bluuebunny/crossref_metadata_2025 huggingface dataset:
Human blood adenosine biomarkers and non‐rapid eye movement sleep stage 3 (NREM3) cortical functional connectivity associations during a 30‐day head‐down‐tilt bed rest analogue: Potential effectiveness of a reactive sledge jump as a countermeasure
Authors: Nday Christiane M. , Frantzidis Christos A. , Plomariti Christina , Gilou Sotiria C. , Ntakakis Giorgos , Jackson Graham , Chatziioannidis Lykourgos , Bamidis Panagiotis D. , Kourtidou‐Papadeli Chrysoula
Published: April 2021

We investigated the alterations of sleep regulation and promotion biomarkers as adenosine through its enzymes total adenosine deaminase (tADA)/adenosine deaminase (ADA2) in a microgravity analogue environment of head‐down‐tilt bed rest and their association with brain connectivity networks during non‐rapid eye movement sleep stage 3 (NREM3), as well as the effectiveness of the reactive sledge (RSL) jump countermeasure to promote sleep. A total of 23 healthy male volunteers were maintained in 6° head‐down‐tilt position for 30 days and assigned either to a control or to a RSL group. Blood collection and polysomnographic recordings were performed on data acquisition day 1, 14, 30 and −14, 21, respectively. Immunochemical techniques and network‐based statistics were employed for adenosine enzymes and cortical connectivity estimation. Our findings indicate that human blood adenosine biomarkers as well as NREM3 cortical functional connectivity are impaired in simulated microgravity. RSL physical activity intervened in sleep quality via tADA/ADA2 fluctuations lack, minor cortical connectivity increases, and limited degree of node and resting‐state networks. Statistically significant decreases in adenosine biomarkers and NREM3 functional connectivity involving regions (left superior temporal gyrus, right postcentral gyrus, precuneus, left middle frontal gyrus, left postcentral gyrus, left angular gyrus and precuneus) of the auditory, sensorimotor default‐mode and executive networks highlight the sleep disturbances due to simulated microgravity and the sleep‐promoting role of RSL countermeasure. The head‐down‐tilt environment led to sleep deterioration projected through NREM3 cortical brain connectivity or/and adenosine biomarkers shift. This decline was more pronounced in the absence of the RSL countermeasure, thereby highlighting its likely exploitation during space missions.
A second riboflavin import system is present in flavinogenic Streptomyces davaonensis and supports roseoflavin biosynthesis
Authors: Schneider Carmen , Mack Matthias
Published: April 2021

The antibiotic roseoflavin is produced by Streptomyces davaonensis in the stationary phase of growth. To support biosynthesis of the secondary metabolite roseoflavin, S. davaonensis underwent several genetic adaptations with regard to metabolism of the roseoflavin precursor and primary metabolite riboflavin. In addition to 17 riboflavin biosynthesis genes at different chromosomal locations, S. davaonensis contains the riboflavin transporter gene ribM being part of the riboflavin biosynthetic operon ribE1MAB5H. Deletion of this operon generated riboflavin auxotrophic S. davaonensis strains. The finding that S. davaonensis ΔribE1MAB5H was able to grow in a culture medium containing low levels of riboflavin indicated that in addition to RibM, a second riboflavin transporter is present in this bacterium. The S. davaonensis genes ribXY (former rosXY) represented candidate genes for such a second riboflavin transport system and the results of our experiments now show that RibXY from S. davaonensis is a highly efficient riboflavin importer but not a roseoflavin importer.
How to kill Pseudomonas—emerging therapies for a challenging pathogen
Authors: Yaeger Luke N. , Coles Victoria E. , Chan Derek C. K. , Burrows Lori L.
Published: April 2021

As the number of effective antibiotics dwindled, antibiotic resistance (AR) became a pressing concern. Some Pseudomonas aeruginosa isolates are resistant to all available antibiotics. In this review, we identify the mechanisms that P. aeruginosa uses to evade antibiotics, including intrinsic, acquired, and adaptive resistance. Our review summarizes many different approaches to overcome resistance. Antimicrobial peptides have potential as therapeutics with low levels of resistance evolution. Rationally designed bacteriophage therapy can circumvent and direct evolution of AR and virulence. Vaccines and monoclonal antibodies are highlighted as immune‐based treatments targeting specific P. aeruginosa antigens. This review also identifies promising drug combinations, antivirulence therapies, and considerations for new antipseudomonal discovery. Finally, we provide an update on the clinical pipeline for antipseudomonal therapies and recommend future avenues for research.
Deformed Complex Vertebral Osteotomy Technique for Management of Severe Congenital Spinal Angular Kyphotic Deformity
Authors: Zhang Hong‐qi , Xiao Li‐ge , Guo Chao‐feng , Wang Yu‐xiang , Wu Jian‐huang , Liu Jin‐yang
Published: April 2021

Objectives

To (i) introduce the deformed complex vertebral osteotomy (DCVO) technique for the treatment of severe congenital angular spinal kyphosis; (ii) evaluate the sagittal correction efficacy of the DCVO technique; and (iii) discuss the advantages and limitations of the DCVO technique.

Methods

Multiple malformed vertebrae were considered a malformed complex, and large‐range and angle wedge osteotomy was performed within the complex using the DCVO technique. Patients with local kyphosis greater than 80° who were treated with DCVO and did not have tumors, infections, or a history of surgery were included. A retrospective case study was performed in these patients with severe angular kyphosis who underwent the DCVO technique from 2008 to 2016. Demographic data, the operating time, and the volume of intraoperative blood loss were collected. Spinopelvic parameters (pelvic incidence [PI], pelvic tilt [PT], and sacral slope [SS]), local and global sagittal parameters (deformity angle, thoracic kyphosis [TK], and lumbar lordosis [LL]), visual analog scale (VAS) score, and Oswestry disability index (ODI) score were recorded pre‐ and postoperatively. Paired t‐tests (α = 0.05) were used for all data (to compare the mean preoperative value with the mean postoperative and most recent follow‐up values). P < 0.05 was considered statistically significant.

Results

Twenty‐nine patients with a mean age of 34 years (range, 15–55) were included in the final analysis. Seventeen patients were male, and 12 were female. The mean follow‐up was 44 months (range, 26–62). The mean operating time was 299 min (range, 260–320 min). The mean blood loss was 2110 mL (range, 1500–2900 mL). Three patients had T7–T8 deformities (3/29, 10.3%), six had T8–T9 deformities (6/29, 20.7%), six had T9–T10 deformities (6/29, 20.7%), 10 had T10–T11 deformities (10/29, 34.5%), three had T11–T12 deformities (3/29, 10.3%), and one had T9–T11 deformities (1/29, 3.4%). The mean local deformity angle significantly improved from 94.9° ± 10.8° to 24.0° ± 2.3° through the DCVO technique, with no significant loss at the follow‐up. Moreover, the global sagittal parameters and spinopelvic parameters exhibited ideal magnitudes of improvement; TK decreased from 86.1° ± 12.1° to 28.7° ± 2.5°, LL improved from 94.5° ± 4.1° to 46.1° ± 3.0°, and PI minus LL improved from −60.9° ± 6.5° to −13.7° ± 2.6°. Both the VAS and ODI scores significantly improved at the last follow‐up. CSF fistula and neural injury did not occur during the perioperative period. At the last follow‐up, fixation failure was not observed.

Conclusion

The DCVO technique provides an alternative and effective method for the treatment of congenital severe angular spinal kyphotic deformities and may decrease the occurrence of perioperative complications.
Can Public Healthcare Afford Marketization? Market Principles, Mechanisms, and Effects in Five Health Systems
Authors: Krachler Nick , Greer Ian , Umney Charles
Published: April 2021

Policymakers now have four decades’ experience using marketization to address cost and quality problems in public‐sector health services. While much is known about the challenges, it is difficult to draw lessons because there remains no agreed‐upon definition of marketization. This article contributes a definition that focuses on the transaction, particularly the effects of funding arrangements on the intensity of competition among providers. Based on prior literature and 106 interviews with practitioners and researchers in five countries, the authors contribute a systematization of 12 concrete market mechanisms enacting three market principles. Furthermore, the authors analyze respondents' perceptions of healthcare marketization's effects on costs and quality. While marketization is a multi‐faceted, sometimes ambiguous phenomenon requiring further research before definite conclusions can be reached, most statements from our respondents about cost and quality effects were negative.

Evidence for Practice

Examining health systems in five countries, we identify 12 different market mechanisms, i.e. concrete procedural changes that stimulate competition among service providers.

While these mechanisms sometimes enable improvements in cost and quality, our respondents identified many more examples of markets driving up costs and compromising quality.

A substantial number of respondents also stated that effects were unclear.

More research is needed to assess the effects of market mechanisms in healthcare, for which the article's conceptualization and findings can serve as a basis.
Regulatory Capture's Self‐Serving Application
Authors: Yackee Susan Webb
Published: April 2021

Observers regularly assert that government regulations are captured—meaning the content of the regulation is diverted away from the public interest and toward the interests of regulated industry. I argue that the label of regulatory capture is often applied differently by policy losers than by policy winners. I hypothesize that when an entity is unsuccessful in achieving its goals during regulatory policy making, that entity is more likely to deem the process captured. With data from 41 FDA regulations and guidance documents, I find that—even when provided a common definition—those interest groups engaged in the same rulemaking vary as to whether or not they would categorize the process as captured. Moreover, this variation is negatively associated with whether the entity achieved its policy goals during the rulemaking. These findings imply that scholars ought to reassess capture's occurrence, as well as the political and policy implications attached to its invocation.

Evidence for Practice

The study provides evidence drawn from policy making at the U.S. Food and Drug Administration (FDA) that the label of regulatory capture is applied inconsistently by interest group participants in the agency rulemaking process.

The research demonstrates a partiality toward categorizing a rulemaking as captured when an interest group participant does not get its way. This finding implies that public agency officials—when they do not heed the advice of public commenters—may need to worry about capture accusations.

The study's results raise the provocative possibility that capture's designation may be employed strategically—or even opportunistically—by an interest group to delegitimize an agency regulation when the group does not agree with it.

Given that policy makers and practitioners from both sides of the political aisle routinely highlight the need to address regulatory capture, the evidence uncovered in this article strongly suggests that more attention from the field of public administration is needed to better understand how regulatory capture is actually used in practice.
Testicular development and spermatogenesis in fish: insights into molecular aspects and regulation of gene expression by different exogenous factors
Authors: Bhat Irfan A. , Dar Jaffer Y. , Ahmad Irshad , Mir Ishfaq N. , Bhat Hussna , Bhat Raja A.H. , Ganie Parvaiz A. , Sharma Rupam
Published: April 2021

In fish, as in higher animals, the normal ontogenesis of the gonads is the basis for successful reproduction. Gonadal differentiation and development depend on the genetic cascade that programmes the events. Eventually, gonads become the sites for the maturation of gametes, which are originally derived from the primordial germ cells (PGCs) and form the cellular basis of reproduction. In fish hormones of the hypothalamic–pituitary–gonadal (HPG) axis regulate reproduction and fertility by promoting or inhibiting the production of gonadal sex steroids and their function. Gonadal sex steroids not only guide proper gonadal development and function but also play a key role in the activation and regulation of the HPG axis through two feedback control systems. In this review, we discuss the general outline and expression pattern of the major genes involved in testicular development and gonadal steroidogenesis in fish. The review attempts, for the first time, to collect and discuss recent information regarding the regulation of sex differentiation and steroidogenic genes during the stages of testicular development and in response to different external factors. Furthermore, clear insights into the important genes and their regulation involved in the HPG axis and spermatogenesis are presented briefly. This review can serve as a guide for fish breeders on the substances that have a positive impact on reproduction in males.
A survey of fish behaviour quantification indexes and methods in aquaculture
Authors: An Dong , Huang Jinze , Wei Yaoguang
Published: April 2021

In aquaculture, fish behaviour monitoring and analysis can provide the information required to guide daily feeding, schedule making and disease diagnosis. Technology such as machine vision, bio‐loggers and acoustic systems is essential to analyse fish behaviour. This paper focuses on tools and algorithms for fish behaviour quantification analysis. The goal is to present their basic concepts and principles, including the quantification analysis procedure and its potential application scenarios. This review shows that the most common behaviour quantification indexes can be categorised into three classes: swimming indexes, physical indexes and context indexes. Typically, swimming indexes are of the most interest to researchers. However, achieving comprehensiveness of the information and quantisation precision remain challenging in fish behaviour analysis. In brief, this paper aims to help researchers and practitioners better understand the current state‐of‐the‐art behavioural quantification analysis, which provides strong support for the implementation of intelligent breeding.
Two roads diverged: Emerging lessons from IVIG about hemolysis
Authors: Asif Maryam , Khor Bernard
Published: April 2021

See article on page 1053–1063, in this issue
Development of a composite film fabricated from carboxymethyl chitosan and magnetite nanoparticles for pH-responsive bioactive agent release
Authors: Reddy Obireddy Sreekanth , Lai Wing-Fu
Published: April 2021

Development of a biocompatible film enabling stimuli-responsive bioactive agent delivery has a high practical value for food and pharmaceutical applications. In this study, we generate a composite film, using the solution casting approach, from carboxymethyl chitosan (CMC) and magnetite nanoparticles (MNPs). The structures and properties of CMC, MNPs, and the generated film are characterized by using various characterization techniques, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, x-ray diffraction spectroscopy, and scanning electron microscopy. With the use of doxorubicin (DOX) as a model agent, the percentage of cumulative release of DOX from the agent-loaded film is found to be increased from 55% to 62% when the pH of the surrounding medium changes from 7.4 to 5.0. Our film warrants further development and optimization as a carrier to mediate pH-responsive bioactive agent release.
Is Rating of Perceived Exertion a Valuable Tool for Monitoring Exercise Intensity During Steady-State Conditions in Elite Endurance Athletes?
Authors: Losnegard Thomas , Skarli Sondre , Hansen Joar , Roterud Stian , Svendsen Ida S. , R. Rønnestad Bent , Paulsen Gøran
Published: April 2021

Purpose: Rating of perceived exertion (RPE) is a widely used tool to assess subjective perception of effort during exercise. The authors investigated between-subject variation and effect of exercise mode and sex on Borg RPE (6–20) in relation to heart rate (HR), oxygen uptake (VO2), and capillary blood lactate concentrations. Methods: A total of 160 elite endurance athletes performed a submaximal and maximal test protocol either during cycling (n = 84, 37 women) or running (n = 76, 32 women). The submaximal test consisted of 4 to 7 progressive 5-minute steps within ∼50% to 85% of maximal VO2. For each step, steady-state HR, VO2, and capillary blood lactate concentrations were assessed and RPE reported. An incremental protocol to exhaustion was used to determine maximal VO2 and peak HR to provide relative (%) HR and VO2 values at submaximal work rates. Results: A strong relationship was found between RPE and %HR, %VO2, and capillary blood lactate concentrations (r = .80–.82, all Ps < .05). The between-subject coefficient of variation (SD/mean) for %HR and %VO2 decreased linearly with increased RPE, from ∼10% to 15% at RPE 8 to ∼5% at RPE 17. Compared with cycling, running induced a systematically higher %HR and %VO2 (∼2% and 5%, respectively, P < .05) with these differences being greater at lower intensities (RPE < 13). At the same RPE, women showed a trivial, but significantly higher %HR and %VO2 than men (<1%, P < .05). Conclusions: Among elite endurance athletes, exercise mode influenced RPE at a given %HR and %VO2, with greater differences at lower exercise intensities. Athletes should manage different tools to evaluate training based on intensity and duration of workouts.
Influence of Neighborhood Characteristics and Weather on Movement Behaviors at Age 3 and 5 Years in a Longitudinal Birth Cohort
Authors: Ezeugwu Victor E. , Mandhane Piush J. , Hammam Nevin , Brook Jeffrey R. , Tamana Sukhpreet K. , Hunter Stephen , Chikuma Joyce , Lefebvre Diana L. , Azad Meghan B. , Moraes Theo J. , Subbarao Padmaja , Becker Allan B. , Turvey Stuart E. , Rosu Andrei , Sears Malcolm R. , Carson Valerie
Published: April 2021

Background: Movement behaviors (physical activity, sedentary time, and sleep) established in early childhood track into adulthood and interact to influence health outcomes. This study examined the associations between neighborhood characteristics and weather with movement behaviors in preschoolers. Methods: A subset of Canadian Healthy Infant Longitudinal Development birth cohort (n = 385, 50.6% boys) with valid movement behaviors data were enrolled at age 3 years and followed through to age 5 years. Objective measures of neighborhood characteristics were derived by ArcGIS software, and weather variables were derived from the Government of Canada weather website. Random forest and linear mixed models were used to examine predictors of movement behaviors. Cross-sectional analyses were stratified by age and season (winter and nonwinter). Results: Neighborhood safety, temperature, green space, and roads were important neighborhood characteristics for movement behaviors in 3- and 5-year-olds. An increase in temperature was associated with greater light physical activity longitudinally from age 3 to 5 years and also in the winter at age 5 years in stratified analysis. A higher percentage of expressways was associated with less nonwinter moderate to vigorous physical activity at age 3 years. Conclusions: Future initiatives to promote healthy movement behaviors in the early years should consider age differences, neighborhood characteristics, and season.
Unexpected Careers: My Environment Made Me Do Them
Authors: McKenzie Thomas L.
Published: April 2021

This essay describes how environmental conditions affected my unexpected evolution from farm life in a rural Canadian community to becoming a physical education specialist and multisport coach and eventually a U.S. kinesiology scholar with a public health focus. I first recount my life on the farm and initial education and then identify the importance of full- and part-time jobs relative to how they helped prepare me for a life in academia. Later, I summarize two main areas of academic work that extended beyond university campuses—the design and implementation of evidence-based physical activity programs and the development of systematic observation tools to assess physical activity and its associated contexts in diverse settings, including schools, parks, and playgrounds. I conclude with a section on people and locations to illustrate the importance of collaborations—essential components for doing field-based work. Without those connections, I would not have had such an extensive and diverse career.
Joint inversion of surface wave and gravity data reveals subbasin architecture of the Congo Basin
Authors: Raveloson A. , Nyblade A. , Durrheim R.
Published: April 2021

We investigated the architecture of the greater Congo Basin, one of the largest and least-well-studied sedimentary basins on any continent. Seismograms from a large number of M > 4.5 earthquakes within and surrounding the African plate were used to make event-to-station Rayleigh wave group velocity measurements between periods of 5 and 100 s. Group velocities for discrete periods across the basin, obtained by inverting the event-station measurements, were jointly modeled with gravity data to obtain a three-dimensional S-wave and density model of the basin. The model corroborates the existence of two previously suggested subbasins, one to the north and one to the south, each ~8 km deep and separated by an east-west structural high. Our results favor a salt tectonics origin for the structural high but cannot rule out uplifted basement rock. The northern subbasin is offset to the west from the southern subbasin, consistent with previous studies suggesting sinistral motion along basement faults during periods of transpressional tectonics in late Neoproterozoic-early Paleozoic times.
Supplemental Material: Climatically driven instability of marine methane hydrate along a canyon-incised continental margin
Authors: Davies Richard , al. et
Published: April 2021

Table S1 (website URLs for the climate models), Figure S2 (additional examples of lines of intersection), and Figure S3 (uninterpreted versions of Figures 2 and 3).
Geological and Geomorphological Characteristics of High-Priority Landing Sites for the Luna-Glob Mission
Authors: Krasilnikov S. S. , Basilevsky A. T. , Ivanov M. A. , Krasilnikov A. S.
Published: April 2021

The geomorphological and geological analysis of the surface of three primary and ten secondary landing ellipses (15 × 30 km) for the Russian Luna-Glob automated scientific station (Luna-25) is presented. The earlier selected landing ellipses are found in the sector of 65°–85° S and 0°–60° E of the lunar southern hemisphere. The geological characteristics of the ellipse include the analysis of the surface age and the identification of the material sources. The analyses of water equivalent hydrogen concentration in the sector of landing and rock content on the surface are also carried out. The constraints, such as the surface inclination and the characteristic of the spacecraft’s flight path are used for prioritization of the ellipses from an engineering-technical perspective. According to the results of the study, landing ellipses 1, 3, 4, 6 and 8 are determined as high-priority, while ellipses 5, 7, 9, 10, 11, as well as B1 and B2 are found the least favorable.
Implementing less invasive surfactant administration on a neonatal unit
Authors: Williamson Sarah Louise , McDermott Helen , Gowda Harsha
Published: April 2021

There is increasing evidence reflected in both UK 2019 NICE and European guidelines suggesting that less invasive surfactant administration (LISA) reduces the need for mechanical ventilation and reduces the combined outcome of death or bronchopulmonary dysplasia, and is now the optimal method for surfactant delivery in spontaneously breathing babies. Despite this, uptake in England has been slow compared with Europe. This quality improvement project outlines the process of implementing LISA in a neonatal intensive care unit over a 2-year period, the barriers and challenges which were encountered, and how they were overcome.
Caesarean delivery in T5 paraplegic following extended ICU stay in second trimester with absolute contraindication to neuraxial blocks
Authors: Granovskiy Felix , Greenwood Adam , Jackson Christopher
Published: April 2021

Pregnancy in patients with spinal cord injury presents unique challenges to their care teams. While spinal cord injury alters the function of several organ systems, one of the most important consequences is autonomic dysreflexia. Anaesthesia providers must be familiar with the pathophysiology and management of gravid patients with spinal cord injury to manage their deliveries successfully. A multidisciplinary team is essential; close collaboration between the obstetrical and anaesthesiology teams is crucial. The authors will present a case of a successful caesarean delivery in a woman with a T5 injury as well as a recent epidural abscess using general endotracheal anaesthesia.
Acute atraumatic peri-arrest tension gastrothorax presenting to the emergency department
Authors: Phelan James , Subramanian Rengarajan , Menon Adeep Krishnan Kutty
Published: April 2021

A 71-year-old woman was brought in by ambulance to the emergency department with sudden-onset difficulty in breathing whilst shopping at a large UK retail shopping centre. She had no respiratory history and portable chest X-ray revealed a huge gastrothorax, secondary pneumothorax and mediastinal shift. Clinical deterioration with haemodynamic instability required urgent decompression. Successful needle decompression followed by tube thoracostomy improved patient condition with no further complications. Surgical repair was performed but was delayed by COVID-19. This case provides a rare presentation of an acute life-threatening tension gastrothorax with difficult management considerations. A review of the management options is undertaken.
Case of second primary breast cancer in ectopic breast tissue and review of the literature
Authors: Addae Jamin Kweku , Genuit Thomas , Colletta Joseph , Schilling Kathy
Published: April 2021

Accessory breast tissue (ABT) is found in approximately 2%–6% of the female population and are subject to most of the physiological and pathological changes that occur in pectoral breast. Primary breast cancer occurring in ABT is a rare occurrence and a second primary breast cancer occurring in an accessory breast has never been reported. We report the case of a 60-year-old woman with a history of mastectomy for left breast cancer 5 years prior to presentation, who presented with an enlarging right axilla mass found to be a second primary breast cancer in an accessory tissue on biopsy. Many physicians are unfamiliar with the clinical presentation of accessory breast cancer due to the rarity of the condition and this ultimately results in delayed diagnosis and advanced disease at presentation. It is therefore prudent that physicians have a high index of suspicion when patients present with axillary masses.
Case of penetrating brain injury caused by a ventriculoperitoneal shunting procedure
Authors: Shimizu Yuzaburo , Suzuki Mario , Akiyama Osamu , Kondo Akihide
Published: April 2021

Brain injury with ventricle puncture is a well-known complication of ventriculoperitoneal (VP) shunting. However, parenchymal injuries caused by a shunt tunneller are rare. Herein, we present a case of penetrating brain injury caused by a shunt tunneller during VP shunting. An 83-year-old woman with brainstem glioma underwent VP shunting to control hydrocephalus due to tumour growth. She underwent brainstem tumour biopsy with a lateral suboccipital approach. After the shunting, CT showed a linear haematoma in the left occipital lobe far from the site of the ventricular puncture. MRI revealed a small contusion in the left cerebellar hemisphere, disconnection of the left tentorial membrane and linear haematoma on a straight line. These facts suggested that the shunt tunneller had penetrated the skull through the craniotomy of the posterior fossa. This is a rare complication of VP shunting, with limited cases reported in the literature.
Surviving cancer or future motherhood? Both are possible: an Ewing sarcoma case in an 8-year-old girl
Authors: Ascensão Tânia , Marques Maria Inês , Leite Helena Barros
Published: April 2021

Ewing’s sarcoma is an aggressive tumour, common in paediatric age, in which treatment often implies a decrease in reproductive potential. We describe a case of a woman who had a lumbar Ewing’s Sarcoma in 1991, at the age of 8. She was submitted to extended tumourectomy, chemotherapy and local radiotherapy without preservation techniques. In adult life, and after two in vitro fertilization (IVF) reproductive cycles without success, she spontaneously conceived at the age of 32. After an uneventful pregnancy, she delivered a healthy child by caesarean section. This is a rare successful case of a spontaneous and uneventful pregnancy without previous preservation techniques. In the last 30 years, there has been significant development in this area, and currently, there are solutions for these patients, including in prepubertal age.
Predicting lying, sitting, walking and running using Apple Watch and Fitbit data
Authors: Fuller Daniel , Anaraki Javad Rahimipour , Simango Bongai , Rayner Machel , Dorani Faramarz , Bozorgi Arastoo , Luan Hui , A Basset Fabien
Published: April 2021

Objectives

This study’s objective was to examine whether commercial wearable devices could accurately predict lying, sitting and varying intensities of walking and running.

Methods

We recruited a convenience sample of 49 participants (23 men and 26 women) to wear three devices, an Apple Watch Series 2, a Fitbit Charge HR2 and iPhone 6S. Participants completed a 65 min protocol consisting of 40 min of total treadmill time and 25 min of sitting or lying time. The study’s outcome variables were six movement types: lying, sitting, walking self-paced and walking/running at 3 metabolic equivalents of task (METs), 5 METs and 7 METs. All analyses were conducted at the minute level with heart rate, steps, distance and calories from Apple Watch and Fitbit. These included three different machine learning models: support vector machines, Random Forest and Rotation forest.

Results

Our dataset included 3656 and 2608 min of Apple Watch and Fitbit data, respectively. Rotation Forest models had the highest classification accuracies for Apple Watch at 82.6%, and Random Forest models had the highest accuracy for Fitbit at 90.8%. Classification accuracies for Apple Watch data ranged from 72.6% for sitting to 89.0% for 7 METs. For Fitbit, accuracies varied between 86.2% for sitting to 92.6% for 7 METs.

Conclusion

This preliminary study demonstrated that data from commercial wearable devices could predict movement types with reasonable accuracy. More research is needed, but these methods are a proof of concept for movement type classification at the population level using commercial wearable device data.
Incidence of emergency calls and out-of-hospital cardiac arrest deaths during the COVID-19 pandemic: findings from a cross-sectional study in a UK ambulance service
Authors: Charlton Karl , Limmer Matthew , Moore Hayley
Published: April 2021

Background

In response to the COVID-19 pandemic, a national lockdown was introduced on 23 March 2020. In the following weeks, emergency departments in the UK reported a reduction in attendances. We aimed to explore the incidence of emergency calls across North East England, as well as the number of out-of-hospital cardiac arrest (OHCA) deaths.

Methods

Data were collected for all patients who contacted North East Ambulance Service between 4 March 2019–2 June 2019 and 2 March 2020–31 May 2020 suffering stroke, ST elevation myocardial infarction, allergy, asthma, chronic obstructive pulmonary disease, falls, intoxication, seizure, sepsis, acute coronary syndrome and OHCA.

Results

There were a reduction in incidence of calls, excluding OHCA, resulting in ambulance activation during the pandemic compared with same period in 2019, 16 743 versus 19 639, respectively (−14.74%). The decline in calls was partially reversed by the end of May 2020. Incidence of OHCA at the time of the national lockdown had increased by 13.79% with a peak increase of 73.56% in the second week in April 2020. OHCA deaths peaked in the first 2 weeks in April 2020, 95.65% and 90.07%, respectively, but by the end May 2020, incidence of OHCA and OHCA deaths had returned to prelockdown levels.

Conclusion

Incidence of emergency calls were reduced during the pandemic compared with 2019. There was a rise in incidence of OHCA and OHCA deaths during the same period; however, these changes appear transient. Further research is required to understand patient behaviour towards seeking help during the pandemic and the long-term consequences of not doing so.
Psychological distress during the acceleration phase of the COVID-19 pandemic: a survey of doctors practising in emergency medicine, anaesthesia and intensive care medicine in the UK and Ireland
Authors: Roberts Tom , Daniels Jo , Hulme William , Hirst Robert , Horner Daniel , Lyttle Mark D , Samuel Katie , Graham Blair , Reynard Charlie , Barrett Michael , Foley James , Cronin John , Umana Etimbuk , Vinagre Joao , Carlton Edward
Published: April 2021

Objective

To quantify psychological distress experienced by emergency, anaesthetic and intensive care doctors during the acceleration phase of COVID-19 in the UK and Ireland.

Methods

Initial cross-sectional electronic survey distributed during acceleration phase of the first pandemic wave of COVID-19 in the UK and Ireland (UK: 18 March 2020–26 March 2020 and Ireland: 25 March 2020–2 April 2020). Surveys were distributed via established specialty research networks, within a three-part longitudinal study. Participants were doctors working in emergency, anaesthetic and intensive medicine during the first pandemic wave of COVID-19 in acute hospitals across the UK and Ireland. Primary outcome measures were the General Health Questionnaire-12 (GHQ-12). Additional questions examined personal and professional characteristics, experiences of COVID-19 to date, risk to self and others and self-reported perceptions of health and well-being.

Results

5440 responses were obtained, 54.3% (n=2955) from emergency medicine and 36.9% (n=2005) from anaesthetics. All levels of doctor seniority were represented. For the primary outcome of GHQ-12 score, 44.2% (n=2405) of respondents scored >3, meeting the criteria for psychological distress. 57.3% (n=3045) had never previously provided clinical care during an infectious disease outbreak but over half of respondents felt somewhat prepared (48.6%, n=2653) or very prepared (7.6%, n=416) to provide clinical care to patients with COVID-19. However, 81.1% (n=4414) either agreed (31.1%, n=2709) or strongly agreed (31.1%, n=1705) that their personal health was at risk due to their clinical role.

Conclusions

Findings indicate that during the acceleration phase of the COVID-19 pandemic, almost half of frontline doctors working in acute care reported psychological distress as measured by the GHQ-12. Findings from this study should inform strategies to optimise preparedness and explore modifiable factors associated with increased psychological distress in the short and long term.

Trial registration number

ISRCTN10666798.
Shed antigen-induced blocking effect on CAR-T cells targeting Glypican-3 in Hepatocellular Carcinoma
Authors: Sun Luan , Gao Fang , Gao Zhanhui , Ao Lei , Li Na , Ma Sujuan , Jia Meng , Li Nan , Lu Peihua , Sun Beicheng , Ho Mitchell , Jia Shaochang , Ding Tong , Gao Wei
Published: April 2021

Background

Glypican-3 (GPC3), a cell surface glycoprotein that is pathologically highly expressed in hepatocellular carcinoma (HCC), is an attractive target for immunotherapies, including chimeric antigen receptor (CAR) T cells. The serum GPC3 is frequently elevated in HCC patients due to the shedding effect of cell surface GPC3. The shed GPC3 (sGPC3) is reported to block the function of cell-surface GPC3 as a negative regulator. Therefore, it would be worth investigating the potential influence of antigen shedding in anti-GPC3 CAR-T therapy for HCC.

Methods

In this study, we constructed two types of CAR-T cells targeting distinct epitopes of GPC3 to examine how sGPC3 influences the activation and cytotoxicity of CAR-T cells in vitro and in vivo by introducing sGPC3 positive patient serum or recombinant sGPC3 proteins into HCC cells or by using sGPC3-overexpressing HCC cell lines.

Results

Both humanized YP7 CAR-T cells and 32A9 CAR-T cells showed GPC3-specific antitumor functions in vitro and in vivo. The existence of sGPC3 significantly inhibited the release of cytokines and the cytotoxicity of anti-GPC3 CAR-T cells in vitro. In animal models, mice carrying Hep3B xenograft tumors expressing sGPC3 exhibited a worse response to the treatment with CAR-T cells under both a low and high tumor burden. sGPC3 bound to CAR-T cells but failed to induce the effective activation of CAR-T cells. Therefore, sGPC3 acted as dominant negative regulators when competed with cell surface GPC3 to bind anti-GPC3 CAR-T cells, leading to an inhibitory effect on CAR-T cells in HCC.

Conclusions

We provide a proof-of-concept study demonstrating that GPC3 shedding might cause worse response to CAR-T cell treatment by competing with cell surface GPC3 for CAR-T cell binding, which revealed a new mechanism of tumor immune escape in HCC, providing a novel biomarker for patient enrolment in future clinical trials and/or treatments with GPC3-targeted CAR-T cells.
Tobacco mythbusting—tobacco is not a major driver of foot traffic in low socio-economic small retail stores
Authors: Wood Lisa , Gazey Angela
Published: April 2021

Background

One of the opposing arguments to restricting or banning the sale of tobacco products stem from a perception that this would adversely impact on small retail stores that rely on tobacco sales for viability. It has also been argued that purchases of tobacco leads to unplanned purchasing of other items that yield income for small store owners. This study tested the veracity of these arguments in the Australian context.

Methods

Consumer intercept surveys (n=1487) were conducted outside a comprehensive sample of small stores (n=136) selling tobacco in lower socioeconomic suburbs. Data were collected over a 2-hour period outside each store using the same methodology (36% consumer response rate). Descriptive statistics examined the proportion of tobacco and non-tobacco purchases and most common products purchased.

Results

Purchasing tobacco was the primary motivation for store visits for only 3% of consumers. The vast majority of products purchased (92%) were not tobacco, with hot food, groceries and lottery tickets most frequent. Only 8% of consumers purchased tobacco. When unplanned purchasing patterns were compared, consumers’ who purchased tobacco were no more likely to buy other products.

Conclusion

Tobacco purchasing was rarely the reason for store visits, indicating that it is not a key driver of consumer foot traffic for small retailers. There was also no evidence that tobacco contributes to spontaneous purchases of other products that might bring retailers profit. Findings suggest that restricting the retail availability of tobacco would be unlikely to have a pronounced negative impact on small retail stores.
Illicit tobacco trade: empty pack survey in eight Argentinean cities
Authors: Pizarro Maria Elisabet , Giacobone Gabriel , Shammah Cinthia , Stoklosa Michal
Published: April 2021

Objective

To estimate the prevalence of illicit tobacco trade (ITT) and different ITT modes—tax stamp counterfeiting and smuggling—in Argentina.

Design

Cross-sectional study using an empty tobacco pack survey with a simple random cluster sampling design. Classification as licit/illicit using forensic analysis of tax stamps and packs and econometric modelling.

Setting

Cities of Buenos Aires, La Matanza, Cordoba, Rosario, Mendoza, Neuquen, Posadas, Salta; January–June 2019.

Results

Of a total sample of 15 658 packs, 83.2% were manufactured in Argentina and 16.8% were foreign packs. Overall ITT prevalence—weighted by district population size—was estimated at 13.7%, where 6.1% was attributable to stamp counterfeiting—that is, a forged stamp not issued by the national tax authority—and 7.6% to contraband smuggling of foreign cigarette packs—that is, illicit trade of packs across national borders.

Conclusions

The ITT problem in Argentina seems to be equally represented by counterfeiting of tobacco tax stamps on packs with domestic features and smuggling of foreign cigarette packs. Foreign cigarettes represent a minor component of the pack sampled in most of the country, except in Salta and Posadas, which are located close to the border with Paraguay. It is essential to implement an effective track-and-trace system including the monitoring of tax stamp authenticity and increase border control to block the entry of smuggled products, particularly from Paraguay. Reducing ITT is necessary to ensure the effectiveness of tobacco taxation measures.
Induction of PDCD4 by albumin in proximal tubule epithelial cells potentiates proteinuria-induced dysfunctional autophagy by negatively targeting Atg5
Authors: Osoro Ezra Kombo , Du Xiaojuan , Liang Dong , Lan Xi , Farooq Riaz , Huang Fumeng , Zhu Wenhua , Ren Jiajun , Sadiq Muhammad , Tian Lifang , Yang Xudong , Li Dongmin , Lu Shemin
Published: April 2021

Autophagy dysfunction is a hallmark of type 1 diabetes. However, the precise molecular mechanism of proteinuria-induced dysfunctional autophagy remains unclear. Herein, we investigated the role of programmed cell death 4 (PDCD4) in the regulation of autophagy in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro. RT-qPCR, immunohistochemistry (IHC), and western blotting demonstrated an upregulation of Pdcd4 mRNA and protein in streptozotocin (STZ)-induced DKD rats, as compared to the control. In addition, IHC and western blotting of a unilateral ureteral obstruction mouse model showed an upregulation of PDCD4 in the disease group, as compared to their respective controls. IHC analysis of kidney biopsy samples of human DKD patients showed an upregulation of PDCD4 compared to the control. Western blotting of the STZ-induced DKD rat tissues displayed a low microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, as compared to the control. It was found that albumin overload in cultured PTECs upregulated the expression of PDCD4 and p62 and decreased the expression of LC3-II and autophagy-related 5 (Atg5) proteins. The knockout of Pdcd4 in cultured PTECs could reduce albumin-induced dysfunctional autophagy, as evidenced by the recovery of Atg5 and LC3-II protein. The forced expression of PDCD4 could further suppress the expression of the crucial autophagy-related gene Atg5. Evidence suggests that endogenous PDCD4 promotes proteinuria-induced dysfunctional autophagy by negatively regulating Atg5. Therefore, PDCD4 may be a potential therapeutic target in DKD.
Analytical discovery of water disinfection byproducts of toxicological relevance: highlighting halobenzoquinones
Authors: Craven Caley B. , Blackstock Lindsay K. Jmaiff , Xie Jiaojiao , Li Jinhua , Yuan Chun-Gang , Li Xing-Fang
Published: April 2021

Analytical advancement enables discoveries in water research, and challenges in the identification and determination of a wide range of trace level toxic compounds in water drives the development of new analytical platforms and tools. The identification of toxic disinfection byproducts (DBPs) in disinfected drinking water is an excellent example. Water disinfection is necessary to protect the public from waterborne disease. However, an unintentional consequence is the formation of DBPs resulting from reactions of disinfectants with natural organic matter in source water. To date, regulated DBPs do not account for the increased bladder cancer risk estimated in epidemiological studies. The majority of halogenated DBPs remain unidentified and the discovery of unknown DBPs of toxicological relevance continues to be a major focus of current water research. This review will highlight halobenzoquinones as a class of DBPs that serves as an example of analytical development and toxicological studies. We will feature recent trends and gaps in analytical technologies for identification of unknown DBPs and bioassays for evaluation of the toxicological effects of specific DBPs and their mixtures.
Secondary disturbance following a deposit of volcanic tephra: a 30-year record from old-growth forest understory
Authors: Zobel Donald B. , Antos Joseph A. , Fischer Dylan G.
Published: April 2021

Forest disturbance is usually described by effects on trees, and small disturbances to forest understory are seldom studied. Nevertheless, effective analyses of succession need to consider both stand-replacing and subsequent “secondary” disturbances in both the canopy and understory. We estimated the characteristics of 13 types of secondary disturbances in old-growth forest understory, as well as change in the canopy cover, after the deposition of tephra (aerially transported volcanic ejecta) in 1980 from Mount St. Helens, Washington. We sampled 100 plots (1 m2) at each of four sites for vegetation change and types of disturbance at 10 different times from 1980 to 2010; we sampled the tree canopy above each plot in 1980 and 2016. The number of canopy gaps increased by 23% and mean gap dimension increased by 68% over 36 years, mostly from the loss of Abies amabilis (Douglas ex Loudon) Douglas ex Forbes. Secondary disturbance in understory affected 1.4% of stand area per year. The areas affected by soil disturbance and effects of woody litter were similar. Erosion, greater in deep than in shallow tephra, peaked in 1981, whereas most litter-caused disturbances increased after 2000. Less frequent litter-based disturbances covered greater area. Our results differ from conclusions about nonvolcanic understory disturbances. Secondary disturbances are variable, need more study, and are likely to affect many other systems.
Monitoring genetic diversity acrossPinus tabuliformisseed orchard generations using SSR markers
Authors: Yang Boning , Niu Shihui , El-Kassaby Yousry A. , Li Wei
Published: April 2021

The maintenance of genetic diversity across seed orchard generations is an important management objective. Here, we used Pinus tabuliformis Carrière as a model to explore the extent of genetic diversity across the species’ breeding activities through their corresponding seed orchard generations. We utilized a large number of simple sequence repeat (SSR) markers selected from P. tabuliformis transcriptomic data, and then assessed the effect of marker number on genetic diversity and genetic relationships of individuals across orchard generations. In total, we designed 125 SSR markers, of which 39 were polymorphic and used in the present study. The genetic diversity and genetic distance parameters tended to increase with an increase in loci number and a stable trend was reached at 24 SSRs. The selected optimal 24 SSR markers were further used to assess the genetic diversity across seed orchard generations, and a decreasing trend was detected with the advancement of orchard’s generations. Genetic distance analysis indicated that individuals in the 2nd generation orchard were more closely related compared with those of the 1st generation and the 1.5 generation. This study provided valuable information on the effect of selection and breeding on genetic diversity and highlighted its role for effective seed orchard management.