bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the level set method in solid propellant grain burnback with dogbone grain as a case study
Authors: Adel H , Belal H
Published: August 2021

Solid propellant grain burnback is a crucial step internal ballistic module. There are different methods to predict grain burnback; the oldest method is the drafting technique where the burning surface is tracked using manual drawing applying surface regression rules. Then there is the analytical method, where a geometric analysis of the surface is performed and analytical expressions for the burning surface segments are derived. These expressions are evaluated at different values of burnt distance to find the evolution of burning surface and port areas with time. A level set method is a different approach which, in some aspects, may be considered a drafting technique where the burning surface segments are tracked. From another point of view, it is a numerical method that tracks the burning surface with no need of trying to derive analytical expressions for burning segments. Dogbone grain is known for its structural superiority; however, researches dealing with dogbone grain design parameters are scarce. In this paper, the level set method is introduced and the main steps for its implementation are elaborated. Validation of the level set method is performed against the drafting technique using CAD and analytical expressions for the well-known star grain. Finally, dogbone grain geometry with different configurations is introduced and a parametric study for the governing parameters that affect dogbone grain burnback is performed.
Experimental investigation of recirculation zone characteristics of a pre-filming airblast injector
Authors: Darwish N , Shanmugadas K P , Chakravarthy S R
Published: August 2021

The toroidal flow at the recirculation zone has a vital role in combustion process as it helps in mixing hot combustion products with incoming fresh air and fuel which increases combustion efficiency. In the present work, characteristics of recirculation zone are investigated using a pre-filming airblast injector. Particle Image Velocimetry is used to characterize the swirl flow field generated by the airblast injector. Moreover, olive oil is used as a tracer to be captured by a high-speed camera. Different flow rates are investigated in order for finding out the effect of varying flow rates on the characteristics of the recirculation zone. Results for recirculation zone shape, velocity field and shear strength at the primary zone of combustion are represented. Additionally, results show that recirculation zone is almost symmetrical with increasing trend in shear strength with increasing flow rates.
Modeling the viral load expelled in saliva droplets carrying SARS-CoV-2
Authors: Calles A , Morán-López J L
Published: August 2021

One of the most likely routes of transmission of COVID-19 is through the saliva droplets that are produced while speaking, coughing or sneezing by infected people. The expelled droplets, measuring between 0.4 and 450 μm, follow trajectories determined, mainly, by the gravitational, and air frictional forces. We solve numerically the equations of motion in which the linear and quadratic velocity terms in the drag force are considered. In order to model the virus load expelled during respiratory events, we assume log-log Gaussian distributions, with peaks around 10 μm, and analyze four size ranges: the aerosol (0.4–5 μm), the small (5.1–10 μm), the middle (10.1–100 μm), and big (100.1–450 μm) droplet size regimes. In the aerosol regime, the frictional forces quickly stop the droplets in their horizontal movement and they fall extremely slowly pulled down by the gravitational force. The residence time, in a calm environment, goes from 3.83 days to 33.3 min. More massive droplets take shorter times and hit the ground meters away from the source. By assuming a constant density of virions per milliliter, we estimate the expelled amount into the environment. The middle and small size droplets contain the highest amount but since the aerosol droplets remain in the air such a long time, they represent also a high risk for infection. We emphasize the importance of face protection to minimize COVID-19, transmission.
The fushi tarazu zebra element is not required for Drosophila viability or fertility
Authors: Graham Patricia L , Fischer Matthew D , Giri Abhigya , Pick Leslie
Published: August 2021

Expression of genes in precisely controlled spatiotemporal patterns is essential for embryonic development. Much of our understanding of mechanisms regulating gene expression comes from the study of cis-regulatory elements (CREs) that direct expression of reporter genes in transgenic organisms. This reporter-transgene approach identifies genomic regions sufficient to drive expression but fails to provide information about quantitative and qualitative contributions to endogenous expression, although such conclusions are often inferred. Here we evaluated the endogenous function of a classic Drosophila CRE, the fushi tarazu (ftz) zebra element. ftz is a pair-rule segmentation gene expressed in seven stripes during embryogenesis, necessary for formation of alternate body segments. Reporter transgenes identified the promoter-proximal zebra element as a major driver of the seven ftz stripes. We generated a precise genomic deletion of the zebra element (ftzΔZ) to assess its role in the context of native chromatin and neighboring CREs, expecting large decreases in ftz seven-stripe expression. However, significant reduction in expression was found for only one stripe, ftz stripe 4, expressed at ∼25% of wild type levels in ftzΔZ homozygotes. Defects in corresponding regions of ftzΔZ mutants suggest this level of expression borders the threshold required to promote morphological segmentation. Further, we established true-breeding lines of homozygous ftzΔZ flies, demonstrating that the body segments missing in the mutants are not required for viability or fertility. These results highlight the different types of conclusions drawn from different experimental designs and emphasize the importance of examining transcriptional regulatory mechanisms in the context of the native genomic environment.
Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries
Authors: Telzrow Calla L , Zwack Paul J , Esher Righi Shannon , Dietrich Fred S , Chan Cliburn , Owzar Kouros , Alspaugh J Andrew , Granek Joshua A
Published: August 2021

RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper sequencing must be performed to compensate for the sequencing reads wasted on rRNA. The ideal RNA enrichment method removes all rRNA without affecting other RNA in the sample. We tested the performance of three RNA enrichment methods on RNA isolated from Cryptococcus neoformans, a fungal pathogen of humans. We find that the RNase H depletion method is more efficient in depleting rRNA and more specific in recapitulating non-rRNA levels present in unenriched controls than the commonly-used Poly(A) isolation method. The RNase H depletion method is also more effective than the Ribo-Zero depletion method as measured by rRNA depletion efficiency and recapitulation of protein-coding RNA levels present in unenriched controls, while the Ribo-Zero depletion method more closely recapitulates annotated non-coding RNA (ncRNA) levels. Finally, we leverage these data to accurately map the C. neoformans mitochondrial rRNA genes, and also demonstrate that RNA-Seq data generated with the RNase H and Ribo-Zero depletion methods can be used to explore novel C. neoformans long non-coding RNA genes.
Insm1, Neurod1, and Pax6 promote murine pancreatic endocrine cell development through overlapping yet distinct RNA transcription and splicing programs
Authors: Dudek Karrie D , Osipovich Anna B , Cartailler Jean-Philippe , Gu Guoquing , Magnuson Mark A
Published: August 2021

Insm1, Neurod1, and Pax6 are essential for the formation and function of pancreatic endocrine cells. Here, we report comparative immunohistochemical, transcriptomic, functional enrichment, and RNA splicing analyses of these genes using gene knock-out mice. Quantitative immunohistochemical analysis confirmed that elimination of each of these three factors variably impairs the proliferation, survival, and differentiation of endocrine cells. Transcriptomic analysis revealed that each factor contributes uniquely to the transcriptome although their effects were overlapping. Functional enrichment analysis revealed that genes downregulated by the elimination of Insm1, Neurod1, and Pax6 are commonly involved in mRNA metabolism, chromatin organization, secretion, and cell cycle regulation, and upregulated genes are associated with protein degradation, autophagy, and apoptotic process. Elimination of Insm1, Neurod1, and Pax6 impaired expression of many RNA-binding proteins thereby altering RNA splicing events, including for Syt14 and Snap25, two genes required for insulin secretion. All three factors are necessary for normal splicing of Syt14, and both Insm1 and Pax6 are necessary for the processing of Snap25. Collectively, these data provide new insights into how Insm1, Neurod1, and Pax6 contribute to the formation of functional pancreatic endocrine cells.
Societies to genes: can we get there from here?
Authors: Page Robert E
Published: August 2021

Understanding the organization and evolution of social complexity is a major task because it requires building an understanding of mechanisms operating at different levels of biological organization from genes to social interactions. I discuss here, a unique forward genetic approach spanning more than 30 years beginning with human-assisted colony-level selection for a single social trait, the amount of pollen honey bees (Apis mellifera L.) store. The goal was to understand a complex social trait from the social phenotype to genes responsible for observed trait variation. The approach combined the results of colony-level selection with detailed studies of individual behavior and physiology resulting in a mapped, integrated phenotypic architecture composed of correlative relationships between traits spanning anatomy, physiology, sensory response systems, and individual behavior that affect individual foraging decisions. Colony-level selection reverse engineered the architecture of an integrated phenotype of individuals resulting in changes in the social trait. Quantitative trait locus (QTL) studies combined with an exceptionally high recombination rate (60 kb/cM), and a phenotypic map, provided a genotype–phenotype map of high complexity demonstrating broad QTL pleiotropy, epistasis, and epistatic pleiotropy suggesting that gene pleiotropy or tight linkage of genes within QTL integrated the phenotype. Gene expression and knockdown of identified positional candidates revealed genes affecting foraging behavior and confirmed one pleiotropic gene, a tyramine receptor, as a target for colony-level selection that was under selection in two different tissues in two different life stages. The approach presented here has resulted in a comprehensive understanding of the structure and evolution of honey bee social organization.
Plasmatic Hippuric Acid as a Hallmark of Frailty in an Italian Cohort: The Mediation Effect of Fruit–Vegetable Intake
Authors: Brunelli Laura , Davin Annalisa , Sestito Giovanna , Mimmi Maria Chiara , De Simone Giulia , Balducci Claudia , Pansarasa Orietta , Forloni Gianluigi , Cereda Cristina , Pastorelli Roberta , Guaita Antonio
Published: August 2021

Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These data point to low plasma hippuric acid as a plausible hallmark of frailty status, associated with lower fruit–vegetable intakes.
ChronoRoot: High-throughput phenotyping by deep segmentation networks reveals novel temporal parameters of plant root system architecture
Authors: Gaggion Nicolás , Ariel Federico , Daric Vladimir , Lambert Éric , Legendre Simon , Roulé Thomas , Camoirano Alejandra , Milone Diego H , Crespi Martin , Blein Thomas , Ferrante Enzo
Published: August 2021

Background

Deep learning methods have outperformed previous techniques in most computer vision tasks, including image-based plant phenotyping. However, massive data collection of root traits and the development of associated artificial intelligence approaches have been hampered by the inaccessibility of the rhizosphere. Here we present ChronoRoot, a system that combines 3D-printed open-hardware with deep segmentation networks for high temporal resolution phenotyping of plant roots in agarized medium.

Results

We developed a novel deep learning–based root extraction method that leverages the latest advances in convolutional neural networks for image segmentation and incorporates temporal consistency into the root system architecture reconstruction process. Automatic extraction of phenotypic parameters from sequences of images allowed a comprehensive characterization of the root system growth dynamics. Furthermore, novel time-associated parameters emerged from the analysis of spectral features derived from temporal signals.

Conclusions

Our work shows that the combination of machine intelligence methods and a 3D-printed device expands the possibilities of root high-throughput phenotyping for genetics and natural variation studies, as well as the screening of clock-related mutants, revealing novel root traits.
Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 inhibit WRKY75 function in abscisic acid-mediated leaf senescence and seed germination
Authors: Zhang Haiyan , Zhang Liping , Ji Yunrui , Jing Yifen , Li Lanxin , Chen Yanli , Wang Ruling , Zhang Huimin , Yu Diqiu , Chen Ligang
Published: August 2021

The plant-specific VQ gene family participates in diverse physiological processes but little information is available on their role in leaf senescence. Here, we show that the VQ motif-containing proteins, Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 are negative regulators of abscisic acid (ABA)-mediated leaf senescence. Loss of SIB1 and SIB2 function resulted in increased sensitivity of ABA-induced leaf senescence. In contrast, overexpression of SIB1 significantly delayed this process. Moreover, biochemical studies revealed that SIBs interact with WRKY75 transcription factor. Loss of WRKY75 function decreased sensitivity to ABA-induced leaf senescence, while overexpression of WRKY75 significantly accelerated this process. Chromatin immunoprecipitation assays revealed that WRKY75 directly binds to the promoters of GOLDEN 2-LIKE1(GLK1) and GLK2, to repress their expression. SIBs repress the transcriptional function of WRKY75 and negatively regulate ABA-induced leaf senescence in a WRKY75-dependent manner. In contrast, WRKY75 positively modulates ABA-mediated leaf senescence in a GLK-dependent manner. In addition, SIBs inhibit WRKY75 function in ABA-mediated seed germination. These results demonstrate that SIBs can form a complex with WRKY75 to regulate ABA-mediated leaf senescence and seed germination.
A randomized iterative approach to optimizing an online substance use intervention for collegiate athletes
Authors: Rulison Kelly L , Milroy Jeffrey J , Wyrick David L
Published: August 2021

Lay Summary

Rates of drug use among collegiate athletes are high, yet there are few evidence-based interventions for this population, and the few existing interventions only address alcohol use. In addition, alcohol and drug use interventions targeting college students are not always as effective or efficient as they could be. Our goal was to strengthen modules from myPlaybook, an online drug use intervention for collegiate athletes as a way to optimize the full intervention package. We conducted three intervention trials. Each trial occurred in separate academic years and included 2,000–3,000 athletes from 40 to 50 colleges and universities. We randomly assigned athletes to receive one or more intervention modules that target known risk factors for drug use (i.e., social norms, expectancies about the effects of drug use, harm prevention strategies, and life skills). We used the results about the effects of each module to improve the module prior to the next trial. After these trials, the revised modules targeting social norms and expectancies about drug use had meaningful effects, increasing the likelihood that the full myPlaybook intervention will lead to clinical reductions in drug use among collegiate athletes.
A Review of the Design and Implementation of a Hybrid Cardiac Rehabilitation Program
Authors: Keteyian Steven J. , Ades Philip A. , Beatty Alexis L. , Gavic-Ott Anne , Hines Stephen , Lui Karen , Schopfer David W. , Thomas Randal J. , Sperling Laurence S.
Published: August 2021

Purpose:

This review describes the considerations for the design and implementation of a hybrid cardiac rehabilitation (HYCR) program, a patient-individualized combination of facility-based cardiac rehabilitation (FBCR) with virtual cardiac rehabilitation (CR) and/or remote CR.

Review Methods:

To help meet the goal of the Millions Hearts Initiative to increase CR participation to 70% by 2022, a targeted review of the literature was conducted to identify studies pertinent to the practical design and implementation of an HYCR program. Areas focused upon included the current use of HYCR, exercise programming considerations (eligibility and safety, exercise prescription, and patient monitoring), program assessments and outcomes, patient education, step-by-step instructions for billing and insurance reimbursement, patient and provider engagement strategies, and special considerations.

A FBCR is the first choice for patient participation in CR, as it is supported by an extensive evidence base demonstrating effectiveness in decreasing cardiac and overall mortality, as well as improving functional capacity and quality of life. However, to attain the CR participation rate goal of 70% set by the Million Hearts Initiative, CR programming will need to be expanded beyond the confines of FBCR. In particular, HYCR programs will be necessary to supplement FBCR and will be particularly useful for the many patients with geographic or work-related barriers to participation in an FBCR program. Research is ongoing and needed to develop optimal programming for HYCR.
Impact of DBP on all-cause and cardiovascular mortality: results from the National Health and Nutrition Examination survey, 1999–2014
Authors: Bae Eunjin , Rocco Michael V. , Lee Jeonghwan , Park Jae Yoon , Kim Yong Chul , Yoo Kyung Don , Kim Eun Young , Park Dong Jun , Lim Chun Soo , Kim Yon Su , Lee Jung Pyo
Published: August 2021

Introduction:

Hypertension is common and has a significant effect on cardiovascular morbidity and death. However, despite the development of several guidelines to manage SBP, there is little research or guidance on the evaluation and management of DBP or isolated diastolic hypertension (IDH).

Method:

To determine the association of DBP with all-cause and cardiovascular mortality, we used NHANES data from 1999 to 2014 and included adults aged at least 18 years. The relationship between DBP, IDH and all-cause, cardiovascular mortality was evaluated.

Results:

Of the 35 109 participants, all-cause death occurred in 10.6%, and cardiovascular death occurred in 2.1% over a median follow-up of 7.2 years. Multivariate Cox regression analysis revealed that the risk of all-cause mortality was significantly higher in the lowest (≤56.9 mmHg) DBP groups than in the reference group (DBP 74–76.9 mmHg). However, the risk of cardiovascular mortality was significantly higher in the lowest and highest (≥83 mmHg) DBP group than in the reference group. The risk of all-cause mortality was higher for most groups with SBP at least 140 mmHg than for the reference group with DBP 74–76.9 mmHg and SBP 100–139.9 mmHg. Both the 2018 ESC/NICE and the 2017 AHA/ACC-defined IDH was not significantly associated with all-cause mortality.

Conclusion:

DBP and all-cause mortality had an inverse relationship, whereas DBP and cardiovascular mortality had a U-shaped relationship, with the DBP reference group having the lowest risk for all-cause and cardiovascular mortality. There was no significant relationship between IDH and death.
Ethnic differences and heritability of blood pressure circadian rhythm in African and European American youth and young adults
Authors: Xu Yanyan , Su Shaoyong , Brown Michelle , Snieder Harold , Harshfield Gregory , Wang Xiaoling
Published: August 2021

Background: The aim of this study was to investigate whether blood pressure (BP) circadian rhythm in African Americans differed from that in European Americans. We further examined the genetic and/or environmental sources of variances of the BP circadian rhythm parameters and the extent to which they depend on ethnicity or sex.

Method: Quantification of BP circadian rhythm was obtained using Fourier transformation from the ambulatory BP monitoring data of 760 individuals (mean age, 17.2 ± 3.3; 322 twin pairs and 116 singletons; 351 African Americans).

Results: BP circadian rhythm showed a clear difference by ethnic group with African Americans having a lower amplitude (P = 1.5e–08), a lower percentage rhythm (P = 2.8e–11), a higher MESOR (P = 2.5e–05) and being more likely not to display circadian rhythm (P = 0.002) or not in phase (P = 0.003). Familial aggregation was identified for amplitude, percentage rhythm and acrophase with genetic factors and common environmental factors together accounting for 23 to 33% of the total variance of these BP circadian rhythm parameters. Unique environmental factors were the largest contributor explaining up to 67--77% of the total variance of these parameters. No sex or ethnicity difference in the variance components of BP circadian rhythm was observed.

Conclusion: This study suggests that ethnic differences in BP circadian rhythm already exist in youth with African Americans having a dampened circadian rhythm and better BP circadian rhythm may be achieved by changes in environmental factors.
Investigating a “Wait and See” Mindset Among Pediatric Health Care Providers
Authors: Edwards Nicole Megan , Kaiser Eileen , Stapel-Wax Jennifer L.
Published: August 2021

In the United States, there is a widespread concern with not referring more infants and toddlers with a risk of or identified autism spectrum disorder (ASD) to Early Intervention (EI) under Part C of the Individuals with Disabilities Education Act (IDEA, 2004). Despite early signs and screening initiatives, most children with ASD are not referred for services covered by IDEA until after the age of 4 years. To explore the prevalence of and factors correlated with a potential “wait and see” mindset among one group of stakeholders influencing referral decisions, we disseminated an expert-reviewed survey to pediatric health care providers in a southeastern metro area (n = 99). They self-reported views on waiting to refer, perceived roadblocks to screening and referral, and viable recommendations. Most participants reported using a “wait and evaluate further” approach instead of “wait and see,” and the large majority were not very comfortable discussing suspected ASD with parents of young children (birth to 5 years of age). Those with more years of experience reported being less likely to wait to refer an infant/toddler and more comfortable speaking with parents about suspected signs of ASD. We discuss findings and implications for a comprehensive, multisector approach to outreach and referral.
New approach to quantifying acute stress in cataract surgeons to investigate the relationship between surgeon experience and intraoperative stress
Authors: Cap Veronika , Palkovits Stefan , Bijak Manfred , Ruiss Manuel , Schmoll Martin , Findl Oliver
Published: August 2021

Purpose:

To quantify intraoperative stress levels in cataract surgeons and investigate the relationship between intraoperative stress and surgeon experience.

Setting:

Department of Ophthalmology, Hanusch Krankenhaus, Vienna, Austria.

Design:

Prospective, observational case series.

Methods:

5 ophthalmologists with surgery experiences of 70 to 15 000 previous surgeries volunteered for this study. Surgeons' heart rate (HR) and heart rate variability (HRV) were measured during a total of 45 cataract surgeries. HR and HRV values were normalized to the minimal HR and maximal HRV of an overnight baseline measurement. The resulting normalized HR measure and HRV stress index are stress dependent and comparable between subjects. No case selection was performed.

Results:

Less experienced surgeons showed higher HRV stress indices; differences between the surgeons with less than 180 and 500 surgeries and the 2 with 600 and 1500 surgeries, respectively, were statistically significant (α = 0.05). No statistically significant difference in stress indices was found between surgeons with 1500 and 15 000 surgeries, suggesting that there may be a plateau effect after 1500 surgeries. HRV stress indices and case times were negatively correlated with the logarithm of experience in the number of previously performed surgeries (r
2 = 0.67 and 0.52). No significant stress buildup over multiple successive surgeries was found (α = 0.05).

Conclusions:

The new HRV stress index is a simple but powerful tool for quantifying intraoperative stress in cataract surgeons. Decreases in stress with increasing experience are congruent with previous works on general surgeons' stress and follow a similar timeline as previously published, proficiency-based learning curves for cataract surgery.
Hepatocyte growth factor, colony-stimulating factor 1, CD40, and 11 other inflammation-related proteins are associated with pain in diabetic neuropathy: exploration and replication serum data from the Pain in Neuropathy Study
Authors: Bäckryd Emmanuel , Themistocleous Andreas , Larsson Anders , Gordh Torsten , Rice Andrew S.C. , Tesfaye Solomon , Bennett David L. , Gerdle Björn
Published: August 2021

One in 5 patients with diabetes suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in patients with diabetic distal symmetrical polyneuropathy (DSP) are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two cohorts exploration–replication study (180 participants in each cohort), serum samples from Pain in Neuropathy Study participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) that enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines, and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were hepatocyte growth factor, colony-stimulating factor 1, and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration–replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of patients with diabetic DSP. The pathophysiological relevance of these proteins for the development of neuropathic pain in patients with diabetic DSP must be explored in more depth in future studies.
Shared decision-making approach to taper postoperative opioids in spine surgery patients with preoperative opioid use: a randomized controlled trial
Authors: Uhrbrand Peter , Rasmussen Mikkel Mylius , Haroutounian Simon , Nikolajsen Lone
Published: August 2021

Persistent opioid use is common after surgery, and patients with preoperative opioid use represent a major challenge in this regard. The aim of this randomized controlled trial was to determine the effect of a personalized opioid tapering plan vs standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. Postoperative outcomes included opioid use, pain, contacts with the healthcare system, patient satisfaction, and withdrawal symptoms. Overall, 110 patients were randomized; 55 into the intervention and control groups each. Five patients (proportion = 0.09, 95% confidence interval [CI] [0.04-0.21]) in the intervention group compared with 13 patients (0.25, 95% CI [0.15-0.39]) in the control group were unable to taper opioids to their preoperative consumption 1 month after discharge (P = 0.03) (primary outcome). Likewise, more patients in the intervention group succeeded in tapering opioids to zero 3 months after discharge (37 patients; 0.71, 95% CI [0.57-0.82] vs 23 patients; 0.43, 95% CI [0.30-0.56], P = 0.003). Fewer patients in the intervention group had pain-related contacts to health care the first 2 weeks after discharge (21 patients; 0.40, 95% CI [0.28-0.54] vs 31 patients; 0.60, 95% CI [0.46-0.73], P = 0.04). There was no difference in satisfaction with pain treatment over the first 2 weeks or the incidence of withdrawal symptoms during the first month after discharge. Pain intensity was similar between both groups at all time points. These results suggest that a personalized tapering plan at discharge combined with telephone counselling 1 week after discharge assists patients in postoperative opioid tapering.
Postnatal development of inner lamina II interneurons of the rat medullary dorsal horn
Authors: Mermet-Joret Noëmie , Alba-Delgado Cristina , Descheemaeker Amelie , Gabrielli Francois , Dallel Radhouane , Antri Myriam
Published: August 2021

Pain processing in young mammals is immature. Despite the central role of the medullary dorsal horn (MDH) in processing orofacial sensory information, the maturation of the neurons within the MDH has been largely overlooked. Combining in vitro electrophysiological recordings and 3D morphological analysis over the first postnatal month in rats, we investigated the age-dependent development of the neurons within the inner lamina II (IIi) of the MDH. We show the lamina IIi neuronal population transition into a more hyperpolarized state, with modification of the action potential waveform, and a shift from single spiking, at early postnatal ages, to tonic firing and initial bursting at later stages. These physiological changes are associated with a strong structural remodelling of the neuronal morphology with most of the modifications occurring after the third postnatal week. Among the lamina IIi neuronal population, the subpopulation of interneurons expressing the γ isoform of the protein kinase C (PKCγ+) are key elements for the circuits underlying facial mechanical allodynia. How do they develop from the rest of the lamina IIi constitute an important question that remained to be addressed. Here, we show that PKCγ+ interneurons display electrophysiological changes over time comparable with the PKCγ− population. However, they show a distinctive increase of the soma volume and primary branches length, as opposed to the PKCγ− population. Together, our data demonstrate a novel pattern of late postnatal maturation of lamina IIi interneurons, with a spotlight on PKCγ+ interneurons, that may be relevant for the development of orofacial sensitivity.
Longitudinal Outcomes in Adolescents After Referral for Metabolic and Bariatric Surgery
Authors: Qureshi Faisal G. , Wiegand Jared G. , O'Neill Grayce , Allen Brandi , Wools Gentry , Klement Jessica , Franklin Elizabeth V. , Messiah Sarah E. , Gupta Olga T.
Published: August 2021

Background:

Metabolic and bariatric surgery (MBS) can be a well tolerated and effective treatment option for severe obesity in adolescents. We compared outcomes for adolescents that did and did not proceed to surgery.

Methods:

A single‐center longitudinal study (2015–2020). Patients were identified as LSG if they completed laparoscopic sleeve gastrectomy within 6 months of initial visit and NoLSG if they did not. Chi‐square, Fisher exact, nonparametric Kruskal‐Wallis tests, and Linear Mixed Models (LMM) were used to compare outcomes over 2 years.

Results:

Three hundred fifty‐two adolescents were referred with a mean age of 15.6 ± 1.4, 69% girls, 38% Hispanic, and 78% had noncommercial insurance. The median baseline weight was 135 kg and body mass index (BMI) was 48 kg/m2; 42% had a BMI >50. Seventy‐nine (22%) underwent LSG whereas 273 (78%) did not complete MBS primarily because of lack of interest. LSG patients had 21% total weight loss and 22% total BMI loss at 24 months whereas NoLSG patients had 4% total weight gain and 3% BMI gain (P < 0.01). Obesity‐associated conditions improved in the LSG group (P < 0.01). Follow‐up in both groups was poor (⩽30% at 24 months). Patients with public insurance and those with BMI from 50 to 59.9 kg/m2 were high performing LSG patients.

Conclusions:

A minority (22%) of adolescents referred for MBS proceeded to surgery, despite its demonstrated efficacy and safety in adolescence. Those that did not undergo surgery continued to gain weight. Further research is needed to understand patient preferences or concerns related to MBS utilization during adolescence.
Early Change in Fecal Calprotectin Predicts One‐Year Outcome in Children Newly Diagnosed With Ulcerative Colitis
Authors: Krishnakumar Chenthan , Ananthakrishnan Ashwin N. , Boyle Brendan M. , Griffiths Anne M. , LeLeiko Neal S. , Mack David R. , Markowitz James F. , Rosh Joel R. , Sauer Cary G. , Walters Thomas D. , Bonkowski Erin , Denson Lee A. , Hyams Jeffrey S. , Kugathasan Subra
Published: August 2021

Introduction:

While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.

Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS‐free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes.

Results:

The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS‐free remission, needed anti‐tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS‐free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87–0.96) were associated with outcomes, with the latter having a stronger association with CS‐free remission. Patients with a >75% decrease by 12 weeks, had a 3‐fold increased likelihood of CS‐free remission at 1 year.

Discussion:

Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
Oral Manifestations of Early Syphilis in Adults: A Systematic Review of Case Reports and Series
Authors: Zhou Xiao , Wu Min-Zhi , Jiang Ting-Ting , Chen Xiang-Sheng
Published: August 2021

Rapid emergence of syphilis and oral sexual behaviors has focused attention on oral syphilis, and published reports of cases with oral syphilis have increased in the recent decades. We performed a systematic literature review by searching articles from PubMed, EMBSE, and Google Scholar, looking for case reports or series that would potentially have the clinical characteristics and outcomes for each individual case with oral syphilis. A total of 145 cases with the infection, from 95 studies, were identified to include in our review. Two main clinical phenotypes (ulcerative lesions and mucous patches) appeared to be of particular relevance to oral manifestations. A solitary ulcer was mostly manifested as the lesion of primary syphilis (91.7%) preferentially located on the upper lip, tongue, palate, and buccal mucosa. The most affected anatomical site in the patients with single location involved was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). It is concluded that oral syphilis has its predominant clinical phenotypes although it can manifest in diverse manners.
Country-level Association of Socioeconomic, Environmental and Healthcare-Related Factors with the Disease-Burden and Mortality Rate of COVID-19
Authors: Chowdhury Tasnuva , Mahbub Upal , Rahman Tauhidur
Published: August 2021

Background

COVID-19 pandemic is rapidly expanding throughout the world right now. Caused by a novel strain of the coronavirus, the manifestation of this pandemic shows a unique level of disease burden and mortality rate in different countries.

Objective

In this paper, we investigated the effects of several socioeconomic, environmental, and healthcare-related factors on the disease burden and mortality rate of COIVID-19 across countries. Our main objective is to provide a macro-level understanding of the most influential socioeconomic, environmental, and healthcare-related factors associated with the disease burden and mortality rate metrics without human bias.

Methods

We developed a multiple linear regression model using backward elimination to find the best fitting between reported death and cases across countries for country-level aggregated independent factors keeping COVID-19 test statistic in consideration. Notably, the method requires minimum human intervention and handles confounding effects intrinsically.

Results

Our results show that while the COVID-19 pandemic is seemingly spreading more rapidly in economically affluent countries, it Is more deadly in countries with inadequate healthcare infrastructure, lower capacity of handling epidemics, and lower allocation of the healthcare budget. We also did not find evidence of any association between environmental factors and COVID-19.

Conclusion

We took the number of tests performed into account and normalized the case and mortality counts based on the cumulative distribution of cases across days. Our analysis of the standardized factors provides both the direction and relative importance of different factors leading to several compelling insights into the most influential socioeconomic and healthcare infrastructure-related factors from a country-level view.
Low risk of SARS-CoV-2 transmission via fomite, even in cold-chain
Authors: Sobolik Julia S. , Sajewski Elizabeth T. , Jaykus Lee-Ann , Cooper D. Kane , Lopman Ben A. , Kraay Alicia NM. , Ryan P. Barry , Guest Jodie L. , Webb-Girard Amy , Leon Juan S.
Published: August 2021

Background

Countries continue to debate the need for decontamination of cold-chain food packaging to reduce possible SARS-CoV-2 fomite transmission among workers. While laboratory-based studies demonstrate persistence of SARS-CoV-2 on surfaces, the likelihood of fomite-mediated transmission under real-life conditions is uncertain.

Methods

Using a quantitative risk assessment model, we simulated in a frozen food packaging facility 1) SARS-CoV-2 fomite-mediated infection risks following worker exposure to contaminated plastic packaging; and 2) reductions in these risks attributed to masking, handwashing, and vaccination.

Findings

In a representative facility with no specific interventions, SARS-CoV-2 infection risk to a susceptible worker from contact with contaminated packaging was 2·8 × 10−3per 1h-period (95%CI: 6·9 × 10−6, 2·4 × 10−2). Implementation of standard infection control measures, handwashing and masks (9·4 × 10−6risk per 1h-period, 95%CI: 2·3 × 10−8, 8·1 × 10−5), substantially reduced risk (99·7%). Vaccination of the susceptible worker (two doses Pfizer/Moderna, vaccine effectiveness: 86-99%) combined with handwashing and masking reduced risk to less than 1·0 × 10−6. Simulating increased infectiousness/transmissibility of new variants (2-, 10-fold viral shedding) among a fully vaccinated workforce, handwashing and masks continued to mitigate risk (2·0 × 10−6-1·1 × 10−5risk per 1h-period). Decontamination of packaging in addition to these interventions reduced infection risks to below the 1·0 × 10−6risk threshold.

Interpretation

Fomite-mediated SARS-CoV-2 infection risks were very low under cold-chain conditions. Handwashing and masking provide significant protection to workers, especially when paired with vaccination.

Funding

U.S. Department of Agriculture
Correlation between Proinflammatory cytokines and severity of COVID-19 within Palestinian Population
Authors: Basha Walid , Nazzal Zaher , El-Hamshary Yousef , Odeh Anwar , Hijjawi Lama , Doden Mahmoud , Musa Ahmad , Ruzzeh Saad
Published: August 2021

COVID-19 was characterized by cytokine storm and endothelial dysfunction in severely ill patients. As the severity of the infection was corelated with ethnicity, this study aimed to assess the correlation of proinflammatory cytokine serum level and COVID-19 symptoms within the Palestinian population. In cross-sectional study, serum samples of 27 non-hospitalized patients and 63 hospitalized patients SARS-CoV-2 infected patients, were tested for total antibodies, IL-6, TNF-α, IFN-γ and IL-1β using the ELISA test. Results showed that most common symptoms within patients were Joint pain, cough, and fever (73.3%, 69.7% and 50% respectively). Serum total antibodies (IGs) levels in non-hospitalized patients were higher than hospitalized patients ((44.7 COI and 9.2 COI). TNF-α and IL-6 were lower in non-hospitalized patients compared to hospitalized patients (48±17.9 pg/ml, 193.3±350.5 pg/ml respectively). On the other hand, IFN-γ, in non-hospitalized patients (1±2 IU/ml) was significantly higher than hospitalized patients (0.4±0.26 IU/ml). IL-1β was slightly lower in hospitalized patients (8.8±13.6 pg/ml) compared to non-hospitalized patients (12.5±24.5 pg/ml). Common mild symptoms of COVID-10 were negatively associated with proinflammatory cytokines serum level. In conclusion as it with other populations worldwide, IL-6 and TNF-α are playing a major role in the complications of SARS-CoV-2 infection. Monitoring the two cytokines is crucial for management and treatment of complicated consequence of COVID-19.
A missense KCNQ1 Mutation Impairs Insulin Secretion in Neonatal Diabetes
Authors: Zhou Zhimin , Gong Maolian , Pande Amit , Lisewski Ulrike , Röpke Torsten , Purfürst Bettina , liang Lei , Jia Shiqi , Frühler Sebastian , Margineanu Anca , Zeng Chun , Zhu Han , Kühnen Peter , Khodaverdi Semik , Krill Winfried , Chen Wei , Sander Maike , Raile Klemens , Izsvak Zsuzsanna
Published: August 2021

KCNQ1/Kv7 is a voltage-gated K+ channel that regulates heart rhythm, glucose and salt homeostasis. Mutations of KCNQ1 are primarily associated with long-QT syndrome and type 2 diabetes; however, thus far KCNQ1 mutations have not been associated with monogenetic diabetes. Here, we identified a homozygous KCNQ1 missense mutation (R397W) in an individual with permanent neonatal diabetes (PND). To identify the mechanisms that link the mutation to the disease, we introduced the mutation into human embryonic stem cells (hESCs), and used them to derived pancreatic β-like cells (hESC-β cell). In early β-like cells, we observed atypical membrane electrical activity, increased levels of cytoplasmic Ca2+, and a hypersecretion of insulin. Upon extended culture, their insulin secretion decreased and the number of apoptotic cells increased, resulting in a reduction in the numbers of β-like cells. Late-stage β-like cells exhibited a decrease in the expression of metabolic genes, e.g. HNF4α, PDX1 and GLUT1, providing a possible mechanism for β-cell dysfunction. Our study identifies KCNQ1 as a novel candidate gene of monogenetic diabetes and shows that KCNQ1 regulates β-cell function and survival.
Interactions between a mechanosensitive channel and cell wall integrity signaling influence pollen germination inArabidopsis thaliana
Authors: Wang Yanbing , Coomey Joshua , Miller Kari , Jensen Gregory S. , Haswell Elizabeth S.
Published: August 2021

Cells employ multiple systems to maintain cellular integrity, including mechanosensitive (MS) ion channels and the cell wall integrity (CWI) pathway. Here, we use pollen as a model system to ask how these different mechanisms are interconnected at the cellular level. MscS-Like (MSL)8 is an MS channel required to protectArabidopsis thalianapollen from osmotic challenges duringin vitrorehydration, germination and tube growth. New CRISPR/Cas9 and artificial microRNA-generatedmsl8alleles produced unexpected pollen phenotypes, including the ability to germinate a tube after bursting, dramatic defects in cell wall structure and disorganized callose deposition at the germination site. We document complex genetic interactions betweenMSL8and two previously established components of the CWI pathway,MARIS, andANXUR1/2. Overexpression ofMARISR240C-FPsuppressed the bursting, germination, and callose deposition phenotypes ofmsl8mutant pollen. Nullmsl8alleles suppressed the internalized callose structures observed inMARISR240C-FPlines. Similarly,MSL8-YFPoverexpression suppressed bursting in theanxur1/2mutant background, whileanxur1/2alleles reduced the strong rings of callose around ungerminated pollen grains inMSL8-YFPover-expressors. These data show that MS ion channels modulate callose deposition in pollen and provides evidence that cell wall and membrane surveillance systems coordinate in a complex manner to maintain cell integrity.