bluuebunny/crossref_metadata_2025_split huggingface dataset:
The current landscape of optogenetics for the enhancement of adoptive T-cell therapy
Authors: Smith George R , Lee Max P , Jennings Emma K , James John R 
Published: December 2024

Abstract
Immunotherapy, the medicinal modulation of a host’s immune response to better combat a pathogen or disease, has transformed cancer treatments in recent decades. T-cells, an important component of the adaptive immune system, are further paramount for therapy success. Recent immunotherapeutic modalities have therefore more frequently targeted T-cells for cancer treatments and other pathologies and are termed adoptive T-cell (ATC) therapies. ATC therapies characterize various types of immunotherapies but predominantly fall into three established techniques: tumour-infiltrating lymphocyte, chimeric antigen receptor T-cell, and engineered T-cell receptor therapies. Despite promising clinical results, all ATC therapy types fall short in providing long-term sustained tumour clearance while being particularly ineffective against solid tumours, with substantial developments aiming to understand and prevent the typical drawbacks of ATC therapy. Optogenetics is a relatively recent development, incorporating light-sensitive protein domains into cells or tissues of interest to optically tune specific biological processes. Optogenetic manipulation of immunological functions is rapidly becoming an investigative tool in immunology, with light-sensitive systems now being used to optimize many cellular therapeutic modalities and ATC therapies. This review focuses on how optogenetic approaches are currently utilized to improve ATC therapy in clinical settings by deepening our understanding of the molecular rationale behind therapy success. Moreover, this review further critiques current immuno-optogenetic systems and speculates on the expansion of recent developments, enhancing current ATC-based therapeutic modalities to pave the way for clinical progress.
Estimated total amyloid burden from 18F-florbetaben positron emission tomography predicts all-cause mortality in light-chain cardiac amyloidosis
Authors: Vergaro Giuseppe , Aimo Alberto , Genovesi Dario , Soares Bezerra Lucas , Castiglione Vincenzo , Fabiani Iacopo , Barison Andrea , Panichella Giorgia , Del Giudice Maria Livia , Camerini Lara , Dugo Giovanni , Chubuchna Olena , Giorgetti Assuero , Buda Gabriele , Emdin Michele 
Published: December 2024

Abstract

Aims
The positron emission tomography (PET) tracer 18F-florbetaben is a promising diagnostic tool for light-chain cardiac amyloidosis (AL-CA). A greater cardiac uptake might signal more amyloid burden and a worse outcome. We aimed to assess the prognostic significance of 18F-florbetaben uptake in AL-CA.

Methods and results
Consecutive patients with AL-CA underwent 18F-florbetaben PET scans. Total amyloid burden (TAB; calculated as mean standardized uptake value multiplied by molecular volume) was assessed in the left and right ventricles (LV/RV) in early (5–15′) and late (50–60′) acquisitions. The endpoint was all-cause mortality. Forty patients (median age 69 years, 73% males, Mayo 2004 Stage III in 80%) underwent 18F-florbetaben PET with a median time from tissue biopsy of 21 days (interquartile range, IQR 7–83). Late LV TAB, but not early LV TAB, correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity (hs)-troponin T. Over 13 months after the PET scan (IQR 5–21), 65% of patients died. A late LV TAB ≥273 cm3 (cut-off derived from spline curve analysis) predicted 18 and 24 month all-cause mortality independently from baseline variables, including NT-proBNP, hs-troponin T, and Mayo 2004 stage. Late RV TAB ≥135 cm3 independently predicted 18 and 24 month all-cause mortality. Patients with both late LV and RV TAB ≥ cut-offs had a shorter survival than those with only LV TAB ≥ cut-off and those with TAB in both ventricles &lt; cut-offs (Log-rank 16.52, P &lt; 0.001).

Conclusion
18F-florbetaben PET imaging offers valuable prognostic information in AL-CA. Values of late TAB measured in the LV and RV are strong predictors of all-cause mortality.
Transcatheter aortic valve replacement for aortic regurgitation following valve sparing root replacement: a case series
Authors: Sharma Harish , Mechery Anthony , Lawton Ewa , Nadir M Adnan , Doshi Sagar N 
Published: December 2024

Abstract

Background
Valve sparing aortic root replacement (VSARR) is a treatment for aortic root dilatation and aortic regurgitation (AR), which preserves the aortic valve. However, AR may recur, and redo surgery often carries high risk. Transcatheter aortic valve replacement (TAVR) can be performed but there is a paucity of literature to guide procedural planning.

Case summary
Two cases are presented herein with recurrence of severe AR following VSARR (David procedure). In both cases, computed tomography (CT) scans demonstrated absence of calcium and a narrow sinus of valsalva. Both cases were considered at prohibitive risk for redo surgery and were successfully treated with TAVR using balloon-expandable valves. The valves were sized based on CT (aiming for moderate oversizing of 10%–11%) and by assessing the anchoring and waist of sizing balloons. Post-procedure aortography and echocardiography revealed no transvalvular or paravalvular regurgitation. Both patients were successfully discharged with follow-up CT scans also showing no migration and preservation of coronary access, together with suitability of future redo TAVR if required.

Discussion
TAVR can be successfully performed after VSARR surgery with a balloon-expandable valve in the absence of aortic valve calcification. Moderate THV oversizing (10%–11%) appears safe and effective. Careful assessment with a sizing balloon is recommended to ensure adequate anchoring, without the need for aggressive oversizing which risks rupture at the graft suture line.
Hypoglycaemia following physical exercise in a patient with novel SLC16A1 variant
Authors: Frampton Ruth , Lewis David , Rahman Yusof , Tchan Michel , Greenfield Jerry R 
Published: December 2024

Abstract
Rare defects in the promoter region of SLC16A1, the gene encoding monocarboxylate transporter 1 (MCT-1), result in exercise-induced hyperinsulinism. In this disorder, inappropriate insulin secretion is triggered by anaerobic exercise with consequent hypoglycaemia. We describe the case of a 41-year-old man presenting with a generalised tonic–clonic seizure and severe hypoglycaemia following strenuous exercise. A subsequent prolonged fast with incorporation of exercise into the protocol demonstrated hyperinsulinaemic hypoglycaemia; genetic testing revealed a variant of unknown significance in the SLC16A1 gene. Administration of subcutaneous octreotide resulted in dose-dependent reduction in hyperinsulinaemia and hypoglycaemia.
Can sexual conflict drive transitions to asexuality? Female resistance to fertilization in a facultatively parthenogenetic insect
Authors: Wilner Daniela , Boldbaatar Jigmidmaa , Miller Soleille M , Burke Nathan W , Bonduriansky Russell 
Published: December 2024

Abstract
Facultatively parthenogenetic animals could help reveal the role of sexual conflict in the evolution of sex. Although each female can reproduce both sexually (producing sons and daughters from fertilized eggs) and asexually (typically producing only daughters from unfertilized eggs), these animals often form distinct sexual and asexual populations. We hypothesized that asexual populations are maintained through female resistance as well as the decay of male traits. We tested this via experimental crosses between individuals descended from multiple natural sexual and asexual populations of the facultatively parthenogenic stick insect Megacrania batesii. We found that male-paired females descended from asexual populations produced strongly female-biased offspring sex ratios resulting from reduced fertilization rates. This effect was not driven by incompatibility between diverged genotypes but, rather, by both genotypic and maternal effects on fertilization rate. Furthermore, when females from asexual populations mated and produced sons, those sons had poor fertilization success when paired with resistant females, consistent with male trait decay. Our results suggest that resistance to fertilization resulting from both maternal and genotypic effects, along with male sexual trait decay, can hinder the invasion of asexual populations by males. Sexual conflict could thus play a role in the establishment and maintenance of asexual populations.
CAT-Posterior Mean Site Frequencies Improves Phylogenetic Modeling Under Maximum Likelihood and Resolves Tardigrada as the Sister of Arthropoda Plus Onychophora
Authors: Giacomelli Mattia , Vecchi Matteo , Guidetti Roberto , Rebecchi Lorena , Donoghue Philip C J , Lozano-Fernandez Jesus , Pisani Davide 
Published: December 2024

Abstract
Tardigrada, the water bears, are microscopic animals with walking appendages that are members of Ecdysozoa, the clade of molting animals that also includes Nematoda (round worms), Nematomorpha (horsehair worms), Priapulida (penis worms), Kinorhyncha (mud dragons), Loricifera (loricated animals), Arthropoda (insects, spiders, centipedes, crustaceans, and their allies), and Onychophora (velvet worms). The phylogenetic relationships within Ecdysozoa are still unclear, with analyses of molecular and morphological data yielding incongruent results. Accounting for across-site compositional heterogeneity using mixture models that partition sites in frequency categories, CATegories (CAT)-based models, has been shown to improve fit in Bayesian analyses. However, CAT-based models such as CAT-Poisson or CAT-GTR (where CAT is combined with a General Time Reversible matrix to account for replacement rate heterogeneity) have proven difficult to implement in maximum likelihood. Here, we use CAT-posterior mean site frequencies (CAT-PMSF), a new method to export dataset-specific mixture models (CAT-Poisson and CAT-GTR) parameterized using Bayesian methods to maximum likelihood software. We developed new maximum likelihood-based model adequacy tests using parametric bootstrap and show that CAT-PMSF describes across-site compositional heterogeneity better than other across-site compositionally heterogeneous models currently implemented in maximum likelihood software. CAT-PMSF suggests that tardigrades are members of Panarthropoda, a lineage also including Arthropoda and Onychophora. Within Panarthropoda, our results favor Tardigrada as sister to Onychophora plus Arthropoda (the Lobopodia hypothesis). Our results illustrate the power of CAT-PMSF to model across-site compositionally heterogeneous datasets in the maximum likelihood framework and clarify the relationships between the Tardigrada and the Ecdysozoa.
Unlocking the power of AI for phenotyping fruit morphology in Arabidopsis
Authors: Atkins Kieran , Garzón-Martínez Gina A , Lloyd Andrew , Doonan John H , Lu Chuan 
Published: December 2024

Abstract
Deep learning can revolutionise high-throughput image-based phenotyping by automating the measurement of complex traits, a task that is often labour-intensive, time-consuming, and prone to human error. However, its precision and adaptability in accurately phenotyping organ-level traits, such as fruit morphology, remain to be fully evaluated. Establishing the links between phenotypic and genotypic variation is essential for uncovering the genetic basis of traits and can also provide an orthologous test of pipeline effectiveness. In this study, we assess the efficacy of deep learning for measuring variation in fruit morphology in Arabidopsis using images from a multiparent advanced generation intercross (MAGIC) mapping family. We trained an instance segmentation model and developed a pipeline to phenotype Arabidopsis fruit morphology, based on the model outputs. Our model achieved strong performance with an average precision of 88.0% for detection and 55.9% for segmentation. Quantitative trait locus analysis of the derived phenotypic metrics of the MAGIC population identified significant loci associated with fruit morphology. This analysis, based on automated phenotyping of 332,194 individual fruits, underscores the capability of deep learning as a robust tool for phenotyping large populations. Our pipeline for quantifying pod morphological traits is scalable and provides high-quality phenotype data, facilitating genetic analysis and gene discovery, as well as advancing crop breeding research.
Ecological histories govern social exploitation by microorganisms
Authors: Schaal Kaitlin A , Manhes Pauline , Velicer Gregory J 
Published: December 2024

Abstract
Exploitation is a common feature of social interactions, which can be modified by ecological context. Here, we investigate effects of ecological history on exploitation phenotypes in bacteria. In experiments with the bacterium Myxococcus xanthus, prior resource levels of different genotypes interacting during cooperative multicellular development were found to regulate social fitness, including whether cheating occurs. Responses of developmental spore production to manipulation of resource-level histories differed between interacting cooperators and cheaters, and relative-fitness advantages gained by cheating after high-resource growth were generally reduced or absent if one or both parties experienced low-resource growth. Low-resource growth also eliminated exploitation in some pairwise mixes of cooperative natural isolates that occurs when both strains have grown under resource abundance. Our results contrast with previous experiments in which cooperator fitness correlated positively with concurrent resource level and suggest that resource-level variation may be important in regulating whether exploitation of cooperators occurs in a natural context.
The role of sympathetic control in bone vasculature: insights from spinal cord injury
Authors: Sukhoplyasova Maria , Hamner Jason W , Draghici Adina E 
Published: December 2024

Abstract
Bone vasculature is richly innervated by an extensive network of sympathetic nerves. However, our understanding of bone blood flow regulation and its contribution to human bone health is limited. Here, we further our previous findings by characterizing bone vascular responses in the absence of sympathetic control—studying individuals with spinal cord injury (SCI), a population with known peripheral sympathetic disruption. We assessed tibial vascular responses to isometric handgrip exercise (IHE) in individuals with SCI (n = 12) and controls (n = 12). When sustained to fatigue, IHE increases perfusion pressure and sympathetic vasoconstriction in the nonactive tissues of the legs. During IHE, we measured blood pressure, whole leg blood velocity (LBV) via ultrasound, and tibial perfusion (as hemoglobin content) via near-infrared spectroscopy. Controls demonstrated active sympathetic vasoconstriction in the whole leg (ie, increased vascular resistance [VR], arterial pressure/LBV) and tibia (ie, decreased hemoglobin). In contrast, SCI individuals demonstrated modest whole leg vasoconstriction with lesser increases in VR than controls (p &lt; .04). Tibial vasculature evidenced absent or blunted vasoconstriction compared to controls (p &lt; .01), indicated by increasing tibial hemoglobin until plateauing at higher pressure levels. This suggests that, in the absence of sympathetic control, tibial vascular response may involve other regulatory mechanisms like myogenic vasoconstriction. Lastly, we leveraged existent whole-body DXA scans in a subgroup of 9 individuals with SCI, and we found a strong relationship between leg BMD and tibial hemoglobin at the end of IHE (r2 = 0.67, p &lt; .01). Our findings indicate that in the absence of sympathetic mechanisms, myogenic control may play a compensatory role in regulating blood flow, though to a lesser extent in bone compared to muscle. The close relationship between lesser declines in bone blood content and higher BMD underscores the link between blood flow and bone health.
A deep intronic PHEX variant associated with X-linked hypophosphatemia in a Finnish family
Authors: Koponen Laura , Pekkinen Minna , Legebeke Jelmer , Muurinen Mari , Rusanen Salla , Hussain Shabir , Wang Fan , Nevalainen Pasi I , Mäkitie Outi 
Published: December 2024

Abstract
Hypophosphatemic rickets is a rare bone disease characterized by short stature, bone deformities, impaired bone mineralization, and dental problems. Most commonly, hypophosphatemic rickets is caused by pathogenic variants in the X-chromosomal PHEX gene, but autosomal dominant and recessive forms also exist. We investigated a Finnish family in which the son (index, 29 yr) and mother (56 yr) had hypophosphatemia since childhood. Both patients had typical clinical, radiographic, and biochemical features of hypophosphatemic rickets, including a pathological fracture in the son. Gene panels and whole-exome sequencing did not reveal any pathogenic variants in the known hypophosphatemia genes. Therefore, we performed whole genome sequencing and identified a deep intronic variant (c.2147 + 1197A &gt; G) in PHEX. Both the affected individuals, but none of the unaffected family members, had the same variant, as confirmed by Sanger sequencing. According to RT-PCR, whole transcriptomic data, and in silico analyses, the variant led to a new splice donor site in intron 21 and an 84 basepair pseudoexon between exons 21 and 22, likely leading to the synthesis of abnormal PHEX protein. Our study underscores the importance of intronic PHEX variants in X-linked hypophosphatemia (XLH). In patients with features of XLH but negative gene panel or whole-exome sequencing results, the combination of whole-genome sequencing and whole transcriptomics should be considered to detect possible deep intronic variants. The methodologies presented have the potential to be used more widely in other rare diseases.
Increasing Number of Clinically Severe Mycoplasma pneumoniae Infections in Children After the COVID-19 Pandemic: A Single-Center Case Series
Authors: McCarthy Karen N , Hatcher James , Best Timothy , Kaliakatsos Marios , Hassell Jane , Turnbull Andrew , Sidgwick Peter , Gavela Javier , Simmonds Jacob , Kucera Filip , Warris Adilia , Kadambari Seilesh 
Published: December 2024

Abstract
In 2024, there have been increases in laboratory-confirmed infections caused by Mycoplasma pneumoniae worldwide. This case series highlights the increasing frequency of M. pneumoniae-positive PCR (polymerase chain reaction) specimens and an increased number of hospital admissions with M. pneumoniae clinical syndromes. Within this case series, we observed a change in the epidemiology and clinical burden of childhood M. pneumoniae disease in the post-COVID-19 era.
CICADA: a circRNA effort toward the ghost proteome
Authors: Fan Liyuan , Zhou Xinyuan , Li Mian , Gao Anwei , Yu Haojie , Tian Hui , Liao Liandi , Xu Liyan , Sun Liang 
Published: December 2024

Abstract
Recent studies have confirmed that certain circRNAs encode proteins that are integral to various biological functions. In this study, we present CICADA, an algorithm specifically designed to assess the protein-coding potential and coding products of circRNAs at high throughput, which enables the identification of previously unknown circRNA-encoded proteins. By harnessing the potential of this algorithm, we identified a variety of functional, protein-coding circRNAs in esophageal squamous cell carcinoma and established circRNA translation profiles for diverse types of cancer. This advancement innovatively explores the hidden proteome within the genome, poised to catalyze discoveries in biomarkers and therapies for cancers and complex diseases. CICADA is accessible as a Python module (https://github.com/SunLab-biotool/CICADA).
Cuproplasia-related gene signature: Prognostic insights for glioma therapy
Authors: Jue Toni Rose , Descallar Joseph , Pham Vu Viet Hoang , Bell Jessica Lilian , Shai-Hee Tyler , Cazzolli Riccardo , Nagabushan Sumanth , Koh Eng-Siew , Vittorio Orazio 
Published: December 2024

Abstract

Background
Adult-type diffuse gliomas encompass nearly a quarter of all primary tumors found in the CNS, including astrocytoma, oligodendroglioma, and glioblastoma. Histopathological tumor grade and molecular profile distinctly impact patient survival. Despite treatment advancements, patients with recurrent glioma have a very poor clinical outcome, warranting improved risk stratification to determine therapeutic interventions. Various studies have shown that copper is a notable trace element that is crucial for biological processes and has been shown to display pro-tumorigenic functions in cancer, particularly gliomas.

Methods
Differential gene expression, Cox regression, and least absolute shrinkage and selection operator regression were used to identify 19 copper-homeostasis-related gene signatures using TCGA lower-grade glioma and glioblastoma (GBM) cohorts. The GLASS Consortium dataset was used as an independent validation cohort. Enrichment analysis revealed the involvement of the signature in various cancer-related pathways and biological processes. Using this CHRG signature, a risk score model and a nomogram were developed to predict survival in glioma patients.

Results
Our prognostic CHRG signature stratified patients into high- and low-risk groups, demonstrating robust predictive performance. High-risk groups showed poorer survival outcomes. The nomogram model integrating CHRG signature and clinical features accurately predicted 1-, 3-, and 5-year survival rates in both training and test sets.

Conclusions
The identified 19-gene CHRG signature holds promise as a prognostic tool, enabling accurate risk stratification and survival prediction in glioma patients. Integrating this signature with clinical characteristics enhances prognostic accuracy, underscoring its potential clinical utility in optimizing therapeutic strategies and patient care in glioma management.
Frequency and impact of paediatric acute-onset neuropsychiatric syndrome/paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections diagnosis in Canada
Authors: Goren Rachel , Bitnun Ari , Doja Asif , Gill Peter J , Laxer Ronald M , Levy Deborah M , Pringsheim Tamara , Sandor Paul , Yeh Eluen Ann , Wilbur Colin , Kronenberg Sefi , Shouldice Michelle 
Published: December 2024

ABSTRACT

Objectives
This study aims to estimate the prevalence of the PANS/PANDAS diagnostic label in Canada and describe its impact on families, patients, and health care.

Methods
Through the Canadian Paediatric Surveillance Program (CPSP), a monthly form was distributed to paediatricians from December 2019 to November 2021, requesting reports of children who received the diagnostic label of PANS/PANDAS between the ages of 3 and 18 years seen in the previous month. Descriptive and association statistical analyses were performed.

Results
Eighty-four cases (57% female, median age of symptom onset 7.8 years interquartile range [IQR] = 5) who received the diagnostic label of PANS/PANDAS were included. Prevalence was found to be 1 in 60,155 (0.0017%). Core diagnostic criteria for PANS/PANDAS (obsessive-compulsive disorder or tics or acute food refusal) were not present in 12% of cases (10/84). Only 22% reported sudden symptom onset. Infection was associated with symptom onset or exacerbation in less than one-third of cases. The majority exhibited two or more neuropsychiatric symptoms (95%). There was significant health care utilization and symptom burden amongst cases. There was a significant difference in the certainty of diagnosis between physicians and families (P &lt; 0.05).

Conclusions
PANS/PANDAS diagnoses, while rare, significantly impact children, families, and the health care system. Diagnostic uncertainty underscores the challenges professionals and families face in accessing effective care, emphasizing the need for education and evidence-based clinical practice guidelines.