bluuebunny/crossref_metadata_2025 huggingface dataset:
GeneXpert: A Rapid and Supplementary Diagnostic Tool for Tuberculous Meningitis, Experience from Tertiary Neurocenter
Authors: Wakode Priyanka , Siddaiah Nagarathna , Manjunath Netravathi , Bahubali Veena Kumari Haradara
Published: February 2022

Background Tuberculous meningitis (TBM) is a highly lethal form of central nervous system tuberculosis (CNS TB) that causes high mortality and morbidity in children and adults. Nonspecific clinical presentation and fewer TB bacilli challenge clinicians resulting in delays in diagnosis and treatment.

Aim This study aimed to evaluate the utility of GeneXpert alone and in combination with culture using 1 mL of cerebrospinal fluid (CSF) in a volume constraint situation.

Methods A total of 125 clinically confirmed TBM and 110 non-TBM cases, comprised of both infectious and noninfectious diseases. were included in the study. Patient details including clinical signs and symptoms, CSF, and imaging data were collected from the case records. CSF samples were obtained from all the patients and were tested by the mycobacterial culture method and GeneXpert test. The performance of both the tests was statistically calculated and reported in the form of sensitivity and specificity.

Results Out of 125 TBM cases, 40 were detected positive by culture and 26 by GeneXpert. All 110 non-TBM cases were identified negative by both methods. The sensitivity and specificity of GeneXpert in comparison with culture were 27 and 100%, respectively. The culture was found to be more sensitive (32%) than GeneXpert. But the assay was able to detect a considerable number of clinically confirmed culture-negative TBM cases.

Conclusion GeneXpert is a rapid test and including this as an adjunctive test along with the culture in routine clinical practice can improve the diagnosis of TBM in volume constraint scenario.
Prevalence of Associated Endocrine Diseases in Patients with Neurofibromatosis Type 1
Authors: Alshahrani Aysha , Abuoliat Zainah , Alshahrani Awad Saad , Al Balwi Mohammed Ali
Published: February 2022

Background Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder that increases the risk of developing benign and malignant tumors. Several associated endocrine diseases in NF-1 patients have been explained in the literature. Thus, this study aims to assess the endocrine manifestations as there no previous local data have discussed this association.

Methods A retrospective cross-sectional study was conducted at KAMC and KASCH, Riyadh, Saudi Arabia by including all patients genetically confirmed with NF1 from 2004 until 2019 using a consecutive non-probability sampling technique. The included data were demographics, consanguinity, genetic variant mutations as well as associated endocrine diseases.

Results The prevalence of patients with associated endocrine diseases was estimated to be 19.4%. Short stature showed the highest frequency of associated endocrine diseases followed by subclinical hypothyroidism. Positive consanguinity, sporadic mutation, and pathogenic variant showed high frequencies.

Conclusion The coexistence of endocrine diseases was found in NF-1 patients. Therefore, screening for endocrine abnormality in patients with NF-1 by comprehensive history and physical exam as well as investigations to minimize complications and the late presentation should be considered; however, further studies are necessary to address the need.
Development and Validation of Structured COVID Perception Interview Guide (COPING) for Assessing the Acute Impact of COVID-19 Diagnosis
Authors: Sutar Roshan , Lahiri Anuja , Singh Gaurav , Chaudhary Swanzil
Published: February 2022

Objective Structured COVID Perception INterview Guide (COPING) is a novel tool developed to understand the acute impact after receiving the diagnosis of coronavirus disease 2019 (COVID-19) in the Indian setting. The approach carries importance for interviewing patients in a state of shock immediately after receiving the diagnosis of COVID. The tool is developed emphasizing the grief, stigma, and acute psychological perception in the immediate aftermath of receiving the positive test results of COVID-19. Since COVID-19 is characteristically different from other infectious illnesses, a structured interview guide could help to address the concerns related to acute loss of health.

Materials and Methods This study follows a mixed method design conducted from August 2020 to January 2021. In-depth telephonic interviews with mild to moderate COVID patients admitted to a tertiary hospital in central India was followed by development of COPING questionnaire.

Statistical Analysis Item-Content Validity Index (I-CVI) and Scale-Content Validity Index Universal Agreement (S-CVI/UA) was computed. Factor analysis, Bartlett's test, and Kaiser–Meier–Olkin measure of sampling adequacy was performed. Principal component analysis, scree plots, and parallel analysis with varimax rotation was used to determine the number of factors to extract. For measuring internal consistency, Cronbach's α was computed.

Results Out of 40 items, the final tool had 15 items after computing content validity, performing factor analysis and achieving desired level of internal consistency (Cronbach's α = 0.702). Five domains identified after factor analysis were awareness, grief/bereavement, stigma, social reciprocity, and stress adaptation/coping.

Conclusion COPING is a valid and reliable interview guide for Indian setting that will allow the assessment of perception of patients with acute COVID-19 infection. Taking into consideration the mental health implications of COVID-19, the availability of such a validated and reliable tool is a timely step to address the public health problem and assist the ongoing research on COVID-19 and similar illnesses in the future.
Typical and Atypical Imaging Findings of Hepatocellular Carcinoma on Multiphasic MDCT Scan in Histologically Proved Cases
Authors: Prasad Umakant , Kumar Deepak , Bharti Rashmi Rani , Suman Sanjay Kumar , Singh Aishwerya , Kumar Ravikant
Published: February 2022

Objective The purpose of this study was to find out the incidence of typical and atypical radiological imaging findings of hepatocellular carcinoma (HCC) on multiphase multidetector computed tomography (MDCT) scans in histologically proven cases.

Materials and Methods A multiphase computed tomography study of 73 patients with histologically proven HCC was evaluated by a radiologist. Our multiphasic protocol was composed of precontrast, arterial, portal, and delayed venous phases. The reviewers analyzed the CT images for tumor size, enhancement patterns of HCC in different phases, relative timing of washout, internal cystic changes, and presence of dysmorphic intratumoral vessel aneurysms or arteriovenous shunt.

Results Most of the cases (95.9%) showed typical enhancement patterns in MDCT, i.e., enhancements in the arterial phase with the portal or delayed venous phase contrast washout. Three cases (4.9%) out of 73 HCC showed enhancements in the portal phase and washout in the delayed venous phase. Seven cases out of total 73 HCC (9.5%) patients showed heterogeneous enhancements in both arterial and portal phases and contrast washout in the delayed venous phase. Venous thrombosis was noted in about 44 cases (60%) out of total 73 patients, in which portal vein thrombosis was more common than hepatic veins/inferior vena cava.

Conclusion Most of the HCC show typical enhancement patterns, i.e., heterogeneous enhancements in the arterial phase and washout in the portal venous phase when we use MDCT. These findings are higher than those described previously. However, in our study, the main difference with MDCT was lower frequency of intratumoral pseudoaneurysm and bile duct invasion, and intratumoral fat and calcification (atypical character of HCC) were not found which were rare findings in previous study.
The Impact of Pneumonia PCR Panel Testing in the PICU: A Quality Improvement Study
Authors: Fireizen Yaron , Babbitt Christopher J. , Adams Susan , Morphew Tricia , Ferro Emanuel T. , Randhawa Inderpal
Published: February 2022

Inappropriate antibiotic usage can contribute to the promotion of resistant bacteria. In an effort to reduce antibiotic length of therapy (LOT), we initiated a performance improvement project utilizing pneumonia polymerase chain reaction (PCR) testing in ventilated pediatric intensive care unit (PICU) patients suspected of tracheitis or pneumonia. This was a single-center cohort intervention study that compared pre- and postimplementation patients. The intervention was the use of a pneumonia PCR panel on all PICU patients undergoing an evaluation for acute tracheitis or pneumonia during the postimplementation period. The inclusion criteria were either acute or acute on chronic respiratory failure. After an 8-month period, the charts were reviewed from both cohorts and baseline data, and outcome data were compared by statistical analysis. A total of 41 preimplementation and 30 postimplementation patients were compared, and no baseline differences were found except postimplementation patients being slightly older (133 vs. 56 months, p-value = 0.040). Analysis of the primary outcome measures found that the time to identification of organism (5 vs. 67 hours) and LOT (5 vs. 9 days, p < 0.001) were shorter in postimplementation patients compared with preimplementation patients. Antibiotics were changed based on the results of the pneumonia PCR on 18 of 30 patients (60%). There was no difference in ventilator-free days, PICU length of stay, or mortality. In conclusion, pneumonia PCR panel testing leads to more rapid results and was associated with reduced antibiotic LOT.
Management of Pathologic Fractures around the Knee: Part 2—Proximal Tibia
Authors: Martin John R. , Auran Richard L. , Duran Michael D. , de Comas Amalia M. , Jacofsky David J.
Published: February 2022

Metastatic disease affecting the proximal tibia is rarer than disease affecting the femur; however, it presents unique challenges that the orthopaedic surgeon must address to ensure successful outcomes and return the patient to an ambulatory status. The essential workup for evaluating and treating these patients is addressed briefly in this review as a summary of the information is provided in part 1 of this series. Part 2 of this series will focus on the surgical treatment of these lesions, which can be complex and is not as well described in the literature. Procedures ranging from open reduction internal fixation with cement augmentation to complex endoprosthetic reconstruction can be employed to address proximal tibia metastatic disease. An awareness of these various treatment modalities allows the orthopaedic surgeon to plan the most effective operation for the patients under their care.
Comparison of Acute-Phase Pain Intensity, Pain Trajectory, and the Number of Analgesics Administered between Total and Unicompartmental Knee Arthroplasties
Authors: Oka Tomohiro , Imai Ryota , Wada Osamu , Mizuno Kiyonori
Published: February 2022

We aimed to compare the variables of pain intensity, pain trajectory, and the number of analgesics administered during the acute phase between total and unicompartmental knee arthroplasties. This prospective cohort study recruited 445 patients who planned to undergo knee arthroplasty. Pain intensity was evaluated during hospitalization, and 1 month postoperatively using a numerical rating scale. Pain trajectory (slope and intercept) was calculated using pain intensity data from postoperative days 1 to 4. The number of analgesics administered for worsening pain was monitored during hospitalization. Multiple linear regression analysis with adjustment for potential confounders was conducted to investigate the impact of surgery type on pain variables. Data for 208 and 189 patients who had undergone total and unicompartmental knee arthroplasties, respectively, were included in this study. Pain intensity and pain trajectory were similar between the two surgeries. The number of analgesics administered on postoperative day 3 (p = 0.01) and day 4 (p = 0.03), as well as total number (p = 0.01), were lower for unicompartmental knee arthroplasty than for total knee arthroplasty. Multiple linear regression analysis showed that the type of surgery affected the total number of analgesics administered (β = − 1.24, p < 0.01, 95% confidence interval: −1.80 to −0.62). This study suggests that pain characteristics observed during the acute phase differ between total and unicompartmental knee arthroplasties. Postoperative pain should be managed, and rehabilitation should be provided at similar levels after the second postoperative day in total and unicompartmental knee arthroplasty patients.
Early Superior Clinical Outcomes in Robotic-Assisted TKA Compared to Conventional TKA in the Same Patient: A Comparative Analysis
Authors: Ali Muzaffar , Kamson Anthony , Yoo Charlie , Singh Inderpreet , Ferguson Christopher , Dahl Raymond
Published: February 2022

Robotic-assisted total knee arthroplasty (RA-TKA) has demonstrated improved alignment and outcome scores when compared with manual total knee arthroplasty (M-TKA); however, few studies compare differences in the same patient. This study is a retrospective review that assesses clinical outcomes of 36 patients who underwent a primary RA-TKA and had undergone a prior contralateral M-TKA. All surgeries were performed by a single surgeon at the same institution. Patients were assessed for differences in hospital length of stay, improvement in pre- versus postoperative range of motion, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Student's t-test and Fisher's exact test were utilized to detect significant differences. Patient demographics showed a mean age of 64.5, 24 females (67%), and mean body mass index of 35.1 ± 5.7. The average follow-up time was 2.9 years for M-TKA and 1.3 years for RA-TKA. Hospital length of stay was decreased by 5.5 hours for RA-TKA (p = 0.03). Total postoperative WOMAC score was not statistically different between RA-TKA and M-TKA (p = 0.061); however, pain and stiffness components were statistically improved in RA-TKA (p = 0.041 and p = 0.007), respectively. KOOS was higher in RA-TKA, which approached statistical significance (p = 0.005). Pre- versus postoperative knee flexion improved significantly in both cohorts. There was a significant difference in pre- versus postoperative range of motion at 3, 6, and 12 months follow-up after RA-TKA in comparison to M-TKA (p < 0.05). There were no postoperative complications. Patients who underwent RA-TKA demonstrated early improvement at 1-year follow-up in pain, stiffness, and knee flexion when compared with their prior contralateral M-TKA. There was a significant decrease in postoperative length of stay by 5.5 hours in the RA-TKA group. Limitations include a small sample size and differences in follow-up times between RA-TKA and M-TKA
Erfahrungsbericht: Lieferengpässe und deren Auswirkungen auf das Gesundheitswesen
Authors: Schönrath Frank
Published: February 2022

Lieferengpässe aufgrund der COVID-19-Pandemie belasten die gesamte Wirtschaft weltweit, darunter auch das Gesundheitswesen. Infolgedessen wird die deutsche Wirtschaft stark ausgebremst. Die erwartete Erholung der weltweiten Lieferketten verzögert sich weiterhin.
Digitalisierung: Wie verändern sich Anforderungsprofile von Einkäufern?
Authors: Schlüchtermann Jörg , Köhler Mathias
Published: February 2022

Mit der digitalen Transformation ändern sich auch die Ansprüche an die Tätigkeiten im Einkauf. Insbesondere soziale und persönliche Kompetenzen nehmen in ihrer Relevanz zu und die menschliche Expertise gewinnt an Bedeutung.
Gesamtübersicht Covid-19-Testung: Der richtige Test zur richtigen Zeit
Authors: Schneider Maria , Jetter Nina
Published: February 2022

Seit knapp zwei Jahren begleitet uns nun das Coronavirus SARS-CoV-2 und stellt uns nicht nur in der Klinik, sondern auch in der Laborwissenschaft mit verschiedenen Fachtermini vor immer neue Herausforderungen. Mittlerweile steht ein breites Spektrum an Nachweismöglichkeiten – von PCR- über Antigen- und Antikörpertests – zur Verfügung.
Circadian rhythm of postural control, sleepiness and verticality perception in older adults
Authors: Langeard Antoine , Zouabi Amira , Martin Tristan , Quarck GaËlle , Gauthier Antoine
Published: February 2022

Introduction

with ageing, the risk of falling increases. It has been reported that fall frequency may depend on the time of the day, suggesting a possible circadian rhythm of postural control. The objective was to test whether postural control in older adults followed a circadian rhythm. Then, in order to examine the possible functions involved in circadian variations in balance performances, circadian rhythm of sleepiness and vertical perception were also tested.

Methods

eight participants (70.7 ± 4.7 years) were included. Baseline circadian rhythm profile was assessed through continuous core temperature measurement. Static and dynamic balance, subjective sleepiness and fatigue, and verticality perception were measured at 2:00, 6:00, 10:00, 14:00, 18:00 and 22:00, on separate weeks in a random order.

Results

temperature followed a circadian rhythm, with lowest temperature occurring at 03:50. Circadian rhythm was detected for the centre of pressure displacement length and velocity, in dynamic condition eyes closed, with lowest performances occurring at 18:33 and 16:59, respectively. Subjective sleepiness and fatigue also followed circadian rhythm with lowest sleepiness occurring at 15:46 and 15:50, for the Karolinska Sleeping Scale and the Visual Analogic Scale of fatigue, respectively. Finally, the vertical perception was not significantly following a circadian rhythm.

Conclusion

older adults present a circadian rhythm of balance, in particular in more challenging conditions, and the lowest performances occurred in the late afternoon These circadian rhythms could explain some of the falls happening at this time in community-dwelling older adults.
Delimiting 33 Carpinus (Betulaceae) species with a further phylogenetic inference
Authors: Dong Congcong , Lu Zhiqiang , Zhang Han , Liu Jianquan , Li Minjie
Published: February 2022

Carpinus (Betulaceae) has approximately 52 species distributed in the Northern Hemisphere, with many species of Carpinus found in China. However, the species boundaries and phylogenetic relationships remain poorly understood. This study reported ITS sequences for 225 individuals of 33 Carpinus species, mainly from China. We also included eight Ostrya species in our analyses, the closely related sister group of Carpinus. We aimed to delimit these species based on ITS sequences and clarify their phylogenetic relationships by constructing tree-like topology and networks at population level. We found that only 17 of 33 species could be delimited from the closely related ones based on species-specific mutations in ITS sequence variation, including all species of sect. Distegocarpus, and sect. Carpinus subsect. Carpinus. Carpinus subsect. Carpinus contained two endangered species, although one seemed to be a recently originated allopolyploid species with genetic additivity from two likely parents in the ITS sequence variation. Sixteen species of sect. Carpinus subsect. Polyneurae were classified into three species complexes, in each of which two or more could be not distinguished from each other. The closely related species of these complexes may still diverge at the early stage without genetic distinction in the nuclear ITS sequences because of too short of divergence time and frequent gene flow. Otherwise, some species may be established based on the intraspecific variations without genetic bases for an independently evolving unit.
TWO-SIGMA-G: a new competitive gene set testing framework for scRNA-seq data accounting for inter-gene and cell–cell correlation
Authors: Van Buren Eric , Hu Ming , Cheng Liang , Wrobel John , Wilhelmsen Kirk , Su Lishan , Li Yun , Wu Di
Published: February 2022

We propose TWO-SIGMA-G, a competitive gene set test for scRNA-seq data. TWO-SIGMA-G uses a mixed-effects regression model based on our previously published TWO-SIGMA to test for differential expression at the gene-level. This regression-based model provides flexibility and rigor at the gene-level in (1) handling complex experimental designs, (2) accounting for the correlation between biological replicates and (3) accommodating the distribution of scRNA-seq data to improve statistical inference. Moreover, TWO-SIGMA-G uses a novel approach to adjust for inter-gene-correlation (IGC) at the set-level to control the set-level false positive rate. Simulations demonstrate that TWO-SIGMA-G preserves type-I error and increases power in the presence of IGC compared with other methods. Application to two datasets identified HIV-associated interferon pathways in xenograft mice and pathways associated with Alzheimer’s disease progression in humans.
seqgra: principled selection of neural network architectures for genomics prediction tasks
Authors: Krismer Konstantin , Hammelman Jennifer , Gifford David K
Published: February 2022

Motivation

Sequence models based on deep neural networks have achieved state-of-the-art performance on regulatory genomics prediction tasks, such as chromatin accessibility and transcription factor binding. But despite their high accuracy, their contributions to a mechanistic understanding of the biology of regulatory elements is often hindered by the complexity of the predictive model and thus poor interpretability of its decision boundaries. To address this, we introduce seqgra, a deep learning pipeline that incorporates the rule-based simulation of biological sequence data and the training and evaluation of models, whose decision boundaries mirror the rules from the simulation process.

Results

We show that seqgra can be used to (i) generate data under the assumption of a hypothesized model of genome regulation, (ii) identify neural network architectures capable of recovering the rules of said model and (iii) analyze a model’s predictive performance as a function of training set size and the complexity of the rules behind the simulated data.

Availability and implementation

The source code of the seqgra package is hosted on GitHub (https://github.com/gifford-lab/seqgra). seqgra is a pip-installable Python package. Extensive documentation can be found at https://kkrismer.github.io/seqgra.

Supplementary information

Supplementary data are available at Bioinformatics online.
Investigation of phase-change materials for interior temperature regulation in public transport
Authors: Islam Md Nahidul , Hossain Md Nahid , Ahmed Dewan Hasan
Published: February 2022

Regulating the indoor temperature of public transport on hot sunny days is a prime concern, as both the external and internal heat sources play an active role in heat gain. Experimental studies have been carried out on a bus model using sodium sulphate decahydrate as a phase-change material (PCM) that is placed in between the ceiling and the roof. Studies are conducted on a sunny day and also for different cases of external (300-W surface heater) and internal (25-W light bulb) heat sources. The results show that PCM, in the presence of an external heat source, can help to keep the indoor temperature lower and delay the time period for increasing the temperature by absorbing heat during the phase change. On the other hand, the presence of the internal heat source contributes to a detrimental effect on the indoor temperature, which gradually increases with the elapse of time. With the combination of the external and internal heat sources, it is found that the internal heat source plays a dominating factor to raise the indoor temperature. It is revealed from the experimental results that a 12.7-mm single layer and a single PCM are not enough to counter the internal heat of 25 W unless the thickness of the PCM layer is increased to delay the increase in the indoor temperature. An additional PCM layer with a lower melting temperature could be placed at the inner portion of the ceiling to have effective thermal-energy storage by absorbing the substantial heat gain from the internal heat sources.
Long-term results of tricuspid valve repair using three-dimensional versus flexible rings in patients with functional tricuspid regurgitation
Authors: Ram Eilon , Peled Yael , Karni Ehud , Dray Efrat Mazor , Cohen Hillit , Sternik Leonid , Raanani Ehud
Published: February 2022

OBJECTIVES

Significant functional tricuspid regurgitation (TR) should be corrected in patients undergoing surgery for left-sided valvular diseases. We hypothesized that ring type may affect outcomes in tricuspid annuloplasty. Herein, we report our experience with three-dimensional semi-rigid rings compared to open simple-band annuloplasty.

METHODS

This is a retrospective study that included all patients who underwent tricuspid annuloplasty concomitant to left-sided valvular surgery. The study's main outcome measure was long-term recurrent TR probability.

RESULTS

Of the 781 study patients, 611 (78%) underwent annuloplasty using flexible band and 170 (22%) underwent rigid ring implantation. Early mortality did not differ significantly between the rigid and flexible groups (4.4% vs 4.1%, P = 1.000). Long-term mortality was similar between the groups [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.69–1.36, P = 0.847]. At a mean follow-up of 62 (50) months, freedom from TR grade 3+/4+ was 96.4% and 96.7% in the rigid and flexible groups, respectively (HR 1.41, 95% CI 0.55–3.61, P = 0.476). Furthermore, 2.4% of the rigid and 1.3% of the flexible groups required reoperation (HR 1.01, 95% CI 0.21–4.82, P = 0.988). Multivariable analysis demonstrated that rheumatic valve aetiology (HR 1.92, CI 1.04–2.98, P = 0.042) and mitral stenosis (HR 1.44, CI 1.01–2.2, P = 0.044) were predictors for recurrent TR (3+/4+). Ring type was not associated with recurrence (HR 0.86, 95% CI 0.3–2.47, P = 0.787).

CONCLUSIONS

Open bands performed at least as well as three-dimensional rings. Our results suggest that late clinical results of tricuspid annuloplasty depend on left-sided pathology and patient factors and less on the type of ring used.
MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults
Authors: Pencina Karol M , Lavu Siva , dos Santos Marcello , Beleva Yusnie M , Cheng Ming , Livingston David , Bhasin Shalender
Published: February 2022

Background

Nicotinamide adenine dinucleotide (NAD) precursors, nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) extend healthspan and ameliorate some age-related conditions in model organisms. However, early-phase trials of NAD precursors have yielded varying results and their pharmacokinetics remain incompletely understood. Here, we report the pharmacokinetics and pharmacodynamics of MIB-626, a microcrystalline unique polymorph βNMN formulation.

Methods

In this double-blind, placebo-controlled study, 32 overweight or obese adults, 55–80 years, were block-randomized, stratified by sex, to 1 000-mg MIB-626 once daily, twice daily, or placebo for 14 days. NMN, NAD, and NAD metabolome were measured using liquid chromatography–tandem mass spectrometry.

Results

Participant characteristics were similar across groups. MIB-626 was well tolerated and frequency of adverse events was similar across groups. Blood NMN concentrations on Day 14 in MIB-626-treated groups were significantly higher compared to placebo (1.7-times and 3.7-times increase above baseline in 1 000 mg once-daily and twice-daily groups in mean AUClast, respectively). MIB-626 treatment was associated with substantial dose-related increases in blood NAD levels. Blood levels of NAD metabolites were higher in NMN-treated participants on Days 8 and 14 than at baseline. Changes in NMN or NAD levels were not related to sex, body mass index, or age. Very little unmodified NMN was excreted in the urine.

Conclusion

MIB-626 1 000 mg once-daily or twice-daily regimens were safe and associated with substantial dose-related increases in blood NAD levels and its metabolome. These foundational data that were obtained using a pharmaceutical-grade βNMN, standardized sample collection, and validated liquid chromatography–tandem mass spectrometry assays, should facilitate design of efficacy trials in disease conditions.
The effects of discontinuity topography in the mantle transition zone on global geodynamic observables and mantle heterogeneity
Authors: Glišović Petar , Grand Stephen P , Lu Chang , Forte Alessandro M , Wei S Shawn
Published: February 2022

Despite progress in tomographic imaging of Earth's interior, a number of critical questions regarding the large-scale structure and dynamics of the mantle remain outstanding. One of those questions is the impact of phase-boundary undulations on global imaging of mantle heterogeneity and on geodynamic (i.e. convection-related) observables. To address this issue, we developed a joint seismic-geodynamic-mineral physical tomographic inversion procedure that incorporates lateral variations in the depths of the 410- and 660-km discontinuities. This inversion includes S-wave traveltimes, SS precursors that are sensitive to transition-zone topography, geodynamic observables/data (free-air gravity, dynamic surface topography, horizontal divergence of tectonic plates and excess core-mantle boundary ellipticity) and mineral physical constraints on thermal heterogeneity. Compared to joint tomography models that do not include data sensitivity to phase-boundary undulations in the transition zone, the inclusion of 410- and 660-km topography strongly influences the inference of volumetric anomalies in a depth interval that encompasses the transition zone and mid-mantle. It is notable that joint tomography inversions, which include constraints on transition-zone discontinuity topography by seismic and geodynamic data, yield more pronounced density anomalies associated with subduction zones and hotspots. We also find that the inclusion of 410- and 660-km topography may improve the fit to the geodynamic observables, depending on the weights applied to seismic and geodynamic data in the inversions. As a consequence, we find that the amplitude of non-thermal density anomalies required to explain the geodynamic data decreases in most of the mantle. These findings underline the sensitivity of the joint inversions to the inclusion of transition-zone complexity (e.g. phase-boundary topography) and the implications for the inferred non-thermal density anomalies in these depth regions. Finally, we underline that our inferences of 410- and 660-km topography avoid a commonly employed approximation that represents the contribution of volumetric heterogeneity to SS-wave precursor data. Our results suggest that this previously employed correction, based on a priori estimates of upper-mantle heterogeneity, might be a significant source of error in estimating the 410- and 660-km topography.
Grapevine rootstock and soil microbiome interactions: Keys for a resilient viticulture
Authors: Darriaut Romain , Lailheugue Vincent , Masneuf-Pomarède Isabelle , Marguerit Elisa , Martins Guilherme , Compant Stéphane , Ballestra Patricia , Upton Steven , Ollat Nathalie , Lauvergeat Virginie
Published: February 2022

Soil microbiota has increasingly been shown to play an integral role in viticulture resilience. The emergence of new metagenomic and culturomic technologies has led to significant advances in the study of microbial biodiversity. In the agricultural sector, soil and plant microbiomes have been found to significantly improve resistance to environmental stressors and diseases, as well as influencing crop yields and fruit quality thus improving sustainability under shifting environments. Grapevines are usually cultivated as a scion grafted on rootstocks, which are selected according to pedoclimatic conditions and cultural practices, known as terroir. The rootstock connects the surrounding soil to the vine’s aerial part and impacts scion growth and berry quality. Understanding rootstock and soil microbiome dynamics is a relevant and important field of study, which may be critical to improve viticulture sustainability and resilience. This review aims to highlight the relationship between grapevine roots and telluric microbiota diversity and activity. In addition, this review explores the concept of core microbiome regarding potential applications of soil microbiome engineering with the goal of enhancing grapevine adaptation to biotic and abiotic stress.
Genetic architecture and genomic predictive ability of apple quantitative traits across environments
Authors: Jung Michaela , Keller Beat , Roth Morgane , Aranzana Maria José , Auwerkerken Annemarie , Guerra Walter , Al-Rifaï Mehdi , Lewandowski Mariusz , Sanin Nadia , Rymenants Marijn , Didelot Frédérique , Dujak Christian , Font i Forcada Carolina , Knauf Andrea , Laurens François , Studer Bruno , Muranty Hélène , Patocchi Andrea
Published: February 2022

Implementation of genomic tools is desirable to increase the efficiency of apple breeding. Recently, the multi-environment apple reference population (apple REFPOP) proved useful for rediscovering loci, estimating genomic predictive ability, and studying genotype by environment interactions (G × E). So far, only two phenological traits were investigated using the apple REFPOP, although the population may be valuable when dissecting genetic architecture and reporting predictive abilities for additional key traits in apple breeding. Here we show contrasting genetic architecture and genomic predictive abilities for 30 quantitative traits across up to six European locations using the apple REFPOP. A total of 59 stable and 277 location-specific associations were found using GWAS, 69.2% of which are novel when compared with 41 reviewed publications. Average genomic predictive abilities of 0.18–0.88 were estimated using main-effect univariate, main-effect multivariate, multi-environment univariate, and multi-environment multivariate models. The G × E accounted for up to 24% of the phenotypic variability. This most comprehensive genomic study in apple in terms of trait-environment combinations provided knowledge of trait biology and prediction models that can be readily applied for marker-assisted or genomic selection, thus facilitating increased breeding efficiency.
Physiological, biochemical, and molecular aspects of grafting in fruit trees
Authors: Habibi Fariborz , Liu Tie , Folta Kevin , Sarkhosh Ali
Published: February 2022

Grafting is a widely used practice for asexual propagation of fruit trees. Many physiological, biochemical, and molecular changes occur upon grafting that can influence important horticultural traits. This technology has many advantages, including avoidance of juvenility, modifying the scion architecture, improving productivity, adapting scion cultivars to unfavourable environmental conditions, and developing traits in resistance to insect pests, bacterial and fungal diseases. A limitation of grafting is scion-rootstock incompatibility. It may be caused by many factors, including insufficient genetic proximity, physiological or biochemical factors, lignification at the graft union, poor graft architecture, insufficient cell recognition between union tissues, and metabolic differences in the scion and the rootstock. Plant hormones, like auxin, ethylene (ET), cytokinin (CK), gibberellin (GA), abscisic acid (ABA), and jasmonic acid (JA) orchestrate several crucial physiological and biochemical processes happening at the site of the graft union. Additionally, epigenetic changes at the union affect chromatin architecture by DNA methylation, histone modification, and the action of small RNA molecules. The mechanism triggering these effects likely is affected by hormonal crosstalk, protein and small molecules movement, nutrients uptake, and transport in the grafted trees. This review provides an overview of the basis of physiological, biochemical, and molecular aspects of fruit tree grafting between scion and rootstock.
Across-population genomic prediction in grapevine opens up promising prospects for breeding
Authors: Brault Charlotte , Segura Vincent , This Patrice , Le Cunff Loïc , Flutre Timothée , François Pierre , Pons Thierry , Péros Jean-Pierre , Doligez Agnès
Published: February 2022

Crop breeding involves two selection steps: choosing progenitors and selecting individuals within progenies. Genomic prediction, based on genome-wide marker estimation of genetic values, could facilitate these steps. However, its potential usefulness in grapevine (Vitis vinifera L.) has only been evaluated in non-breeding contexts mainly through cross-validation within a single population. We tested across-population genomic prediction in a more realistic breeding configuration, from a diversity panel to ten bi-parental crosses connected within a half-diallel mating design. Prediction quality was evaluated over 15 traits of interest (related to yield, berry composition, phenology and vigour), for both the average genetic value of each cross (cross mean) and the genetic values of individuals within each cross (individual values). Genomic prediction in these conditions was found useful: for cross mean, average per-trait predictive ability was 0.6, while per-cross predictive ability was halved on average, but reached a maximum of 0.7. Mean predictive ability for individual values within crosses was 0.26, about half the within-half-diallel value taken as a reference. For some traits and/or crosses, these across-population predictive ability values are promising for implementing genomic selection in grapevine breeding. This study also provided key insights on variables affecting predictive ability. Per-cross predictive ability was well predicted by genetic distance between parents and when this predictive ability was below 0.6, it was improved by training set optimization. For individual values, predictive ability mostly depended on trait-related variables (magnitude of the cross effect and heritability). These results will greatly help designing grapevine breeding programs assisted by genomic prediction.
New insights into flowering date in Prunus: fine mapping of a major QTL in sweet cherry
Authors: Branchereau Camille , Quero-García José , Zaracho-Echagüe Nathalia Helena , Lambelin Laurine , Fouché Mathieu , Wenden Bénédicte , Donkpegan Armel , Le Dantec Loïck , Barreneche Teresa , Alletru David , Parmentier Julien , Dirlewanger Elisabeth
Published: February 2022

Flowering date is an important trait in Prunus fruit species, especially for their adaptation in a global warming context. Numerous quantitative trait loci (QTLs) have been identified and a major one was previously located on LG4. The objectives of this study were to fine-map this QTL in sweet cherry, to identify robust candidate genes by using the new sweet cherry genome sequence of the cultivar “Regina” and to define markers usable in marker-assisted selection (MAS). We performed QTL analyses on two populations derived from crosses using cultivars “Regina” and “Garnet” as parents. The first one (n = 117) was phenotyped over ten years, while the second one (n = 1386) was evaluated during three years. Kompetitive allele specific PCR (KASP) markers located within the QTL region on LG4 were developed and mapped within this region, consisting in the first fine mapping in sweet cherry. The QTL interval was narrowed from 380 kb to 68 kb and candidate genes were identified by using the genome sequence of “Regina”. Their expression was analyzed from bud dormancy period to flowering in cultivars “Regina” and “Garnet”. Several genes, such as PavBOI-E3, PavSR45a and PavSAUR71, were differentially expressed in these two cultivars and could be then considered as promising candidate genes. Two KASP markers were validated using a population derived from a cross between cultivars “Regina” and “Lapins” and two collections, including landraces and modern cultivars. Thanks to the high synteny within the Prunus genus, these results give new insights into the control of flowering date in Prunus species and pave the way for the development of molecular breeding strategies.
BrpNAC895 and BrpABI449 coregulate the transcription of the afflux-type cadmium transporter BrpHMA2 in Brassica parachinensis
Authors: Liu Shuai , Li Limei , Deng Yanwu , Bai Yongsheng , Sun Chao , Huang Shili , Zhou Jiajie , Shi Liyu , Yang Xuewei , Li Ling , Chen Xuemei , Tang Yulin
Published: February 2022

Brassica parachinensis is a popular leafy vegetable. It is able to accumulate high concentrations of cadmium (Cd), but the molecular mechanism of Cd accumulation is unknown. This study investigated the function and regulatory mechanism of the Cd-responsive metal ion transporter gene BrpHMA2. BrpHMA2 was induced by Cd stress and specifically expressed in vascular tissues, and the protein was localized in the plasma membrane. Heterologous expression of BrpHMA2 enhanced Cd accumulation and Cd sensitivity in transgenic Arabidopsis and yeast. After Cd stress, the transcription factors BrpNAC895 and BrpABI449, which may recognize the abscisic acid-responsive elements in the BrpHMA2 promoter, were also differentially expressed. The transcriptional regulation of BrpHMA2 was further investigated using the chromatin immunoprecipitation–quantitative PCR (ChIP–qPCR) assay, the electrophoretic mobility shift assay (EMSA), and luciferase (LUC) reporter activity analysis employing the transient expression system of B. parachinensis protoplasts and tobacco leaves and the Escherichia coli expression system. By binding to the promoter, BrpNAC895 induced the transcription of BrpHMA2. BrpABI449 might bind to the BrpHMA2 promoter or interact with BrpNAC895 to interfere with the action of BrpNAC895. The findings suggest that BrpHMA2 is a membrane-based afflux-type Cd transporter involved in Cd2+ uptake and long-distance transport in plants. BrpNAC895 and BrpABI449, which function as the transcription activator and repressor, respectively, coregulate BrpHMA2 expression.
Functional analysis of the eTM-miR171-SCL6 module regulating somatic embryogenesis in Lilium pumilum DC. Fisch
Authors: Yan Rui , Song Shengli , Li Hongyu , Sun Hongmei
Published: February 2022

Somatic embryogenesis (SE) is of great significance in Lilium bulb production, germplasm preservation, and genetic improvement. miRNAs are important regulators of plant growth and development at the transcriptional level. Previous research by our group has shown that lpu-miR171 and its target gene SCARECROW-LIKE 6 (SCL6) play an important regulatory role in lily SE, and we predicted and identified that endogenous target mimics (eTMs) can regulate lpu-miR171. However, the associated mechanism and internal regulatory network are not yet clear. In the present study, lpu-miR171 was used as an entry point to explore the regulatory network between its upstream eTMs and its downstream target gene LpSCL6, as well as to identify the mechanism of this regulatory network in Lilium SE. Tobacco transient transformation confirmed that miRNA171 significantly inhibited the expression of LpSCL6. On this basis, the Lilium stable genetic transformation system was used to demonstrate that silencing lpu-miR171a and lpu-miR171b and overexpressing LpSCL6-II and LpSCL6-I promoted starch accumulation in calli and the expression of key cell cycle genes, thus providing energy to meet preconditions for SE and accelerate the formation and development of Lilium somatic embryos. LpSCL6-II and LpSCL6-I are nuclear proteins with self-activation activity in yeast cells. In addition, we confirmed in Lilium that lpu-eTM171 is the eTM of lpu-miR171 that binds lpu-miR171 to prevent cleavage of the target gene LpSCL6, thereby promoting SE. Therefore, the present study established a new mechanism whereby the eTM-miR171-SCL6 module regulates SE in Lilium pumilum and provides new insights clarifying the mechanism of SE.
Short-term outcomes of EXCOR Paediatric implantation
Authors: Komori Motoki , Hoashi Takaya , Sakaguchi Heima , Imai Kenta , Okuda Naoki , Fukushima Norihide , Kurosaki Kenichi , Ichikawa Hajime
Published: February 2022

OBJECTIVES

The aim of this study was to review a single institution’s experience with EXCOR Paediatric implantation.

METHODS

Patients <15 years old who underwent EXCOR implantation as a bridge to transplantation between 2015 and 2021 were enrolled. Major adverse events included death, cerebrovascular event resulting in sequelae, major infection (sepsis or surgical site infection requiring open sternal irrigation or device removal) and device malfunction requiring surgical treatment.

RESULTS

Overall median age and weight for all 20 children at implantation were 10.8 (interquartile range, 7.9–33.2) months and 6.3 (4.6–10.2) kg. Ten patients (50%) weighed <5 kg. Primary diagnoses were dilated cardiomyopathy in 13 patients, fulminant myocarditis in 3, restrictive cardiomyopathy in 2 and congenital heart disease in 2. Two patients required biventricular assist support. The median support time was 365 (241–636) days. Six patients (30%) were supported for >20 months. One patient died. Seven patients underwent heart transplant. Heart transplant has not been performed in the last 1.5 years. Five patients were weaned from EXCOR support after native myocardial recovery, including a patient with dilated cardiomyopathy who recovered after 24 months of EXCOR support. Major complication-free survival at 6, 12 and 18 months were 79.3%, 49.6% and 38.6%, respectively. Body weight <5 kg at implantation was a risk factor for decreased major complication-free survival.

CONCLUSIONS

Survival during EXCOR Paediatric support was good, but it prolonged the wait time for a heart transplant. The number of major complications increased over time and was not negligible, especially in small children.
Linear convergence of the subspace constrained mean shift algorithm: from Euclidean to directional data
Authors: Zhang Yikun , Chen Yen-Chi
Published: February 2022

This paper studies the linear convergence of the subspace constrained mean shift (SCMS) algorithm, a well-known algorithm for identifying a density ridge defined by a kernel density estimator. By arguing that the SCMS algorithm is a special variant of a subspace constrained gradient ascent (SCGA) algorithm with an adaptive step size, we derive the linear convergence of such SCGA algorithm. While the existing research focuses mainly on density ridges in the Euclidean space, we generalize density ridges and the SCMS algorithm to directional data. In particular, we establish the stability theorem of density ridges with directional data and prove the linear convergence of our proposed directional SCMS algorithm.