: Chatel Benjamin , Varlet Isabelle , Ogier Augustin C. , Pecchi Emilie , Bernard Monique , Gondin Julien , Westerblad Håkan , Bendahan David , Gineste Charlotte
Published: October 2022

Abstract

Mitochondrial myopathies are rare genetic disorders characterized by muscle weakness and exercise intolerance. Currently, no effective treatment exists for these myopathies. Interestingly, the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extended lifespan and prevented loss of force and mitochondrial Ca2+overload in muscle fibers in the skeletal muscle-specificTfamknockout mouse model of lethal mitochondrial myopathy (TfamKO). The unaffected expression of proteins involved in mitochondrial energy metabolism suggests that these improvements occurred without improvement in metabolism. In this study, we aimed at investigating the effects of four weeks of CsA administration onin vivocontractile function and mitochondrial energy production inTfamKO mice. The treatment started before the terminal phase with severe muscle weakness and weight loss. Our results show that CsA treatment delayed progression into the terminal disease phase. This occurred without any obvious positive effects on mitochondrial energy production at rest or during fatigue induced by repeated contractions. In conclusion, cyclophilin inhibitors may have the potential of counteracting devastating muscle weakness in patients with mitochondrial myopathies most probably by preventing deleterious effects triggered by excessive mitochondrial Ca2+uptake rather than by improving mitochondrial energy production.
REDUCED FOLATE CARRIER 1 IS PRESENT IN RETINAL MICROVESSELS AND CRUCIAL FOR THE INNER BLOOD RETINAL BARRIER INTEGRITY
Authors: Gurler Gokce , Belder Nevin , Beker Mustafa Caglar , Sever-Bahcekapili Melike , Uruk Gokhan , Kilic Ertugrul , Yemisci Muge
Published: October 2022

Background

Reduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known.

Methods

We used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-hour by applying FeCl3to central retinal artery. We used RT-qPCR and Western blotting to determine RFC1. Endothelium (CD31), pericytes (PDGFR-beta, CD13, NG2), tight-junctions (Occludin, Claudin-5 and ZO-1), main basal membrane protein (Collagen-4), endogenous IgG and RFC1 were determined immunohistochemically.

Results

Our analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia.

Conclusion

In conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia–immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas.
Integrated Molecular Characterization of Intraductal Papillary Mucinous Neoplasms: An NCI Cancer Moonshot Precancer Atlas Pilot Project
Authors: Semaan Alexander , Bernard Vincent , Wong Justin , Makino Yuki , Swartzlander Daniel B. , Rajapakshe Kimal I. , Lee Jaewon J. , Officer Adam , Schmidt Christian Max , Wu Howard H. , Scaife Courtney L. , Affolter Kajsa E. , Nachmanson Daniela , Firpo Matthew A. , Yip-Schneider Michele , Lowy Andrew M. , Harismendy Olivier , Sen Subrata , Maitra Anirban , Jakubek Yasminka A. , Guerrero Paola A.
Published: October 2022

Intraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic ductal adenocarcinoma (PDAC). IPMNs undergo multistep progression from low grade (LG) to high grade (HG) dysplasia, culminating in invasive neoplasia. While patterns of IPMN progression have been analyzed using multi-region sequencing for somatic mutations, there is no integrated assessment of molecular events, including copy number alterations (CNAs) and transcriptomics changes, that accompany IPMN progression. We performed laser capture microdissection on surgically resected IPMNs of varying grades of histological dysplasia obtained from 24 patients (total of 74 independent histological lesions), followed by whole exome and whole transcriptome sequencing. Overall, HG IPMNs displayed a significantly greater aneuploidy score than LG lesions, with chromosome 1q amplification, in particular, being associated with HG progression and with cases that harbored cooccurring PDAC. Furthermore, the combined assessment of single nucleotide variants (SNVs) and CNAs identified both linear and branched evolutionary trajectories, underscoring the heterogeneity in the progression of LG lesions to HG and PDAC. At the transcriptome level, upregulation of MYC-regulated targets and downregulation of transcripts associated with the MHC class I antigen presentation machinery was a common feature of progression to HG. Taken together, this work emphasizes the role of 1q copy number amplification as a putative biomarker of high-risk IPMNs, underscores the importance of immune evasion even in non-invasive precursor lesions, and supports a previously underappreciated role of CNA-driven branching evolution as an avenue for IPMN progression. Our study provides important molecular context for risk stratification and cancer interception opportunities in IPMNs.

Significance

Integrated molecular analysis of genomic and transcriptomic alterations in the multistep progression of intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors of pancreatic cancer, identifies features associated with progression of low-risk lesions to high-risk lesions and cancer, which might enable patient stratification and cancer interception strategies.
A metabolomic view on local climate adaptation: Latitudinal divergence of heat and drought responses in a coastal plant
Authors: Schrieber Karin , Gluesing Svea , Peters Lisa , Eichert Beke , Althoff Merle , Schwarz Karin , Erfmeier Alexandra , Demetrowitsch Tobias
Published: October 2022

Studying natural variation in multi-stress resistance is central for predicting and managing the population dynamics of wild plant species under rapid global change. Yet, it remains a challenging goal in this field to integrate knowledge on the complex biochemical underpinnings for the targeted ‘non-model’ species. Here, we studied latitudinal divergence in combined drought and heat stress resistance in European populations of the dune plantCakile maritima, by combining comprehensive plant phenotyping with metabolic profiling via FT-ICR-MS and UPLC-TQ-MS/MS.

We observed pronounced constitutive divergence in growth phenology, leaf functional traits and defence chemistry (glucosinolates, alkaloids) among population origins. Most importantly, the magnitude of growth reduction under stress was partly weaker in southern plants and associated with divergence in plastic growth responses (root expansion, leaf abscission) and the stress-induced modulation of primary and specialized metabolites with known central functions not only in plant abiotic but also biotic stress resistance.

Our study supports that divergent selection has shaped the constitutive and stress-induced expression of numerous morphological and biochemical functional traits to mediate higher abiotic stress resistance in southernCakilepopulations, and highlights that metabolomics is a powerful tool to explore the mechanistic underpinnings of local stress adaptation in ‘non-model’ species.

Highlight

Plant defence chemistry and its modulation by abiotic stress exhibits latitudinal clines across natural populations of a coastal plant.
Multi-view confounder detection for biomedical studies
Authors: Wallner Markus , Kersten Nicolas , Pfeifer Nico
Published: October 2022

In many biomedical studies an important first step is checking for confounding factors. For association studies, confounding can for example be caused by ethnic differences in the case and control groups. In many other settings there might be confounding factors like batch effects or founder effects that also need to be detected and controlled for1. Detecting confounding for data from one data source is well established (e.g., genomics data). Since more and more studies are now based on data from multiple data modalities (e.g., multi-omics), we evaluated whether multi-view confounder detection can benefit from state-of-the-art methods for multi-view data integration. Especially for clustering of multi-omics data, it has been shown that these methods can perform better than methods that treat the data modalities separately2. Our results show that multi-view confounder analysis is possible and that building on multi-view data integration methods is better than treating the different data modalities separately.