bluuebunny/crossref_metadata_2025 huggingface dataset:
Home before Hospital: a whole of system re-design project to improve rates of home-based dialysis therapy: Experience and outcomes over 8 years
Authors: Tombocon Omar , Tregaskis Peter , Reid Catherine , Chiappetta Daniella , Fallon Kethly , Jackson Susannah , Frawley Fiona , Peart Dianne , Weston Ann , Wong Kim , Palaster Leanne , Flanc Robert , Macdonald Sandra , Wilson Scott , Walker Rowan
Published: July 2021

Background

Despite evidence that clinical outcomes for patients treated with peritoneal dialysis (PD) or home haemodialysis are better than for patients treated with conventional satellite or hospital-based haemodialysis, rates of home-based dialysis therapies world-wide remain low. Home-based dialysis care is also cost-effective and indeed the favoured dialysis option for many patients.

Methods & Objectives

Using a lean-thinking framework and established change management methodology, a project embracing a system-wide approach at making a change where a ‘Home before Hospital’ philosophy underpinned all approaches to dialysis care was undertaken. Three multidisciplinary working groups (pathway, outreach and hybrid) were established for re-design and implementation. The primary aim was to improve home-based dialysis therapy prevalence rates from a baseline of 14.8% by ≥2.5%/year to meet a target of 35%, whilst not only maintaining but improving the quality of care provided to patients requiring maintenance dialysis. A ‘future’ state pathway was developed after review of the ‘current’ state (Pathway Working Group) and formed the basis on which a nurse-led outreach service (Outreach Working Group) was established. With the support of the multidisciplinary team, the outreach service model focussed on early, consistent, and frequent education, patient support in decision-making, and clinician engagement.

Results

A target prevalence of >30% for home-based therapies (mainly achieved with PD) was achieved within 2 years. This prevalence rate reached 35% within 3 years and was maintained at 8 years. In addition, selected patients already on maintenance satellite-based haemodialysis (Hybrid Working Group) were educated to achieve high levels of proficiencies in self-care.

Conclusion

Having the system-wide approach to a Quality Improvement Process and using established principles and change management processes, the successful implementation of a new sustainable model of care focussed on home-based dialysis therapy was achieved. A key feature of the model (through outreach) was early nurse-led education and support of patients in decision-making and ongoing support through multidisciplinary care.
Deciphering the PTM codes of the tumor suppressor p53
Authors: Wen Jia , Wang Donglai
Published: July 2021

The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes, including cell cycle arrest, apoptosis, senescence, DNA repair, and metabolic regulation. In response to diverse stresses, p53 undergoes multiple posttranslational modifications (PTMs) that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological contexts. Notably, PTMs can recruit ‘reader’ proteins that exclusively recognize specific modifications and facilitate the functional readout of p53. Targeting PTM–reader interplay has been developing into a promising cancer therapeutic strategy. In this review, we summarize the advances in deciphering the ‘PTM codes’ of p53, focusing particularly on the mechanisms by which the specific reader proteins functionally decipher the information harbored within these PTMs of p53. We also highlight the potential applications of intervention with p53 PTM–reader interactions in cancer therapy and discuss perspectives on the ‘PTMomic’ study of p53 and other proteins.
Miniature microscopes for manipulating and recording in vivo brain activity
Authors: Stamatakis Alice M , Resendez Shanna L , Chen Kai-Siang , Favero Morgana , Liang-Guallpa Jing , Nassi Jonathan J , Neufeld Shay Q , Visscher Koen , Ghosh Kunal K
Published: July 2021

Here we describe the development and application of miniature integrated microscopes (miniscopes) paired with microendoscopes that allow for the visualization and manipulation of neural circuits in superficial and subcortical brain regions in freely behaving animals. Over the past decade the miniscope platform has expanded to include simultaneous optogenetic capabilities, electrically-tunable lenses that enable multi-plane imaging, color-corrected optics, and an integrated data acquisition platform that streamlines multimodal experiments. Miniscopes have given researchers an unprecedented ability to monitor hundreds to thousands of genetically-defined neurons from weeks to months in both healthy and diseased animal brains. Sophisticated algorithms that take advantage of constrained matrix factorization allow for background estimation and reliable cell identification, greatly improving the reliability and scalability of source extraction for large imaging datasets. Data generated from miniscopes have empowered researchers to investigate the neural circuit underpinnings of a wide array of behaviors that cannot be studied under head-fixed conditions, such as sleep, reward seeking, learning and memory, social behaviors, and feeding. Importantly, the miniscope has broadened our understanding of how neural circuits can go awry in animal models of progressive neurological disorders, such as Parkinson’s disease. Continued miniscope development, including the ability to record from multiple populations of cells simultaneously, along with continued multimodal integration of techniques such as electrophysiology, will allow for deeper understanding into the neural circuits that underlie complex and naturalistic behavior.
ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease
Authors: Shinohara Mitsuru , Hirokawa Junko , Shimodaira Akemi , Tashiro Yoshitaka , Suzuki Kaoru , Gheni Ghupurjan , Fukumori Akio , Matsubara Tomoyasu , Morishima Maho , Saito Yuko , Murayama Shigeo , Sato Naoyuki
Published: July 2021

Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.
First Case of Bloodstream Infection Caused by Ruminococcus gnavus in an 85 Year Old Man in China
Authors: Fan Xin , Chen Yejin , Liu Yanqing , Hu Liqing
Published: July 2021

Ruminococcus gnavus (R. gnavus) is a gram positive anaerobe and a member of the normal intestinal flora of humans. Here, we present a case study of bloodstream infection caused by R. gnavus in an 85 year old man. We identified R. gnavus using target DNA sequencing. The patient was treated with intravenous meropenem and ceftriaxone based on antimicrobial susceptibility tests. He recovered well and was discharged.
The “Organic” Descriptor and Its Association With Commercial Cigarette Health Risk Expectancies, Subjective Effects, and Smoking Topography: A Pilot Human Laboratory Study
Authors: Pearson Jennifer L , Watanabe Mika , Sanchez Jennifer , Mann Suman , Drake Cara , Mercincavage Melissa
Published: July 2021

Introduction

The purpose of this mixed-method pilot study was to: (1) examine whether the “organic” descriptor affects smokers’ health risk expectancies, subjective ratings of smoking, and topography, and (2) describe how smokers interpret the “organic” descriptor and relate it to their subjective smoking experience.

Methods

Twenty-two daily smokers (45.5% men, 81.8% non-Hispanic White, M (SD) age = 47.3 [12.7], M (SD) cigarettes/day = 14.5 [5.1]) completed a within-person laboratory study. Following a baseline session, smokers attended 2 experimental sessions where they smoked a study-provided cigarette (identical across conditions) paired with either an “organic” or conventional (e.g., no “organic”) descriptor condition and completed subjective and behavioral measures. Participants completed a semi-structured interview at the last visit.

Results

Relative to the conventional cigarette, more participants rated the “organic” cigarette as healthier, having fewer chemicals, and having a more favorable burn rate (P’s < 0.05). There were no differences in total puff volume by condition (P = 0.42). Stratifying by gender, men inhaled 225 ml (SE = 82.7) more in the conventional condition (P = 0.02); women inhaled 408 ml (SE = 233.3) more in the organic condition (P = 0.11). A common understanding of “organic” was that the product was “…less processed... like less chemicals and it’s more natural.” Some believed that “organic” cigarettes contained fewer chemicals, which in turn produced a “much cleaner and healthier smoking cigarette” and that they could “taste the difference.”

Conclusions

Findings support that smokers associate the “organic” descriptor with health and reduced harm. This descriptor may differentially impact puffing behavior by gender.

Implications

This study provides qualitative and quantitative data regarding how the “organic” descriptor influences adult daily smokers’ perceptions and use of cigarettes. After smoking two identical cigarettes described as “organic” and conventional (e.g., no “organic”), smokers expressed more problematic health expectancies about the “organic” cigarette condition, providing further empirical support that the “organic” descriptor is associated with expectancies of reduced harm. The source of reduced harm was understood to be fewer chemicals in the organic cigarette. Though preliminary, findings suggest that “organic” may differentially affect puffing behavior by gender.
Survey of public library use in the Ambulatory Clinic in the Children’s Hospital Winnipeg
Authors: Burns Jessy , Sharma Atul Kumar , Borland Karin , Rodd Celia J
Published: July 2021

Introduction

Recent studies highlight synergies for families receiving early childhood literacy support from their health care provider and public library, with more reading at home and higher quality book-sharing interactions. Our primary objective was to determine the percentage of Children’s Hospital Winnipeg Ambulatory Clinic’s patients who had ever used a public library. The clinic has a longstanding early-childhood literacy program and serves remote communities and low-income Winnipeg families.

Methods

A structured survey was administered to parents or legal guardians by the first author. It explored library barriers and covariates that might affect library use. Analysis included descriptive statistics and a logistic regression model for predictors of library use.

Results

Ninety-seven nearly consecutive surveys were administered, half prior to the COVID-19 pandemic. Most respondents were female, from Winnipeg, and in the two lowest neighbourhood income quintiles. Roughly half (46.4%) of children had used a library. Most respondents wanted health care providers to promote literacy and provide information about public libraries, and more supported in-clinic distribution of books. The number of children per household positively predicted library use, possibly a proxy for experience with community resources. About 2/3 of respondents believed that library fines should be abolished. Most identified other barriers, for example, inconvenient hours, distance, or concerns about COVID-19.

Conclusion

Less than half of surveyed families used public libraries, citing multiple barriers, including fines. Moreover, not all health care providers can offer new books and anticipatory guidance. Clinics that promote use of public libraries may therefore represent a low-cost, stand-alone alternative.
Advances and prospects of rhodopsin-based optogenetics in plant research
Authors: Zhou Yang , Ding Meiqi , Nagel Georg , Konrad Kai R. , Gao Shiqiang
Published: July 2021

Microbial rhodopsins have advanced optogenetics since the discovery of channelrhodopsins almost two decades ago. During this time an abundance of microbial rhodopsins has been discovered, engineered, and improved for studies in neuroscience and other animal research fields. Optogenetic applications in plant research, however, lagged largely behind. Starting with light-regulated gene expression, optogenetics has slowly expanded into plant research. The recently established all-trans retinal production in plants now enables the use of many microbial opsins, bringing extra opportunities to plant research. In this review, we summarize the recent advances of rhodopsin-based plant optogenetics and provide a perspective for future use, combined with fluorescent sensors to monitor physiological parameters.
Engineering stable carbonic anhydrases for CO2 capture: a critical review
Authors: Mesbahuddin Mirfath Sultana , Ganesan Aravindhan , Kalyaanamoorthy Subha
Published: July 2021

In the search for green CO2-capture technology to combat global warming, bioengineering of carbonic anhydrases (CAs) is being sought for with target adaptabilities of extreme temperatures and alkaline pH conditions. The modern in silico screening of protein engineering complements the conventional in vitro high-throughput via generation of iteratively cumulating e-library of diverse beneficial mutations. As identified through various studies of randomized and rationalized mutagenesis, different features have been explored to engineer stability in CAs, including improving structural contacts in the protein quaternary architecture with disulfide bonds and salt-bridge networks, as well as enhancing the protein surface electrostatics. Advanced molecular dynamic simulation techniques and progressive training of machine learning-assisted databases are now being used to unravel wild-type CA properties and predict stable variants thereof with greater accuracy than ever before. The best fit CA achieved so forth demonstrates tolerances of up to 107°C at pH >10 with 25-fold enhancement in CO2 mass transfer. This review will provide an overview of different approaches that have been utilized for engineering CAs and will highlight potential challenges and strategies for developing CA-based CO2-capture and sequestration.
Epidemiological, clinical and biomarker profile of pediatric patients infected with COVID-19
Authors: Shah K , Upadhyaya M , Kandre Y , Pandya A , Saraf V , Saxena D , Mavalankar D
Published: July 2021

Background

Given the limited and diverse nature of published literature related to COVID-19 in pediatrics, it is imperative to provide evidence-based summary of disease characteristics for guiding policy decisions. We aim to provide comprehensive overview of epidemiological, clinical and biomarker profile of COVID-19 infection in pediatric population.

Methods

For this umbrella review, published systematic reviews from PubMed and pre-print databases were screened. Literature search was conducted from December 2019 to April 2021. Details of clinical, radiological and laboratory features were collected from each review. Qualitative observations were synthesized and pooled prevalence of mortality and asymptomatic cases were assessed using meta-analysis.

Results

Evidence synthesis of 38 systematic reviews included total 1145 studies and 334 398 children and adolescents. Review revealed that COVID-19 is relatively milder with better prognosis in pediatrics. However, patients with comorbidity are at higher risk. Meta-analysis of reviews showed that 21.17% (95% CI: 17.818–24.729) of the patients were asymptomatic and mortality rate was 0.12% (95% CI: 0.0356–0.246). Though there was no publication bias, significant heterogeneity was observed. Fever (48–64%) and cough (35–55.9%) were common symptoms, affecting almost every alternate patient. Ground-glass opacities (prevalence range: 27.4–61.5%) was most frequent radiographic observation. Rise in C-reactive protein, lactate dehydrogenase and D-dimer ranged from 14% to 54%, 12.2–50% and 0.3–67%, respectively. Some of the included reviews (44.7%-AMSTAR; 13.2%-GRADE) were of lower quality.

Conclusion

Current umbrella review provides most updated information regarding characteristics of COVID-19 infection in pediatrics and can be used to guide policy decision regarding vaccination prioritization, early screening and identification of at-risk population.
Consumer acceptance and willingness to pay for direct and indirect entomophagy
Authors: Giotis Thomas , Drichoutis Andreas C
Published: July 2021

Over the last few years, the interest on alternative protein sources, such as edible insects, has been growing rapidly. However, Western consumers’ acceptance of insects as a food source is very low, mainly due to unfamiliarity with insect-based food. We investigate consumers’ attitude and behavior and estimate their willingness to pay (WTP) a premium for three products that vary on a between-subjects basis, direct or indirect consumption of insects. The data were collected through an online questionnaire of 451 consumers in Greece and WTP was elicited using the contingent valuation method (CVM). Our results show that the majority of Greek consumers are not willing to pay a premium for an insect-based energy bar and cookie (direct entomophagy) and they would require a discount to acquire such products. On the other hand, consumer acceptance is higher for a gilt-head bream that is fed with insect-based feed (indirect entomophagy). Results show that younger adults, indirect consumption of insects, looking for new sources of food and evaluating certification and trust as important for innovative products, are all associated with a higher WTP. Consumers with positive WTP are on average willing to pay a premium of 15.8, 17, and 31.8 per cent for the energy bar, cookie, and gilt-head bream, respectively, while consumers that are not WTP a premium would require discounts of 43.8, 42.4, and 30.7 per cent, respectively.
Drought stress recovery of hydraulic and photochemical processes in Neotropical tree saplings
Authors: Manzi Olivier Jean Leonce , Bellifa Maxime , Ziegler Camille , Mihle Louis , Levionnois Sébastien , Burban Benoit , Leroy Céline , Coste Sabrina , Stahl Clément
Published: July 2021

Climate models predict an increase in the severity and the frequency of droughts. Tropical forests are among the ecosystems that could be highly impacted by these droughts. Here, we explore how hydraulic and photochemical processes respond to drought stress and re-watering. We conducted a pot experiment on saplings of five tree species. Before the onset of drought, we measured a set of hydraulic traits, including minimum leaf conductance, leaf embolism resistance and turgor loss point. During drought stress, we monitored traits linked to leaf hydraulic functioning (leaf water potential (ψmd) and stomatal conductance (gs)) and traits linked to leaf photochemical functioning (maximum quantum yield of photosystem II (Fv/Fm) and maximum electron transport rate (ETRmax)) at different wilting stages. After re-watering, the same traits were measured after 3, 7 and 14 days. Hydraulic trait values decreased faster than photochemical trait values. After re-watering, the values of the four traits recovered at different rates. Fv/Fm recovered very fast close to their initial values only 3 days after re-watering. This was followed by ETRmax, Ψmd and gs. Finally, we show that species with large stomatal and leaf safety margin and low πtlp are not strongly impacted by drought, whereas they have a low recovery on photochemical efficiency. These results demonstrate that πtlp, stomatal and leaf safety margin are a good indicators of plant responses to drought stress and also to recovery for photochemical efficiency.
A phylogenomic look into the systematics of oceanic squids (order Oegopsida)
Authors: Fernández-Álvarez Fernando Á , Taite Morag , Vecchione Michael , Villanueva Roger , Allcock A Louise
Published: July 2021

Oceanic squids of the order Oegopsida are ecologically and economically important members of the pelagic environment. They are the most diverse group of cephalopods, with 24 families that are divergent morphologically. Despite their importance, knowledge of phylogenetic relationships among oegopsids is less than that among neritic cephalopods. Here, we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes for 35 selected oceanic squids, which were generated using genome skimming. We performed maximum likelihood and Bayesian inference analyses that included 21 of the 24 oegopsid families. In our analyses, the architeuthid, chiroteuthid and enoploteuthid family groups, which have been proposed previously based on morphological and natural history characteristics, were retrieved as monophyletic. The morphologically divergent Cranchiidae formed a well-supported clade with families Ommastrephidae and Thysanoteuthidae, with a unique mitochondrial gene order. The family Lycoteuthidae was revealed as paraphyletic and contained Pyroteuthidae. Thus, the two lycoteuthid subfamilies are herein elevated to family level, increasing the number of oegopsid squid families to 25. In order to describe the diversity and evolutionary trends of oegopsid squids accurately, the superfamilies Architeuthoidea, Chiroteuthoidea, Cranchioidea and Enoploteuthoidea are resurrected from the literature, and the superfamilies Cycloteuthoidea, Octopoteuthoidea and Pholidoteuthoidea are proposed. The phylogenetic positions of Gonatidae, Histioteuthidae and Onychoteuthidae were not stable in our phylogenetic analyses and are not assigned to a superfamily. This study supports the utility of genome skimming to solve the phylogenetic relationships of oceanic squids.
Development of a Rapid Sporulation Method of Fusarium graminearum Using Liquid Cultivation
Authors: Zhang Xue , Li Chunjie , Xue Baiyan , Ji Pingsheng , Li Yonggang , Sun Lei , Wang Shuang
Published: July 2021

Fusarium graminearum is an important fungus causing a variety of maize diseases, including stalk rot, ear rot, and sheath rot. However, conidia of F. graminearum are not easily obtained under normal culture conditions, which seriously affects the identification and pathogenicity assessment of the isolates and screening of resistance sources. This study was undertaken to develop and utilize a rapid sporulation technique of F. graminearum using liquid cultivation, which could meet the needs of various tests. The results show that the optimum conditions for sporulation of F. graminearum were as follows: culture medium, 0.154 mol/liter of saline; temperature, 28 to 30°C; incubation time, 96 h; initial pH, 9 to 10; illumination, continuous ultraviolet light; and shaking speed, 150 rpm. Using this culture method, conidial concentration of tested F. graminearum strains can reach >1.5 × 105 conidia/ml. Compared with the existing methods using mung bean and carboxylmethyl cellulose as matrix, saline is relatively inexpensive, and the culture process, relatively quick. Overall, this study provided a systematic, rapid, and simple method to obtain a large number of conidia of F. graminearum.
Impacts of Continued Exposure to a Susceptible Host Genotype on Aggressiveness of Phytophthora nicotianae Isolates Adapted to Multiple Sources of Partial Resistance
Authors: Jin Jing , Shew H. David
Published: July 2021

Pathogen adaptation can threaten the durability of partial resistance. Mixed plantings of susceptible and partially resistant varieties may prolong the effectiveness of partial resistance, but little is known about how continued exposure to a susceptible genotype can change the aggressiveness of pathogen isolates adapted to a source of partial resistance. The objective of this study was to examine the effects of continued exposure to a highly susceptible tobacco genotype on isolates of Phytophthora nicotianae that had been adapted to partial resistance. Isolates of P. nicotianae previously adapted to two sources of partial resistance were continually exposed to either the original host of adaptation or a susceptible host. After six generations of host exposure, isolates obtained from the partially resistant and the susceptible hosts were compared for their aggressiveness on the resistant host and for differences in expression of genes associated with pathogenicity and aggressiveness. Results suggested that exposure to the susceptible tobacco genotype reduced aggressiveness of isolates adapted to partial resistance in K 326 Wz/– but not of isolates adapted to partial resistance in Fla 301. Quantification of pathogenicity-associated gene expression using qRT-PCR suggested the rapid change in aggressiveness of isolates adapted to Wz-sourced partial resistance may have resulted from modification in gene expression in multiple genes.
Management of Pythium myriotylum in Tobacco Transplant Production Greenhouses
Authors: Zhang Xuemei , Johnson Charles , Reed David
Published: July 2021

Pythium root rot is a common disease that can threaten tobacco seedling production in greenhouses. However, management tools are limited in tobacco transplant production greenhouses. To identify additional Pythium control options, oomyceticide treatments (ethaboxam, mefenoxam, and copper ethanolamine complex) and nonoomyceticide (ultraviolet light and copper ion) water treatments were compared with etridiazole and an untreated control on TN 90LC tobacco seedlings inoculated with Pythium myriotylum in greenhouses. All the treatments in oomyceticide trials were applied to the bay water once before inoculation, when seedling roots had extended into the water. The inoculum was applied immediately before seeding in nonoomyceticide trials, in which etridiazole was applied to bay water once, 2 weeks after seeding, as a positive control. Nonoomyceticide treatments were applied three times: 24 h before, 2 weeks after, and 4 weeks after seeding. At the end of the tobacco transplant production season, ethaboxam and mefenoxam significantly (P < 0.05) reduced root rot incidence and severity by as much as 100%, compared with the untreated control. Ethaboxam and mefenoxam also significantly (P < 0.05) reduced oospores produced in infected root tissues while significantly (P < 0.05) increasing root length and weight. Ultraviolet radiation and copper ion treatments had no significant effects on tobacco seedling root length or weight compared with the untreated control, although the copper ion treatments significantly (P < 0.05) reduced root rot severity and oospores produced in root tissues. Similar to etridiazole, ethaboxam and mefenoxam consistently reduced the area under the disease progress curve (AUDPC) of Pythium root rot, but copper ion treatments only reduced AUDPC significantly (P < 0.05) in one trial.
The Prognostic Role of DSM-5 Alcohol Use Disorder Severity and Age of Onset in Treatment Outcome Among Adults Aged 60+
Authors: Behrendt Silke , Kuerbis Alexis , Mejldal Anna , Braun-Michl Barbara , Bilberg Randi , Bu¨hringer Gerhard , Bogenschutz Michael , Nielsen Anette Søgaard , Andersen Kjeld
Published: July 2021

Aims

To investigate among older adults with DSM-5 alcohol use disorder (AUD) the relevance of (1) baseline DSM-5 AUD severity, (2) age of DSM-5 AUD onset, and (3) the interactions of DSM-5 AUD severity*treatment condition and age of DSM-5 AUD onset*treatment condition for the prediction of AUD treatment outcomes.

Methods

The international multicenter RCT “ELDERLY-Study” compared outpatient motivational enhancement therapy (4 sessions) with outpatient motivational enhancement therapy followed by community reinforcement approach for seniors (8 sessions) in adults aged 60+ with DSM-5 AUD. Baseline and 1-, 3-, and 6-month follow-up data from the German and Danish ELDERLY-sites (n = 544) were used (6-month participation rate: 75.9%). DSM-5 AUD diagnoses were obtained using the Mini International Neuropsychiatric Interview and alcohol use using Form 90. Associations between DSM-5 AUD severity and age of onset and AUD treatment outcomes were investigated using multiple logistic regression and generalized linear models.

Results

The sample was diverse in AUD severity (severe: 54.9%, moderate: 28.2%, mild: 16.9%) and age of onset (median: 50 years; 12–78 years). Overall, with few exceptions, neither AUD severity, nor age of onset, nor their respective interactions with treatment condition significantly predicted drinking outcomes at the different follow-ups (P ≥ 0.05).

Conclusions

No indication was found for the need to tailor treatment content according to DSM-5 AUD severity and earlier onset in older adults.
Effectiveness of and Access to Medications for Opioid Use Disorder for Adolescents and Young Adults: A Scoping Review
Authors: McCarty Dennis , Chan Brian , Buchheit Bradley M. , Bougatsos Christina , Grusing Sara , Chou Roger
Published: July 2021

Objective

A scoping review assessed access to medications for opioid use disorder (MOUD) and treatment outcomes among adolescents (12 – 17 years) and young adults (18 – 25 years).

Methods

Studies addressing adolescent and young adult opioid use disorder and treatment with MOUD on patient outcomes (eg, retention in care) were included. Randomized trials and controlled observational studies were prioritized. Investigators extracted key information, summarized findings, noted methodological weaknesses, and tabled the details.

Results

The search identified 4 randomized trials (N = 241), 1 systematic review with 52 studies (total N = 125,994), and 5 retrospective analyses of health insurance claims. The trials reported buprenorphine and extended-release naltrexone reduced opioid use. Return to use was observed when pharmacotherapy ceased. A systematic review concluded that adolescents and young adults had lower retention in care than older adults. The observational studies found that adolescents were unlikely to receive MOUD. There was some evidence that non-Hispanic Black adolescents and young adults were less likely than non-Hispanic Whites to receive MOUD.

Conclusions

MOUD therapies reduce opioid use among adolescent and young adults but few receive MOUD. MOUD services for adolescents and young adults should be developed and tested. Randomized clinical trials are necessary to develop appropriate clinical guidelines for using MOUD with adolescents and young adults.
MEK inhibition by trametinib overcomes chemoresistance in preclinical nasopharyngeal carcinoma models
Authors: Gong Xing , Fan Lei , Wang Pu
Published: July 2021

The development of chemoresistance is the major cause of treatment failure in nasopharyngeal carcinoma (NPC). Although ‘paradoxical’ activation of extracellular signal-regulated kinase (ERK) has been shown to contribute resistance to anticancer treatment, the role of ERK in NPC chemoresistance has not been yet revealed. In this work, we report that trametinib, a clinically available mitogen-activated protein kinase inhibitor for melanoma treatment, overcomes NPC chemoresistance via suppressing ERK activation induced by chemotherapy. We first showed that trametinib at nanomolar concentrations was active against NPC cells and acted synergistically with cisplatin. Trametinib remarkably decreased phosphorylation of ERK and its downstream effector in NPC cells. We next showed that cisplatin treatment stimulates ERK signaling, and furthermore that this can be abolished by trametinib. We finally generated cisplatin-resistant NPC models and demonstrated that trametinib was effective in inhibiting cisplatin-resistant NPC growth, colony formation and survival via suppressing ERK signaling in vitro and in vivo. Our work demonstrates the potential of trametinib in overcoming chemoresistance in preclinical NPC models and provides evidence of initializing clinical trials of using trametinib for NPC treatment.
Effect of GADD45G on the radioresistance of nasopharyngeal carcinoma cells
Authors: Lou Dandan , Zhu Daoqi , Wang Zetai , Zhang Ruhua , Yu Zhijian , Gong Fengying , Peng Yan , Zeng Siying , Liu Ying , Li Aiwu , Fan Qin
Published: July 2021

The development of radioresistance by nasopharyngeal carcinoma (NPC) cells almost always results in tumor recurrence and metastasis, making clinical treatment of the disease difficult. In this study, the mechanism of radioresistance in NPC cells was investigated. First, a gene array and quantitative reverse-transcription-PCR assays were used to screen for genes exhibiting significantly altered expression in the DNA damage signaling pathway. Based on those results, GADD45G was further studied in the context of radioresistance. A GADD45G-knockout NPC cell line (CNE-2R-KO) was constructed using CRISPR-Cas9 technology and used for a comparison of differences in radioresistance with other radiosensitive and radioresistant NPC cells, as evaluated using colony formation assays. Cell cycle changes were observed using flow cytometry. Cell proliferation and migration were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and wound healing assays, respectively. The sequencing results revealed the successful construction of the CNE-2R-KO cell line, the radiosensitivity of which was higher than that of its parent radioresistant cell line owing to the GADD45G knockout. This was likely related to the increase in the number of cells in the G1 phase and decrease in those in the S1 phase as well as the increased cell proliferation rate and decreased migratory ability. GADD45G is associated with radioresistance in NPC cells and likely has a role in the occurrence and metastasis of NPC.
Statin therapy in midlife women
Authors: Shufelt Chrisandra L.
Published: July 2021

The menopause transition is associated with adverse changes to the lipid profile. Although there are no specific treatment guidelines for women, current evidence supports the use of statin therapy in women with 1) established clinical atherosclerotic cardiovascular disease (ASCVD); 2) primary hypercholesterolemia, with low-density lipoprotein cholesterol of 190 mg/dL (4.9 mmol/L) or higher; 3) diabetes mellitus regardless of ASCVD risk category (ages 40-75 y); and 4) for primary prevention of ASCVD in women at high risk (10-y risk, ≥20%) or intermediate risk (10-y risk, ≥7.5-20%) with the presence of guideline-derived risk enhancers (age 40-75 y) such as premature menopause or a history of preeclampsia.
Dance practice modifies functional fitness, lipid profile, and self-image in postmenopausal women
Authors: Teixeira Giovana Rampazzo , Veras Allice Santos Cruz , Rocha Ana Paula Rodrigues , Chedid Sylvia Seidinger , Freitas Júnior Ismael Forte , Neto Raul Antônio Fragoso , Gobbo Luis Alberto , Buonani Camila
Published: July 2021

Objective:

The aim of the present study was to analyze the effects of dance practice on body composition, metabolic profile, functional fitness, and self-image/self-esteem in postmenopausal women.

Methods:

A total of 36 postmenopausal participants (mean age 57 years) danced three times per week for 90 minutes each day and were evaluated before and after 16 weeks. The parameters evaluated were body composition (body fat and lean mass), blood lipids, functional fitness, self-image, and self-esteem.

Results:

Statistical analysis was done using Student t test for paired samples and the Wilcoxon test with P values less than 0.05 considered statistically significant. Lower triglycerides (baseline = 156.5 ± 17.0 mg/dL; after 16-weeks = 131.5 ± 12.9 mg/dL; P < 0.01), higher high-density lipoprotein cholesterol (baseline = 55.4 ± 15.9 mg/dL; after 16 weeks = 60.0 ± 15.4 mg/dL; P < 0.001), and higher total cholesterol (baseline = 199.5 ± 26.8 mg/dL; after 16 weeks = 211.8 ± 35.7 mg/dL; P < 0.01) levels were observed in postmenopausal women. Dance intervention improved coordination (baseline = 8.6 ± 2.6; after 16 weeks = 6.7 ± 1.6; P < 0.001), agility (baseline = 55.9 ± 8.8; after 16 weeks = 64.1 ± 8.3; P < 0.001), and aerobic capability (baseline = 446.8 ± 63.4; after 16 weeks = 377.4 ± 53.8; P < 0.001). Classification of general function fitness index (GFFI) was considered regular at baseline (GFFI of 200-299), but improved after 16 weeks of dance practice (GFFI of 300-399, P < 0.001).

Conclusion:

The 16-week dance intervention was effective in improving not only the lipid profile and functional fitness of postmenopausal women, but also self-image and self-esteem.
Different cutoff points to diagnose low muscle mass and prediction of osteoporosis in postmenopausal women
Authors: Miranda Camila , de Morais Vinicius Faria Borges , Martins Fernanda Maria , Pelet Danyelle Cristina Silva , Orsatti Cláudio Lera , Cangussu-Oliveira Luciana Mendes , Petri Nahas Eliana Aguiar , Santagnello Samarita Beraldo , de Paula Rodolfo Ferreira , Campos Souza Markus Vinicius , Orsatti Fábio Lera
Published: July 2021

Objective:

This study aimed to verify which of the different cutoff points of low muscle mass (LMM) based on appendicular lean mass (ALM) is associated with osteoporosis in postmenopausal women (PMW).

Methods:

Cross-sectional study. PMW (n = 355) were classified for the presence of osteoporosis (score <−2.5 standard deviations) at the femoral neck and lumbar spine and LMM (three cutoff points: ALM < 15 kg; ALM/height2 [ALM index] <5.67 kg/m2 and ratio between ALM and body mass index [ALMBMI] <0.512).

Results:

After adjustments for confounding factors, binary logistic regression showed that ALM and ALM index were associated with osteoporosis at the lumbar spine (odds ratio [OR] = 5.3 [95% CI: 2.3-12.5] and OR = 2.5 [95% CI: 1.0-6.2], respectively) and only ALM was associated with osteoporosis at the femoral neck (OR = 16.1 [95% CI: 4.1-62.5]). When women were classified as having osteoporosis in at least one site, only ALM was associated with osteoporosis (OR = 7.7 [95% CI: 3.3-15.6]). There was no association between ALMBMI and osteoporosis. The predictive value of ALM for osteoporosis decreased after BMI or height were included as a covariate in the model.

Conclusion:

Absolute ALM (<15 kg) seems to be the most suitable for predicting osteoporosis based on LMM in PMW.
Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: a Korean community-based cross-sectional study
Authors: Nguyen Hai Duc , Kim Min-Sun
Published: July 2021

Objective:

To determine the associations between metabolic syndrome (MetS) during menopause and serum heavy metal levels and vitamin and curry consumption.

Methods:

A data set of 7,131 pre- and postmenopausal women aged ≥ 20 years collected between 2009 and 2017 was used to obtain information on sociodemographic, lifestyles, family histories, food intakes, and serum heavy metal levels and MetS. Logistic regression was used to identify associations between the presence of MetS and risk factors and to predict risks of MetS based on marginal effects.

Results:

Our results show that postmenopausal women had a higher risk of MetS than premenopausal women. During postmenopause elevations in the levels of serum cadmium by one unit increased the risk of MetS by 33% (OR 1.33; 95% CI, 1.03-1.72, P = 0.028). Risks of MetS in pre- and postmenopausal women, when serum Hb levels increased by 1 unit increased 21% (OR 1.21; 95% CI, 1.09-1.33, P < 0.001) and 26% (OR 1.26; 95% CI, 1.16-1.38, P < 0.001), respectively. Furthermore, the risk of MetS risk in pre- and postmenopausal women was increased 2.49-fold and 2.79-fold by a 1% increase in HbA1c level (OR 2.49; 95% CI, 1.97-3.16, P < 0.001) and (OR 2.79; 95% CI, 2.30-3.38, P < 0.001), respectively. High curry consumption reduced the risk of MetS significantly more than low curry consumption (OR 0.60; 95% CI, 0.39-0.91, P = 0.017) in premenopausal women. Furthermore, an increase in daily vitamin B2 intake by 1 mg reduced the risk of MetS by 45% (OR 0.55; 95% CI, 0.32-0.94, P = 0.028) in postmenopausal women.

Conclusion:

Vitamin B2 and curry supplementation may protect against MetS. Further work is needed to reduce risk factors associated with heavy metals and determine the effects of vitamins and curry consumption on MetS during menopause.

Video Summary:
http://links.lww.com/MENO/A791.
The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches
Authors: Kaastrup Katja , Grønbæk Kirsten
Published: July 2021

Hematopoietic stem and progenitor cells maintain hematopoiesis throughout life by generating all major blood cell lineages through the process of self-renewal and differentiation. In adult mammals, hematopoietic stem cells (HSCs) primarily reside in the bone marrow (BM) at special microenvironments called “niches.” Niches are thought to extrinsically orchestrate the HSC fate including their quiescence and proliferation. Insight into the HSC niches mainly comes from studies in mice using surface marker identification and imaging to visualize HSC localization and association with niche cells. The advantage of mouse models is the possibility to study the 3-dimensional BM architecture and cell interactions in an intact traceable system. However, this may not be directly translational to human BM. Sedentary lifestyle, unhealthy diet, excessive alcohol intake, and smoking are all known risk factors for various diseases including hematological disorders and cancer, but how do lifestyle factors impact hematopoiesis and the associated niches? Here, we review current knowledge about the HSC niches and how unhealthy lifestyle may affect it. In addition, we summarize epidemiological data concerning the influence of lifestyle factors on hematological disorders and malignancies.
The European Medicines Agency Review of Luspatercept for the Treatment of Adult Patients With Transfusion-dependent Anemia Caused by Low-risk Myelodysplastic Syndromes With Ring Sideroblasts or Beta-thalassemia
Authors: Delgado Julio , Voltz Caroline , Stain Milena , Balkowiec-Iskra Ewa , Mueller Brigitte , Wernsperger Johanna , Malinowska Iwona , Gisselbrecht Christian , Enzmann Harald , Pignatti Francesco
Published: July 2021

Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta superfamily, resulting in erythroid maturation and differentiation. On June 25, 2020, a marketing authorization valid through the European Union (EU) was issued for luspatercept for the treatment of adult patients with transfusion-dependent anemia caused by very low-, low-, and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, or those with transfusion-dependent beta thalassemia (BT). Luspatercept was evaluated in 2 separate phase 3, double-blind, placebo-controlled multicentre trials. The primary endpoints of these trials were the percentage of patients achieving transfusion independence over ≥8 weeks or longer for patients with MDS, and the percentage of patients achieving a ≥33% reduction in transfusion burden from baseline to week 13–24 for patients with BT. In the MDS trial, the percentage of responders was 37.91% versus 13.16%, P < 0.0001, for patients receiving luspatercept versus placebo, respectively. In the BT trial, the percentage of responders was 21.4% versus 4.5% (P < 0.0001) for luspatercept versus placebo, respectively. Treatment with luspatercept led to similar incidences of adverse events (AEs), but higher incidences of grade ≥3 AEs and serious AEs compared to placebo. The most frequently reported treatment-emergent AEs (≥15%) in the pooled luspatercept group were headache; back pain, bone pain, and arthralgia; diarrhea; fatigue; pyrexia; and cough. The aim of this article is to summarize the scientific review of the application, which led to the regulatory approval in the EU.
Conjunctival Exophytic Schneiderian-type Papillomas: A Rare Occurrence
Authors: Charles Norman C. , Stagner Anna M. , Raju Leela V. , Belinsky Irina
Published: July 2021

Conjunctival papillomas are common tumors that exhibit an exophytic growth pattern, comprised of multiple filiform fronds of squamous epithelium that contain fibrovascular cores. The inverted (endophytic) variety of papilloma, often termed “Schneiderian,” rarely occurs on the conjunctiva, with only 15 cases reported to date. Endophytic and exophytic papillomas are well described arising in the sinonasal Schneiderian epithelium where a low rate of malignant transformation may occur in the endophytic type; malignant transformation in exophytic sinonasal papillomas is exceedingly rare. The authors describe 2 cases of exophytic conjunctival papillomas with the morphology of a sinonasal or Schneiderian-type papilloma. Both were pink, sessile acquired growths in women in the sixth decade of life involving the inferior conjunctival fornix or nasal limbus. Nonkeratinizing squamous epithelium along with numerous goblet cells, intraepithelial mucinous cysts, and microabscesses were present. Immunohistochemistry showed reactivity for cytokeratin 7 and wild-type staining for p16 and p53, paralleling the findings in common conjunctival papillomas; both were also driven by low-risk human papillomavirus.
New thin-film adhesive for sealing full-thickness corneal incisions in rabbits
Authors: Tan Jackie , Foster Leslie John Ray , Lovicu Frank James , Watson Stephanie Louise
Published: July 2021

Purpose:

To compare the repair of penetrating corneal incisions in an in vivo rabbit model using a laser-activated thin-film adhesive, sutures, or self-seal.

Setting:

The University of Sydney, Camperdown, Australia.

Design:

Animal studies.

Methods:

Under an operating microscope, 2.0 mm penetrating incisions were created in 162 right eyes. Incisions in one group were repaired with the adhesive, the second group received a single 10-0 nylon suture, and the third group was left to self-seal. Rabbits were killed humanely at predetermined timepoints over 2 weeks, and wound healing was assessed using burst pressure and immunohistological studies. A modified McDonald-Shadduck scoring was used to assess eyes.

Results:

The mean burst pressure of the adhesive group was significantly higher than the sutured or self-sealed groups at all timepoints within the first 72 hours. At 0 hour, the burst pressure was 98.0 (±17.0) mm Hg, 30.6 (±2.1) mm Hg, and 3.8 (±0.6) mm Hg (P < .00001) for adhesive-treated (n = 5), sutured (n = 5), and self-sealed wounds (n = 5), respectively. These increased to 229.0 (±53.7) mm Hg, 12.4 (±2.9) mm Hg, and 27.3 (±4.0) mm Hg (P = .0011) at 72 hours. The modified McDonald-Shadduck score was significantly higher for eyes repaired using the adhesive than those sutured or left to self-seal for the first 72 hours. On histology and immunofluorescence, adhesive treatment demonstrated better wound approximation and higher myofibroblastic activation than the other groups.

Conclusions:

The adhesive was efficacious in sealing penetrating corneal incisions and tolerated higher burst pressures than sutures or self-seal. The adhesive was biocompatible in rabbits, and incisions demonstrated a rapid gain in wound strength that sustained over the study period.