bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic engineering of Corynebacterium glutamicum for the production of anthranilate from glucose and xylose
Authors: Mutz Mario , Brüning Vincent , Brüsseler Christian , Müller Moritz‐Fabian , Noack Stephan , Marienhagen Jan
Published: January 2024

Anthranilate and its derivatives are important basic chemicals for the synthesis of polyurethanes as well as various dyes and food additives. Today, anthranilate is mainly chemically produced from petroleum‐derived xylene, but this shikimate pathway intermediate could be also obtained biotechnologically. In this study, Corynebacterium glutamicum was engineered for the microbial production of anthranilate from a carbon source mixture of glucose and xylose. First, a feedback‐resistant 3‐deoxy‐arabinoheptulosonate‐7‐phosphate synthase from Escherichia coli, catalysing the first step of the shikimate pathway, was functionally introduced into C. glutamicum to enable anthranilate production. Modulation of the translation efficiency of the genes for the shikimate kinase (aroK) and the anthranilate phosphoribosyltransferase (trpD) improved product formation. Deletion of two genes, one for a putative phosphatase (nagD) and one for a quinate/shikimate dehydrogenase (qsuD), abolished by‐product formation of glycerol and quinate. However, the introduction of an engineered anthranilate synthase (TrpEG) unresponsive to feedback inhibition by tryptophan had the most pronounced effect on anthranilate production. Component I of this enzyme (TrpE) was engineered using a biosensor‐based in vivo screening strategy for identifying variants with increased feedback resistance in a semi‐rational library of TrpE muteins. The final strain accumulated up to 5.9 g/L (43 mM) anthranilate in a defined CGXII medium from a mixture of glucose and xylose in bioreactor cultivations. We believe that the constructed C. glutamicum variants are not only limited to anthranilate production but could also be suitable for the synthesis of other biotechnologically interesting shikimate pathway intermediates or any other aromatic compound derived thereof.
Uncertainties and opportunities in delivering environmentally sustainable surgery: the surgeons' view
Authors: Ledda V. , George C. , Glasbey J. , Labib P. , Li E. , Lu A. , Kudrna L. , Nepogodiev D. , Picciochi M. , Williams I. , Bhangu A.
Published: January 2024

Surgery is a carbon‐heavy activity and creates a high volume of waste. Surgical teams around the world want to deliver more environmentally sustainable surgery but are unsure what to do and how to create change. There are many interventions available, but resources and time are limited. Capital investment into healthcare and engagement of senior management are challenging. However, frontline teams can change behaviours and drive wider change. Patients have a voice here too, as they would like to ensure their surgery does not harm their local community but are concerned about the effects on them when changes are made. Environmentally sustainable surgery is at the start of its journey. Surgeons need to rapidly upskill their generic knowledge base, identify which measures they can implement locally and take part in national research programmes. Surgical teams in the NHS have the chance to create a world‐leading programme that can bring change to hospitals around the world. This article provides an overview of how surgeons see the surgical team being involved in environmentally sustainable surgery.
Individuals' travel to alcohol outlets: The fallacy of the local bar
Authors: Mehranbod Christina A. , Gobaud Ariana N. , Bushover Brady R. , Morrison Christopher N.
Published: January 2024

Introduction

Studies relating alcohol outlet density around homes to alcohol consumption produce mixed results. One possible explanation is that people travel to outlets away from their homes. This study aims to characterise individuals' trips to outlets, describe these trip locations relative to other activities and estimate associations between alcohol outlet density and trips to outlets.

Methods

This cross‐sectional study used 2014–2018 household travel data from the Victoria Integrated Survey of Travel and Activity. We estimated the average change in the cumulative travel characteristics associated with each additional trip to bars and liquor stores, accounting for complex trips to multiple destinations. Logistic regression models estimated odds that individuals travelled to outlets in relation to outlet density in their home local government area (LGA).

Results

Among 23,512 respondents, 378 (1.6%) travelled to any bar and 79 (0.3%) any liquor store the survey day. Bar trips added 8.2 km (95% confidence interval [CI] 4.6, 11.8) and 18.1 min (95% CI 13.6, 22.6) to cumulative travel; 41% of attended bars were co‐located in participants' home LGA. Greater bar and liquor store density within the home LGA were associated with overall trips to these outlet types.

Discussion and Conclusions

Individuals travel beyond their residential area to bars, but travel to liquor stores closer to home. Bar and liquor store density within individuals' home LGA were associated with trips to outlets. Trips to local bars in near home comprised a minority of trips to bars in this sample. Studies of retail alcohol access should account for trips to bars away from home.
Understanding cultural values, norms and beliefs that may impact participation in genome‐editing related research: Perspectives of local communities in Botswana
Authors: Koloi‐Keaikitse Setlhomo , Kasule Mary , Kwape Irene , Jankie Dudu , Ralefala Dimpho , Ntseane Dolly Mogomotsi , Mokone Gaonyadiwe George
Published: January 2024

Gene‐editing research is a complex science and foreign in most communities including Botswana. Adopting a qualitative deliberative framework with 109 participants from 7 selected ethnic communities in Botswana, we explored the perceptions of local communities on cultural values, norms, and beliefs that may motivate or deter likely participation in the use of gene‐editing related research. What emerged as the ethnic community's motivators for research participation include the potential for gene‐editing technologies to promote access to individualized medications, and the possibility of protecting family members from genetic related diseases. Deterrents for research participation include cultural values such as implications of lineage for chieftainship, trust, fear or anxiety, uncertainty, and sensitivity on the use of gene‐editing. Findings of our study have implications for continuous engagement with local communities to explore potential ways of addressing cultural sensitivities that can further deter their participation in future gene‐editing related research.
Moderate realist ideology critique
Authors: Clark Rebecca L.
Published: January 2024

Realist ideology critique (RIC) is a strand of political realism recently developed in response to concerns that realism is biased toward the status quo. RIC aims to debunk an individual's belief that a social institution is legitimate by revealing that the belief is caused by that very same institution. Despite its growing prominence, RIC has received little critical attention. In this article, I buck this trend. First, I improve on contemporary accounts of RIC by clarifying its status and the role of motivated reasoning. Second, I show that realist ideology critics face a dilemma: either their account makes deeply implausible epistemological assumptions, or they temper its epistemology at the expense of rendering it toothless. I argue for each horn in turn before revealing the dilemma to be a false one by making a novel distinction between varying strengths of RIC based on their underlying epistemological assumptions. I propose Moderate RIC as a solution: upon discovering that one reason for your belief that a social institution is legitimate is likely malignantly epistemically circular, the belief should undergo further epistemic testing. I respond to three potential objections and suggest that Moderate RIC would make a fruitful addition to political theorists' methodological toolkit.
Patients' perception of the benefits of palliative systemic therapy for advanced cancer
Authors: Subramaniam Shalini , Adams Diana H. , Tognela Annette , Roncolato Felicia , Yip Po Y. , Lim Stephanie H.‐S. , Roohullah Aflah , Stockler Martin R. , Kiely Belinda
Published: January 2024

Background

Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy.

Aim

To determine patient perceptions of palliative systemic therapy benefits in advanced cancer.

Methods

We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0–10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4–7 QOL and LOL equal; >7 LOL most important). Patient‐oncologist discordance was defined as a ≥4‐point difference.

Results

The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient‐oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%).

Conclusion

At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions.
Characteristics of restricted selection indices and geometrical interpretation of restricted breeding values
Authors: Satoh Masahiro
Published: January 2024

Restricted selection is used to control genetic changes in one or more characters. Three main selection indices are adopted for this purpose. First, Kempthorne's index is used to maximize aggregate breeding value (BV) with changes in some traits restricted to zero; second, Harville's index is used to maximize aggregate BV with proportional changes for some traits; and third, Yamada's index is mathematically used to achieve the relative desired changes for all traits. Kempthorne's index is equivalent to Harville's index. However, the relationship between Kempthorne's and Yamada's indices has not been clarified. In addition, the characteristics of restricted selection indices and the relationship between BV and restricted BV (RBV) are also unknown. The aim of this study was to clarify the characteristics of restricted selection indices and describe the relationship between BV and RBV by using linear algebra and geometric techniques, respectively. First, I proved that Yamada's index is part of Kempthorne's index. Second, I investigated the relationship between BVs that were estimated using an ordinary selection index (EBVs) and RBVs estimated using a restricted selection index (ERBVs) and proved that the ERBVs of the restricted traits are proportional to the relative desired changes. Third, I proved that RBV is represented by a linear function of BV and geometrically represented the relationship between BV and RBV. In this study, new findings on restricted selection indices and RBV were obtained. This useful clarification of the relationship between BV and RBV will make it possible to evaluate the response to selection using not only a restricted selection index, but also a restricted BLUP in computer simulation studies.
Caudal fluoroscopic guidance for the insertion of transvenous pacing leads
Authors: Morton Matthew B. , William Jeremy , Kistler Peter M. , Prabhu Sandeep , Sugumar Hariharan , Brink Olivier Van Den , Patel Hitesh , Mariani Justin , Voskoboinik Aleksandr
Published: January 2024

Background

Pneumothorax is a well‐recognized complication of cardiac implantable electronic device (CIED) insertion. While AP fluoroscopy alone is the most commonly imaging technique for subclavian or axillary access, caudal fluoroscopy (angle 40°) is routinely used at our institution. The caudal view provides additional separation of the first rib and clavicle and may reduce the risk of pneumothorax. We assessed outcomes at our institution of AP and caudal fluoroscopic guided pacing lead insertion.

Methods

Retrospective cohort study of consecutive patients undergoing transvenous lead insertion for pacemakers, defibrillators, and cardiac resynchronization therapy devices between 2011 and 2023. Both de novo and lead replacement/upgrade procedures were included. Data were extracted from operative, radiology, and discharge reports. All patients underwent postprocedure chest radiography.

Results

Three thousand two hundred fifty‐two patients underwent insertion of pacing leads between February 2011 and March 2023. Mean age was 71.1 years (range 16–102) and 66.7% were male. Most (n = 2536; 78.0%) procedures used caudal guidance to obtain venous access, while 716 (22.0%) procedures used AP guidance alone. Pneumothoraxes occurred in five (0.2%) patients in the caudal group and five (0.7%) patients in the AP group (p = .03). Subclavian contrast venography was performed less frequently in the caudal group (26.2% vs. 42.7%, p < .01).

Conclusion

Caudal fluoroscopy for axillary/subclavian access is associated with a lower rate of pneumothorax and contrast venography compared with an AP approach.
Peter Abelard is not a Proto‐Kantian
Authors: Abadal Lily M.
Published: January 2024

Though there has been much debate about whether Abelard's ethics are dangerously subjective or surprisingly absolutist, one thing is unanimous: they are intentionalist. The goal of this article is to parse out what should be meant by this claim, distancing his ethical account from the popular Kantian appraisal. Though much of the secondary literature on Abelard likens him to Kant, I argue that this is mistaken. For Abelard, an agent's intentions are informed by their affections—whether carnal or spiritual. This becomes clear when contextualizing Abelard's use of intentio with a view to his Commentary on Romans. Using the account of intention I suggest—one nuanced by Abelard's own theological commitments and biblical exegesis—it will be clear that Abelard's ethics is not a case for the moral neutrality of the passions nor an ethic of pure reason.
Employee acceptance of digital transformation strategies: A paradox perspective
Authors: Klein Sascha P. , Spieth Patrick , Söllner Matthias
Published: January 2024

Digital transformation (DT) strategies often aim at innovating an organization's business models (BMs) and developing digital innovations. However, most of the DT strategies fail or result only in incremental innovation. Research predominantly identified critical management capabilities for DT success, neglecting the role of employees, although employee support is vital for the successful implementation of DT strategies. We conceptualize employee acceptance of DT strategies and draw on paradox theory and organizational change literature to shed light on the antecedents of employee acceptance. Using survey‐based data from an incumbent introducing a DT strategy, we find empirical support that employees with a paradox mindset are likely to accept the DT strategy regardless of the expected scope of change, while a high scope of expected changes weakens the effect of a positive attitude toward change on acceptance. The findings contribute to understanding the micro‐level aspects of DT and extend research emphasizing top‐down management approaches in DT with an employee perspective. This study extends previous findings in innovation management that predominantly provide evidence on the acceptance of specific digital technologies and offer insights into the antecedents of DT strategy acceptance. We offer managers insights into how employees perceive DT strategies, which can help to leverage the potential of digital innovation.
Sleep disturbance correlated with severity of neuropathic pain in sciatic nerve crush injury model
Authors: Ho Anh , Lee Sung‐Jun , Drew Victor J. , Jung Jieun , Kang Jiseung , Cheong Chanyoung , Kim Tae
Published: January 2024

The association between sleep and pain has been investigated widely. However, inconsistent results from animal studies compared with human data show the need for a validated animal model in the sleep–pain association field. Our study aims to validate common neuropathic pain models as a tool for evaluating the sleep–pain association. Electrodes electroencephalogram (EEG) and electromyogram (EMG) were surgically implanted to measure sleep. The von Frey test was used to measure pain sensitivity. Following the baseline data acquisition, two pain‐modelling procedures were performed: sciatic nerve crush injury (SCI) and common peroneal nerve ligation (CPL). Post‐injury measurements were performed on days 1, 5, 10, and 15 post‐surgery. The results presented decreased paw withdrawal thresholds and reduced NREM sleep duration in both models on the first post‐surgery day. In the SCI model, NREM sleep duration was negatively correlated with paw withdrawal thresholds (p = 0.0466), but not in the CPL model. Wake alpha and theta EEG powers were also correlated with the pain threshold. The results confirm that the SCI model shows disturbed sleep patterns associated with increased pain sensitivity, suggesting it is a reliable tool for investigating sleep disturbances associated with neuropathic pain.
A multisensory approach to understanding bat responses to wind energy developments
Authors: Jonasson Kristin A. , Adams Amanda M. , Brokaw Alyson F. , Whitby Michael D. , O'Mara M. Teague , Frick Winifred F.
Published: January 2024

Millions of bats are killed at wind energy facilities worldwide, yet the behavioural mechanisms underlying why bats are vulnerable to wind turbines remain unclear. Anthropogenic stimuli that alter perceptions of the environment, known as sensory pollution, could create ecological traps and cause bat mortality at wind farms.

We review the sensory abilities of bats to evaluate potential stimuli associated with wind farms and examine the role of spatial scale on the perceptual mechanisms of sensory pollutants associated with wind energy facilities.

Audition, vision, somatosensation and olfaction are sensory modalities that bats use to perceive their environment, including wind farms and turbine structures, but they will not all be useful at the same spatial scales.

Bats most likely use vision to perceive wind farms on the landscape, and obstruction lighting may be the first sensory cue to attract bats to wind farms from kilometres away.

Research that assesses the risks posed by specific sensory pollutants, when conducted at the appropriate scale, can help identify solutions to reduce bat mortality, such as determining the attractiveness of obstruction lighting to bats at a landscape scale.
Modelling policies to improve affordability and consumption of nutritious foods for complementary feeding in Kenya
Authors: Traoré Fousseini , Omolo Miriam , Beal Ty , Nordhagen Stella , Codjia Patrick , Kiige Laura , Kamudoni Penjani , Arimi Caroline , Kirogo Veronica , Ortenzi Flaminia , Wouabe Eric Djimeu
Published: January 2024

In Kenya 26% of children under age 5 experience stunted growth, 4% are wasted and 11% are underweight. In pregnant women, the prevalence of iron deficiency is 36% and iron‐deficiency anaemia prevalence is 26%. Previous studies have identified affordability as a key barrier to the intake of nutrients, particularly from animal‐source foods (ASFs). Thus, this study analyzes to what extent the affordability of ASF in Kenya can be improved. It focuses on four ASFs: eggs, milk, chicken and beef. Using a computable general equilibrium model, three policy simulations were undertaken to establish the impact of potential changes on nutritious ASF availability and affordability: a 20% increase in total factor productivity (TFP) for the four products; a 20% TFP increase plus a 25% reduction in trade and transportation margins; and a 20% TFP increase for ASF and maize (a key input in animal feed). Simulations suggest increasing the productivity of the four ASF products would increase their availability and lower consumer prices (up to 17% lower). Household consumption of the four commodities would increase, resulting in improved household dietary diversity. Rural households would gain more compared with urban households. Poor households (the lowest 40%) would register larger welfare (Equivalent Variation) gains than other households in both urban and rural areas. The richest 20% of the population would neither lose nor gain following the policy changes. Reducing transportation costs and trade margins and increasing maize productivity could further reduce the price of ASFs through lower production costs and increased consumption.
Improving complementary feeding practices, programs and policies for optimal early childhood nutrition in Kenya: What would work?
Authors: Codjia Patrick , Kiige Laura , Rudert Christiane , Nordhagen Stella , Beal Ty , Kirogo Veronica , Ortenzi Flaminia , Gonzalez Wendy , Kamudoni Penjani , Garg Aashima
Published: January 2024

Complementary feeding practices are greatly influenced by local contexts. Therefore, national home‐grown evidence, policies and guidelines are critical to improving infant and young children's diets. This Special Issue has provided a comprehensive, evidence‐based analysis of the situation, gaps and context‐specific opportunities for improving young children's diets in Kenya. The primary research findings of the Special Issue supported the identification of a set of recommendations articulated across the four systems (food, health, water, sanitation and hygiene [WASH] and social protection) to improve food availability and accessibility in Kenya at the national and subnational levels. It is anticipated that the decentralised government functions seen in Kenya provide a strong opportunity to develop and mainstream context‐specific recommendations into action. This Special Issue recommends adopting a multi‐sectoral systems approach, including a shared vision, joint planning, implementation and monitoring, towards improving young children's diets with a focus on service delivery as well as scaled‐up community social behaviour change interventions. In particular, the approach should entail advocacy for policy revisions for service delivery that support complementary feeding and development of costed implementation strategies in support of the same, across four critical systems—food, health, WASH and social protection, along with, the strengthening of national coordination, monitoring and accountability structures as per the Kenya Nutrition Action Plan. Finally, the development of a legal framework for enhanced accountability from all relevant sectors towards sustainable, nutritious, safe and affordable children's diets. These recommendations provide a clear direction in addressing the complementary feeding challenges, which the primary research of this Special Issue has presented.
Everything alone: Is medical education chasing a harmful myth in its effort to embrace societal need?
Authors: Monteiro Sandra D.
Published: January 2024

'@monteiro_meded reflects on the dangers of treating self‐regulation as an individual activity that demands one to self‐assess, self‐monitor, self‐direct and self‐correct.
Politics makes bastards of us all: Why moral judgment is politically situational
Authors: Hull Kyle , Warren Clarisse , Smith Kevin
Published: January 2024

Moral judgment is politically situational—people are more forgiving of transgressive copartisans and more likely to behave punitively and unethically toward political opponents. Such differences are widely observed, but not fully explained. If moral values are nonnegotiable first‐principle beliefs about right and wrong, why do similar transgressions elicit different moral judgment in the personal and political realm? We argue this pattern arises from the same forces intuitionist frameworks of moral psychology use to explain the origins of morality: the adaptive need to suppress individual behavior to ensure ingroup success. We hypothesize ingroups serve as moral boundaries, that the relative tight constraints morality exerts over ingroup relations loosen in competitive group environments because doing so also serves ingroup interests. We find support for this hypothesis in four independent samples and also find that group antipathy—internalized dislike of the outgroup—pushes personal and political moral boundaries farther apart.
Polarized photoluminescence from Sn, Fe, and unintentionally doped β-Ga2O3
Authors: Cooke Jacqueline , Lou Minhan , Scarpulla Michael A. , Sensale-Rodriguez Berardi
Published: January 2024

In this work, we demonstrate that β-Ga2O3 shows orientation-dependent polarized photoluminescence (PL) emission and give a comprehensive insight into gallium oxide's PL spectral properties. We characterized the polarization and spectral dependencies of both the incident and emitted light for (−201) unintentionally doped (UID) as well as (−201) and (010) Sn-doped and Fe-doped crystals. We observed for UID and Sn-doped samples that the electron to self-trapped hole and native defect-related emission bands are linearly polarized with polarized emission intensities ordered as E || c (and c*) > E || a (and a*) > E || b. Furthermore, the spectral shape of emission does not change between the UID and Sn-doped samples; instead, the Sn-doping quenches the total PL spectral intensity. For Fe-doped samples, polarized red emission caused by unintentional Cr3+ doping generates emission intensities ordered E || b > E || c (and c*) > E || a (and a*). It is also observed that in some circumstances, for some doped crystals, the PL spectra can show variations not only in intensity but also in spectral shape along different polarization directions. As an example, the PL emission band for emission along c is blueshifted relative to that along a in Sn-doped β-Ga2O3.
Auditing the Representation of Females Versus Males in Heat Adaptation Research
Authors: Kelly Monica K. , Smith Ella S. , Brown Harry A. , Jardine William T. , Convit Lilia , Bowe Steven J. , Condo Dominique , Guy Joshua H. , Burke Louise M. , Périard Julien D. , Snipe Rhiannon M.J. , Snow Rodney J. , Carr Amelia J.
Published: January 2024

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18–50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions.
Practical challenges for precision medicine
Authors: Petzschner Frederike H.
Published: January 2024

The prediction of individual treatment responses with machine learning faces hurdles
In Other Journals
Authors: Smith Keith T. , Ash Caroline , Lempriere Sarah A. , Walia Ankit , Maroso Mattia , Funk Michael A. , Yeston Jake S.
Published: January 2024

Editors’ selections from the current scientific literature
U.S. undersea mapping is a boon for science
Authors: Malakoff David
Published: January 2024

New maps of continental shelf could vastly expand U.S. territory and resource claims
Ancient DNA ties modern diseases to ancestry
Authors: Curry Andrew
Published: January 2024

Among Europeans, risk of multiple sclerosis rises with genes from Bronze Age Yamnaya herders
Disrupted degradative sorting of TLR7 is associated with human lupus
Authors: Mishra Harshita , Schlack-Leigers Claire , Lim Ee Lyn , Thieck Oliver , Magg Thomas , Raedler Johannes , Wolf Christine , Klein Christoph , Ewers Helge , Lee-Kirsch Min Ae , Meierhofer David , Hauck Fabian , Majer Olivia
Published: January 2024

Hyperactive TLR7 signaling has long been appreciated as driver of autoimmune disease in mouse models. Recently, gain-of-function mutations in TLR7 were identified as a monogenic cause of human lupus. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes. Here, we show that endosome dysfunction leads to unrestricted TLR7 signaling and is associated with human lupus. The late endosomal BORC complex together with the small GTPase Arl8b controls intracellular TLR7 levels by regulating receptor turnover. This requires a direct interaction between the TLR7-associated trafficking factor Unc93b1 and Arl8b. We identified an UNC93B1 mutation in a patient with childhood-onset lupus, which results in reduced BORC interaction and endosomal TLR7 accumulation. Therefore, a failure to control TLR7 turnover is sufficient to break immunological tolerance to nucleic acids. Our results highlight the importance of an intact endomembrane system in preventing pathological TLR7 signaling and autoimmune disease.
Genomic analysis of diverse environmental
Acinetobacter
isolates identifies plasmids, antibiotic resistance genes, and capsular polysaccharides shared with clinical strains
Authors: Tobin Liam A. , Jarocki Veronica M. , Kenyon Johanna , Drigo Barbara , Donner Erica , Djordjevic Steven P. , Hamidian Mehrad
Published: January 2024

Acinetobacter baumannii,
an important pathogen known for its widespread antibiotic resistance, has been the focus of extensive research within its genus, primarily involving clinical isolates. Consequently, data on environmental
A. baumannii
and other
Acinetobacter
species remain limited. Here, we utilized Illumina and Nanopore sequencing to analyze the genomes of 10
Acinetobacter
isolates representing 6 different species sourced from aquatic environments in South Australia. All 10 isolates were phylogenetically distinct compared to clinical and other non-clinical
Acinetobacter
strains, often tens of thousands of single-nucleotide polymorphisms from their nearest neighbors. Despite the genetic divergence, we identified p
dif
modules (sections of mobilized DNA) carrying clinically important antimicrobial resistance genes in species other than
A. baumannii
, including carbapenemase
oxa58,
tetracycline resistance gene
tet(39
), and macrolide resistance genes
msr(E)-mph(E
). These p
dif
modules were located on plasmids with high sequence identity to those circulating in globally distributed
A. baumannii
ST1 and ST2 clones. The environmental
A. baumannii
isolate characterized here (SAAb472; ST350) did not possess any native plasmids; however, it could capture two clinically important plasmids (pRAY and pACICU2) with high transfer frequencies. Furthermore,
A. baumannii
SAAb472 possessed virulence genes and a capsular polysaccharide type analogous to clinical strains. Our findings highlight the potential for environmental
Acinetobacter
species to acquire and disseminate clinically important antimicrobial resistance genes, underscoring the need for further research into the ecology and evolution of this important genus.

IMPORTANCE

Antimicrobial resistance (AMR) is a global threat to human, animal, and environmental health. Studying AMR in environmental bacteria is crucial to understand the emergence and dissemination of resistance genes and pathogens, and to identify potential reservoirs and transmission routes. This study provides novel insights into the genomic diversity and AMR potential of environmental
Acinetobacter
species. By comparing the genomes of aquatic
Acinetobacter
isolates with clinical and non-clinical strains, we revealed that they are highly divergent yet carry p
dif
modules that encode resistance to antibiotics commonly used in clinical settings. We also demonstrated that an environmental
A. baumannii
isolate can acquire clinically relevant plasmids and carries virulence factors similar to those of hospital-associated strains. These findings suggest that environmental
Acinetobacter
species may serve as reservoirs and vectors of clinically important genes. Consequently, further research is warranted to comprehensively understand the ecology and evolution of this genus.
Mantle flow and olivine fabric transition in the Myanmar continental subduction zone
Authors: Fan Enbo , Ai Yinshuang , Gao Stephen S. , He Yumei , Liu Kelly H. , Jiang Mingming , Hou Guangbing , Yang Shun , Mon Chit Thet , Thant Myo , Sein Kyaing
Published: January 2024

One of the major advances in mineral physics and seismology is the realization that different olivine fabric types are functions of temperature, shear stress, and water content in oceanic subducting systems. The distribution of different olivine fabric types and geodynamic processes in the mantle wedge above a subducting continental slab remain poorly understood. Here, based on splitting analysis of shear waves recorded by 46 stations recently deployed in central Myanmar, we reveal trench-perpendicular fast orientations between the 80 and 100 km slab contours sandwiched between trench-parallel fast orientations from the mantle wedge tip to the backarc. The dramatic change in fast orientations indicates the transition of olivine fabric types in the mantle wedge combined with corner flow. Cold continental subduction and shear stress reduction caused by partial melting favor B-type and C- or E-type olivine fabrics, respectively.
Supplemental Material: Increase in magma supply to Sakurajima volcano’s (Japan) shallow magma chamber over the past 500 years
Authors: Huber Christian , Toramaru Atsushi
Published: January 2024

 The Supplemental Material contains two important additions to the main manuscript. First, it provides a more detailed discussion of the rationale for leaving the Showa inversion out of our modeling effort. The second addition concerns the pumice samples analyzed for crystal volume fraction and importantly for their bubble size distribution. The latter is instrumental in determining whether phenobubbles are present and how their content varied from one eruption to the next.  
Sustained inflation and chest compression versus 3:1 chest compression to ventilation ratio during cardiopulmonary resuscitation of asphyxiated newborns (SURV1VE): A cluster randomised controlled trial
Authors: Schmölzer Georg M , Pichler Gerhard , Solevåg Anne Lee , Law Brenda Hiu Yan , Mitra Souvik , Wagner Michael , Pfurtscheller Daniel , Yaskina Maryna , Cheung Po-Yin
Published: January 2024

Objective

In newborn infants requiring chest compression (CC) in the delivery room (DR) does continuous CC superimposed by a sustained inflation (CC+SI) compared with a 3:1 compression:ventilation (3:1 C:V) ratio decreases time to return of spontaneous circulation (ROSC).

Design

International, multicenter, prospective, cluster cross-over randomised trial.

Setting

DR in four hospitals in Canada and Austria,

Participants

Newborn infants >28 weeks’ gestation who required CC.

Interventions

Hospitals were randomised to CC+SI or 3:1 C:V then crossed over to the other intervention.

Main outcome measure

The primary outcome was time to ROSC, defined as the duration of CC until an increase in heart rate >60/min determined by auscultation of the heart, which was maintained for 60 s. Sample size of 218 infants (109/group) was sufficient to detect a clinically important 33% reduction (282 vs 420 s of CC) in time to ROSC. Analysis was intention-to-treat.

Results

Patient recruitment occurred between 19 October 2017 and 22 September 2022 and randomised 27 infants (CC+SI (n=12), 3:1 C:V (n=15), two (one per group) declined consent). All 11 infants in the CC+SI group and 12/14 infants in the 3:1 C:V group achieved ROSC in the DR. The median (IQR) time to ROSC was 90 (60–270) s and 615 (174–780) s (p=0.0502 (log rank), p=0.16 (cox proportional hazards regression)) with CC+SI and 3:1 C:V, respectively. Mortality was 2/11 (18.2%) with CC+SI versus 8/14 (57.1%) with 3:1 C:V (p=0.10 (Fisher’s exact test), OR (95% CI) 0.17; (0.03 to 1.07)). The trial was stopped due to issues with ethics approval and securing trial insurance as well as funding reasons.

Conclusion

The time to ROSC and mortality was not statistical different between CC+SI and 3:1 C:V.

Trial registration

NCT02858583.
Multistate survival modelling of multimorbidity and transitions across health needs states and death in an ageing population
Authors: Gao Qian , Muniz Terrera Graciela , Mayston Rosie , Prina Matthew
Published: January 2024

Background

Unmet health needs have the potential to capture health inequality. Nevertheless, the course of healthcare needs fulfilment, and the role of multimorbidity in this process remains unclear. This study assessed the bidirectional transitions between met and unmet health needs and the transition to death and examined the effect of multimorbidity on transitions.

Methods

This study was based on the China Health and Retirement Longitudinal Study, a nationally representative survey in 2011–2015 among 18 075 participants aged 45 and above (average age 61.1; SD 9.9). We applied a multistate survival model to estimate the probabilities and the instantaneous risk of state transitions, and Gompertz hazard models were fitted to estimate the total, marginal and state-specific life expectancies (LEs).

Results

Living with physical multimorbidity (HR=1.85, 95% CI 1.58 to 2.15) or physical–mental multimorbidity (HR=1.45, 95% CI 1.15 to 1.82) was associated with an increased risk of transitioning into unmet healthcare needs compared with no multimorbidity. Conversely, multimorbidity groups had a decreased risk of transitioning out of unmet needs. Multimorbidity was also associated with shortened total life expectancy (TLEs), and the proportion of marginal LE for having unmet needs was more than two times higher than no multimorbidity.

Conclusion

Multimorbidity aggravates the risk of transitioning into having unmet healthcare needs in the middle and later life, leading to a notable reduction in TLEs, with longer times spent with unmet needs. Policy inputs on developing integrated person-centred services and specifically scaling up to target the complex health needs of ageing populations need to be in place.
The primordial black holes solution to the cosmological monopole problem
Authors: Wang Xin-Zhe , Deng Can-Min
Published: January 2024

Recently, the pulsar timing array (PTA) collaborations, including CPTA, EPTA, NANOGrav, and PPTA, announced that they detected a stochastic gravitational wave background spectrum in the nHz band. This may be relevant to the cosmological phase transition suggested by some models. Magnetic monopoles and primordial black holes (PBHs), two unsolved mysteries in the universe, may also have their production related to the cosmological phase transition. Inspired by that, we revisit the model proposed by Stojkovic and Freese, which involves PBHs accretion to solve the cosmological magnetic monopole problem. We further develop it by considering the increase in the mass of the PBHs during accretion and taking the effect of Hawking radiation into account. With these new considerations, we find that solutions to the problem still exist within a certain parameter space. In addition, we also generalize the analysis to PBHs with an extended distribution in mass. This may be a more interesting scenario because PBHs that have accreted magnetic monopoles might produce observable electromagnetic signals if they are massive enough to survive in the late universe.
Debris flow at Luib on the A87 strategic road: Isle of Skye, Scotland
Authors: Winter M. G. , Waaser T.
Published: January 2024

A rainfall-induced debris flow occurred on 30 September 2022, closing the A87 trunk (strategic) road on the Isle of Skye for around 2 h. Ground-based and aerial drone inspections were used to describe the event and a comprehensive rainfall analysis was undertaken. It is concluded that the event was triggered by overland water flow from the slopes above the source zone as a result of high rainfall. The resulting translational slide transitioned into a debris flow that reached a pre-existing channel where entrained superficial deposits were deposited, adding to pre-existing levee structures before reaching the road. The rainfall that led to the debris flow was high intensity–low duration; the rainfall analysis encompasses annual, monthly, daily, hourly and 15 min data, each aiding understanding of the climate of the area and/or the event rainfall. Comparison is made with a rainfall event the following month, which was of a greater magnitude but of longer duration and lower intensity. The hazard at this location is a concern but the risk is emphasized by the proximity of the road to the steep slopes above and the lack of a viable detour.
Low-Field, Low-Cost, Point-of-Care Magnetic Resonance Imaging
Authors: Samardzija Anja , Selvaganesan Kartiga , Zhang Horace Z. , Sun Heng , Sun Chenhao , Ha Yonghyun , Galiana Gigi , Constable R. Todd
Published: January 2024

Low-field magnetic resonance imaging (MRI) has recently experienced a renaissance that is largely attributable to the numerous technological advancements made in MRI, including optimized pulse sequences, parallel receive and compressed sensing, improved calibrations and reconstruction algorithms, and the adoption of machine learning for image postprocessing. This new attention on low-field MRI originates from a lack of accessibility to traditional MRI and the need for affordable imaging. Low-field MRI provides a viable option due to its lack of reliance on radio-frequency shielding rooms, expensive liquid helium, and cryogen quench pipes. Moreover, its relatively small size and weight allow for easy and affordable installation in most settings. Rather than replacing conventional MRI, low-field MRI will provide new opportunities for imaging both in developing and developed countries. This article discusses the history of low-field MRI, low-field MRI hardware and software, current devices on the market, advantages and disadvantages, and low-field MRI's global potential.
Central role of podocytes in mediating cellular cross talk in glomerular health and disease
Authors: Gujarati Nehaben A. , Chow Andrew K. , Mallipattu Sandeep K.
Published: January 2024

Podocytes are highly specialized epithelial cells that surround the capillaries of the glomeruli in the kidney. Together with the glomerular endothelial cells, these postmitotic cells are responsible for regulating filtrate from the circulating blood with their organized network of interdigitating foot processes that wrap around the glomerular basement membrane. Although podocyte injury and subsequent loss is the hallmark of many glomerular diseases, recent evidence suggests that the cell-cell communication between podocytes and other glomerular and nonglomerular cells is critical for the development and progression of kidney disease. In this review, we highlight these key cellular pathways of communication and how they might be a potential target for therapy in glomerular disease. We also postulate that podocytes might serve as a central hub for communication in the kidney under basal conditions and in response to cellular stress, which may have implications for the development and progression of glomerular diseases.
No sex differences in oxygen uptake or extraction kinetics in the moderate or heavy exercise intensity domains
Authors: Solleiro Pons Maria , Bernert Lina , Hume Emily , Hughes Luke , Williams Zander J. , Burnley Mark , Ansdell Paul
Published: January 2024

This study demonstrated no sex differences in the oxidative response to moderate- and heavy-intensity cycling exercise. The change in oxygen uptake and deoxyhemoglobin were modeled with monoexponential curve fitting, which revealed no differences in the rate of oxidative energy provision between sexes. This provides insight into previously reported sex differences in the integrative response to exercise.
Horizontal foot orientation affects the distribution of neural drive between gastrocnemii during plantarflexion, without changing neural excitability
Authors: Crouzier Marion , Avrillon Simon , Hug François , Cattagni Thomas
Published: January 2024

Horizontal foot orientation affects the distribution of neural drive between the gastrocnemii during plantarflexion. There is no foot orientation-related modulation in the corticospinal excitability of the gastrocnemii, either at the cortical level or through modulation of the efficacy of Ia-α-motoneuron transmission. Change in motor pathway excitability is not the mechanism controlling the different distribution of neural drive between gastrocnemius medialis and lateralis with foot orientation.
Evaluation of the Effect of Cichorium intybus L. on the Liver Enzymes in Burn Patients: A Randomized Double-Blind Clinical Trial
Authors: Keshavarzi Abdolkhalegh , Akrami Rahimeh , Zarshenas Mohammad M. , Zareie Saeid , Ghadimi Tayyeb , Najafi Ali , Rostami Chijan Mahsa , Dehghan Azizallah , Zarenezhad Elham
Published: January 2024

Burn injuries are considered an important public health problem in the world. Burns are considered the fourth most common kind of trauma in the world, after traffic accidents, falls, and interpersonal violence. Various biochemical agents are involved in the burn healing process such as cytokines (such as IL-6 and TNF-α), antioxidants, and liver and kidney damage biomarkers. Cichorium intybus L. and milk thistle extracts showed a wide range of pharmacological activities such as significant antimicrobial effect and antioxidant activity, as well as anti-inflammatory, antidiabetic, antiproliferative, antiprotozoal, and hepatoprotective effect. Also, these two herbs possess blood-cleansing, detoxifying, laxative, and invigorating activities. Some research confirmed that the preparations of the extract are very suitable for the treatment of nonalcoholic fatty liver disease. This is a double-blind randomized controlled clinical trial. Patients with 2nd and 3rd degree burns have been selected to participate in the study according to the inclusion criteria. A total of 60 patients were selected and divided into intervention and control groups (30 patients in each group). Patients in the intervention group received chicory seed syrup 10 cc three times a day and 1 placebo capsule, and those in the control group received placebo syrup (10 cc three times a day) and one Livergol (140 mg of silymarin in each capsule) capsule. Lab data such as liver function tests, albumin, creatinine, BUN, and hemoglobin were checked every 3 days and 1 week after discharge. The treatment lasted for 4 weeks. According to the results of the study, although the average of liver enzymes at the end of the study does not show a significant difference between the two groups, the level of liver enzymes in each group decreased on the 15th day of the study compared to the first day. This trial is registered with IRCT20180609040016N1.