bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating myokines IL‐6, IL‐15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity
Authors: Pérez‐López Alberto , Gonzalo‐Encabo Paola , Pérez‐Köhler Bárbara , García‐Honduvilla Natalio , Valadés David
Published: June 2021

To examine the effects of a time‐matched endurance vs. concurrent training on circulating IL‐6, IL‐13, IL‐15, IL‐15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre‐ and postmenopause. Thirty‐five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1, N = 10), concurrent training (CON, N = 13) or no training group (CT, N = 12). Additionally, twelve sedentary premenopausal women with obesity were added to an endurance training group (EN2, N = 12). Participants took part in a 12‐week supervised intervention, performing 3 sessions/week of 60 min/session. Before and after the interventions, body composition and fitness were assessed, and blood samples obtained to measure serum myokines levels. Total fat mass decreased in all exercised groups (CON,−5.2%; EN1,−5.3%; EN2,−5.6%). In postmenopausal women, serum IL‐6, IL‐15 and IL‐15Ra decreased after training (P<0.01), finding a pronounced reduction in IL‐6 (−42% vs. −16%) and IL‐15 (−50% vs. −31%) when comparing EN1 to CON (P<0.05). Serum FGF21 was only reduced in the EN1 (−27%; P=0.012). While EN1 and EN2 comparison, reported differences for IL‐15Rα concentration (−28% vs. −40%; P=0.023). Finally, in EN2, the delta change of fat mass and IL‐6, IL‐15 and IL‐15Rα were associated (r = 0.605; r = 0.546; r = 0.515; P<0.05). IL‐13 showed undetected concentrations. Circulating IL‐6, IL‐15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity. Endurance training promotes a higher reduction of these myokines, potentially activating their intricate immune and fat mass regulation roles in postmenopausal women with obesity.
Information Avoidance, Self-affirmation, and Intentions to Receive Genomic Sequencing Results Among Members of an African Descent Cohort
Authors: Peterson Emily B , Taber Jennifer M , Klein William M P
Published: June 2021

Background

Information avoidance tendencies have been found to be associated with lower intentions to pursue medically actionable genomic sequencing results, but less so among individuals who engage more in spontaneous self-affirmation. Yet these results were obtained with a largely non-Hispanic White, high-SES cohort.

Purpose

To assess these variables, their magnitude, and their associations in an African-descent cohort as part of the same ClinSeq® exome sequencing program.

Methods

Participants reported levels of spontaneous self-affirmation, information avoidance, and intentions to receive three types of results – medically actionable, non-medically actionable, and carrier status as part of a baseline survey.

Results

Relative to the original, non-Hispanic White cohort, those in the African-descent cohort had higher levels of spontaneous self-affirmation and lower intentions of learning about carrier genomic results; they reported comparable levels of information avoidance and intentions to receive other results. Information avoidance was negatively associated with intention to receive non-actionable results in the African-descent cohort, as found in the initial cohort, with no moderating effect of spontaneous self-affirmation. Information avoidance, spontaneous self-affirmation, and their interaction were not associated with intentions to receive actionable results (contrary to findings in the initial cohort), or carrier results.

Conclusions

Individuals of African descent may engage in relatively more spontaneous self-affirmation, and do not appear to engage in more information avoidance. Their information avoidance tendencies were associated with pursuit of non-actionable sequencing results, with no moderating effect of self-affirmation, and were not associated with pursuit of actionable results or carrier results.
Invited Commentary: Is the Long Shadow of Childhood Disadvantage on Lifelong Health Getting Worse Over Time?
Authors: Melchior Maria
Published: June 2021

Social inequalities in health and their early-life origins have been extensively documented. Although the complex direct and intermediate mechanisms linking early-life disadvantage to later health are not yet fully understood, new findings on biological markers distinctly related with early-life experiences suggest a causal relationship. In this issue, Fuller-Rowell et al. (Am J Epidemiol. 2021:190(11):2284–2293) step back to examine the role of childhood disadvantage in the United States in different periods, observing that the relationship with later health seems to have strengthened over time. The main explanation the authors bring up has to do with increased income segregation and changes in labor market composition that limit opportunities for persons with low educational attainment. In other words, while the rich get richer, the poor get poorer, the middle class shrinks, and there are fewer interactions across different socioeconomic groups and the social ladder is blocked. Other evidence suggests that investments in children, through early education and academic support programs, could help reduce the consequences of childhood disadvantage on long-term health.
A SARS-CoV-2 sequence submission tool for the European Nucleotide Archive
Authors: Roncoroni Miguel , Droesbeke Bert , Eguinoa Ignacio , De Ruyck Kim , D’Anna Flora , Yusuf Dilmurat , Grüning Björn , Backofen Rolf , Coppens Frederik
Published: June 2021

Many aspects of the global response to the COVID-19 pandemic are enabled by the fast and open publication of SARS-CoV-2 genetic sequence data. The European Nucleotide Archive (ENA) is the European recommended open repository for genetic sequences. In this work, we present a tool for submitting raw sequencing reads of SARS-CoV-2 to ENA. The tool features a single-step submission process, a graphical user interface, tabular-formatted metadata and the possibility to remove human reads prior to submission. A Galaxy wrap of the tool allows users with little or no bioinformatics knowledge to do bulk sequencing read submissions. The tool is also packed in a Docker container to ease deployment.

Availability and implementation

CLI ENA upload tool is available at github.com/usegalaxy-eu/ena-upload-cli (DOI 10.5281/zenodo.4537621); Galaxy ENA upload tool at toolshed.g2.bx.psu.edu/view/iuc/ena_upload/382518f24d6d and github.com/galaxyproject/tools-iuc/tree/master/tools/ena_upload (development); and ENA upload Galaxy container at github.com/ELIXIR-Belgium/ena-upload-container (DOI 10.5281/zenodo.4730785).
EchoNavigator® technology facilitates transapical mitral paravalvular leak closure: a case report
Authors: Buzaev Igor Vyacheslavovich , Khalikova Gulchachak , Plechev Vladimir Vyacheslavovich , Onorato Eustaquio Maria
Published: June 2021

Background

Catheter-based closure has emerged as a less invasive alternative to surgery in high-risk patients with paravalvular leak (PVL) and clinically significant regurgitation with feasibility and efficacy demonstrated in multiple studies.

Case summary

A 72-year-old female with a past history of long-standing rheumatic heart disease underwent mechanical mitral valve replacement in 2008. Ten years later, redo surgery was performed due to a worsening mitral PVL and the leakage was closed by direct pledget-supported sutures, preserving the mechanical valve. She was recently admitted again for haemolytic anaemia and congestive heart failure (New York Heart Association Classes III–IV) due to a recurrent mitral PVL. We report our initial clinical experience using a novel software solution (EchoNavigator®-system) for intuitive guidance during a catheter-based transapical mitral PVL closure.

Discussion

Transapical mitral PVL closure with a specifically designed device demonstrated in our case to be a better option than redo surgery. Recently introduced fusion imaging modalities enhanced visualization of soft tissue anatomy and device location improving enormously the results of this challenging intervention.
Potential for optimizing management of obesity in the secondary prevention of coronary heart disease
Authors: De Bacquer Dirk , Jennings Catriona S , Mirrakhimov Erkin , Lovic Dragan , Bruthans Jan , De Smedt Delphine , Gotcheva Nina , Dolzhenko Maria , Fras Zlatko , Pogosova Nana , Lehto Seppo , Hasan-Ali Hasan , Jankowski Piotr , Kotseva Kornelia , De Backer Guy , Wood David , Rydén Lars
Published: June 2021

Aims

Prevention guidelines have identified the management of obese patients as an important priority to reduce the burden of incident and recurrent cardiovascular disease. Still, studies have demonstrated that over 80% of patients with coronary heart disease (CHD) fail to achieve their weight target. Here, we describe advice received and actions reported by overweight CHD patients since being discharged from hospital and how weight changes relate to their risk profile.

Methods and results

Based on data from 10 507 CHD patients participating in the EUROASPIRE IV and V studies, we analysed weight changes from hospital admission to the time of a study visit ≥6 and <24 months later. At hospitalization, 34.9% were obese and another 46.0% were overweight. Obesity was more frequent in women and associated with more comorbidities. By the time of the study visit, 19.5% of obese patients had lost ≥5% of weight. However, in 16.4% weight had increased ≥5%. Weight gain in those overweight was associated with physical inactivity, non-adherence to dietary recommendations, smoking cessation, raised blood pressure, dyslipidaemia, dysglycaemia, and lower levels of quality of life. Less than half of obese patients was considering weight loss in the coming month.

Conclusions

The management of obesity remains a challenge in the secondary prevention of CHD despite a beneficial effect of weight loss on risk factor prevalences and quality of life. Cardiac rehabilitation programmes should include weight loss interventions as a specific component and the incremental value of telehealth intervention as well as recently described pharmacological interventions need full consideration.
Coffee cell walls—composition, influence on cup quality and opportunities for coffee improvements
Authors: Li Zheng , Zhang Chuntang , Zhang Yuan , Zeng Wei , Cesarino Igor
Published: June 2021

The coffee beverage is the second most consumed drink worldwide after water. In coffee beans, cell wall storage polysaccharides (CWSPs) represent around 50 per cent of the seed dry mass, mainly consisting of galactomannans and arabinogalactans. These highly abundant structural components largely influence the organoleptic properties of the coffee beverage, mainly due to the complex changes they undergo during the roasting process. From a nutritional point of view, coffee CWSPs are soluble dietary fibers shown to provide numerous health benefits in reducing the risk of human diseases. Due to their influence on coffee quality and their health-promoting benefits, CWSPs have been attracting significant research attention. The importance of cell walls to the coffee industry is not restricted to beans used for beverage production, as several coffee by-products also present high concentrations of cell wall components. These by-products include cherry husks, cherry pulps, parchment skin, silver skin, and spent coffee grounds, which are currently used or have the potential to be utilized either as food ingredients or additives, or for the generation of downstream products such as enzymes, pharmaceuticals, and bioethanol. In addition to their functions during plant development, cell walls also play a role in the plant’s resistance to stresses. Here, we review several aspects of coffee cell walls, including chemical composition, biosynthesis, their function in coffee’s responses to stresses, and their influence on coffee quality. We also propose some potential cell wall–related biotechnological strategies envisaged for coffee improvements.
Personal Network Bridging Potential Across Geographic Context
Authors: Roth Adam R , Peng Siyun , Perry Brea L
Published: June 2021

Objectives

Personal networks play a fundamental role in the daily lives of older adults. Although many studies examine how life course factors and personal preferences shape network formation, fewer consider how the places in which older adults live present opportunities and obstacles to cultivate social relationships. In the present study, we explore how geographic context is associated with the ability to bridge social ties within one’s personal network.

Methods

We use data from the Person-to-Person Health Interview Survey (N = 709), a representative sample of Indiana residents. Personal network data were collected using 4 name-generating prompts. Logistic regression models and linear regression models were used to assess 2 measures of network bridging.

Results

A minority of respondents reported the ability to bridge ties within their networks. Respondents residing in rural and mixed counties were less likely than urban respondents to have at least one member of their network who was completely disconnected from all other members.

Discussion

These findings suggest that the communities in which older adults live condition opportunities for accessing unique network resources. Additional research adopting a network perspective is needed to provide insight into geographic disparities occurring among the older population.
Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice
Authors: Yoshioka Hiroki , Li Aimin , Suzuki Akiko , Ramakrishnan Sai Shankar , Zhao Zhongming , Iwata Junichi
Published: June 2021

The etiology of cleft lip with/without cleft palate (CL/P), one of the most frequent craniofacial birth defects worldwide, is complicated by contributions of both genetic and environmental factors. Understanding the etiology of these conditions is essential for developing preventive strategies. This study thus aims to identify regulatory networks of microRNAs (miRNAs), transcriptional factors (TFs) and non-TF genes associated with cleft lip (CL) that are conserved in humans and mice. Notably, we found that miR-27b, miR-133b, miR-205, miR-376b and miR-376c were involved in the regulation of CL-associated gene expression in both humans and mice. Among the candidate miRNAs, the overexpression of miR-27b, miR-133b and miR-205, but not miR-376b and miR-376c, significantly inhibited cell proliferation through suppression of CL-associated genes (miR-27b suppressed PAX9 and RARA; miR-133b suppressed FGFR1, PAX7, and SUMO1; and miR-205 suppressed PAX9 and RARA) in cultured human and mouse lip mesenchymal cells. Taken together, our results suggest that elevated expression of miR-27b, miR-133b and miR-205 may play a crucial role in CL through the suppression of genes associated with CL.
Impact of an educational intervention on WHO surgical safety checklist and pre-operative antibiotic use at a referral hospital in southwestern Uganda
Authors: Ngonzi Joseph , Bebell Lisa M , Boatin Adline A , Owaraganise Aspihas , Tiibajuka Leevan , Fajardo Yarine , Lugobe Henry Mark , Wylie Blair J , Jacquemyn Yves , Obua Celestino , Haberer Jessica E , Geertruyden Jean-pierre van
Published: June 2021

Introduction

The World Health Organization (WHO) recommends adherence to its surgical safety checklist (SSC) to optimize patient safety and reduce cesarean surgical site infection (SSI). Educational interventions combined with audit and feedback mechanisms on the checklist use by clinicians have the potential to improve adherence and clinical outcomes. Despite the increase in cesarean delivery rates, there is a paucity of data on how such interventions can improve adherence in resource-limited settings.

Objective

We performed a quality improvement project to measure the impact of an educational intervention with daily audit and feedback procedures on rates of WHO SSC adherence, including pre-operative antibiotic administration and SSI at Mbarara Regional Referral Hospital maternity ward in Uganda.

Methods

The study involved chart abstraction of WHO SSC and pre-operative antibiotic use during cesarean deliveries and signs of subsequent SSI in three phases. First, we conducted a retrospective review of all charts from May to June 2018 (pre-intervention phase). Second, we instituted an educational intervention on the WHO SSC and pre-operative antibiotics use, followed by a daily audit of charts and feedback to clinicians from July to August 2018 (the intervention phase). Third, we reviewed charts from September to October 2018 (the post-intervention phase). The WHO SSC adherence, pre-operative antibiotic administration and SSI rates were measured as the proportion of the total cesarean deliveries per study phase and then compared across the three phases.

Results

We reviewed 678 patients’ charts (200 in the pre-intervention phase, 230 in the intervention phase and 248 in the post-intervention phase). The mean patient age was 25 years. The use of the WHO SSC was 7% in the pre-intervention phase compared to 92% in the intervention phase (P < 0.001), and 77% in the post-intervention phase (P < 0.001). Pre-intervention antibiotic receipt was 18% compared to 90% in the intervention phase (P < 0.001) and 84% in the post-intervention phase (P < 0.001). The documented SSI rate in the pre-intervention phase was 15% compared to 7% in the intervention phase (P = 0.02) and 11% in the post-intervention phase (P = 0.20).

Conclusions

An educational intervention, daily audit and feedback to clinicians increased the use of the WHO SSC and prophylactic antibiotics for cesarean delivery—although the rates waned with time. Research to understand factors influencing the checklist use and antibiotic prophylaxis including prescriber knowledge, motivation and clinical process is required. Implementation interventions to sustain usage and impact on clinical outcomes need to be explored.
Trading off accuracy and explainability in AI decision-making: findings from 2 citizens’ juries
Authors: van der Veer Sabine N , Riste Lisa , Cheraghi-Sohi Sudeh , Phipps Denham L , Tully Mary P , Bozentko Kyle , Atwood Sarah , Hubbard Alex , Wiper Carl , Oswald Malcolm , Peek Niels
Published: June 2021

Objective

To investigate how the general public trades off explainability versus accuracy of artificial intelligence (AI) systems and whether this differs between healthcare and non-healthcare scenarios.

Materials and Methods

Citizens’ juries are a form of deliberative democracy eliciting informed judgment from a representative sample of the general public around policy questions. We organized two 5-day citizens’ juries in the UK with 18 jurors each. Jurors considered 3 AI systems with different levels of accuracy and explainability in 2 healthcare and 2 non-healthcare scenarios. Per scenario, jurors voted for their preferred system; votes were analyzed descriptively. Qualitative data on considerations behind their preferences included transcribed audio-recordings of plenary sessions, observational field notes, outputs from small group work and free-text comments accompanying jurors’ votes; qualitative data were analyzed thematically by scenario, per and across AI systems.

Results

In healthcare scenarios, jurors favored accuracy over explainability, whereas in non-healthcare contexts they either valued explainability equally to, or more than, accuracy. Jurors’ considerations in favor of accuracy regarded the impact of decisions on individuals and society, and the potential to increase efficiency of services. Reasons for emphasizing explainability included increased opportunities for individuals and society to learn and improve future prospects and enhanced ability for humans to identify and resolve system biases.

Conclusion

Citizens may value explainability of AI systems in healthcare less than in non-healthcare domains and less than often assumed by professionals, especially when weighed against system accuracy. The public should therefore be actively consulted when developing policy on AI explainability.
Improving domain adaptation in de-identification of electronic health records through self-training
Authors: Liao Shun , Kiros Jamie , Chen Jiyang , Zhang Zhaolei , Chen Ting
Published: June 2021

Objective

De-identification is a fundamental task in electronic health records to remove protected health information entities. Deep learning models have proven to be promising tools to automate de-identification processes. However, when the target domain (where the model is applied) is different from the source domain (where the model is trained), the model often suffers a significant performance drop, commonly referred to as domain adaptation issue. In de-identification, domain adaptation issues can make the model vulnerable for deployment. In this work, we aim to close the domain gap by leveraging unlabeled data from the target domain.

Materials and Methods

We introduce a self-training framework to address the domain adaptation issue by leveraging unlabeled data from the target domain. We validate the effectiveness on 4 standard de-identification datasets. In each experiment, we use a pair of datasets: labeled data from the source domain and unlabeled data from the target domain. We compare the proposed self-training framework with supervised learning that directly deploys the model trained on the source domain.

Results

In summary, our proposed framework improves the F1-score by 5.38 (on average) when compared with direct deployment. For example, using i2b2-2014 as the training dataset and i2b2-2006 as the test, the proposed framework increases the F1-score from 76.61 to 85.41 (+8.8). The method also increases the F1-score by 10.86 for mimic-radiology and mimic-discharge.

Conclusion

Our work demonstrates an effective self-training framework to boost the domain adaptation performance for the de-identification task for electronic health records.
Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration
Authors: Sholler Dennis J , Spindle Tory R , Cone Edward J , Goffi Elia , Kuntz David , Mitchell John M , Winecker Ruth E , Bigelow George E , Flegel Ronald R , Vandrey Ryan
Published: June 2021

The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC–MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test.
The protein N-terminal acetyltransferase A complex contributes to yeast mitophagy via promoting expression and phosphorylation of Atg32
Authors: Kubota Mitsutaka , Okamoto Koji
Published: June 2021

Mitophagy is an evolutionarily conserved catabolic process that selectively degrades damaged or superfluous mitochondria via autophagy. Although mitophagy is considered to be critical to maintain cellular homeostasis, detailed mechanisms of mitophagy remain largely unknown. In the budding yeast Saccharomyces cerevisiae, the protein N-terminal acetyltransferase A (NatA) complex is important for transcriptional induction of the pro-mitophagic factor Atg32 and efficient degradation of mitochondria under prolonged respiratory conditions. Overexpression of Atg32 only partially recovers mitophagy in cells lacking NatA, raising the possibility that NatA may contribute to mitophagy via additional mechanisms. Here, we demonstrate that Atg32 phosphorylation, which is required for facilitating mitophagy, is altered in respiring NatA-deficient cells. Hyperphosphorylation of Atg32 partially rescues mitophagy in cells lacking NatA. Notably, mitophagy is mostly restored in NatA-null cells overexpressing hyperphosphorylated Atg32. Loss of NatA does not impair the interaction of phosphorylated Atg32 with Atg11, a scaffold protein critical for selective autophagy, suggesting that NatA-dependent Atg32 phosphorylation promotes mitophagy independently of Atg32–Atg11 interactions. We propose that NatA-mediated protein N-terminal acetylation acts in Atg32 expression and phosphorylation to drive mitophagy.
Synergistic Effects of Quercetin-Modified Silicone Gel Sheet in Scar Treatment
Authors: Jin Jian , Tang Tao , Zhou Hao , Hong Xu-Dong , Fan Hao , Zhang Xu-Dong , Chen Zheng-Li , Ma Bing , Zhu Shi-Hui , Wang Guang-Yi , Xia Zhao-Fan
Published: June 2021

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New Zealand albino rabbits (n = 10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change three times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.
Evaluating the Quality of Ecoinformatics Data Derived From Commercial Agriculture: A Repeatability Analysis of Pest Density Estimates
Authors: Rosenheim Jay A
Published: June 2021

Each year, consultants and field scouts working in commercial agriculture undertake a massive, decentralized data collection effort as they monitor insect populations to make real-time pest management decisions. These data, if integrated into a database, offer rich opportunities for applying big data or ecoinformatics methods in agricultural entomology research. However, questions have been raised about whether or not the underlying quality of these data is sufficiently high to be a foundation for robust research. Here I suggest that repeatability analysis can be used to quantify the quality of data collected from commercial field scouting, without requiring any additional data gathering by researchers. In this context, repeatability quantifies the proportion of total variance across all insect density estimates that is explained by differences across populations and is thus a measure of the underlying reliability of observations. Repeatability was moderately high for cotton fields scouted commercially for total Lygus hesperus Knight densities (R = 0.631) and further improved by accounting for observer effects (R = 0.697). Repeatabilities appeared to be somewhat lower than those computed for a comparable, but much smaller, researcher-generated data set. In general, the much larger sizes of ecoinformatics data sets are likely to more than compensate for modest reductions in measurement precision. Tools for evaluating data quality are important for building confidence in the growing applications of ecoinformatics methods.
A rapid aneurysmal formation after late open conversion of endovascular abdominal aortic repair with complete endograft explant
Authors: Tamagawa Yuki , Kawamura Masashi , Ryugo Masahiro , Monta Osamu , Tsutsumi Yasushi
Published: June 2021

Late open conversion (LOC) after endovascular aneurysm repair (EVAR) is associated with high morbidity and mortality. Standard surgical technique of LOC has not been established. This report presents a rapid aneurysmal formation in the unreplaced infrarenal aorta after LOC with complete endograft explantation without suprarenal fixations. A 76-year-old man presented with a left common iliac artery aneurysm (CIAA), for which he underwent EVAR to embolize the left internal iliac artery. Although his aneurysmal sac size initially showed a reduction, computed tomography at the 3-year interval post-EVAR demonstrated an increased sac size. Thus, he underwent open aortic repair of the CIAA. Though the postoperative course was uneventful, the size of the unreplaced infrarenal aorta showed a significant increase one year after open conversion. Reoperation was performed, but vascular prosthesis infection occurred as a complication and the patient died on the 196th postoperative day.
A precise photometric ratio via laser excitation of the sodium layer – I. One-photon excitation using 342.78 nm light
Authors: Albert Justin E , Budker Dmitry , Chance Kelly , Gordon Iouli E , Pedreros Bustos Felipe , Pospelov Maxim , Rochester Simon M , Sadeghpour H R
Published: June 2021

The largest uncertainty on measurements of dark energy using type Ia supernovae (SNeIa) is presently due to systematics from photometry; specifically to the relative uncertainty on photometry as a function of wavelength in the optical spectrum. We show that a precise constraint on relative photometry between the visible and near-infrared can be achieved at upcoming survey telescopes, such as at the Vera C. Rubin Observatory, via a laser source tuned to the 342.78 nm vacuum excitation wavelength of neutral sodium atoms. Using a high-power laser, this excitation will produce an artificial star, which we term a ‘laser photometric ratio star’ (LPRS) of de-excitation light in the mesosphere at wavelengths in vacuum of 589.16, 589.76, 818.55, and 819.70 nm, with the sum of the numbers of 589.16 and 589.76 nm photons produced by this process equal to the sum of the numbers of 818.55 and 819.70 nm photons, establishing a precise calibration ratio between, for example, the r and $z$ filters of the LSST camera at the Rubin Observatory. This technique can thus provide a novel mechanism for establishing a spectrophotometric calibration ratio of unprecedented precision for upcoming telescopic observations across astronomy and atmospheric physics; thus greatly improving the performance of upcoming measurements of dark energy parameters using type SNeIa. The second paper of this pair describes an alternative technique to achieve a similar, but brighter, LPRS than the technique described in this paper, by using two lasers near resonances at 589.16 and 819.71 nm, rather than the single 342.78 nm on-resonance laser technique described in this paper.
Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity
Authors: Gayle Sophia , Aiello Robert , Leelatian Nalin , Beckta Jason M , Bechtold Jane , Bourassa Patricia , Csengery Johanna , Maguire Robert J , Marshall Dan , Sundaram Ranjini K , Van Doorn Jinny , Jones Kelli , Moore Hunter , Lopresti-Morrow Lori , Paradis Timothy , Tylaska Laurie , Zhang Qing , Visca Hannah , Reshetnyak Yana K , Andreev Oleg A , Engelman Donald M , Glazer Peter M , Bindra Ranjit S , Paralkar Vishwas M
Published: June 2021

Topoisomerase inhibitors are potent DNA damaging agents which are widely used in oncology, and they demonstrate robust synergistic tumor cell killing in combination with DNA repair inhibitors, including poly(ADP)-ribose polymerase (PARP) inhibitors. However, their use has been severely limited by the inability to achieve a favorable therapeutic index due to severe systemic toxicities. Antibody-drug conjugates address this issue via antigen-dependent targeting and delivery of their payloads, but this approach requires specific antigens and yet still suffers from off-target toxicities. There is a high unmet need for a more universal tumor targeting technology to broaden the application of cytotoxic payloads. Acidification of the extracellular milieu arises from metabolic adaptions associated with the Warburg effect in cancer. Here we report the development of a pH-sensitive peptide-drug conjugate to deliver the topoisomerase inhibitor, exatecan, selectively to tumors in an antigen-independent manner. Using this approach, we demonstrate potent in vivo cytotoxicity, complete suppression of tumor growth across multiple human tumor models, and synergistic interactions with a PARP inhibitor. These data highlight the identification of a peptide-topoisomerase inhibitor conjugate for cancer therapy that provides a high therapeutic index, and is applicable to all types of human solid tumors in an antigen-independent manner.
The use of external control data for predictions and futility interim analyses in clinical trials
Authors: Ventz Steffen , Comment Leah , Louv Bill , Rahman Rifaquat , Wen Patrick Y , Alexander Brian M , Trippa Lorenzo
Published: June 2021

Background

External control (EC) data from completed clinical trials and electronic health records can be valuable for the design and analysis of future clinical trials. We discuss the use of EC data for early stopping decisions in randomized clinical trials (RCTs).

Methods

We specify interim analyses (IAs) approaches for RCTs, which allow investigators to integrate external data into early futility stopping decisions. IAs utilize predictions based on early data from the RCT, possibly combined with external data. These predictions at IAs express the probability that the trial will generate significant evidence of positive treatment effects. The trial is discontinued if this predictive probability becomes smaller than a prespecified threshold. We quantify efficiency gains and risks associated with the integration of external data into interim decisions. We then analyze a collection of glioblastoma (GBM) data sets, to investigate if the balance of efficiency gains and risks justify the integration of external data into the IAs of future GBM RCTs.

Results

Our analyses illustrate the importance of accounting for potential differences between the distributions of prognostic variables in the RCT and in the external data to effectively leverage external data for interim decisions. Using GBM data sets, we estimate that the integration of external data increases the probability of early stopping of ineffective experimental treatments by up to 25% compared to IAs that do not leverage external data. Additionally, we observe a reduction of the probability of early discontinuation for effective experimental treatments, which improves the RCT power.

Conclusion

Leveraging external data for IAs in RCTs can support early stopping decisions and reduce the number of enrolled patients when the experimental treatment is ineffective.
Clinical Predictors Impacting Cryptococcal Dissemination and Poor Outcome in Patients With Cirrhosis
Authors: Cheng Jia-Hui , Yip Ching-Wan , Jiang Ying-Kui , Zhou Ling-Hong , Que Chun-Xing , Luo Yu , Wang Xuan , Zhao Hua-Zhen , Zhu Li-Ping
Published: June 2021

Background

Cirrhosis is an end-stage liver disease and is reported as an independent risk factor for cryptococcosis. Information about cryptococcosis in patients with cirrhosis remains sparse.

Methods

Human immunodeficiency virus–uninfected patients with cryptococcosis and cirrhosis admitted to Huashan Hospital from July 2005 to June 2020 were reviewed. Efficacy and safety of antifungal treatments, clinical outcome, and prognostic factors of mortality were evaluated.

Results

A total of 49 cryptococcosis patients with cirrhosis were included. Sites of infection involved central nervous system (n = 38), lung (n = 21), bloodstream (n = 11), skin (n = 1), and bone (n = 1). Nine patients (18.4%) had pulmonary cryptococcosis alone. Viral hepatitis B infection (57.1%) was the most common cause of cirrhosis. Patients with decompensated cirrhosis (Child-Pugh class B and C) were more likely to have extrapulmonary cryptococcosis than those with compensated cirrhosis (90.7% vs 64.7%; P = .049). In patients with cryptococcal meningitis (CM), 7 were treated with amphotericin B with/without flucytosine, 5 with amphotericin B plus fluconazole with/without flucytosine, and 12 with fluconazole with/without flucytosine. Fluconazole (>400 mg/day) was well tolerated and only 1 patient had a mild adverse drug reaction. At 1-year follow-up, all patients treated with fluconazole with or without flucytosine survived, whereas the mortality rate was 14.3%–20.0% in the remaining groups. In addition, Child-Pugh class C cirrhosis (hazard ratio [HR], 7.555 [95% confidence interval {CI}, 1.393–40.971]) and time to diagnosis >120 days (HR, 18.619 [95% CI, 2.117–163.745]) were independent factors for 1-year mortality in patients with CM.

Conclusions

Severity of cirrhosis was associated with developing extrapulmonary cryptococcosis and mortality in CM. Early diagnosis and intervention of cryptococcosis are key for outcome.
Effects of Neuromuscular Electrical Stimulation on Quadriceps Muscle Strength and Mass in Healthy Young and Older Adults: A Scoping Review
Authors: Rahmati Masoud , Gondin Julien , Malakoutinia Fatemeh
Published: June 2021

Objective

Although neuromuscular electrical stimulation (NMES) has been used as a safe and relevant complement to voluntary resistance training, its effectiveness in increasing quadriceps femoris muscle strength and mass in healthy young and older adults has not been determined. The aim of this scoping review was to assess the effects of NMES on quadriceps muscle strength and mass in healthy young and older adults.

Methods

CENTRAL, Pedro, MEDLINE, and PubMed were searched from inception to September 2019. Randomized controlled trials (RCTs) that compared NMES with control group or voluntary resistance training for healthy young and older adults were included. Study characteristics, primary and secondary outcome parameters, and details of the NMES intervention were extracted by 2 reviewers. Only studies for which full text was available in English were included.

Results

Thirty-two RCTs including 796 healthy participants were identified as being eligible for young adults, and 5 RCTs including 123 healthy participants were identified as being eligible for older adults. The available evidence strongly suggests that NMES improves quadriceps muscle strength compared with a control group in young adults, but its efficacy seems lower than that of voluntary resistance training. The available limited evidence regarding the effects of NMES on quadriceps muscle mass compared with control in young adults is inconclusive, with 3 RCTs showing positive effects and 3 RCTs not showing positive effects. The very limited available evidence from 5 RCTs in older adults suggests that NMES might be beneficial for increasing quadriceps muscle strength and mass.

Conclusion

Overall, the evidence indicates that NMES is an efficacious method for increasing quadriceps muscle strength in young adults, whereas its impact on muscle mass requires further investigations. In addition, the effectiveness of NMES needs to be confirmed in older adults on the basis of more high-quality RCTs with larger sample sizes.

Impact

This scoping review of 37 RCTs including 919 people is the first study, to the authors’ knowledge, to show that the use of NMES increases quadriceps muscle strength in young adults and might improve quadriceps muscle strength compared with control interventions in older adults. In both young and older adults, the effects of NMES on quadriceps muscle mass are still unclear.
The Role of Virtual Physical Therapy in a Post–Pandemic World: Pearls, Pitfalls, Challenges, and Adaptations
Authors: Grundstein M Jake , Fisher Charles , Titmuss Matthew , Cioppa-Mosca JeMe
Published: June 2021

Objective

To keep patients healthy and safe during the pandemic, payers and the federal government temporarily relaxed restrictions, expanded the eligible provider list for providing telehealth services, and developed a reimbursement structure. Physical therapists were uniquely challenged during the pandemic, requiring a reassessment of techniques and strategies in order to best support patients. The purpose of this case report is to describe a musculoskeletal institution’s experience with implementing telehealth physical therapy.

Methods

Previous telehealth experience enabled the infrastructure of a wide-scale adoption across institutions to respond to the COVID-19 pandemic. However, to fill in training gaps for Hospital for Special Surgery (HSS) outpatient physical therapists, HSS Rehabilitation developed a robust education and implementation program. This training was influenced by clinician and patient surveys as well as the development of a published HSS Rehabilitation telehealth guide. Prior to performing telehealth physical therapist visits, clinicians were required to complete all training material to ensure comfortability and confidence.

Results

The adoption of telehealth among clinicians was born out of necessaity; however, the speed with which HSS Rehabilitation pivoted was critical to avoid lapses in care. In a 4-week period after the New York City shelter in-place orders, 173 therapists were trained and performing virtual visits. HSS Rehabilitation determined telehealth physical therapy had quicker access to care, similar patient satisifaction, and increased geographical outreach compared with in-person care.

Conclusion

The transition to telehealth physical therapy included a multi-step process that provided clinician training, established protocols and guidelines, and obtained a better understanding of the patient experience. Telehealth physical therapy has shown early benefits such as improving patient access to care and better continuity of care for traveling patients. Even after the current public health emergency, there is a place for high-value telehealth physical therapy in caring for patients with musculoskeletal conditions.
Are schools drivers of COVID-19 infections—an analysis of outbreaks in Colorado, USA in 2020
Authors: Lakha F , King A , Swinkels K , Lee A C K
Published: June 2021

Background

The impact of school closures/reopening on transmission of SARS-CoV-2 in the wider community remains contested.

Methods

Outbreak data from Colorado, USA (2020), alongside data on implemented public health measures were analyzed.

Results

There were three waves (n = 3169 outbreaks; 61 650 individuals). The first was led by healthcare settings, the second leisure/entertainment and the third workplaces followed by other settings where the trajectory was equally distributed amongst essential workplaces, non-essential workplaces, schools and non-essential healthcare.

Non-acute healthcare, essential and non-essential workplace experienced more outbreaks compared to education, entertainment, large-group-living and social gatherings.

Schools experienced 11% of identified outbreaks, yet involved just 4% of total cases. Conversely, adult-education outbreaks (2%) had disproportionately more cases (9%).

Conclusion

Our findings suggest schools were not the key driver of the latest wave in infections. School re-opening coinciding with returning to work may have accounted for the parallel rise in outbreaks in those settings suggesting contact-points outside school being more likely to seed in-school outbreaks than contact points within school as the wave of outbreaks in all other settings occurred either prior to or simultaneously with the schools wave.

School re-opening is a priority but requires mitigation measures to do so safely including staggering opening of different settings whilst maintaining low levels of community transmission.
The occurrence, severity degree, and associated risk factors of dental fluorosis among the 12-year-old schoolchildren in Jilin, China
Authors: Liu Jin-Zhong , Bao Rui , Chen Chong , Wang Rui
Published: June 2021

This study aims to describe the occurrence, severity degree, and correlated risk factors of dental fluorosis among the 12-year-old schoolchildren of Jilin, China.

We conducted a cross-sectional, observational, and descriptive study among 960 12-year-old schoolchildren in Jilin. The Dean index was utilized to evaluate the severity degree of dental fluorosis. A questionnaire was sent to the guardians of children. Community fluorosis index was measured to estimate the importance of enamel fluorosis for the whole population's public health. The logistic regression analysis was also utilized to identify the correlation between fluorotic teeth and the independent variables.

Nine hundred sixty children were assessed. Among them, 480 (50%) were female. 30.5% of subjects had dental fluorosis, 7.19% had very mild dental fluorosis, 10.73% experienced mild dental fluorosis, 9.58% suffered moderate dental fluorosis, and 3.02% encountered severe dental fluorosis. The overall community fluorosis index was 0.73. The results of logistic regression showed that schoolchildren who brushed teeth more frequently (OR: 2.012, 95% CI 1.767–2.342), deficiency of parental supervision (OR: 4.219, 95% CI 3.887–4.573), and lived in rural areas (OR: 2.776, 95% CI 2.163–3.489) were more correlated with enamel fluorosis. Moreover, schoolchildren whose mothers or fathers were of high education level (OR: 0.336, 95% CI 0.217–0.413 and 0.346, 95% CI 0.113–0.512) and only child (OR: 0.378, 95% CI 0.213–0.415) were protective factors for dental fluorosis.

In the Jilin province of China, the risk indicators for dental fluorosis include rural areas, more frequency of brushing, low educational background of parents, and deficiency of parental supervision.