bluuebunny/crossref_metadata_2025 huggingface dataset:
Food security indicators in deltaic and coastal research: a scoping review
Authors: Szabo Sylvia , Navaratne Thilini , Park Seree , Pal Indrajit , Cooper Gregory S.
Published: October 2022

Delta regions occupy a small proportion of the earth’s surface area, yet they are home to more than 500 million people. While numerous regional studies have examined the prevalence and the determinants of food security in specific delta and coastal regions, there is still a paucity of systematic analysis on the food security indicators commonly used by scientists and policymakers. To fill this gap, we carried out a systematic review using Covidence, a Cochrane-adopted systematic review processing software. Only scientific papers were considered for review, and the search was conducted in the following databases: SCOPUS, Thomson Reuters Web of Science, Science Direct, ProQuest, and Google Scholar. Following screening for duplicates, relevance, and full-text eligibility, 80 articles were retained for review. In total, 143 different food security indicators were identified (excluding duplicates), with measures of food availability featuring in 27% of reviewed papers. In contrast, indicators capturing the stability of food security were the least commonly applied (8% of reviewed papers). Furthermore, we find a weak level of alignment between deltaic food security indicators and the SDG 2 indicators, only two targets and their indicators were directly aligned in the papers reviewed. Therefore, in order to achieve the aspirational goal of zero hunger in delta regions and worldwide, we suggest researchers and policymakers directly align their choice of food security indicators with those of SDG 2, whilst simultaneously increasing the diversity of indicators to better capture the utilization and stability of food security in an ever-changing and more chaotic climate.
Eating away T cell responses in lung cancer
Authors: Ferrara Roberto , Roz Luca
Published: October 2022

Despite evidence for clinical benefit in patients suffering from lung cancer following treatment with immune checkpoint inhibitors (ICI), it is still uncertain how to predict which patients are likely to experience a significant response. In their work, Valencia et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220726) identify the DSTYK kinase as a cancer cell–intrinsic modulator of response to immunotherapy. Through regulation of the mTOR pathway and stimulation of protective autophagy, DSTYK blunts CD8+ T cell–mediated killing of cancer cells. Accordingly, lung cancers with increased expression of DSTYK are less responsive to ICI treatment. These observations could be useful in the clinic towards the development of predictive biomarkers and novel therapeutic strategies.
Variations in the thermal conductivity of magnetosensitive elastomers by magnetically induced internal restructuring
Authors: Jäger Gustav J L , Fischer Lukas , Lutz Tyler , Menzel Andreas M
Published: October 2022

Magnetosensitive elastomers respond to external magnetic fields by changing their stiffness and shape. These effects result from interactions among magnetized inclusions that are embedded within an elastic matrix. Strong external magnetic fields induce internal restructuring, for example the formation of chain-like aggregates. However, such reconfigurations affect not only the overall mechanical properties of the elastomers but also the transport through such systems. We concentrate here on the transport of heat, that is thermal conductivity. For flat, thin model systems representing thin films or membranes and modeled by bead-spring discretizations, we evaluate the internal restructuring in response to magnetization of the particles. For each resulting configuration, we evaluate the associated thermal conductivity. We analyze the changes in heat transport as a function of the strength of magnetization, particle number, density of magnetizable particles (at fixed overall particle number), and aspect ratio of the system. We observe that varying any one of these parameters can induce pronounced changes in the bulk thermal conductivity. Our results motivate future experimental and theoretical studies of systems with magnetically tunable thermal but also electric conductivity—both of which have only rarely been addressed so far.
The role of surface states and point defects on optical properties of InGaN/GaN multi-quantum wells in nanowires grown by molecular beam epitaxy
Authors: Concordel Alexandre , Bleuse Joël , Jacopin Gwénolé , Daudin Bruno
Published: October 2022

The optical properties of nanowire-based InGaN/GaN multiple quantum wells (MQWs) heterostructures grown by plasma-assisted molecular beam epitaxy are investigated. The beneficial effect of an InGaN underlayer grown below the active region is demonstrated and assigned to the trapping of point defects transferred from the pseudo-template to the active region. The influence of surface recombination is also investigated. For low InN molar fraction value, we demonstrate that AlO
x
deposition efficiently passivate the surface. By contrast, for large InN molar fraction, the increase of volume non-radiative recombination, which we assign to the formation of additional point defects during the growth of the heterostructure dominates surface recombination. The inhomogeneous luminescence of single nanowires at the nanoscale, namely a luminescent ring surrounding a less luminescent centre part points towards an inhomogeneous spatial distribution of the non-radiative recombination center tentatively identified as intrinsic point defects created during the MQWs growth. These results can contribute to improve the performances of microLEDs in the visible range.
Wrinkle-mediated CVD synthesis of wafer scale Graphene/h-BN heterostructures
Authors: Dimitropoulos Marinos , Trakakis George , Androulidakis Charalampos , Kotsidi Maria , Galiotis Costas
Published: October 2022

The combination of two-dimensional materials (2D) into heterostructures enables their integration in tunable ultrathin devices. For applications in electronics and optoelectronics, direct growth of wafer-scale and vertically stacked graphene/hexagonal boron nitride (h-BN) heterostructures is vital. The fundamental problem, however, is the catalytically inert nature of h-BN substrates, which typically provide a low rate of carbon precursor breakdown and consequently a poor rate of graphene synthesis. Furthermore, out-of-plane deformations such as wrinkles are commonly seen in 2D materials grown by chemical vapor deposition (CVD). Herein, a wrinkle-facilitated route is developed for the fast growth of graphene/h-BN vertical heterostructures on Cu foils. The key advantage of this synthetic pathway is the exploitation of the increased reactivity from inevitable line defects arising from the CVD process, which can act as active sites for graphene nucleation. The resulted heterostructures are found to exhibit superlubric properties with increased bending stiffness, as well as directional electronic properties, as revealed from atomic force microscopy measurements. This work offers a brand-new route for the fast growth of Gr/h-BN heterostructures with practical scalability, thus propelling applications in electronics and nanomechanical systems.
Pulse oximetry SpO
2 signal for automated identification of sleep apnea: a review and future trends
Authors: Sharma Manish , Kumar Kamlesh , Kumar Prince , Tan Ru-San , Rajendra Acharya U
Published: October 2022

Sleep apnea (SA) is characterized by intermittent episodes of apnea or hypopnea paused or reduced breathing, respectively each lasting at least ten seconds that occur during sleep. SA has an estimated global prevalence of 200 million and is associated with medical comorbidity, and sufferers are also more likely to sustain traffic- and work-related injury due to daytime somnolence. SA is amenable to treatment if detected early. Polysomnography (PSG) involving multi-channel signal acquisition is the reference standard for diagnosing SA but is onerous and costly. For home-based detection of SA, single-channel SpO
2 signal acquisition using portable pulse oximeters is feasible. Machine (ML) and deep learning (DL) models have been developed for automated classification of SA versus no SA using SpO
2 signals alone. In this work, we review studies published between 2012 and 2022 on the use of ML and DL for SpO
2 signal-based diagnosis of SA. A literature search based on PRISMA recommendations yielded 297 publications, of which 31 were selected after considering the inclusion and exclusion criteria. There were 20 ML and 11 DL models; their methods, differences, results, merits, and limitations were discussed. Many studies reported encouraging performance, which indicates the utility of SpO
2 signals in wearable devices for home-based SA detection.
First-order phase transition and fate of false vacuum remnants
Authors: Kawana Kiyoharu , Lu Philip , Xie Ke-Pan
Published: October 2022

False vacuum remnants in first-order phase transitions in the early Universe can form
compact objects which may constitute dark matter. Such remnants form because particles develop
large mass gaps between the two phases and become trapped in the old phase. We focus on remnants
generated in a class of models with trapped dark sector particles, trace their development, and
determine their ultimate fate. Depending on model and phase transition parameters, the
evolutionary endpoint of these remnants can be primordial black holes, Fermi-balls, Q-balls, or
thermal balls, and they all have the potential to constitute some portion or the whole of dark
matter within a broad mass range. Notably, dark sector thermal balls can remain at high
temperatures until the present day and are a new compact dark matter candidate which derives its
energy from the thermal energy of internal particles instead of their mass or quantum pressure.
Impact of bound states on non-thermal dark matter production
Authors: Bollig J. , Vogl S.
Published: October 2022

We explore the impact of non-perturbative effects, namely Sommerfeld enhancement and bound
state formation, on the cosmological production of non-thermal dark matter. For this purpose, we
focus on a class of simplified models with t-channel mediators. These naturally combine the
requirements for large corrections in the early Universe, i.e. beyond the Standard Model states
with long range interactions, with a sizable new physics production cross section at the LHC. We
find that the dark matter yield of the superWIMP mechanism is suppressed considerably due to the
non-perturbative effects under consideration in models with color-charged mediators. In models
with only electrically charged mediators the impact of non-perturbative effects is less pronounced
and gets eclipsed by the impact of a possible Higgs portal interaction. In both cases we find
significant shifts in the cosmologically preferred parameter space of non-thermal dark matter in
these models. We also revisit the implications of LHC bounds on long-lived particles associated
with non-thermal dark matter and find that testing this scenario at the LHC is a bigger challenge
than previously anticipated.
Spin transport properties in ferromagnet/superconductor junctions on topological insulator
Authors: Li Hong , Yang Xin-Jian
Published: October 2022

The spin-dependent Andreev reflection is investigated theoretically by analyzing the electronic transport in a thin-film topological insulator (TI) ferromagnet/superconductor (FM/SC) junction. The tunneling conductance and shot noise are calculated based on the Dirac–Bogoliubov–de Gennes equation and Blonder–Tinkham–Klapwijk theory. It is found that the magnetic gap in ferromagnet can enhance the Andreev retro-reflection but suppress the specular Andreev reflection. The gate potential applied to the electrode on top of superconductor can enhance the two types of reflections. There is a transition between the two types of reflections at which both the tunneling conductance and differential shot noise become zero. These results provide a method to realize and detect experimentally the intra-band specular Andreev reflection in thin film TI-based FM/SC structures.
Learning physical states of bulk crystalline materials from atomic trajectories in molecular dynamics simulation
Authors: Liang Tian-Shou , Shi Peng-Peng , Su San-Qing , Zeng Zhi
Published: October 2022

Melting of crystalline material is a common physical phenomenon, yet it remains elusive owing to the diversity in physical pictures. In this work, we proposed a deep learning architecture to learn the physical states (solid- or liquid-phase) from the atomic trajectories of the bulk crystalline materials with four typical lattice types. The method has ultra-high accuracy (higher than 95%) for the classification of solid–liquid atoms during the phase transition process and is almost insensitive to temperature. The atomic physical states are identified from atomic behaviors without considering any characteristic threshold parameter, which yet is necessary for the classical methods. The phase transition of bulk crystalline materials can be correctly predicted by learning from the atomic behaviors of different materials, which confirms the close correlation between atomic behaviors and atomic physical states. These evidences forecast that there should be a more general undiscovered physical quantity implicated in the atomic behaviors and elucidate the nature of bulk crystalline melting.
Achieving traceability to UTC through GNSS measurements
Authors: Defraigne P , Achkar J , Coleman M J , Gertsvolf M , Ichikawa R , Levine J , Uhrich P , Whibberley P , Wouters M , Bauch A
Published: October 2022

Coordinated universal time (UTC) is the international reference for time and frequency measurement, and the basis of civil timekeeping world-wide. The reception of signals from global navigation satellite systems (GNSS) as a source of time and frequency (synchronization and syntonization) has found widespread use in virtually all user sectors, including electrical power supply, telecommunications, and financial institutions. This paper summarizes the concept of metrological traceability and the practices employed in the time and frequency metrology community for achieving it. Practical steps are proposed to ensure that traceability to UTC from GNSS signal reception is available to a wide community of users, addressing different levels of required uncertainty in time and frequency offset from UTC. We suggest some practical measures that can be followed by users, and improvements to the services provided by National Metrology Institutes (NMIs).
PACNav: a collective navigation approach for UAV swarms deprived of communication and external localization
Authors: Ahmad Afzal , Bonilla Licea Daniel , Silano Giuseppe , Báča Tomáš , Saska Martin
Published: October 2022

This article proposes Persistence Administered Collective Navigation (PACNav) as an approach for achieving the decentralized collective navigation of unmanned aerial vehicle (UAV) swarms. The technique is based on the flocking and collective navigation behavior observed in natural swarms, such as cattle herds, bird flocks, and even large groups of humans. As global and concurrent information of all swarm members is not available in natural swarms, these systems use local observations to achieve the desired behavior. Similarly, PACNav relies only on local observations of the relative positions of UAVs, making it suitable for large swarms deprived of communication capabilities and external localization systems. We introduce the novel concepts of path persistence and path similarity that allow each swarm member to analyze the motion of other members in order to determine its own future motion. PACNav is based on two main principles: (a) UAVs with little variation in motion direction have high path persistence, and are considered by other UAVs to be reliable leaders; (b) groups of UAVs that move in a similar direction have high path similarity, and such groups are assumed to contain a reliable leader. The proposed approach also embeds a reactive collision avoidance mechanism to avoid collisions with swarm members and environmental obstacles. This collision avoidance ensures safety while reducing deviations from the assigned path. Along with several simulated experiments, we present a real-world experiment in a natural forest, showcasing the validity and effectiveness of the proposed collective navigation approach in challenging environments. The source code is released as open-source, making it possible to replicate the obtained results and facilitate the continuation of research by the community.
Sustained cost declines in solar PV and battery storage needed to eliminate coal generation in India
Authors: Mohan Aniruddh , Sengupta Shayak , Vaishnav Parth , Tongia Rahul , Ahmed Asim , Azevedo Inês L
Published: October 2022

Unabated coal power in India must be phased out by mid-century to achieve global climate targets under the Paris Agreement. Here we estimate the costs of hybrid power plants—lithium-ion battery storage with wind and solar PV—to replace coal generation. We design least cost mixes of these technologies to supply stylized baseload and load-following generation profiles in three Indian states—Karnataka, Gujarat, and Tamil Nadu. Our analysis shows that availability of low cost capital, solar PV capital costs of at least $250 kW−1, and battery storage capacity costs at least 50% cheaper than current levels will be required to phase out existing coal power plants. Phaseout by 2040 requires a 6% annual decline in the levelized cost of hybrid systems over the next two decades. We find that replacing coal generation with hybrid systems 99% of the hours over multiple decades is roughly 40% cheaper than 100% replacement, indicating a key role for other low cost grid flexibility mechanisms to help hasten coal phaseout. Solar PV is more suited to pairing with short duration storage than wind power. Overall, our results describe the challenging technological and policy advances needed to achieve the temperature goals of the Paris Agreement.
Optimizing SARS-CoV-2 Pooled Testing Strategies Through Differentiated Pooling for Distinct Groups
Authors: Filiatreau Lindsey M , Zivich Paul N , Edwards Jessie K , Mulholland Grace E , Max Ryan , Westreich Daniel
Published: October 2022

Pooled testing has been successfully used to expand SARS-CoV-2 testing, especially in settings requiring high volumes of screening of lower-risk individuals, but efficiency of pooling declines as prevalence rises. We propose a differentiated pooling strategy that independently optimizes pool sizes for distinct groups with different probabilities of infection to further improve the efficiency of pooled testing. We compared the efficiency (results obtained per test kit used) of the differentiated strategy with a traditional pooling strategy in which all samples are processed using uniform pool sizes under a range of scenarios. For most scenarios, differentiated pooling is more efficient than traditional pooling. In scenarios examined here, an improvement in efficiency of up to 3.94 results per test kit could be obtained through differentiated versus traditional pooling, with more likely scenarios resulting in 0.12 to 0.61 additional results per kit. Under circumstances similar to those observed in a university setting, implementation of our strategy could result in an improvement in efficiency between 0.03 to 3.21 results per test kit. Our results can help identify settings, such as universities and workplaces, where differentiated pooling can conserve critical testing resources.
Open tools for quantitative anonymization of tabular phenotype data: literature review
Authors: Haber Anna C , Sax Ulrich , Prasser Fabian ,   the NFDI4Health Consortium
Published: October 2022

Precision medicine relies on molecular and systems biology methods as well as bidirectional association studies of phenotypes and (high-throughput) genomic data. However, the integrated use of such data often faces obstacles, especially in regards to data protection. An important prerequisite for research data processing is usually informed consent. But collecting consent is not always feasible, in particular when data are to be analyzed retrospectively. For phenotype data, anonymization, i.e. the altering of data in such a way that individuals cannot be identified, can provide an alternative. Several re-identification attacks have shown that this is a complex task and that simply removing directly identifying attributes such as names is usually not enough. More formal approaches are needed that use mathematical models to quantify risks and guide their reduction. Due to the complexity of these techniques, it is challenging and not advisable to implement them from scratch. Open software libraries and tools can provide a robust alternative. However, also the range of available anonymization tools is heterogeneous and obtaining an overview of their strengths and weaknesses is difficult due to the complexity of the problem space. We therefore performed a systematic review of open anonymization tools for structured phenotype data described in the literature between 1990 and 2021. Through a two-step eligibility assessment process, we selected 13 tools for an in-depth analysis. By comparing the supported anonymization techniques and further aspects, such as maturity, we derive recommendations for tools to use for anonymizing phenotype datasets with different properties.
A Systematic Review of Human Challenge Trials, Designs, and Safety
Authors: Adams-Phipps Jupiter , Toomey Danny , Więcek Witold , Schmit Virginia , Wilkinson James , Scholl Keller , Jamrozik Euzebiusz , Osowicki Joshua , Roestenberg Meta , Manheim David
Published: October 2022

Background

Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective.

Methods

A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021.

Results

Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded “severe” were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database.

Conclusions

HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218.
Can we attenuate ischaemia-reperfusion injury of allografts in a porcine left lung transplant models by adsorption of cytokines?
Authors: Frick Anna Elisabeth , Orlitová Michaela , Bleeser Tom , Vanstapel Arno , Claes Sandra , Schols Dominique , Mathyssen Carolien , Ceulemans Laurens J , Vos Robin , Verleden Geert M , Vanaudenaerde Bart M , Verleden Stijn E , Van Raemdonck Dirk E , Neyrinck Arne P
Published: October 2022

OBJECTIVES

Primary graft dysfunction resulting from ischaemia-reperfusion injury remains a major obstacle after lung transplantation (LTx) and is associated with morbidity and mortality. Continuous release of inflammatory cytokines, due to the process of ischaemia and reperfusion, triggers a complex cascade of apoptosis and necrosis resulting in graft dysfunction. Previous studies demonstrated successful graft improvement by cytokine filtration during ex vivo lung perfusion. We hypothesize that plasma cytokine filtration with CytoSorb® during in vivo graft perfusion immediately after implantation may attenuate ischaemia-reperfusion injury after left LTx in a porcine model.

METHODS

Left porcine LTx was performed with allografts preserved for 24 h at 4°C. In the treatment group [T] (n = 7), a veno-venous shunt was created to insert the cytokine filter (CytoSorbents, Berlin, Germany). In the sham group [S] (n = 4), the shunt was created without the filter. Haemodynamic parameters, lung mechanics, blood gases and plasma cytokines were assessed during 6 h in vivo reperfusion.

RESULTS

During 6 h of reperfusion, significant differences in plasma pro-inflammatory cytokine [interferon (IFN)-α, IFN-γ and interleukin (IL)-6] concentrations were observed between [T] and [S], but surprisingly with higher plasma levels in the [T] group. Plasma concentrations of other pro-inflammatory cytokines (IL-1β, IL-12p40, IL-4, IL-6, IL-8, IFN-α, IFN-γ and tumour necrosis factor-α) and anti-inflammatory cytokines (IL-10) did not find any evidence for a difference. Furthermore, our study failed to show meaningful difference in haemodynamics and blood gases. Also, no statistically significant differences were found between [T] and [S] in biopsies and wet-to-dry ratio at the end of the experiment.

CONCLUSIONS

In our porcine left LTx model cytokine filtration did not achieve the intended effect. This is in contrast to previous studies with CytoSorb use during ex vivo lung perfusion as a surrogate LTx model. Our findings might highlight the fact that the theoretical benefit of inserting an additional cytokine adsorber to improve graft function in clinical practice should be critically evaluated with further studies.
Bipartite synchronization of discrete-time networks with antagonistic interactions via hybrid control
Authors: Zhang Xiaomei , He Lin , Zhou Lei , Sheng Suying
Published: October 2022

The problem of bipartite synchronization is addressed for discrete-time networks with antagonistic interactions via hybrid control with impulsive effects. Firstly, a hybrid state-feedback controller, which combines a pinning state-feedback controller and an impulsive state-feedback controller, is presented, and the criterion of the bipartite synchronization is derived by applying the average impulsive interval method. Secondly, for the case of the network states not all being measured, a hybrid measurement-feedback controller, which combines a pinning measurement-feedback controller and a pinning impulsive measurement-feedback controller, is proposed. The time-varying Lyapunov function method is utilized to design the hybrid measurement-feedback controller such that the bipartite synchronization is realized. Finally, some numerical simulations are performed to illustrate the efficiency of the proposed controller design methods.
Prospective Surveillance of Respiratory Infections in British Antarctic Survey Bases During the COVID-19 Pandemic
Authors: Ganly Katharine H , Bowyer James C , Bird Paul W , Willford Nicholas J , Shaw Jessica , Odedra Mina , Osborn Georgia , Everett Tom , Warner Matthew , Horne Simon , Dinn Michael , McMurray Claire L , Holmes Christopher W , Koo Sharon S F , Tang Julian Wei-Tze
Published: October 2022

Background

The British Antarctic bases offer a semiclosed environment for assessing the transmission and persistence of seasonal respiratory viruses.

Methods

Weekly swabbing was performed for respiratory pathogen surveillance (including SARS-CoV-2), at 2 British Antarctic Survey bases, during 2020: King Edward Point (KEP, 30 June to 29 September, 9 participants, 124 swabs) and Rothera (9 May to 6 June, 27 participants, 127 swabs). Symptom questionnaires were collected for any newly symptomatic cases that presented during this weekly swabbing period.

Results

At KEP, swabs tested positive for non–SARS-CoV-2 seasonal coronavirus (2), adenovirus (1), parainfluenza 3 (1), and respiratory syncytial virus B (1). At Rothera, swabs tested positive for non–SARS-CoV-2 seasonal coronavirus (3), adenovirus (2), parainfluenza 4 (1), and human metapneumovirus (1). All bacterial agents identified were considered to be colonizers and not pathogenic.

Conclusions

At KEP, the timeline indicated that the parainfluenza 3 and adenovirus infections could have been linked to some of the symptomatic cases that presented. For the other viruses, the only other possible sources were the visiting ship crew members. At Rothera, the single symptomatic case presented too early for this to be linked to the subsequent viral detections, and the only other possible source could have been a single nonparticipating staff member.
Target attainment and pharmacokinetics of cefotaxime in critically ill patients undergoing continuous kidney replacement therapy
Authors: Wieringa André , ter Horst Peter G J , Wagenvoort Gertjan H J , Dijkstra Annemieke , Abdulla Alan , Haringman Jasper J , Koch Birgit C P
Published: October 2022

Objectives

Limited data exist about the antimicrobial target attainment and pharmacokinetics of cefotaxime in critically ill patients in the ICU undergoing continuous kidney replacement therapy (CKRT). We conducted a prospective observational study in two large teaching hospitals [Isala Hospital (IH) and Zwolle and Maasstad Hospital (MH)] to investigate target attainment and pharmacokinetics of cefotaxime in patients undergoing CKRT.

Patients and methods

Patients aged ≥18 years admitted to the ICU treated with IV cefotaxime 1000 mg three times daily (IH) or 4 times daily (MH) were included. Fifteen patients were enrolled in total. Per patient eight cefotaxime plasma and eight ultrafiltrate samples were drawn in IH and four plasma samples in MH on Day 2 of treatment. In ICU patients the recommended antimicrobial target of cefotaxime is a plasma concentration 100% of the time above the MIC.

Results

In IH 10/11 patients had higher plasma trough concentrations than the MIC breakpoint of Enterobacterales of 1 mg/L (clinical breakpoint for susceptible strains) and 9/11 patients had concentrations above 2 mg/L (clinical breakpoint for resistant strains). All patients (4/4) in MH had higher plasma trough concentrations than 2 mg/L. A sieving coefficient of 0.74 was identified, with a median amount of 40% of cefotaxime eliminated by CKRT.

Conclusions

We conclude that cefotaxime 1000 mg 3–4 times daily gives adequate plasma concentrations in patients with anuria or oliguria undergoing CKRT. The 1000 mg four times daily dosage is recommended in patients undergoing CKRT with partially preserved renal function to achieve the target.
Magnitude of non-prescribed antibiotic dispensing in Ethiopia: a multicentre simulated client study with a focus on non-urban towns
Authors: Belachew Sewunet Admasu , Hall Lisa , Selvey Linda A
Published: October 2022

Objectives

Non-prescription dispensing of antibiotics significantly contributes to widespread antibiotic misuse, which in turn hastens the occurrence of antibiotic resistance. It is believed to be common in Ethiopia despite prescription-only regulations. We aimed to quantify non-prescription dispensing of antibiotics in community drug retail outlets (CDROs) with a focus on non-urban towns in the Amhara region of Ethiopia.

Methods

A multicentre simulated client (SC) study was conducted to measure the non-prescription provision of antibiotics in 225 consenting CDROs. Each CDRO was visited twice by two trained SCs, one to present pre-prepared clinical case scenarios and the other to directly request specific antibiotics. Descriptive statistical analysis was performed to report the findings.

Results

The study had 450 interactions across the two visits. Non-prescribed antibiotics were obtained in 198 (88%) of the 225 clinical case scenarios-based visits and in 205 (91%) of the 225 direct antibiotic request visits. Most of the supply was at the first level of demand: 84% of the 198 clinical case scenario visits and 95% of the 205 direct antibiotic request visits. CDRO staff requested further information about the patient or the case in 40% of the clinical case scenarios-based visits and 30% of the direct antibiotic request visits.

Conclusions

It was possible to obtain antibiotics without prescription from a high proportion of CDROs, both in clinical scenario-based and direct antibiotic request interactions. Multifaceted interventions including stringent regulatory enforcement, frequent CDRO practice surveillance, CDRO staff training and community health education are needed with greater emphasis on rural areas.
Pancreatic stone protein as a biomarker for the early diagnosis of post-operative peritonitis, intra-abdominal infection and sepsis
Authors: Ventura François , Gasche Yvan , Rached Aymen Kraiem Ben , Pugin Déborah , Mollard Frédéric , Vora Samir , Charbonnet Pierre , Bühler Léo
Published: October 2022

The diagnosis of intra-abdominal infection and post-operative peritonitis based on clinical examination, biomarkers and radiological signs, should be made as early as possible to improve outcomes and decrease mortality through early and optimal source control, adequate surgery and appropriate antibiotic therapy (Montravers et al. Therapeutic management of peritonitis: a comprehensive guide for intensivists. Intensive Care Med 2016;42:1234–47). However, the indication and the timing of the surgery is often not an easy decision. This case presents the use of a novel early biomarker of infection and sepsis, pancreatic stone protein (Fidalgo et al. Pancreatic stone protein: review of a new biomarker in sepsis. J Clin Med 2022;11:1085), as a tool to aid in the diagnosis of intra-abdominal infection and post-operative peritonitis and to help guide the decision for adequate surgeries in a patient with intra-abdominal infection and post radical prostatectomy peritonitis.
Functional characterization of MANNOSE-BINDING LECTIN 1, a G-type lectin gene family member, in response to fungal pathogens of strawberry
Authors: Ma Lijing , Haile Zeraye Mehari , Sabbadini Silvia , Mezzetti Bruno , Negrini Francesca , Baraldi Elena
Published: October 2022

The mannose-binding lectin gene MANNOSE-BINDING LECTIN 1 (MBL1) is a member of the G-type lectin family and is involved in defense in strawberry (Fragaria × ananassa). Genome-wide identification of the G-type lectin family was carried out in woodland strawberry, F. vesca, and 133 G-lectin genes were found. Their expression profiles were retrieved from available databases and indicated that many are actively expressed during plant development or interaction with pathogens. We selected MBL1 for further investigation and generated stable transgenic FaMBL1-overexpressing plants of F. ×ananassa to examine the role of this gene in defense. Plants were selected and evaluated for their contents of disease-related phytohormones and their reaction to biotic stresses, and this revealed that jasmonic acid decreased in the overexpressing lines compared with the wild-type (WT). Petioles of the overexpressing lines inoculated with Colletotrichum fioriniae had lower disease incidence than the WT, and leaves of these lines challenged by Botrytis cinerea showed significantly smaller lesion diameters than the WT and higher expression of CLASS II CHITINASE 2-1. Our results indicate that FaMBL1 plays important roles in strawberry response to fungal diseases caused by C. fioriniae and B. cinerea.
Clinical Application of Prostatic Exosomal Protein and Prostate-Specific Antigen Levels in the Detection of Prostate-Related Diseases
Authors: Ge Qiuxia , Lou Jianfang
Published: October 2022

Objective

Our aim was to study the use of prostatic exosomal protein (PSEP) and prostate-specific antigen (PSA) in diagnosis of prostate-related diseases.

Methods

A total of 54 cases of acute prostatitis (AP), 72 cases of chronic prostatitis (CP), and 36 cases of prostate cancer (PCa) were enrolled. Levels of PSEP and PSA were analyzed.

Results

The positive rate and level of PSEP in CP was highest (both P < .05). The total PSA (tPSA) level in PCa was the highest (P < .05), followed by AP and CP. The free PSA (fPSA) level was lowest in CP (P < .05); fPSA/tPSA in AP was the highest (P < .05). The PSEP level in type II CP was higher than in type IIIa and type IIIb (both P < .05), and it was higher in type IIIa than in type IIIb (P < .05). The tPSA level in type IIIb was the lowest in the 3 types (both P < .05). The fPSA/tPSA in type IIIb was the highest in the 3 types (P < .05).

Conclusion

The PSEP combined with PSA better distinguishes prostate-related diseases.
Unveiling the main sequence of galaxies at z ≥ 5 with the JWST: predictions from simulations
Authors: D’Silva Jordan C J , Lagos Claudia D P , Davies Luke J M , Lovell Christopher C , Vijayan Aswin P
Published: October 2022

We use two independent galaxy-formation simulations, flares, a cosmological hydrodynamical simulation, and shark, a semi-analytic model, to explore how well the JWST will be able to uncover the existence and parameters of the star-forming main sequence (SFS) at z = 5 → 10, i.e. shape, scatter, normalization. Using two independent simulations allows us to isolate predictions (e.g. stellar mass, star formation rate, SFR, luminosity functions) that are robust to or highly dependent on the implementation of the physics of galaxy formation. Both simulations predict that JWST can observe ≥70–90 per cent (for shark and flares, respectively) of galaxies up to z ∼ 10 (down to stellar masses of ${\approx}10^{8.3}\rm M_{\odot }$ and SFRs of ${\approx}10^{0.5}{\rm M}_{\odot }\,{\rm yr}^{-1}$) in modest integration times and given current proposed survey areas (e.g. the Web COSMOS 0.6 deg2) to accurately constrain the parameters of the SFS. Although both simulations predict qualitatively similar distributions of stellar mass and SFR. There are important quantitative differences, such as the abundance of massive, star-forming galaxies with flares predicting a higher abundance than shark; the early onset of quenching as a result of black hole growth in flares (at z ≈ 8), not seen in shark until much lower redshifts; and the implementation of synthetic photometry with flares predicting more JWST-detected galaxies (∼90 per cent) than shark (∼70 per cent) at z = 10. JWST observations will distinguish between these models, leading to a significant improvement upon our understanding of the formation of the very first galaxies.
Quashing a suspected selection bias in galaxy samples having dynamically measured supermassive black holes
Authors: Sahu Nandini , Graham Alister W , Hon Dexter S-H
Published: October 2022

Local early-type galaxies (ETGs) with directly measured black hole masses, Mbh, have been reported to represent a biased sample relative to the ETG population at large. Such galaxies with Spitzer Space Telescope imaging have been purported to possess velocity dispersions, σ, at least ∼0.1 dex larger for a given galaxy stellar mass, M*,gal, than is typically observed among thousands of ETGs imaged by the Sloan Digital Sky Survey (SDSS). This apparent offset led Shankar et al. to reduce the normalisation of the observed Mbh ∝ σ5 relation by at least ∼0.5 dex to give their ‘intrinsic relations’, including σ-based modifications to the observed Mbh–M*,gal relation. These modifications were based on the untested assumption that the stellar masses had been derived consistently between the two samples. Here, we provide the necessary check using galaxies common to the Spitzer Survey of Stellar Structure in Galaxies (S4G) and the SDSS. We find that the stellar masses of galaxies with and without directly measured black hole masses had appeared offset from each other due to the use of inconsistent stellar mass-to-light ratios, Υ*, for the optical and infrared data. We briefly discuss the ‘intrinsic relations’ and why some of these will at times appear to have had partial success when applied to data based on similarly inconsistent values ofΥ*. Finally, we reiterate the importance of the υ (lower-case Υ) term, which we previously introduced into the Mbh–M* relations to help avoid Υ*-related mismatches.
SURE editing: combining oligo-recombineering and programmable insertion/deletion of selection markers to efficiently edit the Mycoplasma pneumoniae genome
Authors: Piñero-Lambea Carlos , Garcia-Ramallo Eva , Miravet-Verde Samuel , Burgos Raul , Scarpa Margherita , Serrano Luis , Lluch-Senar Maria
Published: October 2022

The development of advanced genetic tools is boosting microbial engineering which can potentially tackle wide-ranging challenges currently faced by our society. Here we present SURE editing, a multi-recombinase engineering rationale combining oligonucleotide recombineering with the selective capacity of antibiotic resistance via transient insertion of selector plasmids. We test this method in Mycoplasma pneumoniae, a bacterium with a very inefficient native recombination machinery. Using SURE editing, we can seamlessly generate, in a single step, a wide variety of genome modifications at high efficiencies, including the largest possible deletion of this genome (30 Kb) and the targeted complementation of essential genes in the deletion of a region of interest. Additional steps can be taken to remove the selector plasmid from the edited area, to obtain markerless or even scarless edits. Of note, SURE editing is compatible with different site-specific recombinases for mediating transient plasmid integration. This battery of selector plasmids can be used to select different edits, regardless of the target sequence, which significantly reduces the cloning load associated to genome engineering projects. Given the proven functionality in several microorganisms of the machinery behind the SURE editing logic, this method is likely to represent a valuable advance for the synthetic biology field.
Two type I topoisomerases maintain DNA topology in human mitochondria
Authors: Menger Katja E , Chapman James , Díaz-Maldonado Héctor , Khazeem Mushtaq M , Deen Dasha , Erdinc Direnis , Casement John W , Di Leo Valeria , Pyle Angela , Rodríguez-Luis Alejandro , Cowell Ian G , Falkenberg Maria , Austin Caroline A , Nicholls Thomas J
Published: October 2022

Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated the subcellular localisation and activity of the six human topoisomerases with a view to understanding the topological maintenance of human mitochondrial DNA. Our results indicate that mitochondria contain two topoisomerases, TOP1MT and TOP3A. Using molecular, genomic and biochemical methods we find that both proteins contribute to mtDNA replication, in addition to the decatenation role of TOP3A, and that TOP1MT is stimulated by mtSSB. Loss of TOP3A or TOP1MT also dysregulates mitochondrial gene expression, and both proteins promote transcription elongation in vitro. We find no evidence for TOP2 localisation to mitochondria, and TOP2B knockout does not affect mtDNA maintenance or expression. Our results suggest a division of labour between TOP3A and TOP1MT in mtDNA topology control that is required for the proper maintenance and expression of human mtDNA.
HiChIPdb: a comprehensive database of HiChIP regulatory interactions
Authors: Zeng Wanwen , Liu Qiao , Yin Qijin , Jiang Rui , Wong Wing Hung
Published: October 2022

Elucidating the role of 3D architecture of DNA in gene regulation is crucial for understanding cell differentiation, tissue homeostasis and disease development. Among various chromatin conformation capture methods, HiChIP has received increasing attention for its significant improvement over other methods in profiling of regulatory (e.g. H3K27ac) and structural (e.g. cohesin) interactions. To facilitate the studies of 3D regulatory interactions, we developed a HiChIP interactions database, HiChIPdb (http://health.tsinghua.edu.cn/hichipdb/). The current version of HiChIPdb contains ∼262M annotated HiChIP interactions from 200 high-throughput HiChIP samples across 108 cell types. The functionalities of HiChIPdb include: (i) standardized categorization of HiChIP interactions in a hierarchical structure based on organ, tissue and cell line and (ii) comprehensive annotations of HiChIP interactions with regulatory genes and GWAS Catalog SNPs. To the best of our knowledge, HiChIPdb is the first comprehensive database that utilizes a unified pipeline to map the functional interactions across diverse cell types and tissues in different resolutions. We believe this database has the potential to advance cutting-edge research in regulatory mechanisms in development and disease by removing the barrier in data aggregation, preprocessing, and analysis.
Thyclotides, tetrahydrofuran-modified peptide nucleic acids that efficiently penetrate cells and inhibit microRNA-21
Authors: Clausse Victor , Zheng Hongchao , Amarasekara Harsha , Kruhlak Michael , Appella Daniel H
Published: October 2022

Peptide nucleic acids (PNAs) are promising therapeutic molecules for gene modulation; however, they suffer from poor cell uptake. Delivery of PNAs into cells requires conjugation of the PNA to another large molecule, typically a cell-penetrating peptide or nanoparticle. In this study, we describe a new PNA-based molecule with cyclic tetrahydrofuran (THF) backbone modifications that in some cases considerably improve cell uptake. We refer to these THF-PNA oligomers as thyclotides. With THF groups at every position of the oligomer, the cell uptake of thyclotides targeted to miR-21 is enhanced compared with the corresponding unmodified PNA based on an aminoethylglycine backbone. An optimized thyclotide can efficiently enter cells without the use of cell-penetrating peptides, bind miR-21, its designated microRNA target, decrease expression of miR-21 and increase expression of three downstream targets (PTEN, Cdc25a and KRIT1). Using a plasmid with the PTEN-3′UTR coupled with luciferase, we further confirmed that a miR-21-targeted thyclotide prevents miR-21 from binding to its target RNA. Additionally, the thyclotide shows no cytotoxicity when administered at 200 times its active concentration. We propose that thyclotides be further explored as therapeutic candidates to modulate miRNA levels.