bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources and environmental fate of halomethoxybenzenes
Authors: Zhan Faqiang , Shunthirasingham Chubashini , Li Yuening , Oh Jenny , Lei Ying Duan , Ben Chaaben Amina , Dalpé Castilloux Abigaëlle , Lu Zhe , Lee Kelsey , Gobas Frank A. P. C. , Alexandrou Nick , Hung Hayley , Wania Frank
Published: October 2023

Halomethoxybenzenes are pervasive in the atmosphere at concentration levels that exceed, often by an order of magnitude, those of the persistent organic pollutants with which they share the attributes of persistence and potential for long-range transport, bioaccumulation, and toxic effects. Long ignored by environmental chemists because of their predominantly natural origin—namely, synthesis by terrestrial wood-rotting fungi, marine algae, and invertebrates—knowledge of their environmental pathways remains limited. Through measuring the spatial and seasonal variability of four halomethoxybenzenes in air and precipitation and performing complementary environmental fate simulations, we present evidence that these compounds undergo continental-scale transport in the atmosphere, which they enter largely by evaporation from water. This also applies to halomethoxybenzenes originating in terrestrial environments, such as drosophilin A methyl ether, which reach aquatic environments with runoff, possibly in the form of their phenolic precursors. Our findings contribute substantially to the comprehension of sources and fate of halomethoxybenzenes, illuminating their widespread atmospheric dispersal.
A marmoset brain cell census reveals regional specialization of cellular identities
Authors: Krienen Fenna M. , Levandowski Kirsten M. , Zaniewski Heather , del Rosario Ricardo C.H. , Schroeder Margaret E. , Goldman Melissa , Wienisch Martin , Lutservitz Alyssa , Beja-Glasser Victoria F. , Chen Cindy , Zhang Qiangge , Chan Ken Y. , Li Katelyn X. , Sharma Jitendra , McCormack Dana , Shin Tay Won , Harrahill Andrew , Nyase Eric , Mudhar Gagandeep , Mauermann Abigail , Wysoker Alec , Nemesh James , Kashin Seva , Vergara Josselyn , Chelini Gabriele , Dimidschstein Jordane , Berretta Sabina , Deverman Benjamin E. , Boyden Ed , McCarroll Steven A. , Feng Guoping
Published: October 2023

The mammalian brain is composed of many brain structures, each with its own ontogenetic and developmental history. We used single-nucleus RNA sequencing to sample over 2.4 million brain cells across 18 locations in the common marmoset, a New World monkey primed for genetic engineering, and examined gene expression patterns of cell types within and across brain structures. The adult transcriptomic identity of most neuronal types is shaped more by developmental origin than by neurotransmitter signaling repertoire. Quantitative mapping of GABAergic types with single-molecule FISH (smFISH) reveals that interneurons in the striatum and neocortex follow distinct spatial principles, and that lateral prefrontal and other higher-order cortical association areas are distinguished by high proportions of
VIP
+
neurons. We use cell type–specific enhancers to drive AAV-GFP and reconstruct the morphologies of molecularly resolved interneuron types in neocortex and striatum. Our analyses highlight how lineage, local context, and functional class contribute to the transcriptional identity and biodistribution of primate brain cell types.
Early
Homo erectus
lived at high altitudes and produced both Oldowan and Acheulean tools
Authors: Mussi Margherita , Skinner Matthew M. , Melis Rita T. , Panera Joaquín , Rubio-Jara Susana , Davies Thomas W. , Geraads Denis , Bocherens Hervé , Briatico Giuseppe , Le Cabec Adeline , Hublin Jean-Jacques , Gidna Agness , Bonnefille Raymonde , Di Bianco Luca , Méndez-Quintas Eduardo
Published: October 2023

In Africa, the scarcity of hominin remains found in direct association with stone tools has hindered attempts to link
Homo habilis
and
Homo erectus
with particular lithic industries. The infant mandible discovered in level E at Garba IV (Melka Kunture) on the highlands of Ethiopia is critical to this issue because of its direct association with an Oldowan lithic industry. Here, we used synchrotron imaging to examine the internal morphology of the unerupted permanent dentition and confirmed its identification as
H. erectus
. Additionally, we used revised paleomagnetic ages to show that (i) the mandible in level E is ~2 million years old and represents one of the earliest
H. erectus
fossils and that (ii) overlying level D, ~1.95 million years old, contains the earliest known Acheulean assemblage.
Comprehensive cell atlas of the first-trimester developing human brain
Authors: Braun Emelie , Danan-Gotthold Miri , Borm Lars E. , Lee Ka Wai , Vinsland Elin , Lönnerberg Peter , Hu Lijuan , Li Xiaofei , He Xiaoling , Andrusivová Žaneta , Lundeberg Joakim , Barker Roger A. , Arenas Ernest , Sundström Erik , Linnarsson Sten
Published: October 2023

The adult human brain comprises more than a thousand distinct neuronal and glial cell types, a diversity that emerges during early brain development. To reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics and uncovered cell states and trajectories in human brains at 5 to 14 postconceptional weeks (pcw). We identified 12 major classes that are organized as ~600 distinct cell states, which map to precise spatial anatomical domains at 5 pcw. We described detailed differentiation trajectories of the human forebrain and midbrain and found a large number of region-specific glioblasts that mature into distinct pre-astrocytes and pre–oligodendrocyte precursor cells. Our findings reveal the establishment of cell types during the first trimester of human brain development.
Interindividual variation in human cortical cell type abundance and expression
Authors: Johansen Nelson , Somasundaram Saroja , Travaglini Kyle J. , Yanny Anna Marie , Shumyatcher Maya , Casper Tamara , Cobbs Charles , Dee Nick , Ellenbogen Richard , Ferreira Manuel , Goldy Jeff , Guzman Junitta , Gwinn Ryder , Hirschstein Daniel , Jorstad Nikolas L. , Keene C. Dirk , Ko Andrew , Levi Boaz P. , Ojemann Jeffrey G. , Pham Thanh , Shapovalova Nadiya , Silbergeld Daniel , Sulc Josef , Torkelson Amy , Tung Herman , Smith Kimberly , Lein Ed S. , Bakken Trygve E. , Hodge Rebecca D. , Miller Jeremy A.
Published: October 2023

Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in the middle temporal gyrus. However, we found interindividual variance in abundances and gene expression signatures, particularly in deep-layer glutamatergic neurons and microglia. A minority of donor variance is explainable by age, sex, ancestry, disease state, and cell state. Genomic variation was associated with expression of 150 to 250 genes for most cell types. This characterization of cellular variation provides a baseline for cell typing in health and disease.
Spatiotemporal molecular dynamics of the developing human thalamus
Authors: Kim Chang N. , Shin David , Wang Albert , Nowakowski Tomasz J.
Published: October 2023

The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially distinct nuclei, but the molecular architecture of thalamic development is poorly understood, especially in humans. To begin to delineate the molecular trajectories of cell fate specification and organization in the developing human thalamus, we used single-cell and multiplexed spatial transcriptomics. We show that molecularly defined thalamic neurons differentiate in the second trimester of human development and that these neurons organize into spatially and molecularly distinct nuclei. We identified major subtypes of glutamatergic neuron subtypes that are differentially enriched in anatomically distinct nuclei and six subtypes of γ-aminobutyric acid–mediated (GABAergic) neurons that are shared and distinct across thalamic nuclei.
Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly
Authors: Rizalar Filiz Sila , Lucht Max T. , Petzoldt Astrid , Kong Shuhan , Sun Jiachen , Vines James H. , Telugu Narasimha Swamy , Diecke Sebastian , Kaas Thomas , Bullmann Torsten , Schmied Christopher , Löwe Delia , King Jason S. , Cho Wonhwa , Hallermann Stefan , Puchkov Dmytro , Sigrist Stephan J. , Haucke Volker
Published: October 2023

Neurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the specialized apparatus characterizing the neuronal presynapse must form de novo. How the components for presynaptic neurotransmission are transported and assembled is poorly understood. Our results show that the rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P
2
] directs the axonal cotransport of synaptic vesicle and active zone proteins in precursor vesicles in human neurons. Precursor vesicles are distinct from conventional secretory organelles, endosomes, and degradative lysosomes and are transported by coincident detection of PI(3,5)P
2
and active ARL8 via kinesin KIF1A to the presynaptic compartment. Our findings identify a crucial mechanism that mediates the delivery of synaptic vesicle and active zone proteins to developing synapses.
Transonic dislocation propagation in diamond
Authors: Katagiri Kento , Pikuz Tatiana , Fang Lichao , Albertazzi Bruno , Egashira Shunsuke , Inubushi Yuichi , Kamimura Genki , Kodama Ryosuke , Koenig Michel , Kozioziemski Bernard , Masaoka Gooru , Miyanishi Kohei , Nakamura Hirotaka , Ota Masato , Rigon Gabriel , Sakawa Youichi , Sano Takayoshi , Schoofs Frank , Smith Zoe J. , Sueda Keiichi , Togashi Tadashi , Vinci Tommaso , Wang Yifan , Yabashi Makina , Yabuuchi Toshinori , Dresselhaus-Marais Leora E. , Ozaki Norimasa
Published: October 2023

The motion of line defects (dislocations) has been studied for more than 60 years, but the maximum speed at which they can move is unresolved. Recent models and atomistic simulations predict the existence of a limiting velocity of dislocation motion between the transonic and subsonic ranges at which the self-energy of dislocation diverges, though they do not deny the possibility of the transonic dislocations. We used femtosecond x-ray radiography to track ultrafast dislocation motion in shock-compressed single-crystal diamond. By visualizing stacking faults extending faster than the slowest sound wave speed of diamond, we show the evidence of partial dislocations at their leading edge moving transonically. Understanding the upper limit of dislocation mobility in crystals is essential to accurately model, predict, and control the mechanical properties of materials under extreme conditions.
Boom-bust cycles in gray whales associated with dynamic and changing Arctic conditions
Authors: Stewart Joshua D. , Joyce Trevor W. , Durban John W. , Calambokidis John , Fauquier Deborah , Fearnbach Holly , Grebmeier Jacqueline M. , Lynn Morgan , Manizza Manfredi , Perryman Wayne L. , Tinker M. Tim , Weller David W.
Published: October 2023

Climate change is affecting a wide range of global systems, with polar ecosystems experiencing the most rapid change. Although climate impacts affect lower-trophic-level and short-lived species most directly, it is less clear how long-lived and mobile species will respond to rapid polar warming because they may have the short-term ability to accommodate ecological disruptions while adapting to new conditions. We found that the population dynamics of an iconic and highly mobile polar-associated species are tightly coupled to Arctic prey availability and access to feeding areas. When low prey biomass coincided with high ice cover, gray whales experienced major mortality events, each reducing the population by 15 to 25%. This suggests that even mobile, long-lived species are sensitive to dynamic and changing conditions as the Arctic warms.
Exploiting the Marcus inverted region for first-row transition metal–based photoredox catalysis
Authors: Chan Amy Y. , Ghosh Atanu , Yarranton Jonathan T. , Twilton Jack , Jin Jian , Arias-Rotondo Daniela M. , Sakai Holt A. , McCusker James K. , MacMillan David W. C.
Published: October 2023

Second- and third-row transition metal complexes are widely employed in photocatalysis, whereas earth-abundant first-row transition metals have found only limited use because of the prohibitively fast decay of their excited states. We report an unforeseen reactivity mode for productive photocatalysis that uses cobalt polypyridyl complexes as photocatalysts by exploiting Marcus inverted region behavior that couples increases in excited-state energies with increased excited-state lifetimes. These cobalt (III) complexes can engage in bimolecular reactivity by virtue of their strong redox potentials and sufficiently long excited-state lifetimes, catalyzing oxidative C(sp
2
)–N coupling of aryl amides with challenging sterically hindered aryl boronic acids. More generally, the results imply that chromophores can be designed to increase excited-state lifetimes while simultaneously increasing excited-state energies, providing a pathway for the use of relatively abundant metals as photoredox catalysts.
β-(1→3)-D-glucan- and mannan-guided early termination of antifungal therapy in ICU patients: a randomized controlled study
Authors: Erb Timothy , Mihai Sidonia , Strauß Richard , Herbst Larissa , Castellanos Ixchel , Diesch Katharina , Cipa Franziska , Bihlmaier Karl , Lang Anne-Katharina , Ganslmayer Marion , Willam Carsten , Bremer Frank , Fürst Julia , Beyer Christian , Bogdan Christian , Rath Anca , Held Jürgen
Published: October 2023

Candida
spp. are frequently encountered in specimens from ICUs. However, most of these detections represent colonization. Nevertheless, clinical practice shows that a considerable proportion of these patients will receive antifungal therapy (AT). β-(1→3)-D-glucan (BDG) and mannan are fungal biomarkers with high negative predictive values. We aimed to examine whether biomarker-guided discontinuation of AT can reduce the antifungal consumption. Therefore, we conducted a prospective, randomized intervention study between 1 April 2019 and 31 March 2020. All adult ICU patients with a newly started systemic AT but without fungal infection were eligible for inclusion. Enrolled patients were randomized into an intervention and a control group. In both groups, serum BDG and mannan were determined on days 1 and 2 of AT. If all measurements were negative, AT was discontinued in the intervention group. The primary endpoint was antifungal use. The study was terminated after 12 months. Until this time-point, 41 patients had been included. In the intervention group (
n
= 19), AT was stopped in only two patients because all others showed either positive BDG and/or mannan levels. One of these two patients developed candidemia and AT had to be restarted. There was no significant difference in the primary and secondary endpoints. In summary, the strategy of using two negative BDG and mannan levels to stop AT failed to reduce antifungal consumption in our cohort. Indeed, there will inevitably be patients with invasive candidiasis in whom necessary AT is discontinued. The optimal patient population, biomarker set, and termination criteria are critical to the success of biomarker-based termination strategies.
Two different types of tandem sequences mediate the overexpression of
TinCYP51B
in azole-resistant
Trichophyton indotineae
Authors: Yamada Tsuyoshi , Maeda Mari , Nagai Hiroaki , Salamin Karine , Chang Yun-Tsan , Guenova Emmanuella , Feuermann Marc , Monod Michel
Published: October 2023

Trichophyton indotineae
is an emerging dermatophyte that causes severe tinea corporis and tinea cruris. Numerous cases of terbinafine- and azole-recalcitrant
T. indotineae
-related dermatophytosis have been observed in India over the past decade, and cases are now being recorded worldwide. Whole genome sequencing of three azole-resistant strains revealed a variable number of repeats of a 2,404 base pair (bp) sequence encoding
TinCYP51B
in tandem specifically at the
CYP51B
locus position. However, many other resistant strains (itraconazole MIC ≥0.25 µg/mL; voriconazole MIC ≥0.25 µg/mL) did not contain such duplications. Whole-genome sequencing of three of these strains revealed a variable number of 7,374 bp tandem repeat blocks harboring
TinCYP51B
. Consequently, two types of
T. indotineae
azole-resistant strains were found to host
TinCYP51B
in tandem sequences (type I with 2,404 bp
TinCYP51B
blocks and type II with 7,374 bp
TinCYP51B
blocks). Using the CRISPR/Cas9 genome-editing tool, the copy number of
TinCYP51B
within the genome of types I and II strains was brought back to a single copy. The azole susceptibility of these modified strains was similar to that of strains without
TinCYP51B
duplication, showing that azole resistance in
T. indotineae
strains is mediated by one of two types of
TinCYP51B
amplification. Type II strains were prevalent among 32 resistant strains analyzed using a rapid and reliable PCR test.
Transcriptional control of carbohydrate catabolism by the CcpA protein in the ruminal bacterium
Streptococcus bovis
Authors: Zhao Xiujuan , Zhang Ying , He Banglin , Han Yu , Shen Ben , Zang Yu , Wang Hongrong
Published: October 2023

As a potent, pleiotropic regulatory protein in Gram-positive bacteria, catabolite control protein A (CcpA) mediates the transcriptional control of carbohydrate metabolism in
Streptococcus bovis
, a lactate-producing bacterium that plays an essential role in rumen acidosis in dairy cows. Although the rumen uptake of carbohydrates is multi-substrate, the focus of
S. bovis
research thus far has been on the glucose. With the aid of gene deletion, whole-genome sequencing, and transcriptomics, we have unraveled the role of CcpA in carbohydrate metabolism, on the one hand, and acidosis, on the other, and we show that the
S. bovis
strain S1 encodes “Carbohydrate-Active Enzymes” and that
ccpA
deletion slows the organism’s growth rate and modulates the organic acid fermentation pathways toward lower lactate, higher formate, and acetate in the maltose and cellobiose. Furthermore, this study revealed the different regulatory functions of the CcpA protein in rumen metabolism and acidosis.

IMPORTANCE

This study is important as it illustrates the varying regulatory role of the
Streptococcus bovis
catabolite control protein A protein in carbohydrate metabolism and the onset of acidosis in dairy cattle.
Direct prediction of carbapenem resistance in
Pseudomonas aeruginosa
by whole genome sequencing and metagenomic sequencing
Authors: Liu Bing , Gao Jianpeng , Liu Xue Fei , Rao Guanhua , Luo Jiajie , Han Peng , Hu Weiting , Zhang Ze , Zhao Qianqian , Han Lizhong , Jiang Zhi , Zhou Min
Published: October 2023

Carbapenem resistance is a major concern in the management of antibiotic-resistant
Pseudomonas aeruginosa
infections. The direct prediction of carbapenem-resistant phenotype from genotype in
P. aeruginosa
isolates and clinical samples would promote timely antibiotic therapy. The complex carbapenem resistance mechanism and the high prevalence of variant-driven carbapenem resistance in
P. aeruginosa
make it challenging to predict the carbapenem-resistant phenotype through the genotype. In this study, using whole genome sequencing (WGS) data of 1,622
P
.
aeruginosa
isolates followed by machine learning, we screened 16 and 31 key gene features associated with imipenem (IPM) and meropenem (MEM) resistance in
P. aeruginosa
, including oprD(HIGH), and constructed the resistance prediction models. The areas under the curves of the IPM and MEM resistance prediction models were 0.906 and 0.925, respectively. For the direct prediction of carbapenem resistance in
P. aeruginosa
from clinical samples by the key gene features selected and prediction models constructed, 72
P
.
aeruginosa
-positive sputum samples were collected and sequenced by metagenomic sequencing (MGS) based on next-generation sequencing (NGS) or Oxford Nanopore Technology (ONT). The prediction applicability of MGS based on NGS outperformed that of MGS based on ONT. In 72
P
.
aeruginosa
-positive sputum samples, 65.0% (26/40) of IPM-insensitive and 63.2% (24/38) of MEM-insensitive
P. aeruginosa
were directly predicted by NGS-based MGS with positive predictive values of 0.897 and 0.889, respectively. By the direct detection of the key gene features associated with carbapenem resistance of
P. aeruginosa
, the carbapenem resistance of
P. aeruginosa
could be directly predicted from cultured isolates by WGS or from clinical samples by NGS-based MGS, which could assist the timely treatment and surveillance of carbapenem-resistant
P. aeruginosa
.
Characterization of a DsbA family protein reveals its crucial role in oxidative stress tolerance of
Listeria monocytogenes
Authors: Xia Jing , Luo Yaru , Chen Mianmian , Liu Yuqing , Wang Zhe , Deng Simin , Xu Jiali , Han Yue , Sun Jing , Jiang Lingli , Song Houhui , Cheng Changyong
Published: October 2023

Listeria monocytogenes
is a facultative, intracellular foodborne pathogen widely distributed in nature and is responsible for severe invasive infection in humans and animals with a mortality rate as high as 30%.
L. monocytogene
s can adapt to various oxidative stresses since it has evolved oxidative modification and regulation mechanisms. The disulfide bond formation protein (Dsb) is required to catalyze the formation of disulfide bonds to promote oxidative folding or modification of proteins involved in bacterial virulence and survival. However, the functions of Lmo1059, a DsbA family protein of
L. monocytogenes
, remain unknown. In this study, we found that Lmo1059 could efficiently catalyze oxidized glutathione (GSSG) reduction, with the residues Cys36 and Cys39 as the key amino acids for its catalytic activity. Moreover, Lmo1059 plays a critical role in oxidative stress tolerance for
L. monocytogenes
, and Cys36 is the crucial amino acid to participate in this process. When Lmo1059 was deleted, the adhesion and invasion of
L. monocytogenes
were reduced while the cell-to-cell spread was increased, suggesting an intricate role of Lmo1059 during bacterial infection. Altogether, these data indicate that the DsbA family protein Lmo1059 is an important participant in the antioxidant stress system and works in concert with other proteins to help protect
L. monocytogenes
from oxidative stress and establish intracellular infection.

IMPORTANCE

The adaption and tolerance to various environmental stresses are the fundamental factors for the widespread existence of
Listeria monocytogenes
. Anti-oxidative stress is the critical mechanism for the survival and pathogenesis of
L. monocytogenes
. The thioredoxin (Trx) and glutaredoxin (Grx) systems are known to contribute to the anti-oxidative stress of
L. monocytogenes
, but whether the Dsb system has similar roles remains unknown. This study demonstrated that the DsbA family protein Lmo1059 of
L. monocytogenes
participates in bacterial oxidative stress tolerance, with Cys36 as the key amino acid of its catalytic activity and anti-oxidative stress ability. It is worth noting that Lmo1059 was involved in the invading and cell-to-cell spread of
L. monocytogenes
. This study lays a foundation for further understanding the specific mechanisms of oxidative cysteine repair and antioxidant stress regulation of
L. monocytogenes
, which contributes to an in-depth understanding of the environmental adaptation mechanisms for foodborne bacterial pathogens.
Genesis of the Samba Cu deposit of the Central African Copperbelt in Zambia: Constraints from geochemistry and geochronology
Authors: Zhang Yong , Zhou Shouyu , Wu Xiaolei , Hu Qiaofan
Published: October 2023

The Samba Cu deposit is located in pre-Katangan Supergroup basement metavolcanic rocks of the Central African Copperbelt in Zambia. To better understand the formation of the Cu deposit, we use geochronologic, geochemical, and S isotopic data obtained for the deposit’s host rocks and sulfide minerals. Laser ablation−inductively coupled plasma−mass spectrometric (LA-ICP-MS) dating of zircon from host rocks, including quartz-sericite schist and biotite-sericite-chlorite schist, yields ages of 1967 ± 17 Ma and 1960 ± 20 Ma, which are interpreted as the crystallization ages of the original volcanic rocks. Re-Os analyses of molybdenite intergrown with chalcopyrite constrain sulfide deposition to 548.1 ± 7.5 Ma and 524.1 ± 7.3 Ma, which correspond to the timing of the Cu mineralization. LA-ICP-MS U-Pb analyses of metamorphic rutile from the biotite-sericite-chlorite schist yield a U-Pb age of 508.3 ± 6.6 Ma, which is interpreted to represent the age of regional metamorphism. The new data suggest that the Cu mineralization at Samba was synchronous with the Lufilian orogeny.
Potential for England’s statutory school entry assessment to identify special educational needs and reveal structural inequalities: a population-based study
Authors: Wood Megan L , Gunning Lydia , Relins Sam , Sohal Kuldeep , Wright John , Mon-Williams Mark , Atkinson Amy L
Published: October 2023

Objective

To investigate at a population level whether England’s universal assessment of ‘school readiness’ is associated with later identification of special educational needs (SEN). Also, whether ethnic differences exist in SEN identification (white British versus ethnic minority) and whether this varies as a function of school readiness.

Method

Analysis included 53 229 individuals aged 5–12 years from the Connected Bradford Database (2012/2013–2019/2020). Logistic regression analyses examined: (1) whether reaching a ‘good level of development’ on England’s ‘school readiness’ assessment was associated with later SEN identification; and (2) whether interactions exist between school readiness and ethnicity.

Results

32 515 of 53 229 children reached a good level of development, of which 3036 (9.3%) were identified as having SEN. In contrast, 10 171 of 20 714 (49.1%) of children who did not reach a good level of development were later identified as having SEN. Children not reaching a good level of development had increased odds of being later identified as having SEN after controlling for covariates (OR: 8.50, 95% CI: 8.10 to 8.91). In children who did not reach a good level of development, white British children had higher odds of being identified as having SEN compared with ethnic minority peers (OR: 1.22, 95% CI: 1.11 to 1.34). No ethnic differences of having SEN were observed in children reaching a good level of development (OR: 1.04, 95% CI: 0.93 to 1.16).

Conclusions

School readiness assessments are associated with later SEN identification. Structural inequalities may exist in SEN identification in children not entering formal education ‘school ready’. Such assessments could facilitate earlier identification of SEN and reduce structural inequalities in its identification.
Prolonged use of closed-loop inspired oxygen support in preterm infants: a randomised controlled trial
Authors: Schouten Tim M R , Abu-Hanna Ameen , van Kaam Anton H , van den Heuvel Maria E N , Bachman Thomas E , van Leuteren Ruud W , Hutten G Jeroen , Onland Wes
Published: October 2023

Objective

This randomised study in preterm infants on non-invasive respiratory support investigated the effectiveness of automated oxygen control (A-FiO2) in keeping the oxygen saturation (SpO2) within a target range (TR) during a 28-day period compared with manual titration (M-FiO2).

Design

A single-centre randomised control trial.

Setting

A level III neonatal intensive care unit.

Patients

Preterm infants (<28 weeks’ gestation) on non-invasive respiratory support.

Interventions

A-FiO2versus M-FiO2control.

Methods

Main outcomes were the proportion of time spent and median area of episodes in the TR, hyperoxaemia, hypoxaemia and the trend over 28 days using a linear random intercept model.

Results

23 preterm infants (median gestation 25.7 weeks; birth weight 820 g) were randomised. Compared with M-FiO2, the time spent within TR was higher in the A-FiO2group (68.7% vs 48.0%, p<0.001). Infants in the A-FiO2group spent less time in hyperoxaemia (13.8% vs 37.7%, p<0.001), but no difference was found in hypoxaemia. The time-based analyses showed that the A-FiO2efficacy may differ over time, especially for hypoxaemia. Compared with the M-FiO2group, the A-FiO2group had a larger intercept but with an inversed slope for the daily median area below the TR (intercept 70.1 vs 36.3; estimate/day −0.70 vs 0.69, p<0.001).

Conclusion

A-FiO2control was superior to manual control in keeping preterm infants on non-invasive respiratory support in a prespecified TR over a period of 28 days. This improvement may come at the expense of increased time below the TR in the first days after initiating A-FiO2control.

Trial registration number

NTR6731.
A cluster-randomised controlled equivalence trial of the Surprise Soap handwashing intervention among older children living in a refugee settlement in Sudan
Authors: Watson Julie , Osman Ibtihal Mohammed-Elhassan , Amon-Tanoh Maud , Deola Claudio , MacDougall Amy , Cumming Oliver
Published: October 2023

Introduction

Increasing handwashing with soap (HWWS) among older children in emergency settings can have a large public health impact, however, evidence on what works is limited. One promising approach is the ‘Surprise Soap’ intervention in which a novel soap with an embedded toy is delivered to children in a short, participatory household session that includes a glitter game and HWWS practice. Here, we evaluate this intervention against a standard intervention in a complex emergency setting.

Methods

A cluster-randomised controlled equivalence trial was conducted in Naivasha refugee settlement, Sudan. Blinding was not possible. 203 randomly selected households, with at least one child aged 5–12, were randomised to receive the Surprise Soap intervention (n=101) or a standard intervention comprising a short household session with health messaging and plain soap distribution (n=102). The primary outcome was the proportion of prespecified potential HWWS events observed for children aged 5–12, accompanied by HWWS, at baseline, 4, 12 and 16 weeks post intervention delivery.

Results

200 households were included in the analyses: 101 intervention and 99 control. No difference in intervention effectiveness was observed at any follow-up (4 weeks: adjusted rate ratio (RR) 1.2, 95% CI 0.8 to 1.7; 12 weeks: RR 0.8, 95% CI 0.5 to 1.1; 16 weeks: RR 1.1, 95% CI 0.8 to 1.5). However, we observed increased HWWS in both arms at 4 weeks (27 and 23 percentage point increase in the intervention and control arm, respectively) that was sustained at 16 weeks.

Conclusions

We find that the Surprise Soap intervention is no more effective at increasing older children’s HWWS than a standard, household-level, health-based intervention in this complex humanitarian emergency. There appears to be no marginal benefit in terms of HWWS that would justify the additional cost of implementing the Surprise Soap intervention. Further trials that include a passive control arm are needed to determine the independent effects of each intervention and guide future intervention design.
Prognostic prediction models for oropharyngeal squamous cell carcinoma (OPSCC): a protocol for systematic review, critical appraisal and meta-analysis
Authors: Lu Zhen , Zhou Xinyi , Fu Leiwen , Li Yuwei , Tian Tian , Liu Qi , Zou Huachun
Published: October 2023

Introduction

Oropharyngeal squamous cell carcinoma (OPSCC) is increasingly prevalent and has significantly heterogeneous risks of survival for diagnosed individuals due to the inter-related risk factors. Precise prediction of the risk of survival for an individual patient with OPSCC presents a useful adjunct to therapeutic decision-making regarding the management of OPSCC. The aim of this systematic review, critical appraisal and meta-analysis is to assess prognostic prediction models for OPSCC and lay a foundation for future research programmes to develop and validate prognostic prediction models for OPSCC.

Methods and analysis

This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocol statement. Based on predefined criteria, electronic databases including MEDLINE, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (CNKI) will be searched for relevant studies without language restrictions from inception of databases to present. This study will systematically review published prognostic prediction models for survival outcomes in patients with OPSCC, describe their characteristics, compare performance and assess risk of bias and real-world clinical utility. Selection of eligible studies, data extraction and critical appraisal will be conducted independently by two reviewers. A third reviewer will resolve any disagreements. Included studies will be systematically summarised using appropriate tools designed for prognostic prediction modelling studies. Risk of bias and quality of studies will be assessed using the Prediction Model Risk of Bias Assessment Tool and the Transparent Reporting of a multivariable prediction model for individual prognosis or diagnosis. Performance measures of these models will be pooled and analysed with meta-analyses if feasible.

Ethics and dissemination

This review will be conducted completely based on published data, so approval from an ethics committee or written consent is not required. The results will be disseminated through a peer-reviewed publication.

PROSPERO registration number

CRD42023400272.
Burden and causes of pregnancy-related mortality in The Gambia: evidence from census and health and demographic surveillance data
Authors: Jasseh Momodou , Sanyang Nyakassi , Bittaye Mustapha , Mohammed Nuredin I , Gazeley Ursula Maria , Antonio Martin , Reniers Georges
Published: October 2023

Background

The Gambia lacks capacity to estimate its burden and causes of pregnancy-related mortality (PRM) to guide reproductive health programming. We used census and Health and Demographic Surveillance System (HDSS) data from Farafenni and Basse to establish levels and causes of PRM in The Gambia.

Methods

Using reported deaths and births in the 2013 Gambian census, national and regional pregnancy-related mortality ratios (PRMRatios) were derived as the ratio of pregnancy-related deaths (PRDs) per 100 000 live births (lbs). Verbal autopsies were interpreted using InterVA-5, and PRDs linked with extracted HDSS data to estimate annual PRMRatios.

Results

The census yielded national PRMRatio of 861 per 100 000 lbs in 2012. Regional levels of 1877, 1232 and 1096 per 100 000 lbs were registered in rural regions of Kuntaur, Mansakonko and Basse, respectively; while urban areas of Banjul and Kanifing registered about half these levels. Women aged 15–19 and 40–49 had greater risks of dying from pregnancy-related causes. HDSS data produced lower PRMRatios (95% CI) ranging from 858 per 100 000 lbs (149–4969) for Farafenni in 2005, and 479 per 100 000 lbs (328–698) for Basse in 2008 to 184 (24–1450) and 173 (61–487) per 100 000 lbs, respectively. InterVA-5 returned pregnancy-induced hypertension and obstetric haemorrhage as the main causes, accounting for at least 70% of all PRDs.

Conclusion

The census-based PRMRatios for 2012 were consistent with the sociodemographic and reproductive health indicators that prevailed at that time and represented the burden of PRM. While HDSS-derived PRMRatios were lower, the cause-of-death distribution produced was consistent with previous observations elsewhere.
Workplace violence in the COVID-19 era: a qualitative analysis of harassment and threats against public health professionals in Canada
Authors: Regehr Cheryl , Regehr Kaitlyn , Goel Vivek , Sato Christa , Lyons Kelly , Rudzicz Frank
Published: October 2023

Objectives

This study reports the results of a qualitative study involving public health professionals and documents their experiences with cyberviolence, harassment and threats during the COVID-19 pandemic.

Method and analysis

The research adopted a discovery-oriented qualitative design, using constructivist grounded theory method and long interview style data collection. Twelve public health professionals from across Canada who held responsibility for COVID-19 response and public health measures in their respective jurisdictions participated. Constant comparative analysis was used to generate concepts through inductive processes.

Results

Data revealed a pattern that began with mainstream media engagement, moved to indirect cyberviolence on social media that fuelled outrage and polarisation of members of the public, followed by direct cyberviolence in the form of email abuse and threats, and finally resulted in physical threats and confrontation—which were then glorified and amplified on social media. The prolonged nature and intensity of harassment and threats led to negative somatic, emotional, professional and social outcomes. Concerns were raised that misinformation and comments undermining the credibility of public health professionals weakened public trust and ultimately the health of the population. Participants provided recommendations for preventing and mitigating the effects of cyber-instigated violence against public health professionals that clustered in three areas: better supports for public health personnel; improved systems for managing communications; and legislative controls on social media including reducing the anonymity of contributors.

Conclusion

The prolonged and intense harassment, abuse and threats against public health professionals during COVID-19 had significant effects on these professionals, their families, staff and ultimately the safety and health of the public. Addressing this issue is a significant concern that requires the attention of organisations responsible for public health and policy makers.
Factors influencing viral shedding time in non-severe paediatric infection with the SARS-CoV-2: a single-centre retrospective study
Authors: Hong Ping , li Chengmei , Tian Xianmin , Che Datian
Published: October 2023

Background

The aim of this study was to determine the factors influencing viral shedding time (VST) in non-severe paediatric infection with SARS-CoV-2).

Methods

We conducted a retrospective analysis of data from 240 non-severe paediatric infection with the SARS-CoV-2. Multivariate Cox regression analysis was used to identify independent predictors associated with VST.

Results

Two hundred and forty patients were included in the study. The median duration of VST was 10 days (IQR, 8–13 days). Compared with patients aged <1 year, children aged 6–12 years (adjusted HR (aHR): 1.849; 95% CI 1.031 to 3.315) and >12 years (aHR: 2.180; 95% CI 1.071 to 4.439) had shorter VST. Non-leucopenia patients (aHR: 1.431; 95% CI 1.005 to 2.038) also had a lower VST.

Discussion

The results of this study show that children aged <1 year and children with leucopenia had longer SARS-CoV-2 VST. These factors should be taken into account when developing policies for the isolation of patients with COVID-19.
Breast feeding in infants diagnosed with phenylketonuria (PKU): a scoping review
Authors: Kalvala Jahnavi , Chong Lydia , Chadborn Neil , Ojha Shalini
Published: October 2023

Background

Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism, characterised by elevated levels of phenylalanine (Phe). There is a lack of infant feeding guidance for those with PKU. From birth to 6 months of age, breast feeding is the optimal nutrition for an infant and continuing breast feeding for infants with PKU is recommended by European guidelines. However, human breast milk contains Phe in varying quantities, and therefore, the effects breast feeding might have on infants with PKU needs careful consideration.

Aim

To assess the effects of breast feeding (exclusive or partial) compared with low-Phe formula feeding in infants diagnosed with PKU, on blood Phe levels, growth and neurodevelopmental scores.

Methods

The Cochrane Inborn Errors of Metabolism Trials Register, MEDLINE and Embase were searched (date of latest search: 9 August 2022). Studies were included if they looked at the effects of breast feeding in infants diagnosed with PKU compared with formula feeding. Predetermined outcomes included blood Phe levels, growth in the first 2 years of life and neurodevelopmental scores.

Results

Seven observational studies (282 participants) met the inclusion criteria. All studies compared continuation of breast feeding with low-Phe formula versus formula feeding only. While most studies concluded that there was no difference in mean serum Phe levels in their follow-up period, two reported that breastfed infants were more likely to have a normal mean Phe level. Two studies described no difference in mean weight gain after birth, while one found that breastfed infants were more likely to have higher mean weight gain. Two studies commented that breastfed infants achieved higher developmental scores in childhood as compared with formula fed infants.

Conclusion

Although there are no randomised trials, observational evidence suggests that continuation of breast feeding and supplementation with low-Phe formula is safe and may be beneficial for infants diagnosed with PKU.
Systematic review of physiological and psychological outcomes of surgery for pectus excavatum supporting commissioning of service in the UK
Authors: Walsh Jamie , Walsh Ross , Redmond Karen
Published: October 2023

Background

Pectus excavatum (PEx) is the most common congenital chest wall abnormality affecting 1 in 400 births in the UK. PEx is associated with significant physiological and psychological impairment. While readily surgically correctable, the benefits that surgery can bring have been debated and proven difficult to objectively measure. In the UK, this has led to the decommissioning of PEx surgery. The aim of this review is to conduct a systematic search of the literature on PEx surgery to assess physiological and psychological outcomes.

Methods

A systematic review of the MEDLINE (PubMed), Embase and Cochrane databases was performed. Articles were sought which included patients undergoing surgery for PEx and reported on changes in cardiopulmonary measures, symptoms, quality of life and psychological assessments before and after surgical repair. Last search was performed in July 2022 and relevant findings were synthesised by narrative review.

Results

Fifty-one articles were included in qualitative synthesis, with 34 studies relating to physiological outcomes and 17 studies relating to psychological and quality of life measures. Twenty-one studies investigated pulmonary function at rest. There was no change in forced vital capacity or forced expiratory volume in 1 second following open repair and transient reductions followed closed repair. In the 11 studies investigating echocardiography, transthoracic rarely demonstrated cardiac compression; however, transoesophageal demonstrated intraoperative relief in cardiac compression in severe cases. Sixteen studies investigated exercise testing (cardiopulmonary exercise testing, CPET), 12 of which demonstrated significant improvement following surgery, both in maximal oxygen consumption and oxygen pulse. Seventeen studies investigated quality of life, all but one of which showed improvement following repair of PEx. All papers that reported on patient satisfaction following surgery found high rates, between 80% and 97%.

Discussion

While the majority of studies to date have been small and data heterogeneous, the literature shows that for many patients with PEx, there exists a cardiopulmonary limitation that while difficult to objectify, is likely to improve with surgical repair. Resting parameters offer little yield in aiding this except in the most severe cases. CPET therefore offers a better option for dynamic assessment of this limitation and improvements following repair. Surgery significantly improves psychological well-being and quality of life for patients with PEx.
Impact on all-cause mortality of a case prediction and prevention intervention designed to reduce secondary care utilisation: findings from a randomised controlled trial
Authors: Bull Lucy M , Arendarczyk Bartlomiej , Reis Sara , Nguyen An , Werr Joachim , Lovegrove-Bacon Thomas , Stone Mark , Sherlaw-Johnson Christopher
Published: October 2023

Background

Health coaching services could help to reduce emergency healthcare utilisation for patients targeted proactively by a clinical prediction model (CPM) predicting patient likelihood of future hospitalisations. Such interventions are designed to empower patients to confidently manage their own health and effectively utilise wider resources. Using CPMs to identify patients, rather than prespecified criteria, accommodates for the dynamic hospital user population and for sufficient time to provide preventative support. However, it is unclear how this care model would negatively impact survival.

Methods

Emergency Department (ED) attenders and hospital inpatients between 2015 and 2019 were automatically screened for their risk of hospitalisation within 6 months of discharge using a locally trained CPM on routine data. Those considered at risk and screened as suitable for the intervention were contacted for consent and randomised to one-to-one telephone health coaching for 4–6 months, led by registered health professionals, or routine care with no contact after randomisation. The intervention involved motivational guidance, support for self-care, health education, and coordination of social and medical services. Co-primary outcomes were emergency hospitalisation and ED attendances, which will be reported separately. Mortality at 24 months was a safety endpoint.

Results

Analysis among 1688 consented participants (35% invitation rate from the CPM, median age 75 years, 52% female, 1139 intervention, 549 control) suggested no significant difference in overall mortality between treatment groups (HR (95% CI): 0.82 (0.62, 1.08), pr(HR<1=0.92), but did suggest a significantly lower mortality in men aged >75 years (HR (95% CI): 0.57 (0.37, 0.84), number needed to treat=8). Excluding one site unable to adopt a CPM indicated stronger impact for this patient subgroup (HR (95% CI): 0.45 (0.26, 0.76)).

Conclusions

Early mortality in men aged >75 years may be reduced by supporting individuals at risk of unplanned hospitalisation with a clear outreach, out-of-hospital nurse-led, telephone-based coaching care model.
Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry
Authors:   UK HFpEF Collaborative Group
Published: October 2023

Objective

Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes.

Methods

The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction >40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort.

Conclusions

UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics.

Trial registration number

NCT05441839.