bluuebunny/crossref_metadata_2025 huggingface dataset:
The public health and health system implications of changes in the utilisation of acute hospital care in Ireland during the first wave of COVID-19: Lessons for recovery planning
Authors: Marron Louise , Burke Sara , Kavanagh Paul
Published: June 2021

Background: Reduced and delayed presentations for non-COVID-19 illness during the COVID-19 pandemic have implications for population health and health systems. The aim of this study is to quantify and characterise changes in acute hospital healthcare utilisation in Ireland during the first wave of COVID-19 to inform healthcare system planning and recovery.

Methods: A retrospective, population-based, interrupted time-trend study was conducted using two national datasets, Patient Experience Time (PET) and Hospital In-Patient Enquiry (HIPE). The study period was 6th January to 5th July 2020.

Results: Comparison between time periods pre- and post-onset of the COVID-19 pandemic within 2020 showed there were 81,712 fewer Emergency Department (ED) presentations (-18.8%), 19,692 fewer admissions from ED (-17.4%) and 210,357 fewer non-COVID-19 hospital admissions (-35.0%) than expected based on pre-COVID-19 activity. Reductions were greatest at the peak of population-level restrictions, at extremes of age and for elective admissions. In the period immediately following the first wave, acute hospital healthcare utilisation remained below pre-COVID-19 levels, however, there were increases in emergency alcohol-related admissions (Rate Ratio 1.22, 95% CI 1.03, 1.43, p-value 0.016), admissions with self-harm (Rate Ratio 1.39, 95% CI 1.01, 1.91, p-value 0.043) and mental health admissions (Rate Ratio 1.28, 95% CI 1.03, 1.60, p-value 0.028).

Discussion: While public health implications of delayed and lost care will only become fully apparent over time, recovery planning must begin immediately. In the short-term, backlogs in care need to be managed and population health impacts of COVID-19 and associated restrictions, particularly in relation to mental health and alcohol, need to be addressed through strong public health and health system responses. In the long-term, COVID-19 highlights health system weakness and is an opportunity to progress health system reform to deliver a universal, high-quality, sustainable and resilient health system, capable of meeting population health needs and responding to future pandemics.
Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases
Authors: Zheng Wei , Zhao Dejian , Zhang Hui , Chinnasamy Prameladevi , Sibinga Nicholas , Pollard Jeffrey W.
Published: June 2021

Background: Metastatic breast cancer cells recruit macrophages (metastasis-associated macrophages, or MAMs) to facilitate their seeding, survival and outgrowth. However, a comprehensive understanding of the gene expression program in MAMs and how this program contributes to metastasis remain elusive.

Methods: We compared the transcriptomes of MAMs recruited to lung metastases and resident alveolar macrophages (RAMs) and identified a large variety of differentially expressed genes and their associated signaling pathways. Some of the changes were validated using qRT-PCR and immunofluorescence. To probe the functional relevance to metastatic growth, a gene-targeting mouse model of female mice in the C57BL6/J background was used to study allograft inflammatory factor 1 (AIF1, also known as ionized calcium-binding adapter molecule 1 or IBA1).

Results: Interferon signaling is one of the most activated pathways in MAMs, with strong upregulation of multiple components of the pathway and a significant enrichment for the gene signatures of interferon-alpha-treated human macrophages. Aif1, an interferon-responsive gene that regulates multiple macrophage activities, was robustly induced in MAMs. Aif1 deficiency in MAMs, however, did not affect development of lung metastases, suggesting that AIF1 indicates MAM activation but is dispensable for regulating metastasis.

Conclusions: The drastically different gene expression profile of MAMs as compared to RAMs suggests an important role in promoting metastatic growth. Dissection of the underlying mechanisms and functional validation of potential targets in the profile may provide novel therapeutic strategies for the treatment of metastatic diseases.
Radiation Hormesis and Epidemiology of Carcinogenesis: ‘Never the Twain Shall Meet’
Authors: Koterov A. , Vaynson A.
Published: June 2021

The review considers the reasons that do not allow the use of radiation hormesis for public health and for the prevention of diseases in the population. It is noted that evidence of the hormesis effects of low doses radiation with low LET was obtained only in laboratory experiments on cells and animals, using a hypothetical-deductive method and adequate controls. Some confirmation was found in balneology (radon therapy) and in the clinic (immunostimulation in cancer patients). At the same time, in epidemiological, observational studies, which mainly involve the induction method, there are no unambiguous data on hormesis effects on the frequency of carcinogenesis. This is due to the fact that in the region of low doses (up to 0.1 Gy), in addition to linear, any forms of dose dependence are equally probable, and it is impossible to isolate the radiation effect due to the iinfluence of non-radiation factors, as well as confounders and biases. The epidemiological designs used to confirm radiation hormesis in terms of the frequency of malignant neoplasms have such significant drawbacks and limitations for small magnitudes of effects that, according to epidemiology, there is no possibility for conclusions about hormesis. The stated is, among other things, the position of UNSCEAR, ICRP, BEIR and NCRP, which in the relevant documents, however, is presented insufficiently. For many experimental researchers and clinicians (of any rank), who are not familiar with the basics of classical epidemiology and descriptive disciplines, this position remains incomprehensible and incomprehensible. It is concluded that although hormesis may exist at low doses of radiation, it will hardly be possible to prove and, moreover, to use it in epidemiology and medicine for the prevention of a healthy population. At the same time, it is necessary to actively develop the clinical use of radiation in low doses, but only as a therapeutic immunostimulation in severe pathologies.
The Influence of Mesenchymal Stem Cells of Adipose Tissue and Paracrine Factors of Conditioned Medium on the Healing of Radiation Ulcers in the Treatment of Severe Radiation Injuries of Skin in Rats
Authors: Lebedev V , Deshevoy Yu. , Temnov A. , Astrelina T. , Rogov K. , Nasonova T. , Lyrshchikova A. , Dobrynina O. , Moroz B. , Sklifas A
Published: June 2021

Purpose: Studying of the effects transplantation of cultured mesenchymal stem cells of adipose tissue (MMSC) and adipose-derived stromal vascular fraction (SVF), as well as the introduction of paracrine factors (PF) of conditioned medium in an isolated or combined application for severe local radiation skin lesions in the experiment.

Material and methods: Rats of the inbred Wistar–Kyoto strain were irradiated to local X-rays exposure in the iliolumbar region of the back at a dose of 110 Gy. The transplantation of cultured MMSC was performed twice at doses of 2.1 × 106 and 2.6 × 106 on the 28th and 35th days after irradiation. Adipose-derived SVF was administered at the same time in doses of 3.2 × 106 and 2.8 × 106, respectively. PF were administered five times from the 1st to the 10th day after irradiation. The severity of radiation damage to the skin and the effects of therapy were evaluated in dynamics by clinical manifestations, using planimetry and histological methods.

Results: Radiation exposure with these parameters caused severe radiation injuries of the skin with non-healing ulcers formed by the 21–25th day after irradiation. The area of radiation ulcers in rats of the control group in the period from the 26th to the 83rd day slowly decreased from 2.76 ± 0.12 cm2 to 1.85 ± 0.13 cm2. In 50 % of the animals in the control group, ulcers persisted for more than 4 months after irradiation. In rats of the experimental groups, more intensive healing and a decrease in the area of radiation ulcers was noted. With isolated administration of cultured MMSC or SVF, a statistically significant decrease in the area of ulcers compared with the control was observed on the 104–125th day, and with the introduction of PF on the 83rd day after irradiation, p <0.05. In the control group, by the118th day after irradiation, radiation ulcers healed only in 25 % of rats, and in the experimental groups with isolated administration of cultured MMSC, SVF and PF in 40–55 % of the rats showed complete epithelialization of wounds with the formation of an atrophic scar. Under the conditions of combined use of stem cells and conditioned medium factors, the number of animals with complete healing of radiation ulcers was 85–100 % by 118th days, p <0.05.

Conclusion: Thus, transplantation of cultured MMSC of adipose tissue and adipose-derived SVF, as well as the introduction of PF of conditioned medium, can enhance the regeneration processes and stimulate skin regeneration, promoting earlier healing of chronic radiation ulcers in severe local radiation injuries. Moreover, with the combined introduction of PF and adipose-derived stem cell transplantation, the effectiveness of the healing of radiation ulcers was increases.
SPECT with a New Radiopharmaceutical Drug 99mTc-1-thio-D-glucose of Dynamic Observation of a Patient with a Diagnosis of a Malignant Brain Tumor
Authors: Zel'chan R. , Sinilkin I. , Medvedeva A. , Bragina O. , Ryabova A , Chernov V. , Choinzonov E
Published: June 2021

This publication demonstrates the possibility of dynamic observation of a patient with a diagnosis of a malignant brain tumor at the stages of combined treatment using SPECT with a new radiopharmaceutical drug 99mTc-1-thio-D-glucose. Also in the described clinical case, an attempt was made to semi-quantitatively assess the accumulation of 99mTc-1-thio-D-glucose drug in the tumor, reflecting the dynamics of changes occurring in the tumor tissue under therapeutic effect. The SPECT data with 99mTc-1-thio-D-glucose in the course of dynamic observation of the patient were supported by the results of MRI and, most importantly, by PET data with 11C-methionine. Based on the results presented, it was suggested that a promising method would appear for evaluating the results of treatment of malignant brain tumors, which is an alternative to PET with labeled amino acids, which favorably differ in the availability and cost of the diagnostic procedure.
A Randomized Controlled Trial Evaluating a Pain Training for Respite Workers Supporting Children With Disabilities Part Two: Training Evaluations and the Impact of Training on Knowledge Application
Authors: Genik Lara M. , Aerts Elisabeth L. , Nauman Hiba , Barney Chantel C. , Lewis Stephen P. , McMurtry C. Meghan
Published: June 2021

Within a parallel-group randomized control trial, pain training's impact on Respite Workers' (RW) care approaches and training evaluations was explored. RW (n = 158) from 14 organizations received pain or control training following randomization. Researchers were blind until randomization; allocations were not shared explicitly with organizations/participants. Participants completed a strategy use questionnaire immediately before and an evaluation immediately after training completion. Four-to-6 weeks later, participants completed the strategy use questionnaire and semistructured focus groups. No differences in pain approaches were noted in strategy use questionnaires. Per focus groups, both groups acquired a “knowing” about pain and applied pain-related care approaches in similarly. Pain training participants identified need for “growing and strengthening” pain knowledge. Training endorsements were favorable. RW pain training has value and may impact practice.
Simultaneously improving multiple imaging parameters with scattering media
Authors: Zhao Fu , Du Shuman , Liang Dong , Liu Jun
Published: June 2021

Traditional optical imaging systems can provide high-quality imaging with a complicated and expensive optical design by eliminating aberrations. With the help of an optical memory effect, rather than independently improving a single imaging parameter, the simultaneous improvement of several imaging parameters by adding scattering media to the imaging systems is, to the best of our knowledge, demonstrated for the first time. As an example, in a simple single lens imaging system, in addition to the depth of field being greatly improved, spherical aberration, coma aberration, and chromatic aberration are simultaneously eliminated by placing a scattering medium between the lens and the camera. The results indicate the potential applications of scattering media in many fields such as optical imaging, optical measurements, and biomedical applications.
Broadband chromatic dispersion in fiber-coupled optical
interferometry
Authors: Allured Ryan , Ashcom Jonathan B.
Published: June 2021

Chromatic dispersion is a well-known technical challenge in optical
interferometry, and the issue is exacerbated when using optical fibers
for beam transport. The important sources of chromatic dispersion in a
fiber-coupled optical interferometer are investigated using a
Mach–Zehnder interferometer operating between 975–1650 nm, with
particular attention paid to various dispersive effects in fibers. The
compensation of chromatic dispersion is also investigated, and a
compensation strategy using bulk glass and fiber stretching is
described. A notional dispersion budget is presented for a
fiber-coupled interferometer operating in the near infrared, showing
that dispersion can be compensated to the

λ

/

20

RMS level over a nearly 700 nm wide
bandpass.
Investigating the depolarization property of skin tissue by degree of polarization uniformity contrast using polarization-sensitive optical coherence tomography
Authors: Zhou Xin , Maloufi Sina , Louie Daniel C. , Zhang Ning , Liu Qihao , Lee Tim K. , Tang Shuo
Published: June 2021

The depolarization property of skin has been found to be important for skin cancer detection. Previous techniques based on light polarization lack the capability of depth differentiation. Polarization-sensitive optical coherence tomography (PS-OCT) has the advantage of both depth-resolved 3D imaging and high sensitivity to polarization. In this study, we investigate the depolarization property of skin tissue using PS-OCT, especially with the degree of polarization uniformity (DOPU) contrast. Well designed skin phantoms with various surface roughness levels and optical properties mimicking skin are imaged by PS-OCT and the DOPU values are quantified. The result shows a correlation between DOPU and surface roughness, where a higher roughness corresponds to a lower DOPU value. An index matching experiment with a water layer confirms the impact of surface condition on light depolarization. Refraction of backscattered photons on the surface boundary is attributed to the broadening of backscattering angle and thus depolarization. To the best of our knowledge, this is the first time the impact of surface roughness on DOPU is reported and its mechanism explained. Furthermore, through preliminary in vivo skin imaging, the capability of DOPU in detecting depolarization in skin is demonstrated. By utilizing the 3D imaging from PS-OCT, DOPU can offer a high-resolution depth differentiation and quantification of depolarization in skin tissue.
UV random laser in aluminum-doped ZnO nanorods
Authors: Ali Abdullah Taha , Maryam W. , Huang Yu-Wei , Hsu Hsu-Cheng , Ahmed Naser M. , Zainal N. , Abu Hassan H. , Dheyab Mohammed Ali
Published: June 2021

Vertically aligned Al-doped ZnO nanorods (AZO-NRs) were grown on glass substrate using a chemical bath deposition (CBD) method at various temperatures between 80°C and 130°C. The results showed the Al content in the AZO-NRs strongly depends on the growth temperature. The optimum doping level was attained at 110°C. The morphology was maintained in each sample, and the lasing properties were investigated against the Al-doped variation. The sample with a high doping level exhibited superior random lasing, with high intensity and spectral width of less than 0.08 nm. The same sample also had the lowest pumping threshold of 0.192 mW. More importantly, this study showed the possibility of utilizing doping as a tuning parameter for random lasing, whereby a 7.3 nm redshift in the lasing peak was observed with increasing doping concentration. This study also placed an emphasis on AZO-NRs as potential candidates for tunable random laser devices.
Substrate-mediated lattice Kerker effect in Al metasurfaces
Authors: Kostyukov A. S. , Ershov A. E. , Bikbaev R. G. , Gerasimov V. S. , Rasskazov I. L. , Karpov S. V. , Polyutov S. P.
Published: June 2021

Surface lattice resonances (SLRs) emerging in regular arrays of plasmonic nanoparticles (NPs) are known to be exceptionally sensitive to the homogeneity of the environment. It is considered necessary to have a homogeneous environment for engineering narrowband SLRs, while in a half-space environment, SLRs rapidly vanish as the contrast between the refractive indices of the substrate and superstrate increases. From this conventional wisdom, it is apparent that the delicate lattice Kerker effect emerging from SLRs and resonances on constituent NPs should be difficult to achieve in a non-homogeneous environment. Using a rigorous theoretical treatment with multipolar decomposition, we surprisingly find and explain a narrowband substrate-mediated lattice Kerker effect in two-dimensional arrays of Al nanocylinders in a half-space geometry. We propose to use this effect for sensing applications and demonstrate its broad tunability across the UV/Vis wavelength range.
Sub-terahertz vortex beam generation using a spiral metal reflector
Authors: Hira Yumina , Monnai Yasuaki
Published: June 2021

We demonstrate sub-terahertz vortex beam generation using a spiral metal reflector that can be used for both polarizations. A vortex beam is a ring-shaped beam that possesses sub-wavelength null in the center formed by angular phase variation. While the sub-terahertz vortex beams have gained increasing attention for a wide range of applications in sensing and communications, techniques for generating them are still accompanied by challenges. For example, the use of a phase plate, which is common in the optical regime, suffers from intrinsic losses of dielectric materials in the sub-terahertz regime. Moreover, holographic diffraction gratings, which could replace transmissive components, are inefficient and sensitive to the polarization. To reconcile these challenges, here we design a reflector type metal component with a spiral surface shape. We firstly derive a direct equation to design its shape. We then experimentally validate the design by mapping the radiation pattern of a vortex beam for the WR10 frequency band (75 to 110 GHz) in both of the orthogonal polarizations. The result confirms an inexpensive and versatile approach to generate a vortex beam in the sub-terahertz regime.
Self-adaptive metasurface platform based on computer vision
Authors: Yu Qian , Zheng Yi Ning , Gu Ze , Liu Jia , Liang Yu Chen , Li Lin Zhou , Zhang Xin Ge , Jiang Wei Xiang
Published: June 2021

Programmable metasurfaces allow real-time electromagnetic (EM) manipulation in a digital manner, showing great potential to construct advanced multifunctional EM devices. However, the current programmable metasurfaces typically need human participation to achieve various EM functions. In this Letter, we propose, design, and construct a self-adaptive metasurface platform that can achieve beam control automatically based on image recognition. Such a platform is composed of a metasurface with

36

×
36

active units, a single-board computer, and two independent cameras that can detect the position of the objects. The single-board computer, Raspberry Pi, is used to calculate the information of the objects and generate the coding sequences to control the digital metasurface based on a low complexity binocular localization algorithm. Such a smart metasurface platform can generate different beams according to the location of the receiver and can be used as intelligent antennas in future communications and radars.
Nonlinear enhanced microresonator gyroscope
Authors: Silver Jonathan M. , Del Bino Leonardo , Woodley Michael T. M. , Ghalanos George N. , Svela Andreas Ø. , Moroney Niall , Zhang Shuangyou , Grattan Kenneth T. V. , Del’Haye Pascal
Published: June 2021

Optical gyroscopes based on the Sagnac effect have been the mainstay of inertial navigation in aerospace and shipping for decades. These gyroscopes are typically realized either as ring-laser gyroscopes (RLGs) or fiber-optic gyroscopes (FOGs). With the recent rapid progress in the field of ultrahigh-quality optical whispering-gallery mode and ring microresonators, attention has been focused on the development of microresonator-based Sagnac gyroscopes as a more compact alternative to RLGs and FOGs. One avenue that has been explored is the use of exceptional points in non-Hermitian systems to enhance the responsivity to rotation. We use a similar phenomenon, namely, the critical point of a spontaneous symmetry-breaking transition between counterpropagating light, to demonstrate a microresonator gyroscope with a responsivity enhanced by a factor of around104. We present a proof-of-principle rotation measurement as well as a characterization of the system’s dynamical response, which shows the universal critical behaviors of responsivity enhancement and critical slowing down, both of which are beneficial in an optical gyroscope. We believe that this concept could be used to realize simple and cheap chip-based gyroscopes with sensitivities approaching those of today’s RLGs and FOGs.
Intersektorale Vernetzung im Gesundheitswesen: Prozessverbesserung durch den Einsatz von Plattformen am Fallbeispiel der Palliativversorgung
Authors: Behne Alina , Teuteberg Frank
Published: June 2021

Eine effiziente Überführung der Patienten in die häusliche Versorgung steht bei der Palliativentlassung insbesondere aufgrund der häufig kurzen Versorgungsdauer im Fokus. Dabei besteht die Herausforderung, dass viele unterschiedliche Akteure an dem Prozess beteiligt sind. Plattformen bieten Potenziale, eine einfache Dokumentation und Kommunikation der an der Versorgung beteiligten Gesundheitsakteure zu ermöglichen. Der vorliegende Beitrag zeigt, wie das Zusammenspiel unterschiedlicher Akteure auf Prozess- und Personenebene untersucht werden kann, um anschließend Prozessschwachstellen zu erkennen und diese mittels Informations- und Kommunikationstechnologien zu verbessern. In Zusammenarbeit mit verschiedenen Praxisakteuren vor allem aus dem Gesundheitswesen aber auch aus der Softwareentwicklung konnten aktuelle Herausforderungen im Palliativbereich erhoben werden. Daran anknüpfend konnte eine Anforderungsanalyse abgeleitet, ein bestehendes System erweitert und anschließend der Entlass- und Versorgungsprozess restrukturiert werden. Dabei werden Bedarfe, Potenziale und Herausforderungen von der Erhebung des aktuellen Prozesses bis zur Implementierung der Restrukturierung hervorgehoben. Es wird deutlich, dass das intersektorale Medikationsmanagement ein Schlüsselelement in der Gesundheitsversorgung ist und die Apotheke die Rolle eines Gesundheitslotsen einnehmen könnte. Bislang ist noch keine standardisierte oder einheitliche intersektorale Kommunikation oder Dokumentation via Plattform im Gesundheitswesen etabliert, jedoch bestehen einsatzbereite Plattformlösungen, die den Austausch erleichtern und den Weg bis zur Entstehung einer einheitlichen Lösung für alle beteiligten Akteure ebnen. Dieser Beitrag zeigt, wie die Erweiterung einer bestehenden Plattform aus dem Palliativsektor es ermöglichen kann, die hier untersuchten Prozesse in Hinblick auf eine sektorenübergreifende, effiziente Zusammenarbeit zu verbessern.
Multiple morphogens and rapid elongation promote segmental patterning during development
Authors: Qiu Yuchi , Fung Lianna , Schilling Thomas F. , Nie Qing
Published: June 2021

The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development.
Behavioral correlates of cortical semantic representations modeled by word vectors
Authors: Nishida Satoshi , Blanc Antoine , Maeda Naoya , Kado Masataka , Nishimoto Shinji
Published: June 2021

The quantitative modeling of semantic representations in the brain plays a key role in understanding the neural basis of semantic processing. Previous studies have demonstrated that word vectors, which were originally developed for use in the field of natural language processing, provide a powerful tool for such quantitative modeling. However, whether semantic representations in the brain revealed by the word vector-based models actually capture our perception of semantic information remains unclear, as there has been no study explicitly examining the behavioral correlates of the modeled brain semantic representations. To address this issue, we compared the semantic structure of nouns and adjectives in the brain estimated from word vector-based brain models with that evaluated from human behavior. The brain models were constructed using voxelwise modeling to predict the functional magnetic resonance imaging (fMRI) response to natural movies from semantic contents in each movie scene through a word vector space. The semantic dissimilarity of brain word representations was then evaluated using the brain models. Meanwhile, data on human behavior reflecting the perception of semantic dissimilarity between words were collected in psychological experiments. We found a significant correlation between brain model- and behavior-derived semantic dissimilarities of words. This finding suggests that semantic representations in the brain modeled via word vectors appropriately capture our perception of word meanings.
Adaptation of metabolite leakiness leads to symbiotic chemical exchange and to a resilient microbial ecosystem
Authors: Yamagishi Jumpei F. , Saito Nen , Kaneko Kunihiko
Published: June 2021

Microbial communities display remarkable diversity, facilitated by the secretion of chemicals that can create new niches. However, it is unclear why cells often secrete even essential metabolites after evolution. Based on theoretical results indicating that cells can enhance their own growth rate by leaking even essential metabolites, we show that such “leaker” cells can establish an asymmetric form of mutualism with “consumer” cells that consume the leaked chemicals: the consumer cells benefit from the uptake of the secreted metabolites, while the leaker cells also benefit from such consumption, as it reduces the metabolite accumulation in the environment and thereby enables further secretion, resulting in frequency-dependent coexistence of multiple microbial species. As supported by extensive simulations, such symbiotic relationships generally evolve when each species has a complex reaction network and adapts its leakiness to optimize its own growth rate under crowded conditions and nutrient limitations. Accordingly, symbiotic ecosystems with diverse cell species that leak and exchange many metabolites with each other are shaped by cell-level adaptation of leakiness of metabolites. Moreover, the resultant ecosystems with entangled metabolite exchange are resilient against structural and environmental perturbations. Thus, we present a theory for the origin of resilient ecosystems with diverse microbes mediated by secretion and exchange of essential chemicals.
X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3
Authors: Sun Jia-Hui , Chen Jiang , Ayala Valenzuela Fernando Eduardo , Brown Carolyn , Masser-Frye Diane , Jones Marilyn , Romero Leslie Patron , Rinaldi Berardo , Li Wenhui Laura , Li Qing-Qing , Wu Dan , Gerard Benedicte , Thorpe Erin , Bayat Allan , Shi Yun Stone
Published: June 2021

The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.
The role of let-7b in the inhibition of hepatic stellate cell activation by rSjP40
Authors: Sun Xiaolei , Zhang Li , Jiang Yuting , Li Aihong , Zhu Dandan , Wu Jiangrong , Duan Yinong
Published: June 2021

Background

Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. In this study, we investigated the role of let-7b in the inhibition of HSC activation by rSjP40.

Methods

Expression of let-7b was detected by quantitative real-time PCR. A dual luciferase assay was used to confirm direct interaction between let-7b and collagen I. We also used western blot to assess protein levels of TGFβRI and collagen type I α1 (COL1A1).

Results

We found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b inhibits collagen I expression by directly targeting the 3’UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40.

Conclusion

Our research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis.
Association between environmental and climatic risk factors and the spatial distribution of cystic and alveolar echinococcosis in Kyrgyzstan
Authors: Paternoster Giulia , Boo Gianluca , Flury Roman , Raimkulov Kursanbek M. , Minbaeva Gulnara , Usubalieva Jumagul , Bondarenko Maksym , Müllhaupt Beat , Deplazes Peter , Furrer Reinhard , Torgerson Paul R.
Published: June 2021

Background

Cystic and alveolar echinococcosis (CE and AE) are neglected tropical diseases caused byEchinococcus granulosus sensu latoandE.multilocularis, and are emerging zoonoses in Kyrgyzstan. In this country, the spatial distribution of CE and AE surgical incidence in 2014-2016 showed marked heterogeneity across communities, suggesting the presence of ecological determinants underlying CE and AE distributions.

Methodology/Principal findings

For this reason, in this study we assessed potential associations between community-level confirmed primary CE (no.=2359) or AE (no.=546) cases in 2014-2016 in Kyrgyzstan and environmental and climatic variables derived from satellite-remote sensing datasets using conditional autoregressive models. We also mapped CE and AE relative risk. The number of AE cases was negatively associated with 10-year lag mean annual temperature. Although this time lag should not be considered as an exact measurement but with associated uncertainty, it is consistent with the estimated 10–15-year latency following AE infection. No associations were detected for CE. We also identified several communities at risk for CE or AE where no disease cases were reported in the study period.

Conclusions/Significance

Our findings support the hypothesis that CE is linked to an anthropogenic cycle and is less affected by environmental risk factors compared to AE, which is believed to result from spillover from a wild life cycle. As CE was not affected by factors we investigated, hence control should not have a geographical focus. In contrast, AE risk areas identified in this study without reported AE cases should be targeted for active disease surveillance in humans. This active surveillance would confirm or exclude AE transmission which might not be reported with the present passive surveillance system. These areas should also be targeted for ecological investigations in the animal hosts.
The gut microbiome and type 2 diabetes status in the Multiethnic Cohort
Authors: Maskarinec Gertraud , Raquinio Phyllis , Kristal Bruce S. , Setiawan Veronica W. , Wilkens Lynne R. , Franke Adrian A. , Lim Unhee , Le Marchand Loïc , Randolph Timothy W. , Lampe Johanna W. , Hullar Meredith A. J.
Published: June 2021

Background

The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).

Methods

In 2013–16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.

Results

Among 1,702 participants (59.9–77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.

Conclusions

T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.
Lived experiences of older adults during the first COVID-19 lockdown: A qualitative study
Authors: Falvo Ilaria , Zufferey Maria Caiata , Albanese Emiliano , Fadda Marta
Published: June 2021

Background and aim

Public health measures used to mitigate the COVID-19 epidemic may have unintended, detrimental consequences particularly on older adults, whose voices and perspectives are often silent or silenced. The aim of this study was to explore the lived experiences of individuals aged 64 or older during the first COVID-19 lockdown.

Methods

We conducted a qualitative study in a convenience sample of 19 older adults (aged 64+) living at home in the Italian-speaking region of Switzerland during the first COVID-19 lockdown, between April and May 2020. Participants varied in terms of gender, education, age, nationality, and socio-economic status. We conducted semi-structured phone interviews to elicit emotions, expectations and hopes in relation to the present situation, and the post-pandemic world. We inquired about opinions on the enforced public health measures, including those specifically targeting older adults, and on the societal portrayal of older adults.

Findings

We found that the epidemic and the public health response to it had both generated a variety of resentments and a high degree of ambivalence at the individual, micro-, meso- and macro-social levels. We also found that labelling older adults as an at-risk sub-population inevitably contributed to public and self-stigmatization.

Discussion

We conducted an in-depth qualitative investigation of lived experiences of older adults during the first wave of the COVID-19 pandemic in one of the most gravely hit region in Europe. Our findings on the complexity of unintended, detrimental consequences of outbreak responses on older adults have relevant implications for local adaptions of public health measures, and suggest that public health authorities should engage vulnerable sub-populations and promote bi-directional communication to inform and support communities.
Environmental drivers of reef manta ray (Mobula alfredi) visitation patterns to key aggregation habitats in the Maldives
Authors: Harris Joanna L. , Stevens Guy M. W.
Published: June 2021

A detailed understanding of the dynamics of small-scale (10s km) habitat use by the reef manta ray (Mobula alfredi) in the Maldives Archipelago is required to develop an effective national conservation management plan for this wide-ranging species. Here, a combination of photo-ID sightings data and acoustic telemetry were used to investigate both long-term M. alfredi visitation trends and small-scale movement patterns to key habitats on the eastern side of Baa Atoll (Hanifaru Bay feeding area, Dhigu Thila multifunctional site, and Nelivaru Thila cleaning station). All tagged and most of the sighted M. alfredi exhibited high affinity to the eastern side of Baa Atoll, where 99% of detections occurred, and 69% of individuals were re-sighted in multiple years. Sightings data suggests that visitation patterns may be associated with differences in habitat use by sex and maturity status. Boosted regression trees indicated that tag detection probability at Hanifaru Bay increased with increased westerly wind speed (>5ms-1) during the day, close to a new and full moon just after high tide, and when the tidal range was low. Interaction effects between predictors suggest that wind-driven oceanographic processes, such as Langmuir Circulation, maybe working to increase zooplankton concentration at this location. Tag detection probability increased at Dhigu Thila under similar conditions. At Nelivaru Thila, it increased at lower wind speeds (<5ms-1), close to a full moon, three hours after high tide. These results suggest that M. alfredi may utilise cleaning stations during the day when environmental conditions are not suitable for feeding. There was a high level of connectivity between these three locations, which suggests they form part of a network of key habitats that provide essential services to M. alfredi locally. Future conservation efforts should focus on identifying all areas of key habitat use for this species within the Maldives; applying strict protective measures to these sites and any connecting migration corridors which link them.
Financial burden of pediatric firearm-related injury admissions in the United States
Authors: Taylor Jordan S. , Madhavan Sriraman , Han Ryan W. , Chandler Julia M. , Tenakoon Lakshika , Chao Stephanie
Published: June 2021

Pediatric firearm-related injuries pose a significant public health problem in the United States, yet the associated financial burden has not been well described. This is the first study examining national data on the cost of initial hospitalization for pediatric firearm-related injuries. In this retrospective review, the Healthcare Cost and Utilization Project Kids’ Inpatient Database from the years 2003, 2006, 2009, and 2012 was used to identify all patients 18 years of age and under who were admitted with firearm-related injuries. We compared demographic and discharge-level data including injury severity score, hospital length of stay, income quartile, injury intent, and inflation-adjusted hospital costs across age groups (0–5, 6–9, 10–15, 16–18 years). There were approximately 4,753 pediatric firearm-related admissions each year, with a median hospitalization cost of $12,984 per patient. Annual initial hospitalization costs for pediatric firearm injuries were approximately $109 million during the study period. Pediatric firearm-related injuries predominately occured among older teenagers (74%, 16–18 years), males (89%), black individuals (55%), and those from the lowest income quartile (53%). We found significant cost variation based on patient race, income quartile, injury severity score, intent, hospital length of stay, disposition, and hospital region. Inflation-adjusted hospitalization costs have increased significantly over the study period (p < 0.001). Pediatric firearm-related injuries are a large financial burden to the United States healthcare system. There are significant variations in cost based on predictable factors like hospital length of stay and injury severity score; however, there are also substantial discrepancies based on hospital region, patient race, and income quartile that require further investigation.
Health risk assessment of exposure to toxic elements resulting from consumption of dried wild-grown mushrooms available for sale
Authors: Orywal Karolina , Socha Katarzyna , Nowakowski Patryk , Zoń Wojciech , Kaczyński Piotr , Mroczko Barbara , Łozowicka Bożena , Perkowski Maciej
Published: June 2021

Mushrooms exhibit a high ability to accumulate potentially toxic elements. The legal regulations in force in the European Union countries do not define the maximum content of elements in dried wild-grown mushrooms. This study presents the content of mercury (Hg), lead (Pb), cadmium (Cd) and arsenic (As) determined in dried wild-grown mushrooms (Boletus edulisandXerocomus badius) available for sale. Moreover, the health risk associated with their consumption is assessed. The inductively coupled plasma mass spectrometry (Cd, Pb, As) and atomic absorption spectrometry (Hg) were used. The mean Hg, Cd, Pb and As concentration inBoletus eduliswas 3.039±1.092, 1.983±1.145, 1.156±1.049 and 0.897±0.469 mg/kg and inXerocomus badius0.102±0.020, 1.154±0.596, 0.928±1.810 and 0.278±0.108 mg/kg, respectively. The maximum value of the hazard index (HI) showed that the consumption of a standard portion of driedBoletus edulismay have negative consequences for health and corresponded to 76.2%, 34.1%, 33% and 4.3% of the maximum daily doses of Hg, Cd, Pb and As, respectively. The results indicate that the content of toxic elements in dried wild-grown mushrooms should be monitored. The issue constitutes a legal niche where unfavourable EU regulations may pose a threat to food safety and consumer health.
Public restrooms, periods, and people experiencing homelessness: An assessment of public toilets in high needs areas of Manhattan, New York
Authors: Maroko Andrew R. , Hopper Kim , Gruer Caitlin , Jaffe Maayan , Zhen Erica , Sommer Marni
Published: June 2021

Access to safe, clean water and sanitation is globally recognized as essential for public health. Public toilets should be accessible to all members of a society, without social or physical barriers preventing usage. A public toilet facility’s design and upkeep should offer privacy and safety, ensure cleanliness, provide required sanitation-related resources, and be gender equitable, including enabling comfortable and safe management of menstruation. Menstrual hygiene management (MHM) refers to the need to ensure that girls, women and all people who menstruate have access to clean menstrual products, privacy to change the materials as often as needed, soap and water for washing the body as required, and access to facilities to dispose of used materials. Challenges around menstruation faced by people experiencing homelessness, which tend to be greater than those facing the general population, include inadequate toilet and bathing facilities, affordability issues around menstrual products, and menstrual stigma. Public toilets are a vital resource for managing menstruation, particularly for vulnerable populations without reliable access to private, safe, and clean spaces and menstrual products. This mixed-methods study sought to: 1) understand the lived experiences of MHM among people experiencing homelessness in New York City with respect to public toilets; 2) describe general and MHM-related characteristics of public toilets in high need areas of Manhattan and analyze their interrelationships; and 3) examine the associations among neighborhood-level demographics and the public toilet characteristics in those areas. Qualitative methods included key informant interviews (n = 15) and in-depth interviews (n = 22) with people with experience living on the street or in shelters, which were analyzed using Malterud’s ‘systematic text condensation’ for thematic cross-case analysis. Quantitative methods included audits and analyses of public toilet facilities (n = 25) using traditional statistics (e.g., Spearman’s correlations) and spatial analyses (e.g., proximity buffers). Qualitative findings suggest cleanliness, access to restrooms, and availability of resources are critical issues for the participants or prospective users. Quantitative analyses revealed insufficiently provided, maintained, and resourced public toilets for managing menstruation in high-needs areas. Findings also suggest that toilets with more MHM-related resource availability, such as menstrual products and toilet stall disposal bins, were more difficult to access. Neighborhood-level characteristics showed a potential environmental injustice, as areas characterized by higher socioeconomic status are associated with more access to MHM-specific resources in public restrooms, as well as better overall quality.