bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke network performance during the first COVID-19 pandemic stage: A meta-analysis based on stroke network models
Authors: Romoli Michele , Eusebi Paolo , Forlivesi Stefano , Gentile Mauro , Giammello Fabrizio , Piccolo Laura , Giannandrea David , Vidale Simone , Longoni Marco , Paolucci Matteo , Hsiao Jessica , Sayles Emily , Yeo Leonard LL , Kristoffersen Espen Saxhaug , Chamorro Angel , Jiao Liqun , Khatri Pooja , Tsivgoulis Georgios , Paciaroni Maurizio , Zini Andrea
Published: August 2021

Background

The effect of the COVID pandemic on stroke network performance is unclear, particularly with consideration of drip&ship vs. mothership models.

Aims

We systematically reviewed and meta-analyzed variations in stroke admissions, rate and timing of reperfusion treatments during the first wave COVID pandemic vs. the pre-pandemic timeframe depending on stroke network model adopted.

Summary of findings

The systematic review followed registered protocol (PROSPERO-CRD42020211535), PRISMA and MOOSE guidelines. We searched MEDLINE, EMBASE, and CENTRAL until 9 October 2020 for studies reporting variations in ischemic stroke admissions, treatment rates, and timing in COVID (first wave) vs. control-period. Primary outcome was the weekly admission incidence rate ratio (IRR = admissions during COVID-period/admissions during control-period). Secondary outcomes were (i) changes in rate of reperfusion treatments and (ii) time metrics for pre- and in-hospital phase. Data were pooled using random-effects models, comparing mothership vs. drip&ship model. Overall, 29 studies were included in quantitative synthesis (n = 212,960). COVID-period was associated with a significant reduction in stroke admission rates (IRR = 0.69, 95%CI = 0.61–0.79), with higher relative presentation of large vessel occlusion (risk ratio (RR) = 1.62, 95% confidence interval (CI) = 1.24–2.12). Proportions of patients treated with endovascular treatment increased (RR = 1.14, 95%CI = 1.02–1.28). Intravenous thrombolysis decreased overall (IRR = 0.72, 95%CI = 0.54–0.96) but not in the mothership model (IRR = 0.81, 95%CI = 0.43–1.52). Onset-to-door time was longer for the drip&ship in COVID-period compared to the control-period (+32 min, 95%CI = 0–64). Door-to-scan was longer in COVID-period (+5 min, 95%CI = 2–7). Door-to-needle and door-to-groin were similar in COVID-period and control-period.

Conclusions

Despite a 35% drop in stroke admissions during the first pandemic wave, proportions of patients receiving reperfusion and time-metrics were not inferior to control-period. Mothership preserved the weekly rate of intravenous thrombolysis and the onset-to-door timing to pre-pandemic standards.
Cerebellar hemorrhages in patients with Dutch-type hereditary cerebral amyloid angiopathy
Authors: Voigt S , de Kruijff PC , Koemans EA , Rasing I , van Etten ES , Terwindt GM , van Osch MJP , van Buchem MA , van Walderveen MAA , Wermer MJH
Published: August 2021

Background

Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA).

Aims

We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA.

Methods

Symptomatic patients with D-CAA (defined as ≥1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei).

Results

We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1–7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4–25%) symptomatic patients and none of the 21 (0%, 95%CI 0–0%) presymptomatic carriers had ≥ 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52–76) participants (median 1.0, range 0–159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located.

Conclusions

Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA.
A novel thermoregulated phase-transfer catalysis system for chiral nano-Pt-catalyzed asymmetric hydrogenation
Authors: Chen Pu , Wang Yanhua
Published: August 2021

The chiral ionic liquid CILTPT-MS [CH3(OCH2CH2)16CD]+[CH3SO3]− (CD = cinchonidine) is found to exhibit cloud point character. Due to this cloud point character, a CILTPT-MS-stabilized chiral nano-Pt catalyst is prepared and utilized to realize transfer in a H2O–1-pentanol biphasic system by simply changing the temperature. Therefore, a fluorine-free, thermoregulated phase-transfer catalysis system is developed and applied to the asymmetric hydrogenation of α-ketoesters with enantiomeric excess of >99% and excellent conversion. In addition, the chiral nano-Pt catalyst can be easily separated and reused efficiently.
Maintenance cost assessment for heterogeneous multi-component systems incorporating perfect inspections and waiting time to maintenance
Authors: Bautista Lucía , Castro Inma T , Landesa Luis
Published: August 2021

Most existing research about complex systems maintenance assumes they consist of the same type of components. However, systems can be assembled with heterogeneous components (for example degrading and non-degrading components) that require different maintenance actions. Since industrial systems become more and more complex, more research about the maintenance of systems with heterogeneous components is needed. For this reason, in this paper, a system consisting of two groups of components: degrading and non-degrading components is analyzed. The main novelty of this paper is the evaluation of a maintenance policy at system-level coordinating condition-based maintenance for the degrading components, delay time to the maintenance and an inspection strategy for this heterogeneous system. To that end, an analytic cost model is built using the semi-regenerative processes theory. Furthermore, a safety constraint related to the reliability of the degrading components is imposed. To find the optimal maintenance strategy, meta-heuristic algorithms are used.
Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorders
Authors: Brummer Tobias , Ruck Tobias , Meuth Sven G. , Zipp Frauke , Bittner Stefan
Published: August 2021

The past decades have yielded major therapeutic advances in many autoimmune conditions – such as multiple sclerosis (MS) – and thus ushered in a new era of more targeted and increasingly potent immunotherapies. Yet this growing arsenal of therapeutic immune interventions has also rendered therapy much more challenging for the attending physician, especially when treating patients with more than one autoimmune condition. Importantly, some therapeutic strategies are either approved for several autoimmune disorders or may be repurposed for other conditions, therefore opening new curative possibilities in related fields. In this article, we especially focus on frequent and therapeutically relevant concomitant autoimmune conditions faced by neurologists when treating patients with MS, namely psoriasis, rheumatoid arthritis and inflammatory bowel diseases. We provide an overview of the available disease-modifying therapies, highlight possible contraindications, show pathophysiological overlaps and finally present which therapeutics can be utilized as a combinatory treatment, in order to ‘kill two birds with one stone’.
Do Non-State Actors Influence Climate Change Policy? Evidence from the Brazilian Nationally Determined Contributions for COP21
Authors: Cia Alves Elia Elisa , de Albuquerque Rodrigo Barros , Ferreira Marcos Alan , Monteiro Cláudio Alves
Published: August 2021

Participation in democratic regimes has been a central issue in foreign policy (FP) studies. This article seeks to contribute to the empirical discussion about FP participation through the analysis of the public consultation process conducted by the Brazilian Ministry of Foreign Affairs with non-state actors in the context of the preparations for the Paris Climate Agreement (2015). We employed automated text analysis using Python and R qualifying open responses submitted to the questionnaire launched at the first round of the consultations process and comparing them to the official document presented by Brazil establishing its own carbon emission targets. We found that the Brazilian academia members had a relevant influence on the content of the final document presented by Brazil, strengthening the literature on the importance of the epistemic community to environmental politics and raising new questions on the paths of foreign policy influence.
The Impact of Local Parties on Party System Institutionalisation in Post-Conflict Aceh
Authors: Budiatri Aisah Putri
Published: August 2021

While there has been a flurry of research on party system institutionalisation (PSI) and regionalist parties, very little research has been conducted on their imbrication. This study aims to fill this gap by analysing the impact of local parties on the party system in post-conflict Aceh, Indonesia. It contends that the presence of local parties in Aceh has had a hybrid effect on the institutionalisation of the party system. Similar to national parties, local parties in Indonesia have weak societal roots and party organisations that obstruct PSI in Aceh. That notwithstanding, local parties in post-conflict Aceh have assisted in solidifying the party system by improving the legitimacy of parties and elections and by creating a less fragmented party system. This hybrid effect is also strongly influenced by Aceh’s long wartime history and its post-conflict status.
Study on Evaluation of Knowledge, Attitude, and Practice of Sri Lankan Traffic Police Officers Related to Examination of Drunk Drivers, in Two Most Populated Districts of Sri Lanka
Authors: Thivaharan Yalini , Kitulwatte Indira Deepthi Gamage , Muthulingam Thanushan , Jayasundara Maleesha , Borukgama Nirmal , Prageeth Udaya , Senevirathna Dumith , Kulathunga Deshan , Aththanayaka Sandamini
Published: August 2021

Introduction:

Driving under the influence (DUI) of alcohol is one of the substantial predisposing factors for mishaps among road users. A traffic police officer will be the first authoritative personnel a drunk driver encounters in the legal system. The absence of accurate skills and knowledge of these officers impedes the structuring of legal procedures and may lead to miscarriage of justice.

Objective:

To assess the knowledge, attitude and practice of Sri Lankan traffic police in handling and managing an alleged case of driving under influence of alcohol.

Methods:

This was a descriptive cross sectional study carried on a sample of 384 traffic police officers attached to the districts of Colombo and Gampaha, through a questionnaire.

Results:

Out of 384, only 75 of police officers knew the correct preliminaries to perform before administering a breathalyzer test. 79.7% knew the correct instructions for using a breathalyzer, but only 3.4% knew the colour changes of the breathalyzer. Significantly poor attitude was observed among the police officers, regarding the importance of producing a drunk driver for medico-legal examination ( P = 0.001) Only 222 (57.8%) answered correctly that a drunk driver needs to be subjected to a medico-legal examination as early as possible. Significantly poor practice and attitude was observed in officers with longer service duration but no significant association was observed between ranks of officers and attitude and practice ( P = 0.199).

Conclusions:

The results of our study demonstrate that the knowledge attitude and practice on efficiently handling a case of DUI among traffic police officers is poor, even though all of them are engaged in DUI duties irrespective of their service duration. The need for continuous professional development programmes was highlighted.
Incidence, Predictors and Outcomes of Delirium in Critically Ill Patients With COVID-19
Authors: Williamson Craig A. , Faiver Laura , Nguyen Andrew M. , Ottenhoff Lauren , Rajajee Venkatakrishna
Published: August 2021

Background and Purpose:

A variety of neurological manifestations have been attributed to COVID-19, but there is currently limited evidence regarding risk factors and outcomes for delirium in critically ill patients with COVID-19. The purpose of this study was to identify delirium in a large cohort of ICU patients with COVID-19, and to identify associated features and clinical outcomes at the time of hospital discharge.

Methods:

This is an observational cohort study of 213 consecutive patients admitted to an ICU for COVID-19 respiratory illness. Delirium was diagnosed by trained abstractors using the CHART-DEL instrument. The associations between key clinical features, sedation and delirium were examined, as were the impacts of delirium on clinical outcomes.

Results:

Delirium was identified in 57.3% of subjects. Delirious patients were more likely to receive mechanical ventilation, had lower P: F ratios, higher rates of renal replacement therapy and ECMO, and were more likely to receive enteral benzodiazepines. Only mechanical ventilation remained a significant predictor of delirium in a logistic regression model. Mortality was not significantly different, but delirious patients experienced greater mechanical ventilation duration, ICU/hospital lengths of stay, worse functional outcomes at discharge, and were less likely to be discharged home.

Conclusions:

Delirium is common in critically ill patients with COVID-19 and appears to be associated with greater disease severity. When present, delirium is associated with worse functional status at discharge, but not increased mortality. Additional studies are necessary to determine the generalizability of these results and the impact of delirium on longer-term cognitive and functional outcomes.
Mitigation strategies of underground tunnels against blast loading
Authors: Kasilingam Senthil , Sethi Muskaan , Pelecanos Loizos , Gupta Narinder K
Published: August 2021

An evaluation of mitigation strategies of underground tunnels against explosions is important to the society. Therefore, a small scale tunnel was modeled against blast loading using finite element software ABAQUS. The inelastic behavior of concrete and steel bar has been incorporated through concrete damage plasticity model and Johnson-cook models respectively, available in ABAQUS. The Drucker-Prager model as well as acoustic infinite medium have been used to model the damage behavior of soil and tunnel respectively. The simulated results thus obtained from the present study were compared with the experimental results available in the literature and found in good agreement. Further, the simulations were carried to predict the damage intensity in tunnel in terms of acceleration, impulse velocity, displacement, and Mises stresses. There are many parameters which were taken into consideration to assess the mitigation strategies for the underground tunnels. The critical parameters include the influence of tunnel shapes, lining materials, lining thickness, burial depth of the tunnels, inclusion of a barrier in between the blast source-the tunnel and layered configuration of tunnel lining, and were considered to evaluate the mitigation strategy. It was concluded that the square shape of tunnel was most vulnerable as compared to circular and U-shaped tunnels. It was also concluded that plain concrete monolithic lining as well as layered configuration consisting of Dytherm foam layer between Steel Fiber reinforced Concrete layers, was found to be more vulnerable among the chosen lining materials. Also, the thickness of lining and burial depth of the tunnel found to be a significant role against blast loading.
Scenting Entertainment: Virtual Reality Storytelling, Theme Park Rides, Gambling, and Video-Gaming
Authors: Spence Charles
Published: August 2021

There has long been interest in both the tonic and phasic release of scent across a wide range of entertainment settings. While the presentation of semantically congruent scent has often been used in order to enhance people’s immersion in a particular context, other generally less successful attempts have involved the pulsed presentation of a range of scents tied to specific events/scenes. Scents have even been released in the context of the casino to encourage the guests to linger for longer (and spend more), at least according to the results of one controversial study. In this narrative review, I want to take a closer look at the use of scent in a range of both physical and digital environments, highlighting the successes (as in the case of scented theme park rides) and frequent failures (as, seemingly, in the context of scent-enabled video games). While digitally inducing meaningful olfactory sensations is likely to remain a pipe dream for the foreseeable future, the digital control of scent release/delivery provides some limited opportunities to enhance the multisensory experience of entertainment. That said, it remains uncertain whether the general public will necessarily perceive the benefit, and hence be willing to pay for the privilege.
Bot, or not? Comparing three methods for detecting social bots in five political discourses
Authors: Martini Franziska , Samula Paul , Keller Tobias R , Klinger Ulrike
Published: August 2021

Social bots – partially or fully automated accounts on social media platforms – have not only been widely discussed, but have also entered political, media and research agendas. However, bot detection is not an exact science. Quantitative estimates of bot prevalence vary considerably and comparative research is rare. We show that findings on the prevalence and activity of bots on Twitter depend strongly on the methods used to identify automated accounts. We search for bots in political discourses on Twitter, using three different bot detection methods: Botometer, Tweetbotornot and “heavy automation”. We drew a sample of 122,884 unique user Twitter accounts that had produced 263,821 tweets contributing to five political discourses in five Western democracies. While all three bot detection methods classified accounts as bots in all our cases, the comparison shows that the three approaches produce very different results. We discuss why neither manual validation nor triangulation resolves the basic problems, and conclude that social scientists studying the influence of social bots on (political) communication and discourse dynamics should be careful with easy-to-use methods, and consider interdisciplinary research.
Sociodemographic Determinants of COVID-19 Vaccine Hesitancy, Fear of Infection, and Protection Self-Efficacy
Authors: McElfish Pearl A. , Willis Don E. , Shah Sumit K. , Bryant-Moore Keneshia , Rojo Martha O. , Selig James P.
Published: August 2021

Objectives:

Arkansas COVID-19 vaccine uptake has been lower than the national average. This study examined associations between sociodemographic factors and COVID-19 vaccine hesitancy, fear of infection, and protection self-efficacy.

Methods:

Adults either residing, having employment, or receiving health care in Arkansas (n = 754) participated in an online survey between October 30, 2020 and January 16, 2021. Participants were recruited in both rural and urban areas from 6 Arkansas primary care clinics. Survey questions addressed sociodemographic factors, COVID-19 infection fear, protection self-efficacy, and COVID-19 vaccine attitudes. Bivariate and multivariable logistic regression models were used to assess associations between dependent variables and respondents’ sociodemographic characteristics, COVID-19 infection fear, and COVID-19 protection self-efficacy.

Results:

About 38% of participants reported COVID-19 vaccine hesitancy. Age, sex, race, and education were significantly associated with COVID-19 and general vaccine attitudes. Odds of COVID-19 vaccine hesitancy decreased as age increased (OR = 0.98; P < .01). Women had higher odds of COVID-19 vaccine hesitancy than men (OR = 1.52; P < .05). Respondents with a high school diploma and below and respondents with some college or a technical degree had greater odds of COVID-19 vaccine hesitancy (OR = 2.58; P < .001; and OR = 1.97; P < .01, respectively) compared to respondents with a 4-year college degree. Black/African American respondents had greater odds of COVID-19 vaccine hesitancy compared to White respondents (OR = 3.08; P < .001). No significant difference was observed among rural and urban respondents regarding COVID-19 vaccine hesitancy; however, respondents in rural areas were more likely to report low general vaccine trust compared to those in urban areas (OR = 1.87; P < .01). Respondents reporting no fear (OR = 5.51; P < .001) and very little fear (OR = 1.95; P < .05) of COVID-19 had greater odds of COVID-19 vaccine hesitancy compared to respondents who feared COVID-19 infection to a great extent.

Conclusions:

COVID-19 vaccine hesitancy and general trust in vaccines differ significantly among age, sex, race, and education. These trust and hesitancy patterns are challenges for achieving population immunity and follow similar patterns of vulnerability to COVID-19. Vaccination programs and interventions must consider these differences in COVID-19 vaccine hesitancy and general vaccine trust to alleviate COVID-19 disparities. Findings make a significant contribution in evaluating vaccine hesitancy among a large, diverse sample from a rural state.
Musculoskeletal Pain and Cardiovascular Risk in Hispanic/Latino Meatpacking Workers
Authors: Rowland Sheri A. , Ramos Athena K. , Carvajal-Suarez Marcela , Trinidad Natalia , Johnson-Beller Rebecca , Struwe Leeza , Quintero Sophia A. , Pozehl Bunny
Published: August 2021

Background

Most meatpacking workers have pain affecting their back, arms, and/or wrists from work-related repetitive motions, forceful exertion, and awkward positioning. Chronic musculoskeletal pain is associated with obesity, hypertension, type II diabetes, heart attack, and stroke. Hispanic/Latino workers in the meatpacking industry are a vulnerable population; limited English, lack of health insurance, and fear of deportation often deter them from seeking care where preventable cardiovascular risks might be detected. The purpose of this study was to examine perceived health and actual cardiovascular risk among Hispanic/Latino meatpacking workers with musculoskeletal pain in Nebraska.

Methods

Structured interviews were used to examine perceived health, awareness of cardiometabolic risk, and capacity for health self-management. Body mass index (BMI), lipids, blood pressure, Hemoglobin A1c (HbA1c), and cardiorespiratory fitness (step test) were used to examine cardiovascular risk.

Findings

Of those interviewed ( n = 39), musculoskeletal pain affected usual life activities in 64% ( n = 25) of participants. Of those tested ( n = 30), 93% ( n = 28) had a BMI > 30 kg/m2, 86% ( n = 26) had at least one lipid abnormality, 50% ( n = 15) had blood pressure > 120/80 mm Hg, and 43% ( n = 13) had an HbA1c > 5.7%. Males had greater fitness than females ( p = .03), but also greater lifetime risk of heart attack or stroke compared with females ( p = .02).

Conclusion/Application to Practice

In this sample, cardiovascular risk exceeded that found in the general Hispanic population in the United States. Occupational health nurses can assist workers to be aware of their risk by measuring and providing culturally and linguistically appropriate education on blood pressure, BMI, cholesterol, and HbA1c.
Chemomechanical magnetorheological finishing: Process mechanism, research trends, challenges and opportunities in surface finishing
Authors: Kumar Yogendra , Singh Harpreet
Published: August 2021

Chemomechanical magnetorheological finishing (CMMRF) has emerged as a nanofinishing method that combines the characteristics of chemical mechanical polishing (CMP) and magneto-rheological finishing (MRF). The CMMRF process was designed to take into account both the chemical and mechanical effects that occur during the finishing process. In the field of material processing science, this article delves into the fundamentals of the CMMRF method. The potential research patterns linked to CMMRF are assessed and their benefits are determined. Furthermore, the challenges of improving CMMRF process capabilities, as well as the wide futuristic opportunities of the research sector, are emphasised, along with meeting all industrial needs. The findings of this analysis paper will also aid researchers in the field of advanced finishing in identifying process realisation for better results.
Myeloproliferative disorders and their effects on bone homeostasis: the role of megakaryocytes
Authors: Karagianni Aikaterini , Ravid Katya
Published: August 2021

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of chronic hematological diseases that arise from the clonal expansion of abnormal hematopoietic stem cells, of which polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have been extensively reviewed in the context of control of clonal expansion, fibrosis, and other phenotypes. Herein, we review current knowledge on the influence of different forms of MPN on bone health. In studies, murine models and human data have implicated various degrees of effect of different forms of MPN on bone density and on osteoblast proliferation and differentiation. Most results have shown that bone volume is generally increased in patients with PMF, whereas it is slightly decreased or not altered in patients with ET or PV, although possible differences between male and female phenotypes were not fully explored in most MPN forms. Osteosclerosis in patients with PMF is a serious complication that can lead to bone marrow failure, and the loss of bone reported in some patients with ET or PV can lead to osteoporotic fractures. Some MPN forms are associated with an increased number of megakaryocytes (MKs), and several of the MK-associated factors in MPN are known to affect bone development. We review known mechanisms involved in these processes, with a focus on the role of MKs and secreted factors. Understanding MPN-associated changes in bone health could improve early intervention and treatment of this side effect of the pathology.
Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in previously untreated intermediate- to high-risk DLBCL
Authors: Martin Peter , Bartlett Nancy L. , Chavez Julio C. , Reagan John L. , Smith Sonali M. , LaCasce Ann S. , Jones Jeffrey , Drew James , Wu Chengqing , Mulvey Erin , Revuelta Maria V. , Cerchietti Leandro , Leonard John P.
Published: August 2021

Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute to chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. CC-486 doses of 100, 150, 200, or 300 mg given 7 days before cycle 1 and on days 8-21 of cycles 1-5 were evaluated; additional patients were enrolled in the expansion phase to examine preliminary efficacy. The primary objectives were to determine the safety and the maximum tolerated dose (MTD) of CC-486 in combination with R-CHOP. The most common grade 3/4 toxicities were hematologic, including neutropenia (62.7%) and febrile neutropenia (25.4%); grade 3/4 nonhematologic toxicities were uncommon (<7%). The MTD was not established; 2 patients had dose-limiting toxicities (1 with grade 4 febrile neutropenia; 1 with grade 4 prolonged neutropenia). The recommended phase 2 dose was established as 300 mg. The overall response rate was 94.9%, with 52 patients (88.1%) achieving complete responses. With a median follow-up of 28.9 months, estimated 1- and 2-year progression-free survival rates were 84.1% and 78.6%, respectively. Overall, epigenetic priming with CC-486 before R-CHOP can be delivered with acceptable safety to patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. ClinicalTrials.gov: NCT02343536.
Correlation between estimated plasma remnant-like particle cholesterol and vegetable fat intake in Uku town, Japan
Authors: Adachi Hisashi , Kakuma Tatsuyuki , Enomoto Mika , Fukami Ako , Nakamura Sachiko , Nohara Yume , Morikawa Nagisa , Sakaue Akiko , Yamamoto Maki , Fukumoto Yoshihiro
Published: August 2021

Background

Remnant-like particle cholesterol (RLP-C) is highly atherogenic, which is associated with atherosclerosis. However, RLP-C has not been routinely measured in the clinical practice. We estimated RLP-C levels using conventional lipid profiles and examined the association between estimated RLP-C and related factors including nutrient intake.

Methods

This study was performed in Uku town, Nagasaki prefecture, Japan in 2019. A total of 225 subjects were enrolled and directly measured RLP-C levels. Estimated RLP-C levels were defined as the following formula [total cholesterol − (LDL-cholesterol) − (HDL-cholesterol)]. Multivariate analyses were used to assess the relationship between estimated RLP-C and atherogenic factors. We calculated cut-off values on dichotomized RLP-C (< 7.5 mg/dL vs. ≥ 7.5 mg/dL) by receiver operating characteristic (ROC) curve.

Results

The mean values of directly measured RLP-C levels and estimated RLP-C were 4.0 mg/dL and 16.4 mg/dL, respectively. In the multiple stepwise linear regression analysis, directly measured and estimated RLP-C levels were independently and commonly associated with apolipoprotein E, triglycerides, and vegetable fat intake (inversely). Using ROC curves, we found the cut-off value of estimated RLP-C was 22.0 mg/dL.

Conclusion

We demonstrated that the estimated RLP-C levels using conventional lipid profiles may substitute for directly measured RLP-C and these levels were independently and inversely associated with vegetable fat intake in the community-dwelling Japanese population.
Effect of calcium content of diet on crystal formation in urine of patients with calcium oxalate stones: a randomized crossover clinical trial
Authors: Gopala Sathish Kumar , Joe Jim
Published: August 2021

Background

Patients with idiopathic calcium oxalate stones are advised to consume a low-oxalate diet to prevent recurrence. In this study, on patients with calcium oxalate stones we have attempted to determine the effect of calcium content of diet on the formation of calcium oxalate crystals in urine by in vitro supersaturation study of fresh postprandial urine samples and observing the morphology of the crystals formed using polarized optical microscopy.

Methods

The trial was conducted as a prospective interventional randomised crossover clinical trial in a repeated measures design. Sixty patients with calcium oxalate stones and no metabolic abnormalities in urine treated by lithotripsy at a tertiary care centre during the period May 2016 to May 2019 were recruited. Following a 14 h overnight fasting, urine samples were collected after providing the patient with either a low- or high-calcium meal for breakfast followed four hours later, by high-oxalate meal for lunch. Urine was tested for multiple parameters including urine pH, specific gravity, calcium/creatinine ratio and supersaturation of urine with sodium oxalate followed by optical density measurement by spectrophotometry and microscopic analysis of crystals formed.

Results

Optical density values and calcium/creatinine ratio of urine samples obtained after high-calcium meal are significantly higher than in corresponding sample obtained after low-calcium meal (p < 0.001). These findings were reflected in the morphology of formed crystals in their size, shape and number. When urinary calcium levels were low, no crystals were formed during supersaturation study of postprandial urine samples following a high-oxalate diet.

Conclusions

High calcium content in diet significantly contributes to kidney stone formation. There is a lower risk of kidney stone formation with a low-calcium meal even on consumption of a high-oxalate diet.
TMC4 is a novel chloride channel involved in high-concentration salt taste sensation
Authors: Kasahara Yoichi , Narukawa Masataka , Ishimaru Yoshiro , Kanda Shinji , Umatani Chie , Takayama Yasunori , Tominaga Makoto , Oka Yoshitaka , Kondo Kaori , Kondo Takashi , Takeuchi Ayako , Misaka Takumi , Abe Keiko , Asakura Tomiko
Published: August 2021

“Salty taste” sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl− receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl− channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl−. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.
Staying in touch: how highly specialised moth pollinators track host plant phenology in unpredictable climates
Authors: Finch Jonathan T. D. , Power Sally A. , Welbergen Justin A. , Cook James M.
Published: August 2021

Background

For specialised pollinators, the synchrony of plant and pollinator life history is critical to the persistence of pollinator populations. This is even more critical in nursery pollination, where pollinators are obligately dependant on female host plant flowers for oviposition sites. Epicephala moths (Gracillariidae) form highly specialised nursery pollination mutualisms with Phyllanthaceae plants. Several hundred Phyllanthaceae are estimated to be exclusively pollinated by highly specific Epicephala moths, making these mutualisms an outstanding example of plant–insect coevolution. However, there have been no studies of how Epicephala moths synchronise their activity with host plant flowering or persist through periods when flowers are absent. Such knowledge is critical to understanding the ecology and evolutionary stability of these mutualisms. We surveyed multiple populations of both Breynia oblongifolia (Phyllanthaceae) and it’s Epicephala pollinators for over two years to determine their phenology and modelled the environmental factors that underpin their interactions.

Results

The abundance of flowers and fruits was highly variable and strongly linked to local rainfall and photoperiod. Unlike male flowers and fruits, female flowers were present throughout the entire year, including winter. Fruit abundance was a significant predictor of adult Epicephala activity, suggesting that eggs or early instar larvae diapause within dormant female flowers and emerge as fruits mature. Searches of overwintering female flowers confirmed that many contained pollen and diapausing pollinators. We also observed diapause in Epicephala prior to pupation, finding that 12% (9/78) of larvae emerging from fruits in the autumn entered an extended diapause for 38–48 weeks. The remaining autumn emerging larvae pupated directly without diapause, suggesting a possible bet-hedging strategy.

Conclusions

Epicephala appear to use diapause at multiple stages in their lifecycle to survive variable host plant phenology. Furthermore, moth abundance was predicted by the same environmental variables as male flowers, suggesting that moths track flowering through temperature. These adaptations may thereby mitigate against unpredictability in the timing of fruiting and flowering because of variable rainfall. It remains to be seen how widespread egg diapause and pre-pupal diapause may be within Epicephala moths, and, furthermore, to what degree these traits may have facilitated the evolution of these highly diverse mutualisms.
Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria
Authors: Tsunematsu Yuta , Hosomi Koji , Kunisawa Jun , Sato Michio , Shibuya Noriko , Saito Emiko , Murakami Haruka , Yoshikawa Yuko , Iwashita Yuji , Miyoshi Noriyuki , Mutoh Michihiro , Ishikawa Hideki , Sugimura Haruhiko , Miyachi Motohiko , Wakabayashi Keiji , Watanabe Kenji
Published: August 2021

Background

The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis. While there have been major advances in the characterization of colibactin-positive E. coli and the toxin it produces, the infection route of the clb + strain remains poorly characterized.

Results

We examined infants and their treatments during and post-birth periods to examine potential transmission of colibactin-positive E. coli to infants. Here, analysis of fecal samples of infants over the first month of birth for the presence of a colibactin biosynthetic gene revealed that the bacterium may be transmitted from mother to infant through intimate contacts, such as natural childbirth and breastfeeding, but not through food intake.

Conclusions

Our finding suggests that transmission of colibactin-positive E. coli appears to be occurring at the very early stage of life of the newborn and hints at the possibility of developing early preventive measures against colorectal cancer.
Inhibition of Streptococcus mutans biofilms with bacterial-derived outer membrane vesicles
Authors: Wang Yihui , Hoffmann Joseph P. , Baker Sarah M. , Bentrup Kerstin Höner zu , Wimley William C. , Fuselier Joseph A. , Bitoun Jacob P. , Morici Lisa A.
Published: August 2021

Background

Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Bacteria within biofilms are 10- to 1000-fold more resistant to antibiotics, making it challenging but imperative to develop new therapeutics that can disperse biofilms and eradicate infection. Gram-negative bacteria produce outer membrane vesicles (OMV) that play critical roles in communication, genetic exchange, cargo delivery, and pathogenesis. We have previously shown that OMVs derived from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi.

Results

Here, we examine the antibiofilm activity of Burkholderia thailandensis OMVs against the oral biofilm-forming pathogen Streptococcus mutans. We demonstrate that OMV treatment reduces biofilm biomass, biofilm integrity, and bacterial cell viability. Both heat-labile and heat-stable components, including 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline and long-chain rhamnolipid, contribute to the antibiofilm activity of OMVs. When OMVs are co-administered with gentamicin, the efficacy of the antibiotic against S. mutans biofilms is enhanced.

Conclusion

These studies indicate that bacterial-derived OMVs are highly effective biological nanoparticles that can inhibit and potentially eradicate biofilms.
Multifoci and multiserotypes circulation of dengue virus in Senegal between 2017 and 2018
Authors: Dieng Idrissa , Ndione Marie Henriette Dior , Fall Cheikh , Diagne Moussa Moïse , Diop Mamadou , Gaye Aboubacry , Barry Mamadou Aliou , Diop Boly , Ndiaye Mamadou , Bousso Abdoulaye , Fall Gamou , Loucoubar Cheikh , Faye Oumar , Sall Amadou Alpha , Faye Ousmane
Published: August 2021

Background

Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal.

Methods

We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment.

Results

Three dengue virus serotypes (DENV-1–3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll.

Conclusions

These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Longitudinal observational study of boxing therapy in Parkinson’s disease, including adverse impacts of the COVID-19 lockdown
Authors: Horbinski Craig , Zumpf Katelyn B. , McCortney Kathleen , Eoannou Dean
Published: August 2021

Background

Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease whose incidence is increasing with an aging population. One of the most serious manifestations of PD is gait instability, leading to falls and subsequent complications that can be debilitating, even fatal. Boxing therapy (BT) uses gait and balance exercises to improve ambulation in people with PD, though its efficacy has not yet been fully proven.

Methods

In the current longitudinal observational study, 98 participants with idiopathic PD underwent twice-weekly BT sessions. Primary outcome was self-reported falls per month; secondary outcomes were quantitative and semi-quantitative gait and balance performance evaluations. Statistical methods included segmented generalized estimating equation with an independent correlation structure, binomial distribution, and log link.

Results

The average number of self-reported falls per month per participant decreased by 87%, from 0.86 ± 3.58 prior to BT, to 0.11 ± 0.26 during BT. During the lockdown imposed by COVID-19, this increased to 0.26 ± 0.48 falls per month. Females and those > 65 years old reported the greatest increase in falls during the lockdown period. Post-lockdown resumption of BT resulted in another decline in falls, to 0.14 ± 0.33. Quantitative performance metrics, including standing from a seated position and standing on one leg, largely mirrored the pattern of falls pre-and post-lockdown.

Conclusions

BT may be an effective option for many PD patients.
Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial
Authors: Zhang Chenjie , Wang Lulu , Sun Wenguang , Chen Lei , Zhang Chen , Li Hong , Yu Jiale , Fan Jianxia , Ruan Huijuan , Zheng Tao , Wu Dongling , Li Shaojing , Lu Huan , Wang Man , Mol Ben W. , Huang Hefeng , Wu Yanting
Published: August 2021

Background

The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model.

Methods/design

A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited.

Discussion

To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods.

Trial registration number

ChiCTR, ChiCTR1900026963. Registered 27 October 2019.