bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Spread of Grapevine Leafroll Disease in Washington State Vineyards
Authors: Donda Bhanu Priya , Kesoju Sandya R. , Arnold Kari , McRoberts Neil , Naidu Rayapati A.
Published: October 2022

The spread of grapevine leafroll disease (GLD) to vineyards planted with certified planting stock is of significant concern to grape growers. In this study, the spatial and temporal spread of GLD was examined in three vineyard blocks planted with virus-tested wine grape (Vitis vinifera) cultivars adjacent to vineyard blocks heavily infected with GLD in two geographic locations in eastern Washington State. During each season, the position of vines showing GLD symptoms was recorded in a matrix representing the planting lattice. Symptomatic vines were positive only for Grapevine leafroll-associated virus 3 (GLRaV-3), the most common virus species consistently associated with GLD in Washington vineyards. The results from multiple seasons showed a gradual increase in disease incidence over time in all three blocks. Spatial and temporal mapping of GLD indicated a disease gradient in which the highest percentage of symptomatic vines was in rows proximal to infected old blocks. Spatial autocorrelation analysis using Moran’s I values suggested random patterns of symptomatic vines in the three blocks during initial years, indicating primary spread of the virus not related to infected vines within the block. Clustering at the scale of neighboring vines during subsequent years suggested secondary spread within the block. Results of quadrat-based spatial analyses of GLD incidence were compared with previously reported data obtained from California and elsewhere for an improved understanding of the dynamics of GLD spread to facilitate area-wide disease management strategies.
RISK OF INTRAOCULAR INFLAMMATION AFTER INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS
Authors: Patil Nikhil S. , Dhoot Arjan S. , Popovic Marko M. , Kertes Peter J. , Muni Rajeev H.
Published: October 2022

Purpose:

This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration.

Methods:

A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model.

Results:

Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40–27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00–2.67]). There were no significant differences between comparators for other secondary end points.

Conclusion:

There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk–benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.
REFRACTIVE ERROR CHANGE DURING TREATMENT OF DIABETIC MACULAR EDEMA
Authors: Salabati Mirataollah , Mahmoudzadeh Raziyeh , Starr Matthew R. , Zhang Qiang , Sharpe James , Hsu Jason , Ho Allen C. , Regillo Carl , Kuriyan Ajay E.
Published: October 2022

Purpose:

To evaluate the impact of anti–vascular endothelial growth factor therapy on the refractive error in eyes with diabetic macular edema.

Methods:

Post hoc analysis of Diabetic Retinopathy Clinical Research protocol T. Spherical equivalent (SE) was calculated for study and fellow eyes at baseline, 1-year, and 2-year visits. The SE change of the eyes with edema was compared with those with resolved edema. The correlation between refractive error changes and central subfield thickness was evaluated.

Results:

Among 543 study eyes, SE changed from −0.17 (2.04) D at baseline visit to −0.16 (2.14) D at 2 years giving a hyperopic shift of 0.04 (0.82) D (P = 0.022). Among fellow eyes, mean (SD) SE changed from −0.19 (2.1) D at baseline to −0.11 (2.1) D at 2 years, giving a hyperopic shift of 0.12 (0.84) D (P = 0.001). No significant difference in SE shift was found between eyes with and without edema at 2 years in phakic (0.12D and 0.08 D, P = 0.87) and pseudophakic eyes (−0.24D and −0.08D, P = 0.30). The SE shift was not correlated with central subfield thickness change at the end of the second year (r = 0.02, P = 0.62).

Conclusion:

Diabetic macular edema patients have minimal changes in refractive error. The correction of refractive error may be considered during treatment, regardless of the presence of edema.
Unilateral Ciliary Madarosis in a Child After Coronavirus Disease 2019 (COVID-19) Infection
Authors: Acar Eser Nazan , Serbest Ceylanoglu Kubra , Malkoc Sen Emine
Published: October 2022

Coronavirus disease 2019 life-threatening signs have aroused a great deal of attention since the beginning of the pandemic. In the initial stages of the pandemic, the pediatric population was mostly protected, and the symptoms in affected children were mild. Here, the authors present a 7-year-old boy with left upper eyelid ciliary madarosis that developed 9 weeks after coronavirus disease 2019 infection. During comprehensive ophthalmologic examination, no conjunctival injection, chemosis, erythema, or crusts on eyelids also no other meibomian gland disease symptoms were detected. Comprehensive laboratory workup was performed to exclude any other possible causes of ciliary madarosis. All laboratory parameters tested within normal limits. In addition to the patient’s ocular surface and physical examination findings, laboratory results and the timing of the symptoms also spontaneous recovery at follow-up visits led the authors to conclude that telogen effluvium was to cause of the isolated, unilateral ciliary madarosis in this case.
Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop: A Single Institution’s Experience
Authors: Reghunathan Meera , Crowley Jiwon S. , Segal Rachel , Aguilar Diaz Marco Alejandro , Gosman Amanda A.
Published: October 2022

Several minority groups and students without home plastic surgery programs remain underrepresented in plastic surgery. To address these barriers, our division created the Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop. Students meeting at least one of the following eligibility criteria were invited in fall of 2020: medical student in years 1 though 3 or a research year who is (1) underrepresented in medicine, including African American, Hispanic/Latinx, Native American, Pacific Islander; (2) lesbian, gay, bisexual, transgender, or queer (LGBTQ); (3) first-generation low-income; or (4) does not have a plastic surgery residency program associated with their medical school. Students participated in quarterly meetings with their resident mentor and the annual hands-on workshop. The workshop was held on March 20, 2020, with both virtual and in-person participants. It included various didactic lectures, a suture laboratory, a resident panel, a social lunch hour, and extremity and head cadaver dissections with fracture plating. Twenty-four students attended the workshop. The course was rated 9.4 of 10 by students. The top met goals were gaining didactic plastic surgery knowledge (100%), exposure to a plastic surgery residency program (100%), resources to help overcome minority-specific barriers (96%), and technical skills such as suturing (96%). At the conclusion of the workshop, students had a significant increase in confidence in various aspects of plastic surgery knowledge and technical skills. The Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop demonstrated preliminary success in providing support for students underrepresented in medicine and students without home programs.
Postmortem Fetal Temperature Estimation with Magnetic Resonance Imaging: Apparent Diffusion Coefficient Measurements in the Vitreous Body and Cerebrospinal Fluid
Authors: Tijssen Maud P.M. , Hofman Paul A.M. , Robben Simon G.F.
Published: October 2022

Objectives:

Magnetic resonance imaging (MRI) is increasingly used in postmortem fetal imaging. Several factors influence the quality of MRI in this setting, such as small size, autolytic and maceration changes, and temperature. Knowing the fetal temperature at the time of scanning can improve the MRI interpretation. Temperature can be calculated using diffusion-weighted imaging with measurements of the apparent diffusion coefficient (ADC) in the cerebrospinal fluid (CSF). However, this is complicated by small ventricle size and hemorrhage and, therefore, may be unreliable in postmortem imaging. The current study evaluated the feasibility and reliability of using the ADC for temperature measurements of the vitreous body compared to that of CSF.

Materials and Methods:

Two lambs were scanned postmortem at five different time points over 28 hours. Furthermore, 10 stillborn fetuses were scanned once, at 4 to 62 hours after birth. The temperature was measured with a digital thermometer and calculated using the ADCs of the vitreous body (lambs and fetuses) and CSF (fetuses).

Results:

There was an excellent correlation between measured and calculated temperatures in vitreous bodies of lambs (r = 0.997, P < 0.001) and fetuses (r = 0.970, P < 0.001). The correlation between measured and calculated temperatures in the CSF was poor (r = 0.522, P = 0.122).

Conclusion:

The calculation of the temperature based on the ADC of the vitreous body is feasible and reliable for postmortem fetal imaging.
Proposal of Membranihabitans gen. nov. as a replacement name for the illegitimate prokaryotic generic name Membranicola Li et al. 2016
Authors: Deshmukh Umakant Bhoopati , Oren Aharon
Published: October 2022

The prokaryotic generic name

Membranicola

Li et al. 2016 is illegitimate because it is a later homonym of the name

Membranicola

Foissner, Berger and Schaumburg 1999 (Tintinnidae) (Principle 2 and Rule 51b(4) of the International Code of Nomenclature of Prokaryotes). We therefore propose the replacement generic name Membranihabitans with type species Membranihabitans marinus comb. nov.
Ideonella alba sp. nov. and Ideonella aquatica sp. nov. isolated from an aquaculture farm
Authors: Du Juan , Liu Yang , Pei Tao , Zhu Honghui
Published: October 2022

The three novel bacterial strains designated as 3Y2T, 4Y16 and 4Y11T were isolated from an aquaculture farm and characterized using a polyphasic taxonomic approach. These strains were determined to be catalase- and oxidase-positive and to hydrolyze gelatin and aesculin. The results of 16S rRNA gene-based phylogenetic analysis indicated that the three strains were related to members of the genus

Ideonella

. The phylogenomic results further indicated that the three strains formed two independent branches distinct from reference type strains within this genus. The digital DNA–DNA hybridization (dDDH), average nucleotide identity (ANI) and average amino acid identity (AAI) values between the three strains and their relatives were far below the thresholds of 70 % dDDH, 95–96 % ANI and 95 % AAI for species definition, respectively, indicating that the three strains represent two novel genospecies. The results of chemotaxonomic characterization indicated that the major cellular fatty acids of the three strains were summed feature 3 (C16 : 1ω6c and/or C16 : 1
ω7c) and C16 : 0; the common main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol; the respiratory quinone was ubiquinone-8. The genomic DNA G+C contents of the three strains were 70.2, 70.1 and 69.7%, respectively. On the basis of the different genotypes and distinctive phenotypes such as the phosphatidylcholine and glycolipid only in 3Y2T and the utilization of malic acid and trisodium citrate only in 4Y11T, strains 3Y2T and 4Y11T are concluded to represent two novel species of the genus

Ideonella

, for which the names Ideonella alba sp. nov. (type strain 3Y2T = GDMCC 1.2584T = KCTC 82813T) and Ideonella aquatica sp. nov. (type strain 4Y11T = GDMCC 1.1935T = JCM 34285T) are proposed.
Reclassification of Clostridium aurantibutyricum Hellinger 1944 and Clostridium roseum (ex McCoy and McClung 1935) Cato et al. 1988
Authors: Schoch Teresa , Höfele Franziska , Odeh Hannah , Winter Lisa-Maria , Stöferle Sophia , Karl Michael , Bengelsdorf Frank , Poehlein Anja , Daniel Rolf , Dürre Peter
Published: October 2022

Clostridium aurantibutyricum

,

Clostridium felsineum

and

Clostridium roseum

share a very high similarity based on multi-locus sequence analysis. In this study, their correct taxonomic status was determined using genomic and phenotypic investigations. Average nucleotide identity based on MUMmer alignment of the genomes and in silico DNA–DNA hybridization resulted in values of 98.55–100 and 78.7–100 %, respectively, strongly indicating that all strains are members of the same species. In addition, morphological investigations, fatty acid analyses and substrate utilization tests revealed no striking differences between the strains. Therefore, we propose the reclassification of

C. aurantibutyricum

and

C. roseum

as later heterotypic synonyms of

C. felsineum

. The type strain is lodged in several culture collections (ATCC 17788T=DSM 794T=NCIMB 10690T).
Mediterranean-DASH Intervention for Neurodegenerative Delay diet and risk of dementia: three prospective studies and meta-analysis of cohort studies
Authors: Chen Hui , Dhana Klodian , Huang Yuhui , Huang Liyan , Tao Yang , Liu Xiaoran , van Lent Debora Melo , Zheng Yan , Ascherio Alberto , Willett Walter , Yuan Changzheng
Published: October 2022

Objective

To evaluate the association of Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with risk of dementia in three prospective cohort studies, and to conduct a meta-analysis of cohort studies.

Design & Setting

Three prospective cohort studies – the Whitehall II study (WII, mean follow-up=13.2 years), the Health and Retirement Study (HRS, mean follow-up=4.3 years) and Framingham Heart Study Offspring cohort (FOS, mean follow-up=10.4 years), and meta-analysis of cohort studies.

Participants

We included 18163 middle-aged and older women and men (8360 in WII, 6758 in HRS, and 3045 in FOS) without baseline prevalent dementia for cohort analyses.

Main outcome measures

Incident all-cause dementia, with cohort-specific definitions.

Results

The mean (SD) of baseline MIND diet score (range: 0-15) was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 171,079 person-years, a total of 802 participants (222 in WII, 338 in HRS, and 242 in FOS) developed incident dementia. In the multivariable-adjusted model, every 3-point increment in MIND diet score (range: 0-15) was related to 20% decreased risk of dementia (pooled hazard ratio (HR) = 0.80; 95% confidence interval (CI): 0.70-0.91, P-trend=0.0014, P-heterogeneity=0.3039). In the WII, the corresponding HRs (95% CIs) was 1.04 (0.71-1.52) for remote MIND score in 1991-1993, and 0.76 (0.53-1.09) for recent score in 2002-2004. In the FOS, the HRs were 0.66 (0.50-0.86) for MIND score in 1991-1995 and 0.67 (0.51-0.88) for that in 1998-2001, respectively. In the meta-analysis of eleven cohorts with 224,140 participants, the highest category of MIND diet score was related to 18% lower risk of dementia (pooled relative risk: 0.82, 95% CI: 0.74-0.92, I2=74%, P-heterogeneity<0.01) compared with the lowest category.

Conclusions

Adherence to the MIND diet was related to lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations.

Systematic review registration

INPLASY202270127

Summary box

What is already known on this topic

-

Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been proposed as a healthy dietary pattern for human brain.

-

The relation of MIND to incident dementia was relatively inconsistent and inconclusive in previous cohort studies.

What this study adds

-

Results from the cohort analyses and the meta-analysis confirmed that adherence to the MIND diet is prospectively related to lower risk of incident dementia.

-

Results in current studies are heterogeneous across different populations, calling for further investigations into the culture-specific MIND diet.
Associations of Cumulative Paternal and Maternal Childhood Maltreament Exposure with Neonate Brain Anatomy
Authors: Tuulari Jetro J. , Kataja Eeva-Leena , Karlsson Linnea , Karlsson Hasse
Published: October 2022

Background

Childhood maltreatment exposure (CME) can lead to adverse long-term consequences for the exposed individual. Emerging evidence suggests that the long-term effect of CME may be transmitted across generations, starting already during prenatal development.

Methods

In this study, we measured brain grey and white matter volumes from MR images in 62 healthy neonates at 2–5 weeks of gestation corrected age and obtained Trauma and Distress Scale (TADS) questionnaire data from both parents.

Results

We found that paternal CME associated positively with neonate supratentorial grey matter volumes while the association for the maternal TADS scores was not statistically significant. Maternal pre-pregnancy BMI associated with supratentorial white matter volumes, but not with parental CME.

Conclusions

We are the first to report that paternal CME is linked with variation in newborn cortical volume. Our results imply an intergenerational transmission of paternal CME to offspring. Elucidating the later relevance of these associations and mechanisms involved remains an enticing avenue for future studies.
A Deep-learning based RNA-seq Germline Variant Caller
Authors: Cook Daniel E. , Venkat Aarti , Yelizarov Dennis , Pouliot Yannick , Chang Pi-Chuan , Carroll Andrew , De La Vega Francisco M.
Published: October 2022

RNA sequencing (RNA-seq) can be applied to diverse tasks including quantifying gene expression, discovering quantitative trait loci, and identifying gene fusion events. Although RNA-seq can detect germline variants, the complexities of variable transcript abundance, target capture, and amplification introduce challenging sources of error. Here, we extend DeepVariant, a deep-learning based variant caller, to learn and account for the unique challenges presented by RNA-seq data. Our DeepVariant RNA-seq model produces highly accurate variant calls from RNA-sequencing data, and outperforms existing approaches such as Platypus and GATK. We examine factors that influence accuracy, how our model addresses RNA editing events, and how additional thresholding can be used to facilitate our models’ use in a production pipeline.
Environmental gradients reveal stress hubs predating plant terrestrialization
Authors: Dadras Armin , Fürst-Jansen Janine M. R. , Darienko Tatyana , Krone Denis , Scholz Patricia , Rieseberg Tim P. , Irisarri Iker , Steinkamp Rasmus , Hansen Maike , Buschmann Henrik , Valerius Oliver , Braus Gerhard H. , Hoecker Ute , Mutwil Marek , Ischebeck Till , de Vries Sophie , Lorenz Maike , de Vries Jan
Published: October 2022

Plant terrestrialization brought forth the land plants (embryophytes). Embryophytes account for most of the biomass on land and evolved from streptophyte algae in a singular event. Recent advances have unraveled the first full genomes of the closest algal relatives of land plants; among the first such species wasMesotaenium endlicherianum. Here, we used fine-combed RNAseq in tandem with photophysiological assessment onMesotaeniumexposed to a continuous range of temperature and light cues. Our data establish a grid of 42 different conditions, resulting in 128 transcriptomes and ~1.5 Tbp (~9.9 billion reads) of data to study combinatory effects of stress response using clustering along gradients. We describe major hubs in genetic networks underpinning stress response and acclimation in the molecular physiology ofMesotaenium. Our data suggest that lipid droplet formation, plastid and cell wall-derived signals denominate molecular programs since more than 600 million years of streptophyte evolution—before plants made their first steps on land.
Protease inhibitor ASP enhances freezing tolerance by inhibiting protein degradation in Kumquat
Authors: Yang Hua , Qiao Ke-wei , Teng Jin-jing , Chen Jia-bei , Zhong Ying-li , Rao Li-qun , Li Huang , Xiong Xing-yao
Published: October 2022

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants. In this study, we demonstrated that cold-induced expression of protease inhibitor FmASP in a citrus relative species kumquat (Fortunella margarita(Lour.) Swingle) contributes to its freezing tolerance by regulating protein degradation. First, we found that only cold-acclimated kumquat plants, although with extensive leaf cellular damage during freezing, are able to resume their normal growth upon stress relief. To dissect the impact of cold acclimation on this extraordinary freezing tolerance, we performed protein abundance assay and quantitative proteomics analysis of kumquat leaves subjected to cold acclimation (4 °C), freezing treatment (−10 °C) and post-stress recovery (25 °C). FmASP and a few non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of freezing treatment. FmASP was further characterized as a robust inhibitor that inhibits the degradation capacity of multiple proteases. In addition, heterogeneous expression ofFmASPin Arabidopsis confirmed its positive function in freezing tolerance. Finally, we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation and consequently maintains essential cellular function for freezing stress recovery. These findings revealed the important role of protease inhibition on freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.

One-sentence summary

A protease inhibitor ofFortunella margaritaenhances protein stability and freezing tolerance by regulating non-specific protease degradation
Fatigue presentation, severity, and related outcomes 12 weeks post-COVID-19 hospitalization
Authors: Magel Tianna , Meagher Emily , Boulter Travis , Albert Arianne , Tsai Melody , Muñoz Carola , Carlsten Chris , Johnston James , Wong Alyson , Shah Aditi , Ryerson Chris , Mckay Rhonda Jane , Nacul Luis
Published: October 2022

Background

Increasing evidence on long-term health outcomes following SARS CoV-2 infection shows post-viral symptoms can persist for months. The aim of the present study was to examine the prevalence and outcome predictors of post-viral fatigue and related symptoms 3 and 6 months following infection.

Methods

A prospective cohort of patients hospitalized with COVID-19 (n=88) were recruited from a Post-COVID-19 Respiratory Clinic (PCRC) in Vancouver, Canada to examine predictors of long-term fatigue and substantial fatigue. Multivariable logistic and linear regression analysis were used to examine the relationship between patient predictors (medical history at the time of hospitalization and follow-up patient-reported outcome measures) and the presentation of fatigue and substantial fatigue at 3 and 6 months follow-up.

Results

The number of patients exhibiting fatigue and substantial fatigue was 58 (67%) and 14 (16%) at 3 months and 47 (60%) and 6 (7%) at 6 months post-infection, respectively. Adjusted analysis revealed the number of pre-existing comorbidities to be associated with fatigue (OR 2.21; 95% CI 1.09-4.49; 0.028) and substantial fatigue (OR 1.73; 95% CI 1.06-2.95; 0.033) at 3 months follow-up. Except for shortness of breath, self-care, and time, all follow-up variables were found to be associated with fatigue and substantial fatigue at 3 months follow-up.

Conclusion

Fatigue and substantial fatigue are common, and decrease from 3 to 6 months; however, a significant number of patients continue to exhibit long-term fatigue at 6 months follow-up. Further research is needed to clarify the causality of viral infections and co-factors in the development and severity of fatigue as a symptom and in meeting post-viral fatigue syndrome or ME/CFS diagnostic criteria.
Evaluating the Utility of EZC Pak, a 5-Day Combination Echinacea-Zinc-Vitamin C Dose Pack with or without Vitamin D, in the Management of Outpatient Upper Respiratory Infections
Authors: Radhakrishnan Aditya , Spencer Stephanie , Yanamala Naveena , Malepati Sarath
Published: October 2022

Background

Growing antibiotic resistance is among the most serious threats to healthcare systems and public health globally with antibiotic misuse considered a leading driver of this problem. One of the largest areas of antibiotic misuse is in outpatient upper respiratory infections (URIs), the most common infection in humans. The purpose of this research is to evaluate the efficacy of EZC Pak, a combination Echinacea-Zinc-Vitamin C dose pack with or without Vitamin D, on the duration of illness and symptom severity of non-specific URIs as an alternative to antibiotics when none are deemed clinically necessary. A secondary analysis was carried out on patient satisfaction with using EZC Pak.

Methods

A total of 360 patients across the United States were enrolled and randomized in a double-blind manner across two intervention groups, EZC Pak, EZC Pak+Vitamin D, and one placebo group. The study was conducted virtually utilizing a smartphone-based app to screen, enroll and capture study data of the participants. Once a study participant reported the first symptoms of a URI, they were advised to take the intervention as directed and complete the daily symptom survey score until their symptoms resolved.

Results

The average EZC Pak participant recovered 1.39 days faster than placebo (p= 0.017) than the average placebo participant. The average EZC Pak participant reported a 17.43% lower symptom severity score versus placebo (p= 0.029). EZC Pak users reported 2.9 times higher patient satisfaction versus users of the placebo (p= 0.012). The addition of Vitamin D during this acute phase of illness neither benefited nor harmed illness duration or symptom severity.

Conclusions

The findings support the potential use of EZC Pak as a viable alternative to patient request for antibiotics when none are deemed clinically necessary at the time of initial clinical presentation. The decision to replete vitamin D in the acute phase of URI is an individualized decision left to the patient and their clinician. EZC Pak may play a critical role in improving outpatient URI management and antibiotic stewardship. (ClinicalTrials.govnumber,NCT04943575.)
A panel of four miRNAs (miR-190b, miR-584-5p, miR-452-5p, and miR-1306-5p) is capable of classifying luminal and non-luminal breast cancers
Authors: Farahmand Faranak , Rahmani Saied , Bayat Hadi , Salimi Adel , Ghanbari Sogol , Shafaroudi Afsaneh Malekzadeh , Sharifi-Zarchi Ali , Vasei Mohammad , Mowla Seyed-Javad
Published: October 2022

BACKGROUND

Identifying the molecular subtypes of breast cancer (BC) plays a crucial role in enhancing the efficacy of therapy. MiRNAs (miRs) with differential expressions in different subtypes of breast tumors can be considered as non-invasive biomarkers for diagnosing BC subtypes.

OBJECTIVE

We aimed to investigate the efficacy of miR-190b, miR-584-5p, miR-452-5p, and miR-1306-5p as novel potent diagnostic biomarkers in discriminating patients with luminal (ER+) and non-luminal (ER–) BCs.

METHODS

A group of miRs significantly associated with estrogen cell receptors (ER) in breast tumors were identified using feature selection methods analysis on miR-Seq datasets retrieved from TCGA and GSE68085. Four abovementioned miRs were selected as novel potential biomarkers, and their relative expression levels were assessed within adjacent non-tumor, ER+ and ER– tumor tissues by quantitative RT-PCR. Their impact on diagnosis was also evaluated by ROC curve analysis.

RESULTS

In ER+ BCs compared to ER– BCs, the expression of miR-190b was remarkably increased, while the expression of miR-584-5p, miR-452-5p, and miR-1306-5p were significantly decreased. This group could discriminate ER+ and ER– BCs at an AUC of 0.973.

CONCLUSIONS

According to our findings, these four miRs are promising biomarkers in discriminating BC subtypes. The candidate miRs in parallel with histologic diagnosis methods can be applied for identifying patients who are most likely responding to specific therapies based on ER status.
Improving case detection through TB contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters. Evaluation of an innovative ACF strategy in Mozambique
Authors: Saavedra Belén , Nguenha Dinis , de la Torre-Pérez Laura , Mambuque Edson , Tembe Gustavo , Oliveras Laura , Rudd Matthew , Philimone Paulo , Jose Benedita , Garcia Juan Ignacio , Gomes Neide , Munguane Shilzia , Chiconela Helio , Nhanommbe Milton , Izco Santiago , Acacio Sozinho , García-Basteiro Alberto L.
Published: October 2022

Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We aimed to determine the impact of the scale-up of Xpert Ultra as frontline test for TB diagnosis, and an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi quantitative results and spatial parameters) on new TB cases diagnosed in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited all incident TB-cases (index cases, ICs) and their household contacts (HCs). Community contacts (CCs) recruitment depended on the semi-quantitative results of Xpert Ultra of the IC and the population density of the area where the IC lived in. TB-contacts, either symptomatic or people living with HIV (regardless of symptoms), were asked for providing a spot sputum for lab-testing. Trends on TB case notification in the intervention area were compared to the previous years and to those of two districts in the south of the Maputo province (control area) using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.2% laboratory-confirmed) were recruited; 3165 HC and 4730 CC were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The ACF intervention increased by 8.2% all forms of TB cases detected in 2018. CITS model showed an increase of laboratory confirmed TB cases in the intervention district, compared to the control area. Xpert Ultratracepositive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). Number needed to screen (NNS) to find a TB case differed widely among HCs (NNS:55) and CCs (153). The intervention resulted in an overall increase in TB diagnoses and higher proportion of laboratory confirmation.
Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders
Authors: Conole Eleanor L.S. , Vaher Kadi , Cabez Manuel Blesa , Sullivan Gemma , Stevenson Anna J. , Hall Jill , Murphy Lee , Thrippleton Michael J. , Quigley Alan J. , Bastin Mark E. , Miron Veronique E. , Whalley Heather C. , Marioni Riccardo E. , Boardman James P. , Cox Simon R.
Published: October 2022

Background

Preterm birth is closely associated with a phenotype that includes brain dysmaturation and neurocognitive impairment, commonly termed Encephalopathy of Prematurity (EoP), of which systemic inflammation is considered a key driver. DNA methylation (DNAm) signatures of inflammation from peripheral blood associate with poor brain imaging outcomes in adult cohorts. However, the robustness of DNAm inflammatory scores in infancy, their relation to comorbidities of preterm birth characterised by inflammation, neonatal neuroimaging metrics of EoP, and saliva cross-tissue applicability are unknown.

Methods

Using salivary DNAm from 258 neonates (n = 155 preterm, gestational age at birth 23.28 – 34.84 weeks, n = 103 term, gestational age at birth 37.00 – 42.14 weeks), we investigated the impact of a DNAm surrogate for C-reactive protein (DNAm CRP) on brain structure and other clinically defined inflammatory exposures. We assessed i) if DNAm CRP estimates varied between preterm infants at term equivalent age and term infants, ii) how DNAm CRP related to different types of inflammatory exposure (maternal, fetal and postnatal) and iii) whether elevated DNAm CRP associated with poorer measures of neonatal brain volume and white matter connectivity.

Results

Higher DNAm CRP was linked to preterm status (−0.0107 ± 0.0008, compared with - 0.0118 ± 0.0006 among term infants; p < 0.001), as well as perinatal inflammatory diseases, including histologic chorioamnionitis, sepsis, bronchopulmonary dysplasia, and necrotising enterocolitis (OR range |2.00 | to |4.71|, p < 0.01). Preterm infants with higher DNAm CRP scores had lower brain volume in deep grey matter, white matter, and hippocampi and amygdalae (β range |0.185| to |0.218|). No such associations were observed for term infants. Association magnitudes were largest for measures of white matter microstructure among preterms, where elevated epigenetic inflammation associated with poorer global measures of white matter integrity (β range |0.206| to |0.371|), independent of other confounding exposures.

Conclusions

Epigenetic biomarkers of inflammation provide an index of innate immunity in relation to neonatal health. Such DNAm measures complement biological and clinical metrics when investigating the determinants of neurodevelopmental differences.
Reducing delays in seeking abortion among women who visit health facilities for safe abortion service in Mekelle City, Ethiopia: Pre-post interventional study
Authors: Legesse Awol Yemane , Welday Mengistu , Hagazi Mengistu , Alemayehu Mussie , Tsadik Mache , Hailemicheal Ambachew , Meressa Beyene , Gebre Daniel , Teka Hale
Published: October 2022

Objectives

This study assessed the effect of health education on reducing the delay in seeking abortion in Mekelle health facilities, Tigray region, Ethiopia.

Design

A pre-post interventional study design with sample size of 322 women.

Setting

The study was conducted in 12 health facilities at Mekelle, Tigray, Ethiopia between February 1stthrough September 30th, 2020

Participants

All women who have attended safe abortion services in Mekelle health facilities during the time of the data collection period were the study population.

Intervention

Women education on the Ethiopian abortion law, availability of abortion services, and optimal time of pregnancy termination using 1000 leaflets, 20 street posters for 3 months.

Results

Compared to the pre-intervention group, a much change in reducing the gestational age in weeks was observed in the post intervention period to terminate the pregnancy with 9.8 decrease per 100 respondents (95% CI 9.25 to 10.36) and a Cohen’s d value of 5.23 was found. Besides, there was statistically significant difference between the pre and post-intervention on the respondent knowledge on the possibility of termination pregnancy based on wish according to Ethiopian abortion law at a p-value of < 0.024.

Conclusions

Women’s health education on the availability of safe service and optimal gestational age for termination has led to a significant reduction of the delay in weeks with large effect size. Moreover, it brings a statistically significant difference on respondent knowledge of Ethiopian abortion law. We recommend further randomized contrail study involving three face delays of safe abortion service.
Malaria parasite density and detailed qualitative microscopy enhances large-scale profiling of infection endemicity in Nigeria
Authors: Oyibo Wellington , Latham Victoria , Oladipo Oladosu , Ntadom Godwin , Uhomoibhi Perpetua , Ogbulafor Nnnena , Okoronkwo Chukwu , Okoh Festus , Mahmoud Aminu , Shekarau Emmanuel , Oresanya Olusola , Cherima Yakubu Joel , Jalingo Innua , Abba Bintu , Audu Mohammed , Conway David J.
Published: October 2022

With global progress towards malaria reduction stalling, further analysis of the epidemiology is required, particularly in countries with the highest burden. National surveys have mostly analysed infection prevalence, while large-scale data on parasite density and different developmental forms are rarely available. In Nigeria, the country with the largest burden globally, blood slide microscopy of children up to five years of age was conducted in the 2018 National Demographic and Health Survey, and infection prevalence previously reported. In the current study, malaria parasite density measurements are reported and analysed for 7783 of the children sampled across the 36 states within the six geopolitical zones of the country, with asexual and sexual stages considered separately and comparisons of infections with different malaria parasite species being performed. Across all states of Nigeria, there was a positive correlation between mean asexual parasite density in peripheral blood of infected individuals and prevalence of infection in the community (Spearman’s rho = 0.39, P = 0.02). Asexual parasite densities were highest in the northern geopolitical zones (geometric means > 2000 μL-1), extending the evidence of exceptionally high infection burden in many areas. Sexual parasite prevalence in each state was highly correlated with asexual parasite prevalence (Spearman’s rho = 0.70, P < 0.001), although sexual parasite densities were low (geometric means < 100 μL-1in all zones). Infants had lower parasite densities than children above one year of age, but there were no differences between male and female children. Most infections were ofP. falciparum, which had higher asexual densities but lower sexual parasite densities thanP. malariaeorP. ovalemono-infections. However, mixed species infections had the highest asexual parasite densities. It is recommended that future large surveys in high burden countries measure parasite densities as well as developmental stages and species, to improve the quality of malaria epidemiology and tracking of future changes.
“Running on goodwill and fairydust” - midwives’ experiences of facilitating and delivering local breastfeeding support via Facebook groups: a qualitative descriptive study
Authors: Morse H. , Brown A.
Published: October 2022

Background

The use of groups for providing and accessing breastfeeding support on Facebook (BSF) is now widespread, including groups aimed specifically at mothers in specific areas. Some of these groups are created and/or facilitated by midwives, but little is known about their motivations or experiences.

Objective

To examine how midwives involved in providing breastfeeding support via a local BSF group perceive the value of this provision and what are their experiences of creating these services and of engaging with mothers online.

Methods

Semi-structured interviews were conducted with midwives between July-September 2021, and thematically analysed.

Results

Three themes were identified in relation to the research question: (1) Imperatives and Value, (2) Goodwill & lack of resources, (3) Community of Practice. Theme 1 described that groups were seen as a necessary part of developing services to meet the needs and expectations of the current generation of mothers, and to improve dire breastfeeding rates. Theme 2 identified that BSF groups are reliant on both midwives and peer supporters working voluntarily, issues of sustainability and frustration at the lack of value placed on their time, skill and investment. Theme 3 highlighted the function of BSF groups as communities of practice, providing opportunities for social learning for all members and personal and professional benefits for midwives.

Conclusions

Findings have identified that midwives become involved in delivering online support motivated by a belief in the value of this provision, but feel unsupported by wider services in doing so. Midwives have concerns about the sustainability of this provision regardless of its value whilst it remains reliant on volunteers, and call for further support. Significant benefits for midwives derived from involvement were highlighted which should inform further research, guidance and investment.
Kinship and genetic variation in aquarium-spawnedAcropora hyacinthuscorals
Authors: López-Nandam Elora H. , Payne Cheyenne Y. , Delbeek J. Charles , Dunker Freeland , Krol Lana , Larkin Lisa , Lev Kylie , Ross Richard , Schaeffer Ryan , Yong Steven , Albright Rebecca
Published: October 2022

Recent scientific advances inex situsystem design and operation make it possible to complete gametogenic cycles of broadcast spawning corals. Breeding corals in aquaria are critical advances for population management, particularly genetic rescue and assisted gene flow efforts. Genetic rescue projects for corals are already underway to bring threatened species intoex situculture and propagation, thereby preserving standing genetic variation. However, while breeding corals is increasingly feasible, the consequences of the aquarium environment on the genetic and phenotypic composition of coral populations is not yet known. The aquarium environment may in itself be a selective pressure on corals, but it also presents relaxed selective pressure in other respects. In 2019 and 2020, gravidAcropora hyacinthuscoral colonies were collected from Palauan reefs and shipped to the California Academy of Sciences (CAS) in San Francisco. In both years, gametes were batch-fertilized to produce larvae that were then settled and reared to recruits. As of April 2021, when they were sampled for sequencing, 23 corals produced at CAS in 2019 and 16 corals produced at CAS in 2020 had survived for two years and one year, respectively. We sequenced the full genomes of the 39 offspring corals and their 15 potential parents to a median 26x depth of coverage. We find clear differential parentage, with some parents producing the vast majority of offspring, while the majority of parents produced no surviving offspring. After scanning 12.9 million single nucleotide polymorphisms (SNPs), we found 887 SNPs that may be under selection in the aquarium environment, and we identified the genes and pathways these SNPs may affect. We present recommendations for preserving standing genetic variation in aquarium-bred corals based on the results of this pilot project.
Changes in calpain-2 expression during glioblastoma progression predisposes tumor cells to temozolomide resistance by minimizing DNA damage and p53-dependent apoptosis
Authors: Stillger Maren Nicole , Chen Chia-Yi , Lai Zon Weng , Li Mujia , Schaefer Agnes , Pagenstecher Axel , Nimsky Christopher , Bartsch Joerg Walter , Schilling Oliver
Published: October 2022

Background

Glioblastoma multiforme (GBM) is characterized by an unfavorable prognosis for patients affected. During standard-of-care chemotherapy using temozolomide (TMZ), tumors acquire resistance thereby causing tumor recurrence. Thus, deciphering essential molecular pathways causing TMZ resistance are of high therapeutic relevance.

Methods

Mass spectrometry based proteomics were used to study the GBM proteome. Immunohistochemistry staining of human GBM tissue for either calpain-1 or −2 was performed to locate expression of proteases.In vitrocell based assays were used to measure cell viability and survival of primary patient-derived GBM cells and established GBM cell lines after TMZ +/− calpain inhibitor administration. shRNA expression knockdowns of either calpain-1 or calpain-2 were generated to study TMZ sensitivity of the specific subunits. The Comet assay and ɣH2AX signal measurements were performed in order to assess the DNA damage amount and recognition. Finally, quantitative real-time PCR of target proteins was applied to differentiate between transcriptional and post-translational regulation.

Results

Calcium-dependent calpain proteases, in particular calpain-2, are more abundant in glioblastoma compared to normal brain and increased in patient-matched initial and recurrent glioblastomas. On the cellular level, pharmacological calpain inhibition increased the sensitivities of primary glioblastoma cells towards TMZ. A genetic knockdown of calpain-2 in U251 cells led to increased caspase-3 cleavage and sensitivity to neocarzinostatin, which rapidly induces DNA strand breakage. We hypothesize that calpain-2 causes desensitization of tumor cells against TMZ by preventing strong DNA damage and subsequent apoptosis via post-translational TP53 inhibition. Indeed, proteomic comparison of U251 control vs. U251 calpain-2 knockdown cells highlights perturbed levels of numerous proteins involved in DNA damage response and downstream pathways affecting TP53 and NF-κB signaling. TP53 showed increased protein abundance, but no transcriptional regulation.

Conclusion

TMZ-induced cell death in the presence of calpain-2 expression appears to favor DNA repair and promote cell survival. We conclude from our experiments that calpain-2 expression represents a proteomic mode that is associated with higher resistance via “priming” GBM cells to TMZ chemotherapy. Thus, calpain-2 could serve as a prognostic factor for GBM outcome.
A histone methylation-MAPK signaling axis drives durable epithelial-mesenchymal transition in hypoxic pancreas cancer
Authors: Brown Brooke A. , Myers Paul J. , Adair Sara J. , Pitarresi Jason R. , Sah-Teli Shiv K. , Campbell Logan A. , Hart William S. , Barbeau Michelle , Leong Kelsey , Seyler Nicholas , Kane William , Lee Kyoung Eun , Stelow Edward , Jones Marieke , Simon M. Celeste , Koivunen Peppi , Bauer Todd W. , Stanger Ben Z. , Lazzara Matthew J.
Published: October 2022

Here, we show that hypoxia drives especially long-lasting epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) primarily through a positive-feedback histone methylation-MAPK signaling axis. We find that transformed cells preferentially undergo EMT in hypoxic tumor regions in multiple model systems and that hypoxia drives a cell-autonomous EMT in PDAC cells which, unlike EMT in response to growth factors, can last for weeks. We further demonstrate that hypoxia reduces histone demethylase KDM2A activity, suppresses PP2 family phosphatase expression, and activates MAPKs to post-translationally stabilize histone methyltransferase NSD2, leading to an H3K36me2-dependent EMT in which hypoxia-inducible factors play only a supporting role. This mechanism can be antagonizedin vivoby combinations of MAPK inhibitors that may be effective in multi-drug therapies designed to target EMT.