bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances in single-cell sequencing technologies
Authors: Wen Lu , Tang Fuchou
Published: January 2022

Single-cell omics sequencing was first achieved for the transcriptome in 2009, which was followed by fast development of technologies for profiling the genome, DNA methylome, 3D genome architecture, chromatin accessibility, histone modifications, etc., in an individual cell. In this review we mainly focus on the recent progress in four topics in the single-cell omics field: single-cell epigenome sequencing, single-cell genome sequencing for lineage tracing, spatially resolved single-cell transcriptomics and third-generation sequencing platform-based single-cell omics sequencing. We also discuss the potential applications and future directions of these single-cell omics sequencing technologies for different biomedical systems, especially for the human stem cell field.
Characterization of two-level system noise for a microwave kinetic inductance detector comprising niobium film on a silicon substrate
Authors: Sueno Y , Honda S , Kutsuma H , Mima S , Otani C , Oguri S , Suzuki J , Tajima O
Published: January 2022

A microwave kinetic inductance detector (MKID) is a cutting-edge superconducting detector. It comprises a resonator circuit constructed with a superconducting film on a dielectric substrate. To expand its field of application, it is important to establish a method to suppress the two-level system (TLS) noise that is caused by the electric fluctuations between the two energy states at the surface of the substrate. The electric field density can be decreased by expanding the strip width (S) and gap width from the ground plane (W) in the MKID circuit, allowing the suppression of TLS noise. However, this effect has not yet been confirmed for MKIDs made with niobium films on silicon substrates. In this study, we demonstrate its effectiveness for such MKIDs. We expanded the dimension of the circuit from (S, W) = (3.00 μm, 4.00 μm) to (S, W) = (5.00 μm, 23.7 μm), and achieved an increased suppression of 5.5 dB in TLS noise.
pRB-Depleted Pluripotent Stem Cell Retinal Organoids Recapitulate Cell State Transitions of Retinoblastoma Development and Suggest an Important Role for pRB in Retinal Cell Differentiation
Authors: Rozanska Agata , Cerna-Chavez Rodrigo , Queen Rachel , Collin Joseph , Zerti Darin , Dorgau Birthe , Beh Chia Shyan , Davey Tracey , Coxhead Jonathan , Hussain Rafiqul , Al-Aama Jumana , Steel David H , Benvenisty Nissim , Armstrong Lyle , Parulekar Manoj , Lako Majlinda
Published: January 2022

Retinoblastoma (Rb) is a childhood cancer of the developing retina, accounting for up to 17% of all tumors in infancy. To gain insights into the transcriptional events of cell state transitions during Rb development, we established 2 disease models via retinal organoid differentiation of a pRB (retinoblastoma protein)-depleted human embryonic stem cell line (RB1-null hESCs) and a pRB patient-specific induced pluripotent (iPSC) line harboring a RB1 biallelic mutation (c.2082delC). Both models were characterized by pRB depletion and accumulation of retinal progenitor cells at the expense of amacrine, horizontal and retinal ganglion cells, which suggests an important role for pRB in differentiation of these cell lineages. Importantly, a significant increase in the fraction of proliferating cone precursors (RXRγ+Ki67+) was observed in both pRB-depleted organoid models, which were defined as Rb-like clusters by single-cell RNA-Seq analysis. The pRB-depleted retinal organoids displayed similar features to Rb tumors, including mitochondrial cristae aberrations and rosette-like structures, and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro. In both models, the Rb cones expressed retinal ganglion and horizontal cell markers, a novel finding, which could help to better characterize these tumors with possible therapeutic implications. Application of Melphalan, Topotecan, and TW-37 led to a significant reduction in the fraction of Rb proliferating cone precursors, validating the suitability of these in vitro models for testing novel therapeutics for Rb.
Development of synthetic biotics as treatment for human diseases
Authors: Brennan Aoife M
Published: January 2022

Advances in synthetic biology have allowed the generation of strains of bacteria that are genetically altered to have specific therapeutic benefits. These synthetic biotics, also widely referred to as engineered living therapeutics, have tremendous potential as a new therapeutic modality, and several have advanced into the clinic and human testing. This review outlines some of the unique attributes of synthetic biotics as well as some of the challenges in their development as prescription products. Regulatory considerations are discussed, and a case study of a program that has advanced into Phase 2 testing is provided: SYNB1618 for the treatment of PKU.
The Role of the Artery of Ligamentum Teres in Revascularization in Legg-Calve-Perthes Disease
Authors: Morris William Z. , Valencia Angel A. , McGuire Molly F. , Kim Harry K.W.
Published: January 2022

Introduction:

A recent cadaveric study supported that most immature hips are supplied by the artery of ligamentum teres and suggested this medial vascular source may influence the pattern of revascularization in Legg-Calve-Perthes disease (LCPD). The purposes of this study were to characterize the perfusion pattern of the capital femoral epiphysis and determine the role of the artery of ligamentum teres in early revascularization of LCPD.

Methods:

Retrospective review of perfusion magnetic resonance imaging (pMRI) from 64 hips in early stage LCPD (Waldenström stage I to IIa) was performed. Two independent graders categorized perfusion pattern based on the presence of perfusion medially (from artery of ligamentum teres) and/or laterally (from the medial femoral circumflex artery) on coronal and sagittal MRI series: type 1—lateral perfusion only, type 2—separate medial and lateral perfusion, or type 3—coalescent medial and lateral perfusion. Lateral pillar classification was obtained for hips that reached mid-fragmentation.

Results:

We identified 64 patients (75% male) with mean age at diagnosis of 8.5±2.1 years. 36% (23/64) hips underwent pMRI during stage I and 64% (41/64) during stage IIa. pMRI revealed separate and distinct medial and lateral sources of perfusion (type 2) in 50% (32/64) hips. In stage I, the distribution of type 1/2/3 hips was found to be 26%/52%/22%. However, in stage IIa there was a nonsignificant trend toward greater coalescence of the medial and lateral perfusion with a distribution of type 1/2/3 of 7%/49%/44% (P=0.07). There was a nonsignificant trend toward weak negative linear correlation between lower initial perfusion grade and worsened lateral pillar classification at mid-fragmentation (r=−0.25, P=0.05).

Conclusion:

The presence of separate and distinct areas of perfusion of medial and lateral capital femoral epiphysis provides further evidence of the role of the ligamentum teres vessels in revascularization during the early stages of LCPD. The changes in perfusion pattern with disease progression likely reflect that medial femoral circumflex artery and ligamentum teres vessel revascularization occur separately, but ultimately coalesce posteriorly over time.

Level of Evidence:

Level II—prognostic study.
Stem cells to reverse aging
Authors: Chang Le , Fan Weiwen , Pan Xinghua , Zhu Xiangqing
Published: January 2022

As human life expectancy continues to increase and the birth rate continues to decline, the phenomenon of aging is becoming more prominent worldwide. Therefore, addressing the problems associated with global aging has become a current research focus. The main manifestations of human aging are structural degeneration and functional decline of aging tissues and organs, quality of life decline, decreased ability to resist diseases, and high incidence rates of a variety of senile degenerative diseases. Thus far, no ideal treatments have been found. Stem cell (SC) therapies have broad application prospects in the field of regenerative medicine due to the inherent biological characteristics of SCs, such as their plasticity, self-renewal, and multidirectional differentiation potential. Thus, SCs could delay or even reverse aging. This manuscript reviews the causes of human aging, the biological characteristics of SCs, and research progress on age reversal.
Respective Impact of Day and Night Bed Baths on Critical Care Patients
Authors: Bernard Mélanie , Godard Baptiste , Camara Corika , Gaultier Alexandra , Hudry Cédric , Marlot Thibault , Sergent Jérémy , Coadic Delphine , David Vanessa , Damoisel Charles , Sztrymf Benjamin ,   The ToNu investigators
Published: January 2022

Background

Despite data supporting the reduction of interactions with patients during nighttime, bed bathing is sometimes performed within this period in sedated patients unable to manage their own hygiene care.

Objectives

To compare patient physiologic variables and adverse effect incidence between night and day bed baths.

Methods

This was a single-center prospective observational study in a 12-bed intensive care unit during 2 months. Night period was defined to run from 10 pm to 6 am. Night bed baths were provided to sedated ventilated patients whatever their sedation, if their Richmond Agitation Sedation Scale score was −2 or deeper. Bed bath–induced changes in physiological variables, treatments, and related unscheduled events were registered during both night and day bed baths.

Results

Twenty-one patients (aged 62.9 [52.5-73.2] years, 14 male patients) were included. We registered 97 night bed baths and 95 day bed baths. Heart rate increased only after day bed baths (85 beats/min [bpm] [69-97 bpm] vs 88 bpm [73-98 bpm], P = .02). Increase in Richmond Agitation Sedation Scale score occurred, respectively, during 13 (13.4%) and 8 (8.4%) night and day bed baths, without significant differences. Body temperature significantly decreased during both night and day bed baths (respectively, 37°C [36.6°C-37.4°C] vs 36.6°C [36.2°C-37.2°C], P < .0001; and 36.9°C [36.5°C-37.2°C] vs 36.7°C [36.2°C-37.2°C], P = .0006). Overall, unscheduled events, whether physiologic changes, pain, or calling a physician in rescue occurred in 97 procedures (50.5%), irrespective of their timing (night vs day, respectively 53% [54.6%] vs 44% [46.3%], P = .31).

Discussion

Although unscheduled events occurred in half of bed baths, differences evidenced between nighttime and daytime bed baths were scarce. The appropriateness of nighttime bed bathing remains questionable.
Thirst Interventions in Adult Acute Care—What Are the Recommended Management Options and How Effective Are They?
Authors: Clark Jenny , Archer Sally K.
Published: January 2022

Purpose

The aim of this study was to review the scope and quality of evidence for thirst treatment in adult acute care.

Methods

A systematic review was completed by 2 independent reviewers using MEDLINE, PubMed, BNI, EMBASE, EMCARE, and CINAHL databases and additional hand searching in June 2020. Interventions to relieve thirst for inpatients receiving acute care were included. Evidence was appraised against the levels of evidence for therapeutic studies, and a risk-of-bias assessment was completed for included studies. Outcomes are presented via narrative synthesis. Meta-analysis was planned.

Results

Four studies (out of 844) were eligible reporting thirst outcomes from 611 critical care patients. Meta-analysis could not be completed because a priori criteria were not met. Two randomized controlled trials represented the highest level of evidence. Thirst assessment was completed via a self-reported scale in all reviewed works. Interventions included cold water sprays or swabs, menthol lip moisturizer, and use of humidification. Three works demonstrate reduced thirst scores; all interventions in these studies exploit cooling effects to the oropharynx with the aim of preabsorptive satiation of thirst. A humidified oxygen circuit showed a neutral response when compared with a nonhumidified circuit.

Conclusions

There is a limited but growing evidence base related to thirst treatment in the acute setting. Studies using a “bundle” of topical interventions incorporating cooling and menthol treatments showed positive effects in reducing symptom burden. Work to explore the scope of application for thirst treatment for patients unable to self-report, consideration of sustained effects, and a study of individual versus combined effects of bundle elements would be welcomed as the evidence base continues to develop.
Massachusetts Intensive Care Unit Nurses From Multiple Hospitals Develop a Collaborative to Improve Delirium Assessment Accuracy
Authors: O'Donoghue Sharon C. , Meyers Karen , Manning Cathie R. , Pellegrino Linda S. , Ryan Colleen P. , Crowell Amanda M. , Nolan Lisa M. , Gallagher Gail E.
Published: January 2022

Background and Relevance

Early recognition of delirium mobilizes nurses to intervene in a timely manner to minimize cognitive, physical, and mental health burdens. The life-altering challenges of unrecognized delirium in intensive care unit (ICU) patients motivated a group of Massachusetts ICU nurse leaders to form a collaborative and improve delirium screening accuracy in 4 area hospitals.

Local Problem

Baseline audits confirmed a lack of delirium screening accuracy across multiple institutions. The purpose of this article is to describe how our collaborative was developed and to outline our delirium accuracy assessment program.

Methods

In March of 2015, 2 graduates from the Clinical Scene Investigator Academy contacted members within the Boston cohort to form a regional collaborative to improve patient outcomes. The purpose of our project was to improve our delirium assessment accuracy to greater than 80% in patients across our ICUs. Using a successful project, we scaled this work based on the needs of each institution. A preaudit-postaudit design was used to evaluate the effectiveness of our programs.

Results

Data showed an improved overall accuracy assessment of 88.3% (P < .01), whereas the patients with an altered Richmond Agitation Sedation Scale markedly improved to 87.7% (P < .01).

Conclusions

Every ICU in the United States is working on improving reportable quality metrics, but all too often, this work is being done in silos. When critical care nurses have the knowledge, skills, and time to work together, they can begin to transform health care.
Prenatal exposure to metal mixtures and newborn neurobehavior in the Rhode Island Child Health Study
Authors: Tung Pei Wen , Burt Amber , Karagas Margaret , Jackson Brian P. , Punshon Tracy , Lester Barry , Marsit Carmen J.
Published: January 2022

Background:

Prenatal exposure to metals can affect the developing fetus and negatively impact neurobehavior. The associations between individual metals and neurodevelopment have been examined, but little work has explored the potentially detrimental neurodevelopmental outcomes associated with the combined impact of coexisting metals. The objective of this study is to evaluate prenatal metal exposure mixtures in the placenta to elucidate the link between their combined effects on newborn neurobehavior.

Method:

This study included 192 infants with available placental metal and NICU Network Neurobehavioral Scale data at 24 hours–72 hours age. Eight essential and nonessential metals (cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, zinc) detected in more than 80% of samples were tested for associations with atypical neurobehavior indicated by NICU Network Neurobehavioral Scale using logistic regression and in a quantile g-computation analysis to evaluate the joint association between placental metal mixture and neurobehavioral profiles.

Results:

Individually, a doubling of placental cadmium concentrations was associated with an increased likelihood of being in the atypical neurobehavioral profile (OR = 2.39; 95% CI = 1.05 to 5.71). In the mixture analysis, joint effects of a quartile increase in exposure to all metals was associated with 3-fold increased odds of newborns being assigned to the atypical profile (OR = 3.23; 95% CI = 0.92 to 11.36), with cadmium having the largest weight in the mixture effect.

Conclusions:

Prenatal exposure to relatively low levels of a mixture of placental metals was associated with adverse newborn neurobehavior. Examining prenatal metal exposures as a mixture is important for understanding the harmful effects of concomitant exposures in the vulnerable populations.
A Real-world Claims Data Analysis of Meningococcal Serogroup B Vaccine Series Completion and Potential Missed Opportunities in the United States
Authors: Packnett Elizabeth R. , Zimmerman Nicole M. , Kim Gilwan , Novy Patricia , Morgan Laura C. , Chime Nnenna , Ghaswalla Parinaz
Published: January 2022

Background:

In the United States, meningococcal serogroup B (MenB) vaccination is recommended for 16–23-year-olds based on shared clinical decision-making. We estimated series completion among individuals initiating MenB vaccination for the 2 available vaccines: MenB 4-component (MenB-4C, doses at 0 and ≥1 month) and MenB factor H binding protein (MenB-FHbp, doses at 0 and 6 months).

Methods:

This retrospective health insurance claims data analysis included 16–23-year-olds who initiated MenB vaccination (index date) during January 2017 to November 2018 (MarketScan Commercial Claims and Encounters Database) or January 2017 to September 2018 (MarketScan Multi-State Medicaid Database) and had continuous enrollment for ≥6 months before and ≥15 months after index. The main outcome was MenB vaccine series completion within 15 months. Among noncompleters, preventive care/well-child and vaccine administrative office visits were identified as potential missed opportunities for series completion. Robust Poisson regression models identified independent predictors of series completion.

Results:

In the Commercial (n = 156,080) and Medicaid (n = 57,082) populations, series completion was 56.7% and 44.7%, respectively, and was higher among those who initiated MenB-4C versus MenB-FHbp (61.1% versus 49.8% and 47.8% versus 33.9%, respectively; both P < 0.001). Among noncompleters, 40.2% and 34.7% of the Commercial and Medicaid populations, respectively, had ≥1 missed opportunity for series completion. Receipt of MenB-4C and younger age were independently associated with a higher probability of series completion.

Conclusions:

Series completion rates were suboptimal but were higher among those who initiated MenB-4C. To maximize the benefits of MenB vaccination, interventions to improve completion and reduce missed opportunities should be implemented.
Evaluation of Biomechanical Effects and Patient Benefits of a New Orthotic Ankle Joint in Stance Control Orthosis Fittings
Authors: Schmalz Thomas , Köhler Thomas Maximilian , Burkhardt Katharina , Dlugoszek Annika , Overdevest Etienne , Kannenberg Andreas , Bellmann Malte
Published: January 2022

Introduction

A newly introduced generation of orthotic ankle joints with adjustable dorsiflexion and plantarflexion resistances and increased range of motion (ROM) has been well established in orthotic fittings of neurological patients with ankle foot orthoses. The aim of the present study was to investigate whether users of stance control orthoses (SCOs) may also benefit from this orthotic ankle joint principle using a biomechanical test design.

Methods

Six patients unilaterally fitted with an SCO (E-MAG Active) with the orthotic ankle joint NexGearTango (NGT; Ottobock, Duderstadt, Germany), an ankle joint representing the new principle, were enrolled in the study. The modular principle of the ankle joint allowed testing both the new functionality and the characteristics of a conventional orthotic ankle joint (CAJ; limited uncontrolled ROM). Level walking at slow, medium, and fast speed and with given short steps, ascending and descending a ramp with 10° inclination and standing (level ground as well as 10° incline and decline standing), were assessed while using NGT or CAJ, respectively. Kinematic and kinetic data were captured with an optoelectronic camera system and two force plates.

Results

The reliability of switching from stance to swing of the orthotic knee joint was clearly enhanced with NGT for short-step level walking and ascending ramps. For ascending ramps, a significantly increased dorsiflexion of 5° during stance and an earlier transition from decelerating to accelerating forces were found with NGT.

When standing on slopes, the symmetry of weight distribution between the orthotic and unaffected limb was significantly increased with NGT.

Conclusions

The increased and resistance-controlled dorsiflexion of the new orthotic ankle joint principle resulted in relevant benefits in gait situations with unlevel conditions and higher demands. Therefore, this orthotic ankle joint principle may represent an additional option to optimize patient fittings with SCOs.

Clinical Relevance Statement

The use of the new orthotic ankle principle tested in the present study results in relevant benefits, especially in gait situations in unlevel conditions. Therefore, this principle represents an additional option to optimize patient fittings with SCOs.
Expansion of Reconstructive Surgical Capacity in Vietnam: Experience from the ReSurge Global Training Program
Authors: Luan Anna , Hau Le Thua Trung , Thom Dang Hoang , Viet Phu Quoc , Auten Brieanne , Chang James
Published: January 2022

Background:

Building local surgical capacity in low-income and middle-income countries is critical to addressing the unmet global surgical need. Visiting educator programs can be utilized to train local surgeons, but the quantitative impact on surgical capacity has not yet been fully described. The authors’ objective was to evaluate the effectiveness of training utilizing a visiting educator program on local reconstructive surgical capacity in Vietnam.

Methods:

A reconstructive surgery visiting educator program was implemented in Vietnam. Topics of training were based on needs defined by local surgeons, including those specializing in hand surgery, microsurgery, and craniofacial surgery. A retrospective analysis of annual case numbers corresponding to covered topics between the years 2014 and 2019 at each hospital was conducted to determine reconstructive surgical volume and procedures per surgeon over time. Direct costs, indirect costs, and value of volunteer services for each trip were calculated.

Results:

Over the course of 5 years, 12 visiting educator trips were conducted across three hospitals in Vietnam. Local surgeons subsequently independently performed a total of 2018 operations corresponding to topics covered during visiting educator trips, or a mean of 136 operations annually per surgeon. Within several years, the hospitals experienced an 81.5 percent increase in surgical volume for these reconstructive clinical conditions, and annual case volume continues to increase over time. Total costs were $191,290, for a mean cost per trip of $15,941.

Conclusions:

Surgical capacity can be successfully expanded by utilizing targeted visiting educator trips to train local reconstructive surgeons. Local providers ultimately independently perform an increased volume of complex procedures and provide further training to others.
Perceptions of Doctors’ Empathy and Patients’ Subjective Health Status at an Online Clinic: Development of an Empathic Anamnesis Questionnaire
Authors: Martikainen Silja , Falcon Mari , Wikström Valtteri , Peltola Soili , Saarikivi Katri
Published: January 2022

Objective

Medical doctors’ empathy is known to support patients’ health status after face-to-face clinical visits. However, the role of doctors’ empathy in chat-based encounters is not yet well understood. This study investigates whether patients’ evaluations of doctors’ empathy are associated with their health perceptions after a meeting at an online clinic and whether experiences of empathy could be enhanced by augmenting an automated anamnesis questionnaire completed before the visit.

Methods

A total of 209 adult patients agreed to participate in the study. First 103 patients filled out the regular version of the questionnaire (June–August 2019) and then 106 filled out the augmented version of the online anamnesis questionnaire (August–November 2019). Patients’ perceptions of doctors’ empathy were measured with the Consultation and Relational Empathy questionnaire. Patients’ self-perceived health status, potential confounders, and demographic background information were measured via questionnaires.

Results

Patients’ perceptions of doctors’ empathy during a chat-based encounter were associated with patients being less concerned about their symptoms (estimated odds ratios varied between 0.45 and 0.55 depending on the model, p values < .003) and considering their symptoms as less severe (estimated odds ratios = 0.54–0.61, p values < .007), as well as a higher probability of alleviation of symptoms as rated by the patients (estimated odds ratios = 2.16–2.24, p values < .001). Augmenting the anamnesis questionnaire did not affect patient reports on doctors’ overall empathy, but it did have positive effects on specific areas of doctors’ empathy covered by the questionnaire.

Conclusions

These results show that patients’ experience of doctors’ empathy not only is important during face-to-face encounters but also supports patients’ perceptions of health when the interaction is text based. The results also encourage further development of means to support patients’ experiences of empathy during online interaction with medical doctors.
Age Trends in Actigraphy and Self-Report Sleep Across the Life Span: Findings From the Pittsburgh Lifespan Sleep Databank
Authors: Wallace Meredith L. , Kissel Nicholas , Hall Martica H. , Germain Anne , Matthews Karen A. , Troxel Wendy M. , Franzen Peter L. , Buysse Daniel J. , Reynolds Charles , Roecklein Kathryn A. , Gunn Heather E. , Hasler Brant P. , Goldstein Tina R. , McMakin Dana L. , Szigethy Eva , Soehner Adriane M.
Published: January 2022

Objective

Sleep changes over the human life span, and it does so across multiple dimensions. We used individual-level cross-sectional data to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human life span.

Methods

The Pittsburgh Lifespan Sleep Databank consists of harmonized participant-level data from sleep-related studies conducted at the University of Pittsburgh (2003–2019). We included data from 1065 (n = 577 female; 21 studies) Pittsburgh Lifespan Sleep Databank participants aged 10 to 87 years without a major psychiatric, sleep, or medical condition. All participants completed wrist actigraphy and the self-rated Pittsburgh Sleep Quality Index. Main outcomes included actigraphy and self-report sleep duration, efficiency, and onset/offset timing, and actigraphy variability in midsleep timing.

Results

We used generalized additive models to examine potentially nonlinear relationships between age and sleep characteristics and to examine sex differences. Actigraphy and self-report sleep onset time shifted later between ages 10 and 18 years (23:03–24:10 [actigraphy]; 21:58–23:53 [self-report]) and then earlier during the 20s (00:08–23:40 [actigraphy]; 23:50–23:34 [self-report]). Actigraphy and self-report wake-up time also shifted earlier during the mid-20s through late 30s (07:48–06:52 [actigraphy]; 07:40–06:41 [self-report]). Self-report, but not actigraphy, sleep duration declined between ages 10 and 20 years (09:09–07:35). Self-report sleep efficiency decreased over the entire life span (96.12–93.28), as did actigraphy variability (01:54–01:31).

Conclusions

Awareness of age trends in multiple sleep dimensions in healthy individuals—and explicating the timing and nature of sex differences in age-related change—can suggest periods of sleep-related risk or resilience and guide intervention efforts.
The local wavenumber model for computation of turbulent mixing
Authors: Kurien Susan , Pal Nairita
Published: January 2022

We present an overview of the current status in the development of a two-point spectral closure model for turbulent flows, known as the local wavenumber (LWN) model. The model is envisioned as a practical option for applications requiring multi-physics simulations in which statistical hydrodynamics quantities such as Reynolds stresses, turbulent kinetic energy, and measures of mixing such as density-correlations and mix-width evolution, need to be captured with relatively high fidelity. In this review, we present the capabilities of the LWN model since it was first formulated in the early 1990s, for computations of increasing levels of complexity ranging from homogeneous isotropic turbulence, inhomogeneous and anisotropic single-fluid turbulence, to two-species mixing driven by buoyancy forces. The review concludes with a discussion of some of the more theoretical considerations that remain in the development of this model.

This article is part of the theme issue ‘Scaling the turbulence edifice (part 2)’.
Relaxed solutions for incompressible inviscid flows: a variational and gravitational approximation to the initial value problem
Authors: Brenier Yann , Moyano Iván
Published: January 2022

Following Arnold’s geometric interpretation, the Euler equations of an incompressible fluid moving in a domain

D

are known to be the optimality equation of the minimizing geodesic problem along the group of orientation and volume preserving diffeomorphisms of
D
. This problem admits a well-established convex relaxation that generates a set of ‘relaxed’, ‘multi-stream’, version of the Euler equations. However, it is unclear that such relaxed equations are appropriate for the initial value problem and the theory of turbulence, due to their lack of well-posedness for most initial data. As an attempt to get a more relevant set of relaxed Euler equations, we address the multi-stream pressure-less gravitational Euler–Poisson system as an approximate model, for which we show that the initial value problem can be stated as a concave maximization problem from which we can at least recover a large class of smooth solutions for short enough times.

This article is part of the theme issue ‘Scaling the turbulence edifice (part 2)’.
Helical fluid and (Hall)-MHD turbulence: a brief review
Authors: Pouquet Annick , Yokoi Nobumitsu
Published: January 2022

Helicity, a measure of the breakage of reflectional symmetry representing the topology of turbulent flows, contributes in a crucial way to their dynamics and to their fundamental statistical properties. We review several of their main features, both new and old, such as the discovery of bi-directional cascades or the role of helical vortices in the enhancement of large-scale magnetic fields in the dynamo problem. The dynamical contribution in magnetohydrodynamic of the cross-correlation between velocity and induction is discussed as well. We consider next how turbulent transport is affected by helical constraints, in particular in the context of magnetic reconnection and fusion plasmas under one- and two-fluid approximations. Central issues on how to construct turbulence models for non-reflectionally symmetric helical flows are reviewed, including in the presence of shear, and we finally briefly mention the possible role of helicity in the development of strongly localized quasi-singular structures at small scale.

This article is part of the theme issue ‘Scaling the turbulence edifice (part 2)’.
The effectiveness of acupoint herbal patching for non-specific low back pain: A Protocol for systematic review and meta-analysis
Authors: Ma Tianshu , Liu WU , Dong Yan , Cheng Lei , Wang Ziyuan , Liu Xiaona , Li Tie , Liu Chengyu
Published: January 2022

Background

Non-specific low back pain(NS-LBP) is related to disability and work absence and accounts for high economical costs of global.It is a problem that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching(AHP) as an adjuvant therapy is currently undergoing clinical trials in different medical centers. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on non-specific low back pain(NS-LBP).

Methods

We will search the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database,the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation.

Results

This systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom and safety of acupoint herbal patching therapy for non-specific low back pain.

Conclusion

The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of acupoint herbal patching for non-specific low back pain.
High performance liquid chromatography-based metabolomics of Psidium guajava Linn. leaf extracts
Authors: Gholkar Manasi S. , Daswani Poonam G. , Iyer Vidhya V. , Birdi Tannaz J.
Published: January 2022

Background

Over the years, a number of methods have been introduced in the field of herbal medicine. Amongst these, metabolomics has rapidly emerged as a method of choice due to its wide applicability and versatility. High performance liquid chromatography (HPLC) is a preferred method for fingerprinting with advantages such as easy and wide availability, and relatively low maintenance cost. The current study used HPLC profiling and attempted to correlate it to anti-diarrhoeal activity of Psidium guajava (guava) extracts.

Methods

Ninety samples of guava leaves were collected from three locations in Maharashtra, India over three seasons. Hydroalcoholic extracts (50:50, ethanol:water) were prepared and the HPLC chromatogram of all 90 extracts obtained. A total of eight bioassays representing the important features of diarrhoeal pathogenesis were performed and the extracts were differentiated as ‘good’ or ‘poor’ according to cut-offs for each assay. The numerical data of the bioassays and the HPLC chromatogram was correlated using suitable mathematical models comprising Principal component analysis (PCA), orthogonal partial least squares (OPLS, regression) and orthogonal partial least squares discriminant analysis (OPLS-DA).

Results

OPLS-DA showed good seasonal and regional segregation of extracts. For most of the bioassays, PCA was unsuccessful in showing significant discrimination. Hence, OPLS plots were further developed; differentiation of good and poor extracts among the 90 extracts was successfully demonstrated for antibacterial activity against Shigella flexneri and Vibrio cholerae, inhibition of invasion of enteropathogenic Escherichia coli into HEp-2 epithelial cells, and cholera toxin (CT) production by V. cholerae. However, for other assays, namely, inhibition of adherence of E. coli, invasion of S. flexneri into HEp-2 cells, and inhibition of E. coli labile toxin (LT), subsets of 90 extracts were selected to demonstrate a significant correlation.

Conclusion

HPLC-based metabolomics has the potential to differentiate good and poor activities of guava leaf extracts. This approach can be extended for identifying phytoconstituents responsible for the anti-diarrhoeal activity of guava leaf and help standardization of crude extracts.
Programmable eukaryotic protein expression with RNA sensors
Authors: Jiang Kaiyi , Koob Jeremy , Chen Xi Dawn , Krajeski Rohan N. , Zhang Yifan , Villiger Lukas , Zhou Wenyuan , Abudayyeh Omar O. , Chen Fei , Gootenberg Jonathan S.
Published: January 2022

The diversity of cell types and states can be scalably measured and defined by expressed RNA transcripts. However, approaches to programmably sense and respond to the presence of specific RNAs within living biological systems with high sensitivity are lacking. RNA sensors that gate expression of reporter or cargo genes would have diverse applications for basic biology, diagnostics and therapeutics by enabling cell-state specific control of transgene expression. Here, we engineer a novel programmable RNA-sensing technology, Reprogrammable ADAR Sensors (RADARS), which leverages RNA editing by adenosine deaminases acting on RNA (ADAR) to gate translation of a protein payload on the presence of endogenous RNA transcripts. In mammalian cells, we engineer RADARS with diverse payloads, including luciferase and fluorescent proteins, with up to 164-fold activation and quantitative detection in the presence of target RNAs. We show RADARS are functional either expressed from DNA or as synthetic mRNA. Importantly, RADARS can function with endogenous cellular ADAR. We apply RADARS to multiple contexts, including RNA-sensing induced cell death via caspases, cell type identification, and in vivo control of synthetic mRNA translation, demonstrating RADARS as a tool with significant potential for gene and cell therapy, synthetic biology, and biomedical research.

One Sentence Summary

A new technology utilizing ADAR mediated RNA-editing enables robust reprogrammable protein expression based on target RNA transcripts in mammalian cells, leading to broad applications in basic science research, cell engineering, and gene therapy.
How dangerous is omicron and how effective are vaccinations?
Authors: Nesteruk Igor , Rodionov Oleksii
Published: January 2022

The sharp increase in the number of new COVID-19 cases in late 2021 and early 2022, which is associated with the spread of a new strain of coronavirus - omicron - is of great concern and makes it necessary to make at least approximate forecasts for the pandemic dynamics of the epidemic. As this rapid growth occurs even in countries with high levels of vaccinations, the question arises as to their effectiveness. The smoothed daily number of new cases and deaths per capita and the ratio of these characteristics were used to reveal the appearance of new coronavirus strains and to estimate the effectiveness of quarantine, testing and vaccination. The third year of the pandemic allowed us to compare the pandemic dynamics in the period from September 2020 to January 2021 with the same period one year later for Ukraine, EU, the UK, USA, India, Brazil, South Africa, Argentina, Australia, and in the whole world. Record numbers of new cases registered in late 2021 and early 2022 once again proved that existing vaccines cannot prevent new infections, and vaccinated people can spread the infection as intensively as non-vaccinated ones. Fortunately, the daily number of new cases already diminishes in EU, the UK, USA, South Africa, and Australia. In late January - early February 2022,the maximum averaged numbers of new cases are expected in Brazil, India, EU, and worldwide. “Omicron” waves can increase the numbers of deaths per capita, but in highly vaccinated countries, the deaths per case ratio significantly decreases.
Antagonistic regulation of Drosophila mitochondrial uncoupling protein UCP4b by cold and BMP signaling
Authors: Chatterjee Nirmalya , Song Wei , Dumesic Phillip A. , Spiegelman Bruce , Perrimon Norbert
Published: January 2022

Regulation of energy metabolism and response to cold are intimately linked in mammals. Central to these two processes are the mitochondrial uncoupling proteins (UCPs), which by promoting proton leakage across the inner mitochondrial membrane lead to the generation of heat instead of ATP synthesis. In addition to heat generation, UCPs also influence energy storage and can protect against obesity and diabetes. Cold-blooded animals like flies also contain UCPs that protect from cold, however their regulations are poorly understood. We find that Drosophila UCP4b is induced by cold in a cell-intrinsic manner and protects against cold and obesity in fly models. Mechanistically, cold regulates UCP4b expression through calcium signaling and Spargel (Srl), the Drosophila ortholog of mammalian PGC1α. To the opposite, MAD, acting downstream of the BMP branch of the TGFβ signaling pathway, represses UCP4b expression independently of cold. Interestingly, the two mechanisms of UCP4b regulation are integrated as MAD binding to the UCP4b promoter is displaced by cold in a Srl-dependent manner. We discuss the similarities between the regulation of mammalian and Drosophila UCPs.

Significance

Mitochondrial uncoupling proteins (UCPs) that uncouple the mitochondrial respiration from ATP synthesis regulate energy metabolism, non-shivering thermogenesis, and redox balance in vertebrates and invertebrates. However, their regulation in Drosophila is poorly understood. We found that Drosophila uncoupling protein UCP4b is induced by cold in a cell-autonomous fashion. Conversely, MAD, acting downstream of BMP signaling, inhibits UCP4b expression. MAD is displaced from the upstream regions of the UCP4b gene by cold. UCP4b protects Drosophila against cold and diet-induced obesity. The regulation of UCP4b by cold and BMP signaling is reminiscent of the regulation of mammalian uncoupling protein UCP1. Altogether, we discovered an important regulator of Drosophila energy metabolism which is controlled by regulatory processes that are similar between Drosophila and mammals.
A Complete Set of Equations and Parameters for the Computational Model of Mitochondrial Function for the Proximal Convoluted Tubule and Medullary Thick Ascending Limb Cells in the Rat Kidney
Authors: Bell T. William , Layton Anita T.
Published: January 2022

To investigate mitochondrial function of renal epithelial cells under different tissue oxygenation levels, we have developed and applied computational models of mitochondrial function of the proximal convoluted tubule and medullary thick ascending limb cells. The models predict several key cellular quantities, including ATP generation, P/O (phosphate/oxygen) ratio, proton motive force, electrical potential gradient, oxygen consumption, the redox state of important electron carriers, and ATP consumption. The complete set of model equations and parameters are presented here, together with local and global sensitivity analysis results.
Cell Centred Finite Element Model for Intestinal Organoids Shape Analysis: From tissue architecture to mechanics
Authors: laussu julien , michel deborah , segonds stephane , marguet steven , barreau frederick , hamel dimitri , mas emmanuel , ferrand audrey , bugarin florian
Published: January 2022

Organoids, established from stem cells owing to their self-renewal and differentiation capacities, are self-organised three-dimensional tissue culture recapitulating the original cell populations and their associated functions, as well as tissue architecture. The intestinal organoids established from adult stem cells isolated from the intestinal crypts, recreate 3D epithelial mini-intestines. They represent an excellent tool to study intestinal stem cell capacities and their ability to reconstitute a fully polarised and functional epithelium. These 3D cultures recapitulate \textit{in vitro} the tissue characteristics, including architecture, either in physiological or disease conditions whether they are established from healthy or pathological tissue samples respectively. In this regard, their use for potential treatments screening carries the hopes for a future personalized medicine for which image-analysis such as HCS are increasingly being developed. Numerous numerical models have been developed to study the effects of organoid development on their shape. Most of them remain mainly restricted in their physical description due to the complex inter-relationship between cell physics, phenotypes and behaviors, exploding the number of variables in modeling formulation. Finite Element Method (FEM) is a numerical analysis method employed in mechanics to model deformation and evaluate residual stress of complex structures making it difficult to obtain analytical solutions. Considering epithelial architecture as a homogeneous material where each cell is an elemental equivalent part of the problem, FEM allows a direct link between tissue architecture deformations and local mechanical constraints. Here we formalise a new organoid cell centred FEM with a physical description borrowed from the engineering world. This model can allow a better understanding of the individual contribution of physical/mechanical properties of individual cells on general tissue architecture.
Viral Cultures for Assessing Airborne Transmission of SARs-CoV-2: a Systematic Review Protocol (version 1)
Authors: Heneghan Carl J. , Spencer Elizabeth A. , Brassey Jon , Rosca Elena C. , Plüddemann Annette , Evans David H. , Conly John M. , Maltoni Susanna , Jefferson Tom , Onakpoya Igho J.
Published: January 2022

This is a protocol for a systematic review that aims to evaluate the role of viral cultures for assessing airborne transmission of SARS-CoV-2. The review will address the following research questions:

Are airborne samples infectious?

If so, what proportion are infectious, and what is the distance and duration of infectiousness in the air?

What is the relationship between infectiousness and airborne PCR cycle threshold (Ct)?

Is there evidence of a chain of transmission that establishes an actual instance of airborne transmission of SARS-CoV-2?

What circumstances might facilitate infectious viruses being airborne over long distances?

We will search LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database to identify relevant studies. We will include studies reporting airborne transmission attempting viral culture or serial qRT-PCR with or without genomic sequencing. Predictive or modelling studies will be excluded. We will assess the quality of included studies using previously published criteria.
A snapshot of the root phenotyping landscape in 2021
Authors: Delory Benjamin M. , Hernandez-Soriano Maria C. , Wacker Tomke S. , Dimitrova Anastazija , Ding Yiyang , Greeley Laura A. , Ng Jason Liang Pin , Mesa-Marín Jennifer , Xie Limeng , Zheng Congcong , York Larry M.
Published: January 2022

Root phenotyping describes methods for measuring root properties, or traits. While root phenotyping can be challenging, it is advancing quickly. In order for the field to move forward, it is essential to understand the current state and challenges of root phenotyping, as well as the pressing needs of the root biology community.

In this letter, we present and discuss the results of a survey that was created and disseminated by members of the Graduate Student and Postdoc Ambassador Program at the 11th symposium of the International Society of Root Research. This survey aimed to (1) provide an overview of the objectives, biological models and methodological approaches used in root phenotyping studies, and (2) identify the main limitations currently faced by plant scientists with regard to root phenotyping.

Our survey highlighted that (1) monocotyledonous crops dominate the root phenotyping landscape, (2) root phenotyping is mainly used to quantify morphological and architectural root traits, (3) 2D root scanning/imaging is the most widely used root phenotyping technique, (4) time-consuming tasks are an important barrier to root phenotyping, (5) there is a need for standardised, high-throughput methods to sample and phenotype roots, particularly under field conditions, and to improve our understanding of trait-function relationships.