bluuebunny/crossref_metadata_2025 huggingface dataset:
Fiscal policy and dimensions of inequality in South Africa: A time‐varying coefficient approach
Authors: Terblanche Jeanne , van Lill Dawie , Hollander Hylton
Published: January 2024

South Africa continues to face high inequality levels despite its progressive tax and extensive social protection systems. We compare the dynamic impact of fiscal policy on the distribution of incomes, wages and wealth in South Africa from 1993 to 2019. For this purpose, we use a time‐varying parameter vector autoregression to estimate the impact of direct tax revenue and total transfer spending on three distinct inequality datasets. The analysis of various dimensions of inequality is the main contribution of the paper as the literature typically focuses on income inequality. A second contribution lies in the incorporation of time‐varying effects, which enables the analysis of the changing relationship between fiscal policy and inequality. The results suggest that this relationship is indeed time‐varying and that the impact of direct taxes and transfers differs markedly across the inequality dimensions, both in terms of magnitude and sign. Overall, we find that both transfers and direct taxes have not significantly reduced income, wage or wealth inequality in South Africa.
Kidney transplantation in patients on anti‐tubercular therapy: A single centre observational study
Authors: Prasad Pallavi , Bagai Sahil , Prasad Vandana , Grover Rahul , Chhabra Gagandeep , Khullar Dinesh
Published: January 2024

Background

Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT).

Methods

This was a retrospective single‐center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT.

Results

Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosed by ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post‐transplantation fluoroquinolone‐based non‐rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post‐transplantation was 71.9, 64.7, and 67 mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%.

Conclusion

Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase of ATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.

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Porcine embryonic stem cells: An alternative solution for the shortage of human islets to treat type 1 diabetes?
Authors: Nottle Mark B. , Vassiliev Ivan , Hawthorne Wayne J. , Cowan Peter J.
Published: January 2024

Transplantation of human embryonic stem cell (ESC) derived beta‐like cells and xenotransplantation of porcine islets are two potential cures for type 1 diabetes (T1D). We have previously reported the isolation of porcine ESCs and have also separately shown that islets from genetically modified pigs can effectively cure diabetes in a preclinical baboon model. Here we discuss the possibility of combining these technologies to produce gene‐edited porcine ESC‐derived islets as an alternative for treating T1D, which may offer several advantages compared with these approaches.
Sleep extension and cardiometabolic health: what it is, possible mechanisms and real‐world applications
Authors: Duraccio Kara M. , Kamhout Sarah , Baron Kelly G. , Reutrakul Sirimon , Depner Christopher M.
Published: January 2024

Short sleep duration is associated with heightened cardiometabolic disease risk and has reached epidemic proportions among children, adolescents and adults. Potential mechanisms underlying this association are complex and multifaceted, including disturbances in circadian timing, food intake and appetitive hormones, brain regions linked to control of hedonic eating, physical activity, an altered microbiome and impaired insulin sensitivity. Sleep extension, or increasing total sleep duration, is an emerging and ecologically relevant intervention with significant potential to advance our understanding of the mechanisms underlying the association between short sleep duration and the risk of cardiometabolic disease. If effective, sleep extension interventions have potential to improve cardiometabolic health across the lifespan. Existing data show that sleep extension is feasible and might have potential cardiometabolic health benefits, although there are limitations that the field must overcome. Notably, most existing studies are short term (2–8 weeks), use different sleep extension strategies, analyse a wide array of cardiometabolic health outcomes in different populations and, frequently, lack adequate statistical power, thus limiting robust scientific conclusions. Overcoming these limitations will require fully powered, randomized studies conducted in people with habitual short sleep duration and existing cardiometabolic risk factors. Additionally, randomized controlled trials comparing different sleep extension strategies are essential to determine the most effective interventions. Ongoing and future research should focus on elucidating the potential cardiometabolic health benefits of sleep extension. Such studies have high potential to generate crucial knowledge with potential to improve health and quality of life for those struggling with short sleep duration.

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Big Data and Lots of Data are Not the Same Things: Small data sources in the social science of archaeologists
Authors:   Landward Research, Aitchison Kenneth
Published: January 2024

'Big Data' is a misunderstood but technically definable concept; it is large volume, unstructured, heterogenous information, that is being generated at a high velocity - which normally means it is being constantly updated in real time. And, in many situations, this is very difficult to work with; an analogy might be to compare the curated content of Netflix, which is a (very) large but structured data set, with the unending chaos of YouTube content, which is Big Data. The first part of this paper considers big data, and how it is defined and used, with the second part considering how large amounts of small data can be used in sociology as applied to archaeology.
The Ever-Expanding Toolbox
Authors: Sukel Kayt
Published: January 2024

Enhancements to engineering software platforms are purported is to make life easier for mechanical engineers, who are increasingly being asked to do more on shorter timelines. While these upgrades are powerful, it is uncertain whether working engineers know what’s available and how to use it.
Derivation of “Double-Loop” Theory and Mechanism of Cavitation-Vortex Interaction in Turbulent Cavitation Boundary Layer
Authors: Jin Weiwei
Published: January 2024

“Double-loop” theory was determined by deriving a correlation between turbulent fluctuating kinetic energy and water vapor volume fraction from the momentum equation, which further logically revealed the mystery of cavitation breaking around a three-dimensional symmetry hydrofoil based on the numerical results of large eddy simulation and Zwart–Gerber–Belamri cavitation model. When the second-order fluctuation moment Vx′Vx′ and the streamwise velocity Vx are depleted, a vortex is generated, leading to alternating cavitation interface fluctuations. In one state, cavitation naturally breaks outward from the inner zone, triggering an up-and-down fluctuation in the normal velocity in the gap vortex and transferring external energy to the inner zone. In another state, cavitation collapse caused by a reentrant jet stagnates the reverse Vx so that Vx′Vx′ tends to zero. It triggers a rise in an upward normal velocity in the attached vortex, creating an exchange of energy through the wake. The pressure implosion resulting from the Shrinkage of the “Like-Rayleigh–Plesset” cavity at the cavitation onset is stronger than the pressure implosion created by the vortex field during cavitation breaking.
Variable Pivot Gait Based a Novel Dynamics Correction Method for Human Lower Limbs Model
Authors: Ai Cunjin , Wei Jun , Zhang Jianjun , Song Jingke , Lv Weilin , Liu Chenglei
Published: January 2024

The rationality of gait analysis directly affects the dynamics of human lower limbs in the sagittal plane, and recent studies on gait stage redivision lack the stage when both feet are not in complete contact with the ground. This paper proposes a novel variable pivot gait, which includes the stage when the heel of one foot and the toe of the other are in contact with the ground and a dynamics correction method based on this gait. First, the relative motion data between the foot and the ground are measured by motion capture experiments, and then a variable pivot gait is proposed in terms of the pivot transformation between the foot and the ground. Second, the dynamics modeling is conducted based on the principle of mechanisms of human lower limbs in each stage of the variable pivot gait. Third, a dynamics correction method is proposed to correct the foot dynamics when the foot is not in complete contact with the ground. The experiment and simulation show that the variable pivot gait is consistent with the actual motion of the foot relative to the ground. The effectiveness of the dynamics correction method is proved by comparing dynamics results (hip, knee, and ankle moments) with previous studies. The variable pivot gait and the dynamics correction method can be applied to the human lower limbs and lower-limb robots, providing a new avenue.
Solutions of Time-Space Fractional Partial Differential Equations Using Picard's Iterative Method
Authors: Kumar Manoj , Jhinga Aman , Majithia J. T.
Published: January 2024

In this paper, we present Picard's iterative method (PIM) for solving time–space fractional partial differential equations, where the derivatives are considered in the Caputo sense. We prove the existence and uniqueness of solutions. Additionally, we demonstrate the versatility of our proposed approach by obtaining exact solutions for a diverse set of equations. This method is user-friendly and directly applicable to any computer algebra system. The proposed method avoids intricate computations associated with the Adomian decomposition method, such as calculating Adomian polynomials, or the requirements of other methods like choosing a homotopy in the homotopy perturbation method, identification and manipulation of the invariant subspace in invariant subspace method or constructing a variational function in the variational iteration method. Thus, the proposed method is a versatile and efficient tool for exploring systems that involve both temporal and spatial fractional derivatives.
Automated self-optimization, intensification, and scale-up of photocatalysis in flow
Authors: Slattery Aidan , Wen Zhenghui , Tenblad Pauline , Sanjosé-Orduna Jesús , Pintossi Diego , den Hartog Tim , Noël Timothy
Published: January 2024

The optimization, intensification, and scale-up of photochemical processes constitute a particular challenge in a manufacturing environment geared primarily toward thermal chemistry. In this work, we present a versatile flow-based robotic platform to address these challenges through the integration of readily available hardware and custom software. Our open-source platform combines a liquid handler, syringe pumps, a tunable continuous-flow photoreactor, inexpensive Internet of Things devices, and an in-line benchtop nuclear magnetic resonance spectrometer to enable automated, data-rich optimization with a closed-loop Bayesian optimization strategy. A user-friendly graphical interface allows chemists without programming or machine learning expertise to easily monitor, analyze, and improve photocatalytic reactions with respect to both continuous and discrete variables. The system's effectiveness was demonstrated by increasing overall reaction yields and improving space-time yields compared with those of previously reported processes.
Establishing a synthetic orthogonal replication system enables accelerated evolution in
E. coli
Authors: Tian Rongzhen , Rehm Fabian B. H. , Czernecki Dariusz , Gu Yangqi , Zürcher Jérôme F. , Liu Kim C. , Chin Jason W.
Published: January 2024

The evolution of new function in living organisms is slow and fundamentally limited by their critical mutation rate. Here, we established a stable orthogonal replication system in
Escherichia coli.
The orthogonal replicon can carry diverse cargos of at least 16.5 kilobases and is not copied by host polymerases but is selectively copied by an orthogonal DNA polymerase (O-DNAP), which does not copy the genome. We designed mutant O-DNAPs that selectively increase the mutation rate of the orthogonal replicon by two to four orders of magnitude. We demonstrate the utility of our system for accelerated continuous evolution by evolving a 150-fold increase in resistance to tigecycline in 12 days. And, starting from a GFP variant, we evolved a 1000-fold increase in cellular fluorescence in 5 days.
Retractions lag for wave of suspect papers
Authors: Brainard Jeffrey
Published: January 2024

Years after whistleblowers questioned nearly 300 papers, journals are slow to respond
Is NASA too pessimistic about space-based solar power?
Authors: Clery Daniel
Published: January 2024

Agency says orbiting power stations would be costly, but rocketry breakthroughs could make it economical
Vibrio fischeri
: a model for host-associated biofilm formation
Authors: Fung Brittany L. , Esin Jeremy J. , Visick Karen L.
Published: January 2024

Multicellular communities of adherent bacteria known as biofilms are often detrimental in the context of a human host, making it important to study their formation and dispersal, especially in animal models. One such model is the symbiosis between the squid
Euprymna scolopes
and the bacterium
Vibrio fischeri
. Juvenile squid hatch aposymbiotically and selectively acquire their symbiont from natural seawater containing diverse environmental microbes. Successful pairing is facilitated by ciliary movements that direct bacteria to quiet zones on the surface of the squid’s symbiotic light organ where
V. fischeri
forms a small aggregate or biofilm. Subsequently, the bacteria disperse from that aggregate to enter the organ, ultimately reaching and colonizing deep crypt spaces. Although transient, aggregate formation is critical for optimal colonization and is tightly controlled.
In vitro
studies have identified a variety of polysaccharides and proteins that comprise the extracellular matrix. Some of the most well-characterized matrix factors include the symbiosis polysaccharide (SYP), cellulose polysaccharide, and LapV adhesin. In this review, we discuss these components, their regulation, and other less understood
V. fischeri
biofilm contributors. We also highlight what is currently known about dispersal from these aggregates and host cues that may promote it. Finally, we briefly describe discoveries gleaned from the study of other
V. fischeri
isolates. By unraveling the complexities involved in
V. fischeri
’s control over matrix components, we may begin to understand how the host environment triggers transient biofilm formation and dispersal to promote this unique symbiotic relationship.
Resolving pressure differences within the Grand Canyon Precambrian basement: Implications for Proterozoic tectonics
Authors: Autrey-Mulligan Suzanne , Bonamici Chloe , Williams Michael L. , Karlstrom Karl , Condit Cailey B.
Published: January 2024

Burial pressures (depths) within mountain belts place fundamental constraints on the growth and stabilization of continental crust. We report precise metamorphic pressures for ca. 1.7 Ga rocks from the Upper Granite Gorge (UGG) of the Grand Canyon (southwestern United States) and, for the first time, resolve pressure variations across this continuous exposure of mid-crustal rocks. We applied quartz-in-garnet (QuiG) barometry and pseudosection modeling to determine pressures in domains (“blocks”) with evidence of higher and lower peak metamorphic grades. New pressure-temperature (P-T) paths constructed using this integrated approach show that a hot block sample reached 7 kbar and a cold block sample never surpassed 5 kbar, revealing an ~2 kbar P difference between hot and cold blocks and delineating distinct P-T paths for these domains in the UGG. Our findings suggest that hot and cold blocks were likely metamorphosed at different crustal levels within a pre-Yavapai, Paleoproterozoic orogen and were subsequently juxtaposed during and/or after the Yavapai Orogeny at mid-crustal levels. The deformation that produced differential vertical displacement of crustal blocks post-dated peak metamorphism and could reflect extensional collapse of a large orogen and/or renewed folding and thrusting at the Paleoproterozoic Laurentian plate margin.
Erratum to: Highly Aggressive Invasive Race Group PstS2 in Russian Populations of the Wheat Yellow Rust Pathogen
Authors: Shaydayuk E. L. , Gultyaeva E. I.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050071
Erratum to: Finding of an Unusually Colored Sporocyst of the Genus Leucochloridium in a Succinea putris Snail
Authors: Usmanova R. R. , Prokhorova E. E.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050083
Erratum to: A New Species of Hapalodectes (Hapalodectidae, Mesonychia) from the Paleocene of Mongolia
Authors: Lopatin A. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050101
Simultaneous Observation of the Cyclotron Resonances of Electrons and Holes in a HgTe/CdHgTe Double Quantum Well under “Optical Gate” Effect
Authors: Bovkun L. S. , Krishtopenko S. S. , Aleshkin V. Ya. , Mikhailov N. N. , Dvoretsky S. A. , Teppe F. , Orlita M. , Gavrilenko V. I. , Ikonnikov A. V.
Published: January 2024

Spectral studies of the photoconductivity in the temperature range of T = 5–70 K, as well as studies of the magneto-absorption and magnetotransport at T = 4.2 K, have been performed in a HgTe/CdHgTe heterostructure with a double quantum well under an “optical gate” effect. Studies of magneto-absorption spectra under the controlled optical exposure have made it possible to observe absorption lines caused by both the cyclotron resonances of electrons and holes simultaneously. The coexistence of electrons and holes in the HgTe/CdHgTe double quantum well with a relatively large bandgap (~80 meV) indicates the appearance of a strongly inhomogeneous light-induced distribution of charge carriers in the plane of the structure. Experimental results obtained clearly demonstrate disadvantages of the control of the Fermi level positions in heterostructures with HgTe/CdHgTe quantum wells by means of the optical gate.
Erratum to: First Data on Vertical Particle Fluxes and Environmental Conditions in the Northern Segment of the Mohns Ridge, Norwegian Sea
Authors: Klyuvitkin A. A. , Kravchishina M. D. , Novigatsky A. N. , Politova N. V. , Bulokhov A. V. , Gulev S. K.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1028334X23060132
Erratum to: First Results of U–Th/He Dating of Epigenetic Pyrite from Rocks of the Bazhenov Formation, Western Siberia
Authors: Yakubovich O. V. , Vasilyeva N. A. , Vasilyeva K. Yu. , Anosova M. O. , Kotov A. B. , Podolskaya M. M. , Gorokhovskiy B. M.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1028334X23060181
Air pollution and childhood respiratory consultations in primary care: a systematic review
Authors: Fonderson Mata Sabine , van Meel Evelien R , Bindels Patrick , Bohnen Arthur , Burdorf Alex , de Schepper Evelien
Published: January 2024

Background

Outdoor air pollution is a known risk factor for respiratory morbidity worldwide. Compared with the adult population, there are fewer studies that analyse the association between short-term exposure to air pollution and respiratory morbidity in children in primary care.

Objective

To evaluate whether children in a primary care setting exposed to outdoor air pollutants during short-term intervals are at increased risk of respiratory diagnoses.

Methods

A search in Medline, the Cochrane Library, Web of Science and Embase databases throughout March 2023. Percentage change or risk ratios with corresponding 95% CI for the association between air pollutants and respiratory diseases were retrieved from individual studies. Risk of bias assessment was conducted with the Newcastle–Ottawa Scale (NOS) for cohort or case–control studies and an adjusted NOS for time series studies.

Results

From 1366 studies, 14 were identified as meeting the inclusion criteria. Most studies had intermediate or high quality. A meta-analysis was not conducted due to heterogeneity in exposure and health outcome. Overall, studies on short-term exposure to air pollutants (carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter ≤10 µm (PM10)) were associated with increased childhood respiratory consultations in primary care. In general, exposure to ozone was associated with a reduction in respiratory consultations.

Conclusions

The evidence suggests CO, SO2, NO2, PM10and PM2.5are risk factors for respiratory diseases in children in primary care in the short term. However, given the heterogeneity of the studies, interpretation of these findings must be done with caution.

PROSPERO registration number

CRD42022259279.
Neurological development in children born moderately or late preterm: national cohort study
Authors: Mitha Ayoub , Chen Ruoqing , Razaz Neda , Johansson Stefan , Stephansson Olof , Altman Maria , Bolk Jenny
Published: January 2024

Objective

To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term).

Design

Nationwide cohort study.

Setting

Sweden.

Participants

1 281 690 liveborn singleton children without congenital malformations born at 32+0to 41+6weeks between 1998 and 2012.

Main outcome measures

The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment.

Results

During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term.

Conclusions

The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.
Adverse perinatal outcomes in gestational diabetes mellitus with and without SARS-CoV-2 infection during pregnancy: results from two nationwide registries in Germany
Authors: Liedtke Tatjana P , Weber Katharina S , Adamczewski Heinke , Weber Dietmar , Ramsauer Babett , Schaefer-Graf Ute M , Groten Tanja , Strathmann Eike A , Lieb Wolfgang , Rüdiger Mario , Pecks Ulrich , Kleinwechter Helmut J
Published: January 2024

Introduction

Pregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM.

Research design and methods

We compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018–2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight>4500 g and cesarean delivery were considered as secondary outcomes.

Results

Women with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09).

Conclusions

GDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection.
Baseline characteristics of children in the International PANS Registry (IPR) Epidemiology Study
Authors: Masterson Erin E , Gavin Jessica M
Published: January 2024

Purpose

The International PANS Registry (IPR) Epidemiology Study is a registry-based, longitudinal study. We designed this study to improve phenotyping and characterisation of children with paediatric acute-onset neuropsychiatric syndrome (PANS) and PANS-like features and facilitate multidisciplinary and translational health research. This cohort provides new opportunities to address unresolved research questions related to the broad spectrum of heterogenous PANS-like conditions.

Participants

Inclusion in the IPR Epidemiology Study remains open indefinitely via IPR enrolment online. Participants include children with PANS or who have PANS-like features and their healthy siblings. We collected cross-sectional survey data based on parent report, including details on phenotypic traits and characteristics that, to our knowledge, have not been previously collected for this patient population. We describe the baseline characteristics of cases and their healthy siblings here.

Findings to date

The IPR Epidemiology Study currently includes 1781 individuals (1179 cases, 602 siblings; from 1010 households). Many households include a sibling (n=390, 39%) and some include multiple cases (n=205, 20%). Mean enrolment age was 11.3±4.3 years for cases and 10.1±5.3 for siblings. Leading PANS-like features include anxiety (94%), emotional lability (92%) and obsessions (90%). Onsets were sudden and dramatic (27%), gradual with a subsequent sudden and dramatic episode (68%) or a gradual progression (5%). The mean age at early signs/symptom onset was 4 years and 7 years at sudden and dramatic increases, respectively. Infection/illness was the most common suspected symptom trigger (84%). Nearly all cases had been treated with antibiotics (88%) and/or non-steroidal anti-inflammatory drugs (79%). Parents reported immune-related conditions in cases (18%) and their nuclear, biological family (48%; 39% in biological mothers).

Future plans

Future plans include increasing sample size, collecting longitudinal survey data, recruiting appropriate study controls and expanding the scope of the database, prioritising medical record data integration and creating a linked biorepository. Secondary data analyses will prioritise identifying subgroups by phenotypic traits, maternal health and disease characteristics.
Artificial intelligence-supported diabetic retinopathy screening in Tanzania: rationale and design of a randomised controlled trial
Authors: Cleland Charles R , Bascaran Covadonga , Makupa William , Shilio Bernadetha , Sandi Frank A , Philippin Heiko , Marques Ana Patricia , Egan Catherine , Tufail Adnan , Keane Pearse A , Denniston Alastair K , Macleod David , Burton Matthew J
Published: January 2024

Introduction

Globally, diabetic retinopathy (DR) is a major cause of blindness. Sub-Saharan Africa is projected to see the largest proportionate increase in the number of people living with diabetes over the next two decades. Screening for DR is recommended to prevent sight loss; however, in many low and middle-income countries, because of a lack of specialist eye care staff, current screening services for DR are not optimal. The use of artificial intelligence (AI) for DR screening, which automates the grading of retinal photographs and provides a point-of-screening result, offers an innovative potential solution to improve DR screening in Tanzania.

Methods and analysis

We will test the hypothesis that AI-supported DR screening increases the proportion of persons with true referable DR who attend the central ophthalmology clinic following referral after screening in a single-masked, parallel group, individually randomised controlled trial. Participants (2364) will be randomised (1:1 ratio) to either AI-supported or the standard of care DR screening pathway. Participants allocated to the AI-supported screening pathway will receive their result followed by point-of-screening counselling immediately after retinal image capture. Participants in the standard of care arm will receive their result and counselling by phone once the retinal images have been graded in the usual way (typically after 2–4 weeks). The primary outcome is the proportion of persons with true referable DR attending the central ophthalmology clinic within 8 weeks of screening. Secondary outcomes, by trial arm, include the proportion of persons attending the central ophthalmology clinic out of all those referred, sensitivity and specificity, number of false positive referrals, acceptability and fidelity of AI-supported screening.

Ethics and dissemination

The London School of Hygiene & Tropical Medicine, Kilimanjaro Christian Medical Centre and Tanzanian National Institute of Medical Research ethics committees have approved the trial. The results will be submitted to peer-reviewed journals for publication.

Trial registration number

ISRCTN18317152.
Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study
Authors: Ho Wei-Li , Chen Hsin-Hua , Chen Po-Ku , Liao Tsai-Ling , Chang Shih-Hsin , Chen Yi-Ming , Lin Ching-Heng , Tang Kuo-Tung , Chen Der-Yuan
Published: January 2024

Background

Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors.

Design

Retrospective study.

Setting

Taiwan.

Participants

2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence.

Outcomes

In this retrospective study using the 2000–2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs.

Results

The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development.

Conclusions

We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.
Perceptions of family medicine among long-term patients of a family medicine clinic in Japan: a mixed-methods study
Authors: Sato Kotaro , Michinobu Ryoko , Kusaba Tesshu
Published: January 2024

Objectives

To examine the perceptions of family medicine among patients attending a family medicine clinic for over 10 years in Japan and explore the unique characteristics of a family medicine which was developed in the local community in northern Japan.

Design

Explanatory, sequential mixed-method design comprising a survey by questionnaires and semistructured interviews.

Setting

The study was conducted at one of the oldest family medicine primary care clinics in Japan. We surveyed and interviewed participants from November 2019 to March 2020.

Participants

144 patients who have attended a family medicine clinic since April 2009 completed the questionnaires. Semistructured interviews with nine participants were conducted.

Results

Among the respondents, 131 (91%) reported having attended a family medicine clinic. In terms of their perceptions of what ‘family physicians’ do, 42 (35%) stated ‘a doctor who treats various diseases with a general view’, 34 (29%) stated ‘a doctor who treats outpatients and visit patients’ houses’, and 15 (13%) stated ‘a doctor whom one can consult for anything and is familiar with one’s family and lifestyle’. The results of the qualitative analysis revealed two themes with regard to patients’ perceptions of family medicine: ‘seeing the whole person and referring suitably’ and ‘medical care at home’. Patients’ perceptions of family medicine identified in the quantitative study were strongly associated with the characteristics extracted from the qualitative study.

Conclusion

Patients attending the family medicine clinic had clear perceptions of what family physicians do. The two major perceptions of the characteristics of family medicine were identified as ‘seeing the whole person and referring suitably’ and ‘medical care at home’.
Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma
Authors: Zhang Feng , Liu Wenfeng , Meng Fansheng , Jiang Qiuyu , Tang Wenqing , Liu Zhiyong , Lin Xiahui , Xue Ruyi , Zhang Si , Dong Ling
Published: January 2024

Background

Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy.

Methods

Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy.

Results

Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7highmacrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models.

Conclusions

Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.
LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy
Authors: Sun Lingjuan , Ma Zhibo , Zhao Xiangli , Tan Xiaosheng , Tu Yuhao , Wang Jingzeng , Chen Li , Chen Zhishui , Chen Gang , Lan Peixiang
Published: January 2024

Background

Tumor-infiltrating T cells enter an exhausted or dysfunctional state, which limits antitumor immunity. Among exhausted T cells, a subset of cells with features of progenitor or stem-like cells has been identified as TCF1+CD8+T cells that respond to immunotherapy. In contrast to the finding that TCF1 controls epigenetic and transcriptional reprogramming in tumor-infiltrating stem-like T cells, little is known about the regulation of TCF1. Emerging data show that elevated body mass index is associated with outcomes of immunotherapy. However, the mechanism has not been clarified.

Methods

We investigated the proliferation of splenic lymphocytes or CD8+T cells induced by CD3/CD28 stimulation in vitro. We evaluated the effects of low-density lipoprotein (LDL) and LRP11 inhibitors, as well as MAPK13 inhibitors. Additionally, we used shRNA technology to validate the roles of LRP11 and MAPK13. In an in vivo setting, we employed male C57BL/6J injected with B16 cells or MC38 cells to build a tumor model to assess the effects of LDL and LRP11 inhibitors, LRP11 activators, MAPK13 inhibitors on tumor growth. Flow cytometry was used to measure cell proportions and activation status. Molecular interactions and TCF1 status were examined using Western blotting. Moreover, we employed RNA sequencing to investigate the effects of LDL stimulation and MAPK13 inhibition in CD8+T cells.

Results

By using a tumor-bearing mouse model, we found that LDL-induced tumor-infiltrating TCF1+PD1+CD8+T cells. Using a cell-based chimeric receptor screening system, we showed that LRP11 interacted with LDL and activated TCF1. LRP11 activation enhanced TCF1+PD1+CD8+T-cell-mediated antitumor immunity, consistent with LRP11 blocking impaired T-cell function. Mechanistically, LRP11 activation induces MAPK13 activation. Then, MAPK13 phosphorylates TCF1, leading to increase of stem-like T cells.

Conclusions

LRP11-MAPK13-TCF1 enhanced antitumor immunity and induced tumor-infiltrating stem-like T cells.
Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer
Authors: Gu Chuanjia , Wang Xue , Wang Kaiyu , Xie Fangfang , Chen Luonan , Ji Hongbin , Sun Jiayuan
Published: January 2024

Background

Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC.

Methods

We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP (KrasG12D/+,Tp53−/−) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC.

Results

We found that cryoablation significantly increased circulating CD8+T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8+T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8+T cell infiltration in patients with unresectable NSCLC.

Conclusions

Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.
Using scale-derived estimates of body size in analyses of Atlantic salmon life-history variation: a cautionary note
Authors: Burton Tim , Ugedal Ola , Karlsson Sten O. , Thorstad Eva B. , Bolstad Geir H.
Published: January 2024

Measurements of individual body length at different life stages are critical in understanding fish ecology and evolution. Such data can be obtained via back-calculation from measurements of fish scales or by using the size of the scale as a direct proxy for body length. Using data from Atlantic salmon, we test key assumptions associated with each approach and their implications for investigating how variation in growth earlier in life is associated with age at maturity. The scaling of scale size approximated isometry and was similar among individuals who matured at different ages—validating a key assumption of back-calculation. However, we observed that individuals genetically predisposed to delay maturation have smaller scales for their body size—challenging a key assumption of the “direct scale-size” approach. Depending on the method of body length estimation, the relationship between body length growth earlier in life and age at maturity was observed to differ. Thus, when using scale material to study the relationship between growth and maturation in salmon, we recommend back-calculation and an assumed allometric scaling coefficient.
Governing for transboundary environmental justice: a scientific and policy analysis of fish consumption advisory programs in the Upper St Lawrence River
Authors: Lowitt K. , Francis A. , Gunther L. , Madison B.N. , McGaughey L. , Echendu A. , Kaur M. , Roussel K.A. , Pierre Z. St , Weppler A.
Published: January 2024

This paper examines fish consumption advisories (FCAs) as a site of transboundary governance in the Upper St Lawrence River with the aim of identifying opportunities for enhanced coordination and power sharing to address environmental injustices. The Upper St Lawrence River is part of the Great Lakes watershed of North America and the traditional territory of multiple Indigenous Nations, as well as the present-day jurisdictions of Ontario (Canada), Quebec (Canada), and New York State (USA). Through an analysis of publicly available information on FCA programs, we examine similarities and differences in these programs across jurisdictions. We find an overall lack of coordination in fish monitoring and differences in consumption advice for a waterway in which fish may easily move between transboundary areas. We offer recommendations for improving FCAs in this transboundary waterway from the lens of environmental justice, focusing on (1) a shared and transparent approach to monitoring contaminant levels and fish species; (2) integration of cultural food practices; (3) enhanced outreach to angler populations; and (4) upholding the self-determination of Indigenous communities. We also underscore that FCAs should not be seen as a permanent solution. Preventing and reducing contaminants, including associated harm reduction in communities affected by FCAs, need to be priorities.
Developing predictions for pion fragmentation functions
Authors: Xing H.-Y. , Yao Z.-Q. , Li B.-L. , Binosi D. , Cui Z.-F. , Roberts C. D.
Published: January 2024

Exploiting crossing symmetry, the hadron scale pion valence quark distribution function is used to predict the kindred elementary valence quark fragmentation function (FF). This function defines the kernel of a quark jet fragmentation equation, which is solved to obtain the full pion FFs. After evolution to a scale typical of FF fits to data, the results for quark FFs are seen to compare favourably with such fits. However, the gluon FF is markedly different. Notably, although FF evolution equations do not themselves guarantee momentum conservation, inclusion of a gluon FF which, for four quark flavours, distributes roughly 11% of the total light-front momentum fraction, is sufficient to restore momentum conservation under evolution. Overall, significant uncertainty is attached to FFs determined via fits to data; hence, the features of the predictions described herein could potentially provide useful guidance for future such studies.
Talking about Large Language Models
Authors: Shanahan Murray
Published: January 2024

Interacting with a contemporary LLM-based conversational agent can create an illusion of being in the presence of a thinking creature. Yet, in their very nature, such systems are fundamentally not like us.