bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of 5 years of hepatitis C testing and treatment in the North East of England prisons
Authors: Johnson Amy , Shearer Jessica , Thompson Craig , Jelley Ryan , Aldridge Jodi , Allsop Caroline , Kerry Jenna , Jones Dee , McCullough Francesca , Miller Carolyn , Valappil Manoj , Taha Yusri , Masson Steven , Jefferson Tony , Lawton Colin , Christensen Lee , McPherson Stuart
Published: September 2023

Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme. Between July 2017 and June 2022, data were collected prospectively on HCV test offer and uptake rates, HCV Antibody (HCV‐Ab) and HCV‐RNA positivity, treatment starts and outcomes for new inmates incarcerated in three prisons. Rates of HCV‐Ab and RNA positivity at reception, incidence of new HCV infections and reinfection following treatment were determined. From a total of 39,652 receptions, 33,028 (83.3%) were offered HCV testing and 20,394 (61.7%) completed testing. Including all receptions, 24.5% of tests (n = 4995) were HCV‐Ab positive and 8.4% of tests (n = 1713) were HCV‐RNA positive. When considering the first test for each individual (median age 34 years; 88.1% male), 14.8% (n = 1869) and 7.2% (n = 905) were HCV‐Ab and HCV‐RNA positive, respectively. The incidence of new HCV‐Ab and RNA positivity was 5.1 and 3.3 per 100 person‐years, respectively. Of 1145 HCV viraemic individuals, 18 died within 6 months and 150 were rapidly transferred out of area, leaving 977 individuals with outcomes. Of these, 835 (85.5%) received antivirals and 47 spontaneously cleared the infection, leaving 95 (9.7%) untreated. 607 (72.7%) achieved SVR. 95 patients had reinfection post‐treatment (rate 10.1 cases per 100 person‐years). Testing for HCV has increased in our prisons and the majority with viraemia are initiated on antiviral treatment. Reassuringly, a significant fall in frequency of HCV‐RNA positivity at prison reception was observed suggesting progress towards HCV elimination.
Seasonal distribution of solitary and colonial benthic ascidians (Chordata) with ecological gradients in and around Andaman and Nicobar Islands, India
Authors: Murugan R. , Ananthan G. , Balachandar K. , Sathiskumar R. S. , Praveena V.
Published: September 2023

Ascidians are rapidly emerging biofouling organisms that generally occur on the natural and artificial substratum of the marine environment. However, very few studies have been reported on their species diversity and distribution patterns. This present investigation focuses on the seasonal impact on ascidians diversity. The distributions of ascidians were recorded by the collection of samples in six sampling stations from Andaman and Nicobar Islands. A total of 43 species of ascidians (32 colonial, 11 solitary) were recorded and most of the species are under the Didemnidae family. Various diversity indexes were utilized to examine the diversity, richness and evenness of species and to look at the assorted variety among tests and their likeness regarding species composition. The greatest (3.227) individuals were observed during summer season in Pigeon Island and the lowest (2.063) number of species were recorded during the monsoon season in Haddowharf harbour. The Margalef richness (d) fluctuated between in the range of 2.033 and 5.53 during the monsoon in Haddowharf harbour and Carbyns Cove beach in summer seasons. The Pielou's evenness record (J′) changed from 0.7409 to 0.9713. Diversity indexes were recorded as followed the order of 0.9642, 0.9552, 0.9482 and 0.9292 at Carbyns Cove shoreline, Burmanella, Pigeon Island and Campbell Bay individually during summer season. Present findings in the cluster examination uncovered that the species at various stations have framed four gatherings. Most elevated species rates were spread in summer. Field observation shows that species distribution is able to tolerate temperature ranges of 26.9–30.3°C and salinity of 32.1–34.64 ppt. Occasional examples of space occupation by colonial ascidians corresponded with seasonal changes in seawater temperature and salinity.
White coats and red tops
Authors: Ghosh Helen
Published: September 2023

Reflections on how policy decisions are made from over 30 years as a civil servant
A perspective on the clinical relevance of weak or nonacid reflux
Authors: Jodorkovsky Daniela , Katzka David A. , Gyawali C. Prakash
Published: September 2023

Background

Advances in ambulatory esophageal reflux monitoring that incorporated impedance electrodes to pH catheters have resulted in better characterization of retrograde bolus flow in the esophagus. With pH‐impedance monitoring, in addition to acid reflux episodes identified by pH drops below 4.0, weakly acid reflux (WAR, pH 4–7) and nonacid reflux (NAR, pH >7.0) are also recognized, although both may be included under the umbrella term NAR. However, despite identification of ambulatory pH‐impedance monitoring, data on clinical relevance and prognostic value of NAR are limited. The Lyon Consensus, an international expert review that defines conclusive metrics for gastroesophageal reflux disease (GERD), identifies NAR as “supportive” but not conclusive for GERD.

Purpose

This review provides perspectives on whether NAR fulfills three criteria for clinical relevance: whether NAR sufficiently explains pathogenesis of symptoms, whether it is associated with meaningful manifestations of GERD, and whether it can predict treatment efficacy.
Mechanosensitive enteric neurons in the guinea pig gastric fundus and antrum
Authors: Mayr Sophia , Schliep Ronja , Elfers Kristin , Mazzuoli‐Weber Gemma
Published: September 2023

Background

Coping with the ingested food, the gastric regions of fundus, corpus, and antrum display different motility patterns. Intrinsic components of such patterns involving mechanosensitive enteric neurons (MEN) have been described in the guinea pig gastric corpus but are poorly understood in the fundus and antrum.

Methods

To elucidate mechanosensitive properties of myenteric neurons in the gastric fundus and antrum, membrane potential imaging using Di‐8‐ANEPPS was applied. A small‐volume injection led to neuronal compression. We analyzed the number of MEN and their firing frequency in addition to the involvement of selected mechanoreceptors. To characterize the neurochemical phenotype of MEN, we performed immunohistochemistry.

Key Results

In the gastric fundus, 16% of the neurons reproducibly responded to mechanical stimulation and thus were MEN. Of those, 83% were cholinergic and 19% nitrergic. In the antrum, 6% of the neurons responded to the compression stimulus, equally distributed among cholinergic and nitrergic MEN. Defunctionalizing the sensory extrinsic afferents led to a significant drop in the number of MEN in both regions.

Conclusion

We provided evidence for MEN in the gastric fundus and antrum and further investigated mechanoreceptors. However, the proportions of the chemical phenotypes of the MEN differed significantly between both regions. Further investigations of synaptic connections of MEN are crucial to understand the hardwired neuronal circuits in the stomach.
Host‐induced gene silencing is a promising biological tool to characterize the pathogenicity of Magnaporthe oryzae and control fungal disease in rice
Authors: Jin Byung Jun , Chun Hyun Jin , Choi Cheol Woo , Lee Su Hyeon , Cho Hyun Min , Park Mi Suk , Baek Dongwon , Park Sook‐Young , Lee Yong‐Hwan , Kim Min Chul
Published: September 2023

The rice blast fungus Magnaporthe oryzae is a devastating plant pathogen that threatens rice production worldwide. Host‐induced gene silencing (HIGS) has been effectively applied to study pathogenic gene function during host–microbe interactions and control fungal diseases in various crops. In this study, the HIGS system of M. oryzae was established using transgenic fungus expressing green fluorescence protein (GFP), KJ201::eGFP and 35S::dsRNAi plants, which produce small interfering RNAs targeting fungal genes. Through this system, we verified the HIGS of rice blast fungus quantitatively and qualitatively in both Arabidopsis and rice. Then, we showed that the HIGS of M. oryzae's pathogenic genes, including RGS1, MgAPT2 and LHS1, significantly alter its virulence. Both 35S::dsRNAi_MgAPT2 and 35S::dsRNAi_LHS1 plants showed a considerably enhanced fungal resistance, characterized by the formation of H2O2‐containing defensive granules and induction of rice pathogenesis‐related (PR) genes. In addition, the enhanced susceptibility of 35S::dsRNAi_RGS1 plants to blast fungus suggested a novel mode of action of this gene during fungal infection. Overall, the results of this study demonstrate that HIGS is a very effective and efficient biological tool not only to accurately characterize the functions of fungal pathogenic genes during rice‐M. oryzae interactions, but also to control fungal disease and ensure a successful rice production.
Effects of macrocyclic lactone anthelmintics on seed germination of temperate grassland species
Authors: Laber L. , Eichberg C. , Zimmerbeutel A. , Düring R.‐A. , Donath T. W.
Published: September 2023

Macrocyclic lactone anthelmintics are widely used to control invertebrate pests in livestock, such as sheep. While anthelmintic effects on non‐target animals, such as dung‐dwelling insects, are well studied, effects on seed germination are largely unknown. Seeds can come into contact with anthelmintics either during passage through the gastro‐intestinal tract of grazing animals or when anthelmintics are excreted with their dung into the environment, which may result in changed germination patterns.

We used four commonly applied macrocyclic lactones to assess their effects on germination: moxidectin, ivermectin, abamectin and doramectin as pure substances; moxidectin and ivermectin also in formulated form. We tested these pharmaceuticals on 17 different temperate grassland species from five plant families. Seeds were exposed to three concentrations of macrocyclic lactones (0.1, 1.0 and 10.0 mg·l−1) under controlled conditions, and germination was assessed over a 6‐week period. From these data, we calculated germination percentage, mean germination time and germination synchrony.

Most of the tested species were significantly affected in germination percentage and/or mean germination time by at least one of the tested pharmaceuticals, with formulated moxidectin having the largest impact. In general, the effects found were species‐ and pharmaceutical‐specific. While formulated substances generally reduced germination percentage and increased mean germination time, pure substances increased germination percentage. Synchrony showed less clear patterns in all pharmaceuticals.

Although effect size and sign varied between species, our study shows that non‐target effects of macrocyclic lactones commonly occur in terrestrial plants. This may impede successful seed exchange between habitats via sheep, and even translate into profound changes to grazed ecosystems.
The Suicide Dot Probe Task: Psychometric properties and validity in relation to suicide‐related outcomes
Authors: Rogers Megan L. , Carosa Catarina L. , Haliczer Lauren A. , Hughes Christopher D. , Schofield Casey A. , Armey Michael F.
Published: September 2023

Background

Attentional biases to suicide‐related stimuli have been linked to suicide‐related outcomes. However, behavioral tasks that have been previously modified to capture suicide‐specific attentional biases have demonstrated inconsistent reliability and validity. Adaptation of the Dot Probe Task, a computerized assessment that has been adapted to study a wide variety of biases, may be a promising candidate for assessing suicide‐specific biases.

Methods

In 280 recently discharged inpatients (51% male; Mage = 40.22 years), we evaluated the psychometric properties of a modified Suicide Dot Probe Task. Participants completed this task and assessments of suicidal thoughts and behaviors at baseline and 6‐month follow‐up.

Results

The Suicide Dot Probe Task demonstrated poor‐to‐moderate internal consistency and poor test‐retest reliability, and participant response times were slower to suicide‐specific and dysphoric stimuli than positive stimuli. However, there were no differences based on the presence or characteristics of recent or lifetime suicidal ideation or attempts. Participants' suicide‐specific biases were not predictive of suicidal ideation or attempts at follow‐up.

Conclusions

The Suicide Dot Probe Task exhibited questionable reliability, and differences in attentional biases were not associated with suicidal ideation or attempts. This study contributes to a body of research demonstrating the questionable utility of several behavioral tasks to study suicide‐specific attentional biases.
Learning to labour in the gym: Training to fight to reimagine the self and work under neoliberalism
Authors: Singh Amit
Published: September 2023

This paper explores the motivations of those who train to fight at a Muay Thai and Kickboxing gym in East London, who view fighting (and training in the gym) as a means of coping with the harshness of work, as a financial supplement to work, and as an alternative form of work. It explores how the repetitive regimes of the body employed by fighters, such as dieting, twice‐daily training sessions and sparring, as both individual and collective bodily work, contrasts with their experiences of social life under capitalism, which is seen as unfair and unmeritocratic. This, it argues, leads people to seek refuge within the meritocratic sphere of the gym, which offers new opportunities, possibilities and a unique ability to master the self. It subsequently argues that we can understand training to fight as a response to class exclusion, stigmatisation, and helplessness under neoliberalism.
Identification of the novel HLA‐B*15:270 allele by Sanger dideoxy nucleotide sequencing
Authors: Li Jian‐Ping , Liu Ying , Zhang Xu , Wei Ying‐Dong , Li Xiao‐Feng
Published: September 2023

HLA‐B*15:270 differs from HLA‐B*15:12:01 by one nucleotide substitution at position 679 in exon 4.
Cultivating biodiverse futures at the (postcolonial) botanical garden
Authors: Hassouna Silvia
Published: September 2023

This article examines ecological practices at the Palestine Museum of Natural History in Bethlehem, West Bank. Through an analysis of the museum's botanical gardens, the article explores what it calls ‘biodiverse futures’ as a spatio‐temporal alternative to the ecological domination of settler colonialism in Israel/Palestine. While much scholarship has focused on the environmental imaginaries that have informed colonial conquest in Palestine, this paper draws attention to the ways in which these relationships extend into constructions of the future. Combining the literature on environmental violence with the literature on futurity and decolonisation, this article develops an approach that foregrounds the relevance of ‘ecological temporalities’ in examining alternatives to settler futures in Israel/Palestine. To date, only a limited number of contributions have examined environmentalism as a powerful discursive tool for constructing the future. The case of the museum gardens highlights three interrelated aspects of the production of ecological counter‐futures: futures as knowledge, futures as (bio)diversity, and futures as survival. Drawing on ethnographic material and interviews with museum staff and volunteers, this paper contributes to the study of the temporalities of environmental violence and ecological resistance in Israel/Palestine.
Detection of unreported usage of the antiretroviral drug lamivudine in two blood donors
Authors: Nishiya Anna , Salles Nanci , de Almeida‐Neto Cesar , Ferreira Suzete , Nogueira Fátima , Rocha Vanderson , Mendrone‐Júnior Alfredo
Published: September 2023

Background

Unreported HIV antiretroviral (ARV) drug usage by blood donors compromises the ability to detect evidence of HIV infection in blood screening tests and represents a risk for blood transfusion safety. Our objective was to determine the frequency of undeclared ARV drug use by blood donors with altered HIV markers.

Study Design and Methods

This was a retrospective cross‐sectional analysis of donations that were tested for HIV antibody (ab), antigen (ag), and RNA by chemiluminescent immunoassay and nucleic acid screening tests. Positive samples were retested and were subjected to ARV drug testing by high‐performance liquid chromatography–tandem mass spectrometry.

Results

Of 345,252 blood donations, 361 (0.1%) were positive on initial testing. Samples from 296 (81.9%) of these donations were available for further analysis. The presence of HIV ab/ag and/or RNA was confirmed in 83 (28.0%) of these samples. All 296 bloods were subjected to ARV testing. The ARV drug lamivudine, at 11.3 and 6.7 ng/mL, was detected in 2 of 83 (2.4%) donations that were HIV positive. Other drugs were not detected.

Conclusion

Unreported ARV usage was identified in two candidates for blood donation. More intensive efforts to educate donors about disclosure and to investigate the extent of this phenomenon in Brazil are needed.
A Robust Image Encryption Scheme Based on Block Compressive Sensing and Wavelet Transform
Authors: Abed Qutaiba K , Mahmoud Al-Jawher Waleed A
Published: September 2023

In this paper, a modified robust image encryption scheme is developed by combining block compressive sensing (BCS) and Wavelet Transform. It was achieved with a balanced performance of security, compression, robustness and running efficiency. First, the plain image is divided equally and sparsely represented in discrete wavelet transform (DWT) domain, and the coefficient vectors are confused using the coefficient random permutation strategy and encrypted into a secret image by compressive sensing. In pursuit of superior security, the hyper-chaotic Lorenz system is utilized to generate the updated secret code streams for encryption and embedding with assistance from the counter mode. This scheme is suitable for processing the medium and large images in parallel. Additionally, it exhibits superior robustness and efficiency compared with existing related schemes. Simulation results and comprehensive performance analyses are presented to demonstrate the effectiveness, secrecy and robustness of the proposed scheme. The compressive encryption model using BCS with Walsh transform as sensing matrix and WAM chaos system, the scrambling technique and diffusion succeeded in enhancement of secure performance.
Integrated treatment for comorbid eating disorders and substance use disorders: a scoping review protocol
Authors: Miller Molly , Bartel Sara , Hunter Abbey , Boulos Leah , Lacroix Emilie
Published: September 2023

Objective:

This review will identify and summarize the literature on the integrated treatment of comorbid eating disorders and substance use disorders, focusing on clinical practice guidelines and treatment studies.

Introduction:

Eating disorders and substance use disorders are the deadliest psychiatric conditions, frequently co-occur, and are linked to greater symptom severity and poorer treatment outcomes. Despite repeated calls for their integrated treatment, such an approach has rarely been empirically evaluated. To advance the development of integrated treatments for comorbid eating disorders and substance use disorders, a critical first step is to describe existing treatment guidelines and summarize research evidence for this approach.

Inclusion criteria:

This review will consider all peer-reviewed and gray literature describing the integrated treatment of comorbid eating disorders and substance use disorders, focusing on (i) clinical practice guidelines; and (ii) treatment studies. We will not place limitations on populations, types of eating disorders, types of substance use disorders, or other contextual factors.

Methods:

Databases to be searched will include MEDLINE (Ovid), Embase, CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Scopus, and clinical practice guidelines databases identified by CADTH Grey Matters. No date or language limits will be applied to the search. At the screening stage, we will only consider literature in English or French. Two independent reviewers will screen studies at the title/abstract and full-text levels, and extract relevant studies. Disagreements will be resolved through discussion. Findings will be presented in tabular format and a narrative summary.

Details of the review project available at Open Science Framework:

https://osf.io/za35j/
Scaling Overall Effectiveness in Low-Temperature Experiments
Authors: Bryant Carol E. , Rutledge James L.
Published: September 2023

The design of film-cooled engine components requires an understanding of the expected temperature distributions while in service, thus requiring accurate predictions through low-temperature testing. Overall effectiveness, ϕ, is the integrated indicator of overall cooling performance. An experiment to measure ϕ at low temperature requires appropriate scaling through careful selection of not only the coolant and freestream gases but also the model material itself. Matching ϕ requires that the experiment has matched values of the adiabatic effectiveness, Biot number, coolant warming factor, and ratio of external to internal heat transfer coefficient. Previous research has shown the requirements to match each of those four parameters individually. However, matching all those parameters simultaneously presents an overconstrained problem, and no comprehensive recommendations exist for the practical experimentalist who wishes to conduct an appropriately scaled, low-temperature experiment truly suitable for determining ϕ. Four fluidic parameters are identified, which in an experiment must be as close as possible to their values at engine conditions. A normalized root-mean-square difference (NRMSD) of the residuals of those parameters is proposed to quantify how well a proposed wind tunnel experiment is likely to yield engine-relevant ϕ values. We show that this process may be used by any experimentalist to identify the appropriate fluids, conditions, and materials for a matched ϕ experiment. Several case studies were performed using computational fluid dynamics (CFD) to show the utility of this process. Of the common experimental techniques examined here, a matched Biot number experiment with 500 K freestream air and 250 K coolant appears to be particularly adept at simulating engine conditions, even better than experiments that make use of CO2 coolant.
Investigation of the seat-dip effect using finite-difference time-domain simulations
Authors: Meyer Julie , Tahvanainen Henna , Saarelma Jukka , Lokki Tapio
Published: September 2023

The seat-dip effect (SDE) occurs when low-frequency sounds propagate through the seating area of a performance space. The physical aspects governing the effect still puzzle acousticians mostly due to the large variety of seating configurations. In this study, the SDE is investigated in three parameterized hall models using the finite-difference time-domain method to simulate a large number of seat configurations in order to quantify the contribution of different geometric properties related to the seating area. The results show that the step size defining the inclination angle of the seating area and the opening underneath the seats (or underpass) are significant factors contributing to the SDE, whereas the stage height and the source position are found to be less important. The results also demonstrate that with an underpass greater than the step size, the first frequency dip occurring between 80 and 100 Hz is mitigated regardless of the hall type considered. The phenomenon is also found to be predominant in the early part of the room response. Visualizations of spatial and time-frequency evolution in the halls are also provided for the cases where the seat properties are found to visibly affect the magnitude spectrum.
Dialect and gender perception in relation to the intelligibility of low-pass and high-pass filtered spontaneous speech
Authors: Jacewicz Ewa , Fox Robert A. , Holt Christopher E.
Published: September 2023

Most cues to speech intelligibility are within a narrow frequency range, with its upper limit not exceeding 4 kHz. It is still unclear whether speaker-related (indexical) information is available past this limit or how speaker characteristics are distributed at frequencies within and outside the intelligibility range. Using low-pass and high-pass filtering, we examined the perceptual salience of dialect and gender cues in both intelligible and unintelligible speech. Setting the upper frequency limit at 11 kHz, spontaneously produced unique utterances (n = 400) from 40 speakers were high-pass filtered with frequency cutoffs from 0.7 to 5.56 kHz and presented to listeners for dialect and gender identification and intelligibility evaluation. The same material and experimental procedures were used to probe perception of low-pass filtered and unmodified speech with cutoffs from 0.5 to 1.1 kHz. Applying statistical signal detection theory analyses, we found that cues to gender were well preserved at low and high frequencies and did not depend on intelligibility, and the redundancy of gender cues at higher frequencies reduced response bias. Cues to dialect were relatively strong at low and high frequencies; however, most were in intelligible speech, modulated by a differential intelligibility advantage of male and female speakers at low and high frequencies.
Noninvasive morpho-molecular imaging reveals early therapy-induced senescence in human cancer cells
Authors: Bresci Arianna , Kim Jeong Hee , Ghislanzoni Silvia , Manetti Francesco , Wu Lintong , Vernuccio Federico , Ceconello Chiara , Sorrentino Salvatore , Barman Ishan , Bongarzone Italia , Cerullo Giulio , Vanna Renzo , Polli Dario
Published: September 2023

Anticancer therapy screening in vitro identifies additional treatments and improves clinical outcomes. Systematically, although most tested cells respond to cues with apoptosis, an appreciable portion enters a senescent state, a critical condition potentially driving tumor resistance and relapse. Conventional screening protocols would strongly benefit from prompt identification and monitoring of therapy-induced senescent (TIS) cells in their native form. We combined complementary all-optical, label-free, and quantitative microscopy techniques, based on coherent Raman scattering, multiphoton absorption, and interferometry, to explore the early onset and progression of this phenotype, which has been understudied in unperturbed conditions. We identified TIS manifestations as early as 24 hours following treatment, consisting of substantial mitochondrial rearrangement and increase of volume and dry mass, followed by accumulation of lipid vesicles starting at 72 hours. This work holds the potential to affect anticancer treatment research, by offering a label-free, rapid, and accurate method to identify initial TIS in tumor cells.
Therapeutic blockade of ER stress and inflammation prevents NASH and progression to HCC
Authors: Boslem Ebru , Reibe Saskia , Carlessi Rodrigo , Smeuninx Benoit , Tegegne Surafel , Egan Casey L. , McLennan Emma , Terry Lauren V. , Nobis Max , Mu Andre , Nowell Cameron , Horadagoda Neil , Henstridge Darren C. , Mellett Natalie A. , Timpson Paul , Jones Matthew , Denisenko Elena , Forrest Alistair R. R. , Tirnitz-Parker Janina E. E. , Meikle Peter J. , Rose-John Stefan , Karin Michael , Febbraio Mark A.
Published: September 2023

The incidence of hepatocellular carcinoma (HCC) is rapidly rising largely because of increased obesity leading to nonalcoholic steatohepatitis (NASH), a known HCC risk factor. There are no approved treatments to treat NASH. Here, we first used single-nucleus RNA sequencing to characterize a mouse model that mimics human NASH–driven HCC, the
MUP-uPA
mouse fed a high-fat diet. Activation of endoplasmic reticulum (ER) stress and inflammation was observed in a subset of hepatocytes that was enriched in mice that progress to HCC. We next treated
MUP-uPA
mice with the ER stress inhibitor BGP-15 and soluble gp130Fc, a drug that blocks inflammation by preventing interleukin-6 trans-signaling. Both drugs have progressed to phase 2/3 human clinical trials for other indications. We show that this combined therapy reversed NASH and reduced NASH-driven HCC. Our data suggest that these drugs could provide a potential therapy for NASH progression to HCC.
Widespread aquifer depressurization after a century of intensive groundwater use in USA
Authors: Hilton Annette , Jasechko Scott
Published: September 2023

Water supplies for household use and irrigated agriculture rely on groundwater wells. When wells are drilled into a highly pressurized aquifer, groundwater may flow up the well and onto the land surface without pumping. These flowing artesian wells were common in the early 1900s in the United States before intensive groundwater withdrawals began, but their present-day prevalence remains unknown. Here, we compile and analyze ten thousand well water observations made more than a century ago. We show that flowing artesian conditions characterized ~61% of wells tapping confined aquifers before 1910, but only ~4% of wells tapping confined aquifers today. This pervasive loss of flowing artesian conditions evidences a widespread depressurization of confined aquifers after a century of intensive groundwater use in the United States. We conclude that this depressurization of confined aquifers has profoundly changed groundwater storage and flow, increasing the vulnerability of deep aquifers to pollutants and contributing to land subsidence.
CRISPR-based engineering of RNA viruses
Authors: Nemudryi Artem , Nemudraia Anna , Nichols Joseph E. , Scherffius Andrew M. , Zahl Trevor , Wiedenheft Blake
Published: September 2023

CRISPR RNA–guided endonucleases have enabled precise editing of DNA. However, options for editing RNA remain limited. Here, we combine sequence-specific RNA cleavage by CRISPR ribonucleases with programmable RNA repair to make precise deletions and insertions in RNA. This work establishes a recombinant RNA technology with immediate applications for the facile engineering of RNA viruses.
Possible beneficial interactions of ciliated protozoans with coral health and resilience
Authors: Ravindran Chinnarajan , Irudayarajan Lawrance , Raveendran Haritha P.
Published: September 2023

Microbial interactions contribute significantly to coral health in the marine environment. Most beneficial associations have been described with their bacterial communities, but knowledge of beneficial associations between protozoan ciliates and corals is still lacking. Ciliates are important bacterial predators and provide nutrition to higher trophic-level organisms. The mucus secreted by corals and the microenvironment of the coral surface layer attract ciliates based on their food preferences. The mixotrophic and heterotrophic ciliates play a major role in nutrient cycling by increasing nitrogen, phosphorus, and extractable sulfur, which can enhance the proliferation of coral beneficial microbe. Besides, bacterial predator ciliates reduce the pathogenic bacterial population that infects the coral and also act as bioindicators for assessing the toxicity of the reef ecosystem. Thus, these ciliates can be used as a beneficial partner in influencing coral health and resilience under various stress conditions. Herein, we explore the urgent need to understand the complex beneficial interactions of ciliates that may occur in the coral reef ecosystem.
Jingmen tick virus: an emerging arbovirus with a global threat
Authors: Wu Zhen , Zhang Ming , Zhang Yuli , Lu Ke , Zhu Wenbing , Feng Shuo , Qi Jun , Niu Guoyu
Published: September 2023

Jingmen tick virus (JMTV), belonging to the
Flaviviridae
family, is a novel segmented RNA virus identified in 2014 in the Jingmen region of Hubei Province, China. Up to now, JMTV has been detected in a variety of countries or regions in Asia, Europe, Africa, and the Americas, involving a wide range of arthropods and mammals, and even humans. The JMTV genome is composed of four linear RNA segments, two of which are derived from flaviviruses, while the other two segments are unique to JMTV and has no matching virus. Currently, JMTV has been shown to have a pathogenic effect on humans. Humans who had been infected would develop viremia and variable degrees of clinical symptoms. However, the pathogenic mechanism of JMTV has not been elucidated yet. Therefore, it is crucial to strengthen the epidemiological surveillance and laboratory studies of JMTV.
AMPK protects endothelial cells against HSV-1 replication via inhibition of mTORC1 and ACC1
Authors: Doshi Heena , Spengler Katrin , Godbole Amod , Gee Yi Sing , Baell Jonathan , Oakhill Jonathan S. , Henke Andreas , Heller Regine
Published: September 2023

Herpes simplex virus type 1 (HSV-1) is a widespread contagious pathogen, mostly causing mild symptoms on the mucosal entry side. However, systemic distribution, in particular upon reactivation of the virus in immunocompromised patients, may trigger an innate immune response and induce damage of organs. In these conditions, HSV-1 may infect vascular endothelial cells, but little is known about the regulation of HSV-1 replication and possible defense mechanisms in these cells. The current study addresses the question of whether the host cell protein AMP-activated protein kinase (AMPK), an important metabolic sensor, can control HSV-1 replication in endothelial cells. We show that downregulation of the catalytic subunits AMPKα1 and/or AMPKα2 increased HSV-1 replication as monitored by TCID
50
titrations, while a potent AMPK agonist, MK-8722, strongly inhibited it. MK-8722 induced a persistent phosphorylation of the AMPK downstream targets acetyl-CoA carboxylase (ACC) and the rapamycin-sensitive adaptor protein of mTOR (Raptor) and, related to this, impairment of ACC1-mediated lipid synthesis and the mechanistic target of the rapamycin complex-1 (mTORC1) pathway. Since blockade of mTOR by Torin-2 as well as downregulation of ACC1 by siRNA also decreased HSV-1 replication, MK-8722 is likely to exert its anti-viral effect via mTORC1 and ACC1 inhibition. Importantly, MK-8722 was able to reduce virus replication even when added after HSV-1. Together, our data highlight the importance of endothelial cells as host cells for HSV-1 replication upon systemic infection and identify AMPK, a metabolic host cell protein, as a potential target for antiviral strategies against HSV-1 infection and its severe consequences.

IMPORTANCE

Herpes simplex virus type 1 (HSV-1) is a common pathogen that causes blisters or cold sores in humans. It remains latent in infected individuals and can be reactivated multiple times. In adverse conditions, for instance, in immunocompromised patients, HSV-1 can lead to serious complications such as encephalitis, meningitis, or blindness. In these situations, infection of endothelial cells lining the surface of blood vessels may contribute to the manifestation of disease. Here, we describe the role of AMP-activated protein kinase (AMPK), a potent regulator of cellular energy metabolism, in HSV-1 replication in endothelial cells. While downregulation of AMPK potentiates HSV-1 replication, pharmacological AMPK activation inhibits it by limiting the availability of required host cell macromolecules such as proteins or fatty acids. These data highlight the role of metabolic host cell proteins as antiviral targets and reveal activation of endothelial AMPK as a potential strategy to protect from severe consequences of HSV-1 infection.
Asymmetry and evolution of craton-influenced rifted margins
Authors: Raghuram G. , Pérez-Gussinyé M. , Andrés-Martínez M. , García-Pintado J. , Araujo M. Neto , Morgan J.P.
Published: September 2023

Rifting can result in asymmetric conjugate margins. In numerical models with laterally homogeneous lithosphere, the polarity of the asymmetry is random and results from spontaneous strain localization on a dominant fault/shear zone. However, along the central South Atlantic, margin width is well correlated to the proximity of the rift to a craton during rifting. To understand the evolution of rifting close to a craton, we used numerical experiments that included a thick craton lithosphere adjacent to a thinner, mobile-belt lithosphere. When rifting starts close to the craton, i.e., ≤ 100 km, deformation focuses along a fault/shear zone dipping toward the craton, leading to cratonward asymmetric asthenospheric uplift and rift migration. This results in a narrow margin on the craton side and a wide margin on the mobile-belt side. Craton-related asymmetry results in the wide margin subsiding more than the narrow one, inducing the formation of large synrift sag basins in the wide conjugate, as in the South Atlantic. This differential subsidence is preserved for ~100 m.y. after breakup and may partly explain the present-day higher dynamic topography close to cratons in the central South Atlantic. Mantle flow during asymmetric rifting leads to weakening of the craton lithosphere, partial intermixing, and recycling into the convective mantle, as interpreted for this sector of the South Atlantic ridge. Thus, rifting adjacent to a craton may have wide-ranging tectonic, stratigraphic, and compositional consequences that affect not only margin architecture, but also the development of subsequent dynamic topography and the spreading system.
Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study
Authors: Stack Roisin , Doherty Jayne , O'Moráin Neil , Nolan Blathnaid , Sheridan Juliette , Cullen Garret , Mulcahy Hugh , Buckley Maire , Horgan Gareth , Hamed Mohamed , McDermott Edel , Doherty Glen
Published: September 2023

Objective

To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application.

Design

A retrospective review of BS colonoscopies performed in 2015–2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing ‘European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis’ (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed.

Results

Total number of index BS colonoscopies performed in 2015–2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the ‘potentially deferred’ procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort.

Conclusion

BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies.
Understanding pre-hospital blood transfusion decision-making for injured patients: an interview study
Authors: Marsden Max E R , Kellett Suzie , Bagga Rahul , Wohlgemut Jared M , Lyon Richard L , Perkins Zane B , Gillies Katie , Tai Nigel RM
Published: September 2023

Background

Blood transfusion for bleeding trauma patients is a promising pre-hospital intervention with potential to improve outcomes. However, it is not yet clear which patients may benefit from pre-hospital transfusions. The aim of this study was to enhance our understanding of how experienced pre-hospital clinicians make decisions regarding patient blood loss and the need for transfusion, and explore the factors that influence clinical decision-making.

Methods

Pre-hospital physicians, from two air ambulance sites in the south of England, were interviewed between December 2018 and January 2019. Participants were involved in teaching or publishing on the management of bleeding trauma patients and had at least 5 years of continuous and contemporary practice at consultant level. Interviews were semi-structured and explored how decisions were made and what made decisions difficult. A qualitative description approach was used with inductive thematic analysis to identify themes and subthemes related to blood transfusion decision-making in trauma.

Results

Ten pre-hospital physicians were interviewed and three themes were identified:recognition-primed analysis,uncertaintyandimperfect decision analysis. The first theme describes how participants make decisions using selected cues, incorporating their experience and are influenced by external rules and group expectations. What made decisions difficult for the participants was encapsulated in the uncertainty theme. Uncertainty emerged regarding the patient’s true underlying physiological state and the treatment effect of blood transfusion. The last theme focuses on the issues with decision-making itself. Participants demonstrated lapses in decision awareness, often incomplete decision evaluation and described challenges to effective learning due to incomplete patient outcome information.

Conclusion

Pre-hospital clinicians make decisions about bleeding and transfusion which are recognition-primed and incorporate significant uncertainty. Decisions are influenced by experience and are subject to bias. Improved understanding of the decision-making processes provides a theoretical perspective of how decisions might be supported in the future.
Hospital-administered ECPR for out-of-hospital cardiac arrest: an observational cohort study
Authors: Puolakka Tuukka , Salo Ari , Varpula Marjut , Nurmi Jouni , Skrifvars Markus B , Wilkman Erika , Lemström Karl , Kuisma Markku
Published: September 2023

Background

Extracorporeal cardiopulmonary resuscitation (ECPR) is a treatment method for refractory out-of-hospital cardiac arrest (OHCA) requiring a complex chain of care.

Methods

All cases of OHCA between 1 January 2016 and 31 December 2021 in the Helsinki University Hospital catchment area in which the ECPR protocol was activated were included in the study. The protocol involved patient transport from the emergency site with ongoing mechanical cardiopulmonary resuscitation (CPR) directly to the cardiac catheterisation laboratory where the implementation of extracorporeal membrane oxygenation (ECMO) was considered. Cases of hypothermic cardiac arrest were excluded. The main outcomes were the number of ECPR protocol activations, duration of prehospital and in-hospital time intervals, and whether the ECPR candidates were treated using ECMO or not.

Results

The prehospital ECPR protocol was activated in 73 cases of normothermic OHCA. The mean patient age (SD) was 54 (±11) years and 67 (91.8%) of them were male. The arrest was witnessed in 67 (91.8%) and initial rhythm was shockable in 61 (83.6%) cases. The median ambulance response time (IQR) was 9 (7–11) min. All patients received mechanical CPR, epinephrine and/or amiodarone. Seventy (95.9%) patients were endotracheally intubated. The median (IQR) highest prehospital end-tidal CO2was 5.5 (4.0–6.9) kPa.

A total of 37 (50.7%) patients were treated with venoarterial ECMO within a median (IQR) of 84 (71–105) min after the arrest. Thirteen (35.1%) of them survived to discharge and 11 (29.7%) with a cerebral performance category (CPC) 1–2. In those ECPR candidates who did not receive ECMO, 8 (22.2%) received permanent return of spontaneuous circulation during transport or immediately after hospital arrival and 6 (16.7%) survived to discharge with a CPC 1–2.

Conclusions

Half of the ECPR protocol activations did not lead to ECMO treatment. However, every fourth ECPR candidate and every third patient who received ECMO-facilitated resuscitation at the hospital survived with a good neurological outcome.
Epidemiology of traumatically injured Yemeni civilians treated at the Omani National Trauma Centre over a 2-year period: a retrospective cohort study
Authors: Ramaraj Prashanth , Al-Buluchi T , Al-Shaqsi S , Al-Kashmiri A , Perkins Z B , De'Ath H D
Published: September 2023

Introduction

Armed conflict is a growing global cause of death, posing a significant threat to the resilience of global health systems. However, the burden of disease resulting from the Yemeni Civil War remains poorly understood. Approximately half of healthcare facilities in Yemen are non-operational, and around 15% of the population has been displaced. Consequently, neighbouring countries’ trauma systems have been providing care to the injured. The objective of this study was to investigate the epidemiology and management of Yemeni civilian victims injured during the war who were subsequently extracted and treated at the study centre in Oman.

Methods

We conducted a retrospective cohort study, including all Yemeni civilians treated for traumatic injuries at the study centre from January 2015 to June 2017. We extracted data on age, sex, date of attendance, mechanism of injury, injuries sustained and treatment.

Results

A total of 254 injured patients were identified. Their median age was 25 (range 3–65) years and 244 (96.1%) were male. Explosions (160 patients, 63.0%) were the most common mechanism of injury, and fractures (n=232 fractures, 42.3% of all injuries; in 149 patients, 58.7% of all patients) the most common injury. Eighty-four of the 150 patients (56%) who received operative management at the study centre were receiving a second procedure after an index procedure outside of Oman.

One hundred and twenty-eight (50.4%) patients experienced permanent loss of function in at least one body part and/or limb loss.

Conclusions

This study demonstrates the downstream needs of Yemeni civilians who were evacuated to the study centre, revealing a considerable burden of morbidity associated with this population. The findings emphasise key areas that receiving hospitals should prioritise in resource allocation when managing conflict-wounded evacuees. Additionally, the study underscores the need for holistic rehabilitation for civilian casualties displaced by conflict.