bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data
Authors: Dai Rujia , Chu Tianyao , Zhang Ming , Wang Xuan , Jourdon Alexandre , Wu Feinan , Mariani Jessica , Vaccarino Flora M. , Lee Donghoon , Fullard John F. , Hoffman Gabriel E. , Roussos Panos , Wang Yue , Wang Xusheng , Pinto Dalila , Wang Sidney H. , Zhang Chunling ,   PsychENCODE consortium, Chen Chao , Liu Chunyu
Published: May 2024

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expressions. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The results showed that decon-eQTLs explained more schizophrenia GWAS heritability than bulk tissue or single-cell eQTLs did alone. Differential gene expressions associated with Alzheimer’s disease, schizophrenia, and brain development were also examined using the deconvoluted data. Our findings, which were replicated in bulk tissue and single-cell data, provided insights into the biological applications of deconvoluted data in multiple brain disorders.
Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements
Authors: Pratt Henry E. , Andrews Gregory , Shedd Nicole , Phalke Nishigandha , Li Tongxin , Pampari Anusri , Jensen Matthew , Wen Cindy , Consortium PsychENCODE , Gandal Michael J. , Geschwind Daniel H. , Gerstein Mark , Moore Jill , Kundaje Anshul , Colubri Andrés , Weng Zhiping
Published: May 2024

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements’ sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type–specific gene regulation in various types of glia and neurons. The elements’ evolutionary history suggests that new regulatory information in the brain emerges primarily via smaller sequence mutations within conserved mammalian elements rather than entirely new human- or primate-specific sequences. However, primate-specific candidate elements, particularly those active during fetal brain development and in excitatory neurons and astrocytes, are implicated in the heritability of brain-related human traits. Additionally, we introduce PsychSCREEN, a web-based platform offering interactive visualization of PsychENCODE-generated genetic and epigenetic data from diverse brain cell types in individuals with psychiatric disorders and healthy controls.
CK2-dependent degradation of CBX3 dictates replication fork stalling and PARP inhibitor sensitivity
Authors: Ma Jian , Ren Dianyun , Wang Zixi , Li Wei , Li Lei , Liu Tianjie , Ye Qi , Lei Yuzeshi , Jian Yanlin , Ma Bohan , Fan Yizeng , Liu Jing , Gao Yang , Jin Xin , Huang Haojie , Li Lei
Published: May 2024

DNA replication is a vulnerable cellular process, and its deregulation leads to genomic instability. Here, we demonstrate that chromobox protein homolog 3 (CBX3) binds replication protein A 32-kDa subunit (RPA2) and regulates RPA2 retention at stalled replication forks. CBX3 is recruited to stalled replication forks by RPA2 and inhibits ring finger and WD repeat domain 3 (RFWD3)–facilitated replication restart. Phosphorylation of CBX3 at serine-95 by casein kinase 2 (CK2) kinase augments cadherin 1 (CDH1)–mediated CBX3 degradation and RPA2 dynamics at stalled replication forks, which permits replication fork restart. Increased expression of CBX3 due to gene amplification or CK2 inhibitor treatment sensitizes prostate cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors while inducing replication stress and DNA damage. Our work reveals CBX3 as a key regulator of RPA2 function and DNA replication, suggesting that CBX3 could serve as an indicator for targeted therapy of cancer using PARP inhibitors.
Constraining effects of aerosol-cloud interaction by accounting for coupling between cloud and land surface
Authors: Su Tianning , Li Zhanqing , Henao Natalia Roldan , Luan Qingzu , Yu Fangqun
Published: May 2024

Aerosol-cloud interactions (ACIs) are vital for regulating Earth’s climate by influencing energy and water cycles. Yet, effects of ACI bear large uncertainties, evidenced by systematic discrepancies between observed and modeled estimates. This study quantifies a major bias in ACI determinations, stemming from conventional surface or space measurements that fail to capture aerosol at the cloud level unless the cloud is coupled with land surface. We introduce an advanced approach to determine radiative forcing of ACI by accounting for cloud-surface coupling. By integrating field observations, satellite data, and model simulations, this approach reveals a drastic alteration in aerosol vertical transport and ACI effects caused by cloud coupling. In coupled regimes, aerosols enhance cloud droplet number concentration across the boundary layer more homogeneously than in decoupled conditions, under which aerosols from the free atmosphere predominantly affect cloud properties, leading to marked cooling effects. Our findings spotlight cloud-surface coupling as a key factor for ACI quantification, hinting at potential underassessments in traditional estimates.
Spatiotemporal dynamics of the proton motive force on single bacterial cells
Authors: Biquet-Bisquert Anaïs , Carrio Baptiste , Meyer Nathan , Fernandes Thales F. D. , Abkarian Manouk , Seduk Farida , Magalon Axel , Nord Ashley L. , Pedaci Francesco
Published: May 2024

Electrochemical gradients across biological membranes are vital for cellular bioenergetics. In bacteria, the proton motive force (PMF) drives essential processes like adenosine triphosphate production and motility. Traditionally viewed as temporally and spatially stable, recent research reveals a dynamic PMF behavior at both single-cell and community levels. Moreover, the observed lateral segregation of respiratory complexes could suggest a spatial heterogeneity of the PMF. Using a light-activated proton pump and detecting the activity of the bacterial flagellar motor, we perturb and probe the PMF of single cells. Spatially homogeneous PMF perturbations reveal millisecond-scale temporal dynamics and an asymmetrical capacitive response. Localized perturbations show a rapid lateral PMF homogenization, faster than proton diffusion, akin to the electrotonic potential spread observed in passive neurons, explained by cable theory. These observations imply a global coupling between PMF sources and consumers along the membrane, precluding sustained PMF spatial heterogeneity but allowing for rapid temporal changes.
Brain cell-type shifts in Alzheimer’s disease, autism, and schizophrenia interrogated using methylomics and genetics
Authors: Yap Chloe X. , Vo Daniel D. , Heffel Matthew G. , Bhattacharya Arjun , Wen Cindy , Yang Yuanhao , Kemper Kathryn E. , Zeng Jian , Zheng Zhili , Zhu Zhihong , Hannon Eilis , Vellame Dorothea Seiler , Franklin Alice , Caggiano Christa , Wamsley Brie , Geschwind Daniel H. , Zaitlen Noah , Gusev Alexander , Pasaniuc Bogdan , Mill Jonathan , Luo Chongyuan , Gandal Michael J.
Published: May 2024

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types—the functional unit of life—contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer’s disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer’s disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial cell loss contributes to Alzheimer’s disease, with comparable effect size to
APOE
genotype among older people. Genome-wide association identified five genetic loci related to cell-type composition, involving plausible genes for the neurovascular unit (
P2RX5
and
TRPV3
) and excitatory neurons (
DPY30
and
MEMO1
). These results implicate specific cell-type shifts in the pathophysiology of neuropsychiatric disorders.
Predicting the next sentence (not word) in large language models: What model-brain alignment tells us about discourse comprehension
Authors: Yu Shaoyun , Gu Chanyuan , Huang Kexin , Li Ping
Published: May 2024

Current large language models (LLMs) rely on word prediction as their backbone pretraining task. Although word prediction is an important mechanism underlying language processing, human language comprehension occurs at multiple levels, involving the integration of words and sentences to achieve a full understanding of discourse. This study models language comprehension by using the next sentence prediction (NSP) task to investigate mechanisms of discourse-level comprehension. We show that NSP pretraining enhanced a model’s alignment with brain data especially in the right hemisphere and in the multiple demand network, highlighting the contributions of nonclassical language regions to high-level language understanding. Our results also suggest that NSP can enable the model to better capture human comprehension performance and to better encode contextual information. Our study demonstrates that the inclusion of diverse learning objectives in a model leads to more human-like representations, and investigating the neurocognitive plausibility of pretraining tasks in LLMs can shed light on outstanding questions in language neuroscience.
Molecular cascades and cell type–specific signatures in ASD revealed by single-cell genomics
Authors: Wamsley Brie , Bicks Lucy , Cheng Yuyan , Kawaguchi Riki , Quintero Diana , Margolis Michael , Grundman Jennifer , Liu Jianyin , Xiao Shaohua , Hawken Natalie , Mazariegos Samantha , Geschwind Daniel H.
Published: May 2024

Genomic profiling in postmortem brain from autistic individuals has consistently revealed convergent molecular changes. What drives these changes and how they relate to genetic susceptibility in this complex condition are not well understood. We performed deep single-nucleus RNA sequencing (snRNA-seq) to examine cell composition and transcriptomics, identifying dysregulation of cell type–specific gene regulatory networks (GRNs) in autism spectrum disorder (ASD), which we corroborated using single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) and spatial transcriptomics. Transcriptomic changes were primarily cell type specific, involving multiple cell types, most prominently interhemispheric and callosal-projecting neurons, interneurons within superficial laminae, and distinct glial reactive states involving oligodendrocytes, microglia, and astrocytes. Autism-associated GRN drivers and their targets were enriched in rare and common genetic risk variants, connecting autism genetic susceptibility and cellular and circuit alterations in the human brain.
Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms
Authors: Patowary Ashok , Zhang Pan , Jops Connor , Vuong Celine K. , Ge Xinzhou , Hou Kangcheng , Kim Minsoo , Gong Naihua , Margolis Michael , Vo Daniel , Wang Xusheng , Liu Chunyu , Pasaniuc Bogdan , Li Jingyi Jessica , Gandal Michael J. , de la Torre-Ubieta Luis
Published: May 2024

RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, the role of cell type–specific splicing and transcript-isoform diversity during human brain development has not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone and cortical plate regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 distinct isoforms, of which 72.6% were novel (not previously annotated in Gencode version 33), and uncovered a substantial contribution of transcript-isoform diversity—regulated by RNA binding proteins—in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to reprioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders.
Impact of early visual experience on later usage of color cues
Authors: Vogelsang Marin , Vogelsang Lukas , Gupta Priti , Gandhi Tapan K. , Shah Pragya , Swami Piyush , Gilad-Gutnick Sharon , Ben-Ami Shlomit , Diamond Sidney , Ganesh Suma , Sinha Pawan
Published: May 2024

Human visual recognition is remarkably robust to chromatic changes. In this work, we provide a potential account of the roots of this resilience based on observations with 10 congenitally blind children who gained sight late in life. Several months or years following their sight-restoring surgeries, the removal of color cues markedly reduced their recognition performance, whereas age-matched normally sighted children showed no such decrement. This finding may be explained by the greater-than-neonatal maturity of the late-sighted children’s color system at sight onset, inducing overly strong reliance on chromatic cues. Simulations with deep neural networks corroborate this hypothesis. These findings highlight the adaptive significance of typical developmental trajectories and provide guidelines for enhancing machine vision systems.
Crows “count” the number of self-generated vocalizations
Authors: Liao Diana A. , Brecht Katharina F. , Veit Lena , Nieder Andreas
Published: May 2024

Producing a specific number of vocalizations with purpose requires a sophisticated combination of numerical abilities and vocal control. Whether this capacity exists in animals other than humans is yet unknown. We show that crows can flexibly produce variable numbers of one to four vocalizations in response to arbitrary cues associated with numerical values. The acoustic features of the first vocalization of a sequence were predictive of the total number of vocalizations, indicating a planning process. Moreover, the acoustic features of vocal units predicted their order in the sequence and could be used to read out counting errors during vocal production.
Chiral-structured heterointerfaces enable durable perovskite solar cells
Authors: Duan Tianwei , You Shuai , Chen Min , Yu Wenjian , Li Yanyan , Guo Peijun , Berry Joseph J. , Luther Joseph M. , Zhu Kai , Zhou Yuanyuan
Published: May 2024

Mechanical failure and chemical degradation of device heterointerfaces can strongly influence the long-term stability of perovskite solar cells (PSCs) under thermal cycling and damp heat conditions. We report chirality-mediated interfaces based on
R
-/
S
-methylbenzyl-ammonium between the perovskite absorber and electron-transport layer to create an elastic yet strong heterointerface with increased mechanical reliability. This interface harnesses enantiomer-controlled entropy to enhance tolerance to thermal cycling–induced fatigue and material degradation, and a heterochiral arrangement of organic cations leads to closer packing of benzene rings, which enhances chemical stability and charge transfer. The encapsulated PSCs showed retentions of 92% of power-conversion efficiency under a thermal cycling test (−40°C to 85°C; 200 cycles over 1200 hours) and 92% under a damp heat test (85% relative humidity; 85°C; 600 hours).
Mapping the brain’s gene-regulatory maze
Authors: Novarino Gaia , Bock Christoph
Published: May 2024

DNA sequences are connected to genes and functions in the developing and adult brain
A struggle to reionize the Universe?
Authors: Scarlata Claudia
Published: May 2024

Reservoirs of neutral hydrogen may block ionizing radiation from escaping distant galaxies
An emerging target for male contraception
Authors: Holdaway Jerrett , Georg Gunda I.
Published: May 2024

An inhibitor of a nonhormonal target is identified using a DNA-encoded chemical library
In vitro
and
in vivo
efficacy of the amiodarone and praziquantel combination against the blood fluke
Schistosoma mansoni
Authors: Cajas Rayssa A. , Santos Silvia S. B. , Espírito-Santo Maria Cristina C. , Garedaghi Yagoob , de Moraes Josué
Published: May 2024

Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus
Schistosoma
, affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against
Schistosoma mansoni
through comprehensive
in vitro
and
in vivo
experiments.
In vitro
experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%–70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.
Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity
Authors: Gao Yingqin , Zhou Jienan , Wang Meilan , Liang Yanqi , Zhang Ting , Mao Yunxiang , Ma Jing , Li Li , Zhang Tiesong , Guo Lei
Published: May 2024

Allergic rhinitis (AR) is a global health challenge that particularly affects the quality of life of children. Human rhinovirus (HRV) infection usually causes common cold in the upper respiratory tract (URT) and can also affect airway allergy development, such as asthma exacerbation, but its relationship with AR is poorly understood. The study aimed to gain insight into the characteristics of HRV that is prevalent in AR children and its role in AR severity. A total of 362 children with symptomatic AR were enrolled from southwestern China during 2022–2023, and nasal lavage samples were collected for HRV molecular characterization and cytokine measurement. HRV was detected in 40% of the AR children, with peak detection in autumn. The positive rate was not correlated with whether the subjects were under allergen-specific immunotherapy (AIT). Among the detected HRVs, 42% were species A, 36% were species B, and 22% were species C, involving 21 A genotypes, 6 B genotypes, and 7 C genotypes. HRV positivity was significantly associated with symptom severity (visual analog scale [VAS] score) and elevated levels of local nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 in AR children who did not receive antiallergic treatment. All three species of HRV strains (A1B, A21, B27, B70, and C17) had been isolated and were able to infect respiratory epithelial tissue
in vitro
. Complete genome sequencing showed that the antigenic epitopes of the isolated HRVs had certain variations. Our work reveals the etiological characteristics of URT-HRV in AR children and suggests a role of HRV infection in the pathogenesis of childhood AR.

IMPORTANCE

Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.
Insights into the Phanerozoic evolution of the São Francisco Craton based on detrital zircon thermochronology and U-Pb-Hf geochronology
Authors: Dias Airton N.C. , Martins-Ferreira Marco Antonio C. , Pereira Vinicius Q. , Sales Antonio S.W. , Chemale Farid
Published: May 2024

Basins within cratonic environments offer valuable insights into the fragmentation, dispersion, and agglutination of the lithosphere within supercontinents. The southern São Francisco Craton is home to sedimentary basins that formed in both intraplate tectonic settings (late Paleoproterozoic to Neoproterozoic and Mesozoic) and convergent tectonic settings (Ediacaran to Cambrian). To elucidate the Phanerozoic thermal history of the craton and the long-term depositional history of the southern São Francisco Craton’s cover, a comprehensive study was conducted utilizing detrital zircons through zircon fission-track (ZFT) thermochronology and U-Pb-Hf geochronology. This study analyzed samples from the following units: (1) the intracratonic basin—Lower and Upper Espinhaço Supergroup, with depositional age intervals ranging 1800–1600 Ma and 1200–920 Ma, respectively; (2) the rift-related passive margin basin—Lower Macaúbas Group (720 Ma and 640 Ma) and Jequitaí Formation, which is likely of Cryogenian age (650–635 Ma); (3) and the foreland basin—Bambui Group and Três Marias Formation, with ages of ca. 600–520 Ma and 520–480 Ma, respectively. U-Pb-Hf detrital zircon geochronology revealed the complex depositional history of the southern São Francisco Craton, and indicated changing source rocks over time. Conversely, the ZFT analysis of Precambrian to Cambrian samples allowed for the identification and characterization of Phanerozoic events in the southern São Francisco Craton. These events include: (1) the exhumation and late orogenic uplift of the foreland at ca. 500–480 Ma (mean age of 499 ± 5.5 Ma) during the late stages of the Brasiliano–Pan-African Cycle, which was associated with the Araçuaí Belt and lithospheric rebound of the peripheral cratonic margin of the southern São Francisco Craton; and (2) an age of 330–280 Ma (mean age of 306.6 ± 4.8 Ma) that possibly resulted from ice retreat and isostatic rebound interior of the Gondwana Paleocontinent. Additionally, analysis of detrital zircons from the Areado Group shows a later tectonic event recorded at 128.1 ± 9.4 Ma, which indicates Mesozoic intracontinental rifting. Based on these results and interpretations, the timing and exhumation of the southern São Francisco Craton during the Phanerozoic can be attributed to the final stages of the continental collision of the southern São Francisco Craton and Congo Craton and large-scale continental uplift during the Permo-Carboniferous late Paleozoic Ice Age of Gondwana. Overall, the findings demonstrate a direct correlation between known tectonic events at the plate margins of Western Gondwana and periods of cratonic basin formation.
Late Oligocene–Miocene evolution of deep-water circulation in the abyssal South China Sea: Insights from Nd isotopes of fossil fish teeth
Authors: Shu Wei , Colin Christophe , Liu Zhifei , Dapoigny Arnaud
Published: May 2024

A long-term neodymium isotope (εNd) record of fossil fish teeth was investigated to constrain the evolution of deep-water circulation in the abyssal South China Sea (SCS) during the late Oligocene–Miocene (27–10 Ma). Fish teeth samples were collected from the oceanic red beds at International Ocean Discovery Program Expedition 367 Site U1499 (water depth 3758 m). Seawater εNd values (from –7.1 to –4.8, average –6.1) prior to 15 Ma indicate that water masses in the abyssal SCS resulted from the mixing of more radiogenic Upper Circumpolar Deep Water (UCDW, average –4.5) and less radiogenic Lower Circumpolar Deep Water (LCDW, average –6.4). The general decrease in εNd values was attributed to an increasing influence of the unradiogenic LCDW at the studied site, consistent with the subsidence and the associated deepening of the SCS plain. After 15 Ma, seawater εNd dropped significantly to a range of –8.9 to –6.1 (average –7.5), indicating a slowdown in the hydrological connection between the deep-water masses in the SCS and the western Pacific Ocean. We argue that the formation of the Luzon Strait due to the uplift of the Luzon arc in the late Miocene led to the shallowing and narrowing of the SCS-Pacific channels. Consequently, penetration of LCDW was reduced and water masses in the abyssal SCS would have been less ventilated and strongly influenced by lithogenic input from the unradiogenic sediments of large Asian rivers draining the peri-Himalayan region.
Fingerprinting enhanced floodplain reworking during the Paleocene–Eocene Thermal Maximum in the Southern Pyrenees (Spain): Implications for channel dynamics and carbon burial
Authors: Prieur Marine , Whittaker Alexander C. , Nuriel Perach , Jaimes-Gutierrez Rocío , Garzanti Eduardo , Roigé Marta , Sømme Tor O. , Schlunegger Fritz , Castelltort Sébastien
Published: May 2024

The sedimentary record of the Paleocene–Eocene Thermal Maximum (PETM, ca. 56 Ma) allows the study of feedback mechanisms over the entire duration of a climatic event, from carbon release to the subsequent recovery phase. Clay sedimentation increase in the oceans during the PETM is linked to enhanced terrestrial erosion. Fluvial channel mobility has been invoked to explain this increase in fine sediment export based on more frequent transitional avulsions. In this study, we test whether the reworking of Microcodium (prismatic calcite concretions) from the floodplain to marine environments can serve to fingerprint floodplain reworking due to channel mobility. We quantified the abundance of floodplain-sourced Microcodium grains reworked in fluvial to marine sandstones pre-dating and coeval to the PETM in the Southern Pyrenees (Tremp Basin, Spain). Laser ablation–inductively coupled plasma–mass spectrometry U-Pb ages on calcite confirm the Thanetian age of the Microcodium grains. Our data show a four-fold increase in the export of floodplain sediments to the marine domain during the PETM. Moreover, we show that this is predominantly due to enhanced channel mobility, reworking channel banks and interfluves, with increased erosion in the hinterland as a secondary factor. This increase in floodplain reworking would correspond to an increase in biospheric carbon burial flux by a factor of 2.2. Therefore, enhanced channel mobility and fine-grain sediment transport to the oceans during a climatic perturbation such as the PETM may constitute an important negative feedback mechanism.
Thyroid pyocele with systemic sepsis: a rare clinical scenario
Authors: Dorasala Ramanna Surya Prakash , Channegowda Chandrakiran , Shanmugananthan Shabna Lakshmi , Sajith Milu
Published: May 2024

A late middle-aged woman presented with a large, painful neck mass, with a history of rapid increase of size since 1 week and associated voice change, dyspnoea and odynophagia. Prior radiological investigation showed a multiloculated cystic mass in the left thyroid lobe. Fine needle aspiration revealed a predominant cluster of neutrophils. Blood investigations showed leucocytosis and high blood glucose levels suggestive of sepsis. The patient underwent surgical drainage of the thyroid abscess with total thyroidectomy which was managed through multidisciplinary teamwork between surgeons, haematologists, endocrinologists and anaesthesiologists. In addition, urine culture and thyroid pus culture both showedEscherichia coligrowth suggestive of bacterial sepsis. The patient was treated successfully and made a complete recovery following surgery with normalisation of voice.
Reverse pupillary block with pigment dispersion and elevated intraocular pressure following bilateral phakic intraocular lens implantation
Authors: Cardoza Namratha Judith , Murthy Somasheila I , Senthil Sirisha
Published: May 2024

The authors describe a case of reverse pupillary block with pigment dispersion following sequential phakic intraocular lens (pIOL) implantation for high myopia, in a young female patient. The intraocular pressure (IOP) elevation began 3 weeks postoperatively, for which Nd-YAG laser peripheral iridotomies (PIs) were attempted elsewhere. Despite maximum medical therapy, the IOP was uncontrolled. She was referred to our institute for further management. Examination showed anteriorly displaced iris-pIOL diaphragm, iris pigment dispersion and raised IOP. The PIs were incomplete. Based on clinical evaluation and investigations, we concluded that the excess area of contact of the posterior iris over the pIOL caused a reverse pupillary block and pigment dispersion. The IOPs were controlled by repeating laser iridotomies and with medical therapy. Subsequently, the patient developed a low lens vault leading to bilateral cataract. Sequential explantation of the pIOL along with cataract extraction was performed and her vision was restored.
OHVIRA syndrome: clinical implications of a delayed diagnosis
Authors: Mohd Adzlan Fadzlin , Mohd Karimah , Ahmad Nasriah , Ramli Roziana
Published: May 2024

Obstructed Hemi Vagina with Ipsilateral Renal Agenesis (OHVIRA) syndrome is a rarely encountered müllerian duct anomaly. Delayed diagnosis is common due to normal onset of puberty and menstruation. We report a case of a woman in her early 20s with a background history of multiple emergency department visits, ward admissions and surgeries for chronic abdominal pain. She was reviewed at 1 month postlaparotomy for recurrent pelvic abscess and was finally diagnosed to have an OHVIRA syndrome, 11 years after her first clinical presentation. Excision of the vaginal septum completely resolved her symptoms. We are reporting this case to highlight the clinical implications resulting from the delayed diagnosis, to look into factors contributing to the delay and to highlight the importance of having a high index of suspicion to diagnose this unique condition.
Clostridium perfringens-induced liver abscess with severe haemolysis
Authors: Takanosu Tomotaka , Izawa Yoshimitsu , Yonekawa Chikara , Mato Takashi
Published: May 2024

Clostridium perfringensis notorious for causing skin and soft tissue infections and food poisoning. Rarely,C. perfringensinfections are associated with severe haemolysis, with a mortality rate of >80%. A previously healthy man in his 70s who presented with fever as his chief symptom was promptly admitted to a regional core hospital. Over the next 3 hours, shock and multiple organ failure ensued, leading to referral to our hospital for intensive care. We suspected a liver abscess caused byC. perfringensinfection with haemolysis, findings of severe haemolysis and a liver mass with gas production that appeared within a few hours. Though surgical drainage was contemplated, low blood pressure resulted in death within 3 hours of arrival at our hospital. The next day, a blood culture confirmedC. perfringens, proving the diagnosis. Improving patient outcomes requires increased awareness of the disease and early detection.
Traumatic abdominal wall hernia in childhood: a bicycle handlebar injury
Authors: Poppe Mariana , Duarte Catarina Marques , Fernandes Sofia , Goulão João
Published: May 2024

A female patient in her middle childhood presented to the paediatric emergency room (ER) after a bicycle accident with an abdominal impact on the bicycle handlebar. On physical examination, a painful ecchymosis on the upper left quadrant was the only abnormal finding. Abdominal ultrasound showed no intra-abdominal lesions, and the patient was discharged home after 24 hours under monitoring. Nine days after the accident, she returned to the ER due to the emergence of an abdominal mass around the area of impact. Abdominal examination detected a tender non-fluctuating mass on the epigastric and left hypochondrium, and abdominal ultrasound revealed a muscle and aponeurosis disruption of the rectus muscle, with fat herniation and cytosteatonecrosis. A conservative approach was chosen, with ambulatory follow-up. One month after the accident, the patient was asymptomatic, no abdominal mass was palpable, and an abdominal CT showed a reduction of the muscle disruption and hernial content.
Finding the place for nutrition in healthcare education and practice
Authors: Agwara Ebiambu , Martyn Kathy , Macaninch Elaine , Nyaga Wanja , Buckner Luke , Lepre Breanna , Laur Celia , Ray Sumantra
Published: May 2024

Background

Malnutrition continues to impact healthcare outcomes, quality of life and costs to healthcare systems. The implementation of nutrition care in healthcare practice may improve health outcomes for patients and the community. This paper describes the iterative development and implementation of nutrition medical education resources for doctors and healthcare professionals in England. These resources are part of the Nutrition Education Policy for Healthcare Practice initiative.

Method

Action research methodology was employed to develop and implement nutrition education workshops for medical students and doctors. The workshop was developed iteratively by an interdisciplinary project team, and the content was initially based on the General Medical Council outcomes for graduates. It was evaluated using quantitative evaluation tools and informal qualitative feedback captured from attendees using tools provided by the host organisations and developed by the roadshow team.

Results

A total of 6 nutrition education workshops were delivered to 169 participants. This simple educational package demonstrated potential for delivery in different healthcare settings; however, formal feedback was difficult to obtain. Evaluation results indicate that workshops were better received when delivered by doctors known to the participants and included local context and examples. Reported barriers to the workshops included difficulty for participants in finding the time to attend, beliefs that peers gave a low priority to nutrition and uncertainty about professional roles in the delivery of nutrition care.

Conclusion

A key outcome of this project was the development of resources for nutrition training of doctors, adapted to local needs. However, relatively low attendance and multiple barriers faced in the delivery of these workshops highlight that there is no ideal ‘place’ for nutrition training in current healthcare teaching. Interprofessional education, through relevant clinical scenarios may increase awareness of the importance of nutrition in healthcare, support the alignment of health professional roles and improve subsequent knowledge and skills.
Preliminary adaptation of the systems thinking for everyday work cue card set in a US healthcare system: a pragmatic and participatory co-design approach
Authors: Fell Samantha E , Bowie Paul , Spalding Karen , Medves Jennifer
Published: May 2024

Introduction

Healthcare is a highly complex adaptive system, requiring a systems approach to understand its behaviour better. We adapt the Systems Thinking for Everyday Work (STEW) cue cards, initially introduced as a systems approach tool in the UK, in a US healthcare system as part of a study investigating the feasibility of a systems thinking approach for front-line workers.

Methods

The original STEW cards were adapted using consensus-building methods with front-line staff and safety leaders.

Results

Each card was examined for relevance, applicability, language and aesthetics (colour, style, visual cues and size). Two sets of cards were created due to the recognition that systems thinking was relatively new in healthcare and that the successful use of the principles on the cards would need initial facilitation to ensure their effective application. Six principles were agreed on and are presented in the cards: Your System outlines the need to agree that problems belong to a system and that the system must be defined. Viewpoints ensure that multiple voices are heard within the discussion. Work Condition highlights the resources, constraints and barriers that exist in the system and contribute to the system’s functions. Interactions ask participants to understand how parts of the system interact to perform the work. Performance guides users to understand how work can be performed daily. Finally, Understanding seeks to promote a just cultural environment of appreciating that people do what makes sense to them. The two final sets of cards were scored using a content validity survey, with a final score of 1.

Conclusions

The cards provide an easy-to-use guide to help users understand the system being studied, learn from problems encountered and understand the everyday work involved in providing excellent care. The cards offer a practical ‘systems approach’ for use within complex healthcare systems.
Impact of a debrief tool in acute child and adolescent mental health inpatient units: a centre’s experience
Authors: Shepherd William Billal , Patterson Kyna , Blake Jessica , Ward Danielle , Clarke Ashlee , Diaz-Navarro Cristina , Abdulsatar Farah
Published: May 2024

This manuscript presents the pioneering use of a post-event staff debriefing tool, TALK, in Acute Child and Adolescent Mental Health Units (CAMHU). While unsuccessful in reducing the rate and severity of patient behavioural events, our centre observed promising psychological benefits for CAMHU staff as a result of debriefing, with the tool promoting emotional resiliency and providing a platform for open conversations. Debriefing also served as a venue for patient concerns with care to be raised by staff, addressed and reflected in updated care plans. This initiative demonstrates the utility of debriefing to foster a culture of learning, improve staff wellness and enhance patient safety in CAMHU settings.
Psychological safety in an ECMO retrieval team: a qualitative study to inform improvement
Authors: Passariello Maurizio , Tarrant Carolyn
Published: May 2024

Introduction

In healthcare teams, psychological safety is associated with improved performance, communication, collaboration and patient safety. Extracorporeal membrane oxygenation (ECMO) retrieval teams are multidisciplinary teams that initiate ECMO therapy for patients with severe acute respiratory failure in referring hospitals and transfer patients to regional specialised centres for ongoing care. The present study aimed to explore an ECMO team’s experience of psychological safety and generate recommendations to strengthen psychological safety.

Methods

The study was conducted in the Royal Brompton Hospital (RBH), part of Guy’s and St Thomas’ NHS Foundation Trust in London. RBH is one of six centres commissioned to provide ECMO therapy in the UK. 10 participants were recruited: 2 consultants, 5 nurses and 3 perfusionists. Semistructured interviews were used to explore the team members’ views on teamwork, their perceived ability to discuss concerns within the team and the interaction between speaking up, teamwork and hierarchy. A Reflexive Thematic Analysis approach was used to explore the interview data.

Results

The analysis of the interview dataset identified structural and team factors shaping psychological safety in the specific context of the ECMO team. The high-risk environment in which the team operates, the clearly defined process and functions and the structured opportunities that provide legitimate moments to reflect together influence how psychological safety is experienced. Furthermore, speaking up is shaped by the familiarity among team members, the interdependent work, which requires boundary spanning across different roles, and leadership behaviour. A hierarchy of expertise is privileged over traditional institutional ranking.

Conclusion

This study surfaced the structural and team factors that influence speaking up in the specific context of an ECMO retrieval team. Such information is used to suggest interventions to improve and strengthen psychological safety.
Role of nebulised magnesium sulfate in treating acute asthma in children: a systematic review and meta-analysis
Authors: Kumar Jogender , Kumar Prawin , Goyal Jagdish Prasad , Rajvanshi Nikhil , Prabhakaran Kalyana , Meena Jitendra , Gupta Atul
Published: May 2024

Objectives

To review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children.

Methods

The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO4as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them.

Results

10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO4/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: −0.09; 95% CI: −0.2 to +0.02, I2=21%). Children in the MgSO4group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I2=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups.

Conclusions

There is low-certainty evidence that nebulised MgSO4as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO4in paediatric acute asthma management.

PROSPERO registration number

CRD42022373692.
Exploring the role of blood pressure in the black-white disparity in cardiovascular disease mortality: a causal mediation analysis
Authors: Zhao Fan , Gidwani Risha , Wang May C , Chen Liwei , Nianogo Roch A
Published: May 2024

Background

Cardiovascular diseases (CVDs) are the leading cause of death in the USA, and high blood pressure is a major risk factor for CVD. Despite the overall declining rates of CVD mortality in the USA in recent years, marked disparities between racial and ethnic groups persist, with black adults having a higher mortality rate than white adults. We investigated the extent to which blood pressure mediated the black-white disparity in CVD mortality.

Methods

Data came from the Multi-Ethnic Study of Atherosclerosis, a diverse longitudinal cohort. We included 1325 black and 2256 white community-based adults aged 45–80 years free of clinical CVD at baseline and followed for 14 years. We used causal mediation analysis to estimate the effect of race on CVD mortality that was mediated through blood pressure.

Results

Black participants had a higher hazard of dying from CVD compared with white participants (adjusted hazard ratio (HR): 1.28 (95% CI 0.88, 1.88)), though estimates were imprecise. Systolic blood pressure mediated 27% (HR: 1.02, 95% CI 1.00, 1.06) and diastolic blood pressure mediated 55% (HR: 1.07, 95% CI 1.01, 1.10) of the racial disparities in CVD mortality between white and black participants. Mediation effects were present in men but not in women.

Conclusions

We found that black-white differences in blood pressure partially explain the observed black-white disparity in CVD mortality, particularly among men. Our findings suggest that public health interventions targeting high blood pressure prevention and management could be important strategies for reducing racial disparities in CVD mortality.
Epistemic injustice, healthcare disparities and the missing pipeline: reflections on the exclusion of disabled scholars from health research
Authors: Hunt Joanne , Blease Charlotte
Published: May 2024

People with disabilities are subject to multiple forms of health-related and wider social disparities; carefully focused research is required to inform more inclusive, safe and effective healthcare practice and policy. Through lived experience, disabled people are well positioned to identify and persistently pursue problems and opportunities within existing health provisions that may be overlooked by a largely non-disabled research community. Thus, the academy can play an important role in shining a light on the perspectives and insights from within the disability community, and combined with policy decisions, these perspectives and insights have a better opportunity to become integrated into the fabric of public life, within healthcare and beyond. However, despite the potential benefits that could be yielded by greater inclusivity, in this paper we describe barriers within the UK academy confronting disabled people who wish to embark on health research. We do this by drawing on published findings, and via the lived experience of the first author, who has struggled for over 3 years to find an accessible PhD programme as a person with energy limiting conditions who is largely confined to the home in the UK. First, we situate the discussion in the wider perspective of epistemic injustice in health research. Second, we consider evidence of epistemic injustice among disabled researchers, focusing primarily on what philosophers Kidd and Carel (2017, p 184) describe as ‘strategies of exclusion’. Third, we offer recommendations for overcoming these barriers to improve the pipeline of researchers with disabilities in the academy.
Failing to deliver: why pregnancy is not a disease
Authors: Rezkalla Paul , Smith Emmanuel
Published: May 2024

In their article ‘Is Pregnancy a Disease? A Normative Approach’, Anna Smajdor and Joona Räsänen contend that, on several of the most prominent accounts of disease, pregnancy should be considered a disease. More specifically, of the five accounts they discuss, each renders pregnancy a disease or suffers serious conceptual problems otherwise. They take issue specifically with the dysfunction account of disease and argue that it suffers several theoretical difficulties. In this response, we focus on defending the dysfunction account against their main objections and show why a version of the dysfunction account is viable on account of the indispensability of normativity in biology and medicine. After disarming their main objections to the dysfunction account, we briefly respond to their treatment of the normality of pregnancy and then draw a distinction between adverse symptoms and underlying causes to show why even though pregnancy may have ‘disease-like’ features, it is not a disease.