bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutional formalism and criminal sentencing on the frontier: evidence from British Columbia’s Jails, 1864–1913
Authors: Inwood Kris , Keay Ian , Long Blair
Published: February 2025

In this article, we study historical sentencing outcomes in British Columbia’s civilian criminal justice system during a period of transformative institutional change. We find that average sentences in the civilian system got longer as codification, judicial oversight, and institutional formalism increased. At the same time, sentences also became less dispersed around the mean, less discretionary, and more predictable. Even after controlling for changes in the composition of the prison population, significant increases in sentence length and decreases in sentence dispersion can still be identified, suggesting an important role for judicial decision-making. Using dynamic two-way fixed effect difference-in-differences specifications, we compare sentencing outcomes in the civilian system to outcomes in the institutionally stable military criminal justice system. We find that increases in sentence length, decreases in judicial discretion, and increases in sentence predictability can only be identified among prisoners sentenced in the civilian system after that system moved toward greater institutional formalism. (JEL K14, N21, N41, O43)
Technique for repair of recurrent aortic valve dehiscence
Authors: Van Hung Dung , Chau Chi Linh , Van Nguyen Minh Chau
Published: February 2025

Re-operation for aortic paravalvular leak or multiple dehiscences due to Behcet's disease or unknown causes remains a challenge. We describe a modified transmural sub-coronary suturing technique to address this issue. Between August 2022 and May 2024, the modified transmural sub-coronary suturing technique was applied in five cases of severe aortic paravalvular leak. The median follow-up period was 14 months (ranging from 8 to 19 months) with promising outcomes: no mortality, no significant paravalvular leak, no atrioventricular block, and no need of re-operation. Our transmural sub-coronary suturing technique with external Dacron strip reinforcement demonstrates good short-term outcomes. Further long-term follow-up is needed to evaluate the long-term effectiveness of this technique.
Reducing false positives in strong lens detection through effective augmentation and ensemble learning
Authors: Rezaei Samira , Chegeni Amirmohammad , Nagam Bharath Chowdhary , McKean J P , Baratchi Mitra , Kuijken Koen , Koopmans Léon V E
Published: February 2025

This research studies the impact of high-quality training datasets on the performance of Convolutional Neural Networks (CNNs) in detecting strong gravitational lenses. We stress the importance of data diversity and representativeness, demonstrating how variations in sample populations influence CNN performance. In addition to the quality of training data, our results highlight the effectiveness of various techniques, such as data augmentation and ensemble learning, in reducing false positives while maintaining model completeness at an acceptable level. This enhances the robustness of gravitational lens detection models and advancing capabilities in this field. Our experiments, employing variations of DenseNet and EfficientNet, achieved a best false positive rate (FP rate) of 10−4, while successfully identifying over 88 per cent of genuine gravitational lenses in the test dataset. This represents an 11-fold reduction in the FP rate compared to the original training dataset. Notably, this substantial enhancement in the FP rate is accompanied by only a 2.3 per cent decrease in the number of true positive samples. Validated on the KiDS dataset, our findings offer insights applicable to ongoing missions, like Euclid.
Inter-domain communication in the dimeric DEAD-box helicase Hera from T. thermophilus and implications for the mechanism of RNA unwinding
Authors: Donsbach Pascal , Kwas Carolin , Steimer Lenz , Samatanga Brighton , Andreou Alexandra Z , Klostermeier Dagmar
Published: February 2025

The Thermus thermophilus DEAD-box helicase Hera consists of the conserved helicase core, followed by a dimerization domain (DD) and an RNA-binding domain (RBD). The RBD mediates high-affinity binding to an RNA hairpin; the DD mediates formation of a stable dimer. In the dimer, the active sites of the two helicase cores face each other in an ideal configuration to cooperate functionally in RNA unwinding. Here, we dissect the communication between the two RBDs and helicase cores by characterizing dimeric deletion variants with two cores, but two, one, or no RBDs, variants with both RBDs, but two, one, or no functional core, and variants with one core and one RBD, either on the same or opposite protomers. We show that RNA binds to Hera in a two-step mechanism, with an initial interaction between the RBD and a hairpin, followed by the interaction of the core with the flanking single- or double-stranded region. The duplex preferentially interacts with the core on the same protomer in the absence of ATP, but in the presence of ATP, interactions with the other core become possible. Overall, our results point to limited but significant cooperativity between the two protomers in RNA unwinding.
Structural basis of ssDNA-guided NADase activation of prokaryotic SPARTA system
Authors: Hu Rong , Guo Chenmin , Liu Xiaotian , Lin Yuanyi , Yang Zixin , Li Zhixin , Yang Ye , Ma Erman , Li Yiyi , Chen Jiyun , Liu Liang
Published: February 2025

Short prokaryotic Argonaute and the associated TIR-APAZ (SPARTA) proteins constitute a prokaryotic immune system, mediating RNA- or DNA-guided target single-stranded DNA (ssDNA) to activate NADase activity and induce cell death by degrading NAD+ in response to invading plasmids. Although the guide RNA-mediated targeting mechanism of SPARTA has been established, the functional role and mechanisms of guide DNA-mediated SPARTA remain poorly understood. Here, we report two crystal structures of Crenotalea thermophila SPARTA complexes with 5′-phosphorylated 21-nt guide DNA and complementary target ssDNA lengths of 15 or 20 nt. The structures demonstrate specific recognition of the 5′-OH or 3′-OH groups in target DNA by SPARTA, while not recognizing the 5′-P group in guide DNA. This suggests distinct recognition models for guide DNA and guide RNA, indicating different activation mechanisms. Furthermore, these two structures reveal disparate models for recognizing guide DNA and target DNA, providing insights into the length requirement for SPARTA activation.
Structure of the tilapia lake virus nucleoprotein bound to RNA
Authors: Arragain Benoît , Pelosse Martin , Huard Karine , Cusack Stephen
Published: February 2025

Tilapia Lake virus (TiLV) belongs to the Amnoonviridae family within the Articulavirales order of segmented negative-strand RNA viruses and is highly diverged from more familiar orthomyxoviruses, such as influenza. The viral nucleoprotein (NP), a key component of the replication machinery, packages the viral genome into protective ribonucleoprotein particles. Here we describe the electron cryo-microscopy (cryo-EM) structure of TiLV-NP bound to RNA within in vitro reconstituted, small ring-like, pseudo-symmetrical oligomers. Although TiLV-NP is considerably smaller than its influenza counterpart and unrelated in sequence, it maintains the same topology and domain organisation. This comprises a head and body domain between which is a positively charged groove, where single-stranded RNA binds. In addition, an oligomerisation loop inserts into a hydrophobic pocket in the neighbouring NP, the flexible hinges of which allow variable orientation of adjacent NPs. Focused cryo-EM maps unambiguously define the 5′ to 3′ direction of the bound RNA, confirmed by double stranded, A-form RNA regions that extrude out from some of the NP–NP interfaces. This is the first fully resolved description of how single-stranded and stem-loop RNA binds to an articulaviral NP assembly. Superposition with orthomyxoviral NPs suggest that the mode of RNA binding is likely similar across the Articulavirales order.
Dynamics and evolutionary conservation of B complex protein recruitment during spliceosome activation
Authors: Fu Xingyang , Hoskins Aaron A
Published: February 2025

Spliceosome assembly and catalytic activation involve dozens of protein and snRNA binding and unbinding events. The B-complex specific proteins (Prp38, Snu23, and Spp381) have critical roles in stabilizing the spliceosome during rearrangements essential for activation. While these proteins are conserved, different mechanisms have been proposed for their recruitment to spliceosomes. To visualize recruitment directly, we used Colocalization Single Molecule Spectroscopy (CoSMoS) to study the dynamics of Prp38, Snu23, and Spp381 during splicing in real time. These proteins can bind to and release from spliceosomes simultaneously and are likely associated with one another. We designate the assembly minimally containing Prp38, Snu23, and Spp381 as a potential B complex protein (BCP) subcomplex of the spliceosome. Under splicing conditions, BCP proteins associate with pre-mRNA after tri-snRNP binding. BCP protein release predominantly occurs after U4 snRNP dissociation and after NineTeen Complex (NTC) association. Under low concentrations of ATP, BCP proteins preassociate with the tri-snRNP resulting in their simultaneous binding to pre-mRNA. Together, our results reveal that BCP protein recruitment to the spliceosome is conserved between Saccharomyces cerevisiae and humans. The binding of BCP proteins to the tri-snRNP when ATP is limiting may result in the formation of unproductive complexes that could be used to regulate splicing.
On the complexity of metacognitive judgments of memory: evidence from retrospective confidence, feeling of knowing, and older adults
Authors: Meunier-Duperray Lucile , Mazancieux Audrey , Souchay Céline , Bastin Christine , Angel Lucie , Moulin Chris J.A
Published: February 2025

Dissociations in types of memory tasks emerge when comparing feeling-of-knowing (FOK) judgments, predictions of upcoming performance, and retrospective confidence. This pattern has been used to construct theories of metacognitive access to memory, particularly in memory-impaired groups. In particular, older adults’ metacognitive sensitivity appears to vary between episodic (impaired) and semantic (intact) memory. However, this could be explained by the limitations of metacognitive measures and/or memory differences. We aimed to test these dissociations of metacognition with aging by comparing metacognitive efficiency in episodic and semantic tasks using two types of judgment: retrospective confidence judgments (RCJs) and FOK judgments. Metacognitive efficiency was estimated in 240 participants aged 19–79 years using a hierarchical Bayesian framework. Results showed that metacognitive efficiency for RCJs declined with age in the semantic task, even though task performance increased with age, while metacognitive efficiency was stable in the episodic task. Surprisingly, metacognitive efficiency was very low (although significantly higher than zero) for both FOK tasks regardless of age compared to similar previous studies. We suggested this might be due to the online testing. These results point to metacognition being multifaceted and varying according to judgment, domains, and populations.
Formation of massive star clusters with and without iron abundance spreads in a dwarf galaxy merger
Authors: Matsui Hidenori , Bekki Kenji , McKenzie Madeleine , Saitoh Takayuki R
Published: February 2025

To study the formation of star clusters and their properties in a dwarf–dwarf merging galaxy, we have performed a numerical simulation of a dwarf–dwarf galaxy merger by using the Tree+GRAPE $N$-body/SPH code ASURA. In our simulation, 13 young star clusters are formed during the merger process. We show that our simulated star clusters can be divided into two types: with and without [Fe$/$H] abundance variations. The former is created by a seed star cluster (the first-generation stars) formed in compressed gas. These stars contaminate the surrounding gas by Type II supernovae. At that time, the energy injection is insufficient to induce an outflow of the surrounding gas. After that, the contaminated gas falls into the seed, thereby forming a new generation of stars from the contaminated gas. We also show that most star clusters are formed in the galactic central region after the second encounter and fall into the galactic center due to dynamical friction within several hundred Myr. As a result, close encounters and mergers between the clusters take place. Although the clusters with shallower gravitational potential are tidally disrupted by these close encounters, others survive and finally merge at the center of the merged dwarf galaxies to create a nuclear star cluster. Therefore, the nuclear star cluster comprises various stellar components in ${[\rm Fe/H]}$ abundance and age. We discuss our work in the context of observations and demonstrate the diagnostic power of high-resolution simulations in the context of star cluster formation.
Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis
Authors: Jia Hongshuai , Yue Guang , Li Pin , Peng Renjun , Jin Ruyue , Chen Yuhan , Cao Hualin , Yang Kangning , Zhang Xiaowei , Yi Xiaoyu , Wu Yangyang , Deng Xiangling , Chen Xiaoye , Ma Lifei , Zhao Yang , Zhou Xiaoguang , Tao Tian , Shen Xiaoli , Zhang Xu , Tao Yuandong , Zhou Huixia
Published: February 2025

Renal fibrosis is a common mechanism leading to kidney failure in chronic kidney diseases (CKDs), including obstructive nephropathy (ON). Dysregulated inflammation is central to the development of renal fibrosis, but how local immune cells within the tissue microenvironment integrate and coordinate to drive this condition remains largely unknown. Herein, we documented that neutrophils were abundantly recruited and expelled neutrophil extracellular traps (NETs) in human and mouse fibrotic kidneys. Importantly, circulating levels of NET components displayed a significant correlation with worsened kidney function in ON patients. In the unilateral ureteral obstruction (UUO) mouse model, blocking NETs by protein-arginine deiminase type 4 (PAD4) deletion or DNase treatment significantly impaired NET formation and inhibited renal fibrosis and inflammation, whereas NET adoptive transfer exacerbated the fibrotic process. Moreover, NET-mediated renal fibrosis was associated with enhanced infiltration of cytotoxic CD8+ T cells, which produced granzyme B (GZMB) to drive tubular cell epithelial-mesenchymal transition (EMT) and fibroblast activation. Accordingly, pharmacological inhibition of GZMB resulted in blunted kidney inflammation and fibrosis. Furthermore, NETs profoundly potentiated the production of T-cell chemokines CXCL9/10/11 in macrophages, but not in tubular cells or fibroblasts, thus driving T-cell infiltration and fueling inflammatory cascades in the kidneys. Mechanistically, the NET-macrophage interaction was partially mediated by the TLR2/4 signaling. Thus, our work reveals a previously unexplored role of the collaboration between NETs and macrophages in supporting CD8+ T cell infiltration, which orchestrates kidney inflammation and fibrosis.
Can Colonial Institutions Be Good for Democracy? A Review of Sean Gailmard's Agents of Empire”
Authors: Grzymala-Busse Anna
Published: February 2025

Sean Gailmard's Agents of Empire is a fascinating argument about imperial institutional legacies and a major contribution to the flourishing literature in historical political economy. Gailmard argues that British strategies of colonial governance in the seventeenth and eighteenth centuries in what would become the United States had lasting and counterintuitive consequences. Colonial autonomy and legislative independence fused in a self-reinforcing bundle, even if British colonial rule itself consisted of a hodgepodge of imperfect institutions and various workarounds and patches layered on top of these institutions. Agents of Empire both contributes to and challenges the burgeoning new literature in historical political economy (HPE). Although much of the scholarship in historical political economy skates over causal mechanisms, Gailmard's analytical move is to emphasize these processes and mechanisms. This is a provocative and powerful argument that points out both the challenges of colonial rule and its surprising institutional consequences.
Treatment guidelines for idiopathic inflammatory myopathies in adults: a comparative review
Authors: Paik Julie J , Werth Victoria P , Chinoy Hector , Masri Karim R , Jambekar Amruta , Hasan Feza , Borlenghi Cecilia E , Gold David A
Published: February 2025

Myositis, or idiopathic inflammatory myopathy, encompasses a group of autoimmune diseases with broad-spectrum clinical presentations, with a common presentation of muscle weakness and inflammation. The management of myositis presents significant challenges due to the rarity and variability of the disease and lack of large-scale, randomised controlled trials. Due to limited evidence available from smaller studies as well as variation in treatment practices across geographical regions and disease subtypes, available published treatment recommendations vary significantly. There is a need, therefore, to develop multidisciplinary consensus-driven guidelines which appropriately reflect the diverse and complex nature of the disease. This comparative review presents an in-depth analysis of existing myositis treatment guidelines from diverse organisations, highlighting similarities and key differences in diagnoses, treatment and management recommendations. We propose that there is a need for developing globally unified, consensus-driven standardised set of guidelines for effective myositis management.
‘None Regardless of Reputation Will Be Received’: Midwifery and Commercial Bodywork in Urban Scotland c. 1780–c. 1840
Authors: Bujokova Eliska
Published: February 2025

This article presents two case studies of Scottish midwives, Mrs Laidlaw from Edinburgh and Mrs Alexander from Aberdeen who used newspaper advertising to promote their establishments. Primarily providing for women wishing to conceal their pregnancies and find alternative provisions for their children, the two providers marketed the discreet nature of their practice. Together their stories contradict the dominant strands of historiography on early nineteenth-century midwifery focussed either on its increasingly professionalised and masculinised nature or its rootedness in community practice, largely resistant to commodification. Instead, this article centres on female care and bodyworkers who found opportunities for entrepreneurship in the commercialised care sector. Through focussing on the services offered and their clandestine nature, it elucidates the experiences of lying-in of unmarried mothers of means. Highlighting the midwives’ ability to adapt to the socio-cultural fabric of motherhood, it contributes to the histories of female entrepreneurship and its many forms within the care sector.
Realistic Scenarios of Phenotypic Variation and Errors in High-Throughput Phenotyping Experiments Minimally Impact the Results of QTL Mapping Analysis
Authors: Brewer Aliyah , Underhill Anna , Sapkota Surya , Hwang Chin-Feng , Riaz Summaira , Oravec Madeline , Cadle-Davidson Lance
Published: February 2025

High-throughput phenotyping technologies increase the efficiency of breeding programs, but with larger data sets, errors can accumulate. Plant breeders often conduct quantitative trait locus (QTL) mapping, where large sample size and accurate quantitative response estimates are important for detecting small effect QTL. This study examined how phenotype error, inconsistency, and replication changed QTL magnitude and location. Three real sets of phenotype data were used from microscopy robot analysis of grapevine powdery mildew (Erysiphe necator) severity, which previously resulted in discovery of large (R2 = 85%), intermediate (R2 = 45%), and small (R2 = 9%) effect QTL. Custom R scripts were written to induce several realistic sources of error, inconsistency, and varied replication. The results were remarkably robust to these changes. Swapping or shifting 2% of samples or changing disease severity by 50% on one replicate had negligible impact on QTL. Unreplicated simulations produced the largest LOD score range (5.55 to 8.27) and mean LOD score deviation (-1.72 to -3.22; Cohen’s D = 1.48 to 2.12). The large effect size QTL (REN12) was always detected. The intermediate effect size QTL (REN13) was detected except when three of the eight replicates were analyzed individually. Even for the small effect size locus (NYVPLG9), error scenarios rarely (2 of 9000 cases) eliminated significant QTL detection, versus no replication (9 of 10). Thus, the benefits of data volume associated with high-throughput phenotyping technologies outweigh the cost of the increased errors tested here. Instead, focus should be spent on examining how each experimental replicate contributes to the result of the QTL mapping analysis.
Myocardial infarction with nonobstructive coronary arteries
Authors: Barnes Jonathan
Published: February 2025

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an important, often underrecognized working diagnosis. MINOCA is defined as an acute MI in a patient whose coronary angiography reveals no significant obstructive coronary artery disease. A comprehensive diagnostic approach beyond the initial coronary angiogram is essential for identifying this heterogeneous infarction pathophysiology. Distinguishing disease-specific causes affects patient management and prognosis, especially in female patients. This article provides an evidence-based overview of the tailored management strategies and ongoing clinical research likely to shape future guidelines.
Caring for youth in foster care
Authors: Quick Christina , Halasz Tracy W.
Published: February 2025

Providing comprehensive healthcare to children in foster care can be challenging. Youth placed in foster care are a vulnerable population of patients who often have complex trauma histories and chronic healthcare needs that are further compounded by fragmented and transient healthcare. With an estimated 368,000 children in foster care in the US in 2022 based on the most recently available national data, it is critical for providers to understand the challenges associated with providing care to this population and to know how to address them. This discussion provides healthcare providers with a practical, trauma-informed guide to caring for youth in foster care rooted in evidence-based practice and current guidelines.
Adopting national recommendations for clinical management of pediatric obesity in primary care
Authors: Davila Natalia , Garcia Julia , Reneau Marcelaine G. , Smith Whitney
Published: February 2025

The World Health Organization reports that more than 390 million children and adolescents have obesity, with the US facing a prevalence of 14 million among this population and incurring an annual medical cost of $1.3 billion. Childhood and adolescent obesity stems from genetic, environmental, and socioecological factors, indicating the need for an evolving approach to pediatric obesity management. The updated 2023 American Academy of Pediatrics guideline for evaluation and treatment of pediatric obesity advocates for a child-centric strategy, considering health equity, racism, weight bias stigmatism, and adverse childhood experiences. Management includes intensive health behavior and lifestyle treatment, partnership with communities to build comprehensive treatment programs, promotion of early intervention, consideration of pharmacotherapy for children age 12 years and older, selective use of bariatric surgery, screening for and treatment of comorbidities, integration of mental health treatment, and use of motivational interviewing to engage patients in their care. Pediatric primary care providers play a key role in identification of obesity and encouragement of obesity treatment. Proactive management of childhood obesity benefits individuals, families, and the nation. Early intervention holds the promise of substantial cost savings on obesity-related healthcare. Healthcare providers wield significant influence in reducing childhood morbidity and enhancing the overall health of US children and adolescents.
Prognostic Impact of Diabetes Mellitus and Extended Hepatectomy on Perihilar Cholangiocarcinoma
Authors: Shibamoto Jun , Otsuka Shimpei , Okawa Yuta , Ashida Ryo , Ohgi Katsuhisa , Kato Yoshiyasu , Dei Hideyuki , Uesaka Katsuhiko , Sugiura Teiichi
Published: February 2025

Objective:

To evaluate the prognostic impact of diabetes mellitus (DM) in patients who underwent resection for perihilar cholangiocarcinoma (PHCC) and the influence of remnant liver volumes on postoperative glycemic profiles and survival outcomes.

Background:

The impact of DM and extended hepatectomy on survival outcomes of patients with PHCC remains unclear.

Methods:

A total of 184 patients who underwent hepatectomy with extrahepatic bile duct resection for PHCC between 2002 and 2020 were retrospectively analyzed and divided into groups based on DM and future liver remnant (FLR) ≥40% or <40%. Survival outcomes and glycemic profiles were analyzed.

Results:

Patients with DM (n = 34) had significantly worse overall survival compared with those without DM (n = 150; median survival time: 23.3 vs 46.7 months; P = 0.003) although cancer-specific survival was comparable (P = 0.894). Patients with DM had a higher incidence of death from infections (P < 0.001). Multivariate analysis identified DM as an independent prognostic factor (hazard ratio, 1.742; P = 0.021). DM with FLR <40% (n = 11) exhibited worse survival (median survival time: 13.7 vs 35.0 months; P = 0.026) and a higher incidence of death from infections (P = 0.016) compared with those with FLR ≥40% (n = 23). The median glucose fluctuation was larger in patients with DM and FLR <40% (80 vs 39 mg/dL; P = 0.023).

Conclusions:

DM was an independent prognostic factor in patients with PHCC undergoing hepatectomy. DM and FLR <40% were associated with worse survival and larger glucose fluctuation postoperatively.
The ability of shock index to predict refractory postpartum haemorrhage
Authors: Daghmouri Mohamed Aziz , Repplinger Sébastien , Weiss Emmanuel , Bonnet Marie-Pierre , Le Guen Morgan , Dahmani Souhayl , Ducloy Bouthors Anne Sophie , Mebazaa Alexandre , Gayat Etienne , Deniau Benjamin
Published: February 2025

BACKGROUND

The predictability of severe and refractory postpartum haemorrhage (PPH) remains a challenge for clinicians and researchers.

OBJECTIVE

We aimed to evaluate the ability of the shock index to predict refractory PPH.

DESIGN

This study was a secondary analysis of a multicentre, prospective, observational study investigating the association between severe postpartum haemorrhage (PPH) and the subsequent development of mental disorders.

SETTING

Participants were patients who experienced severe PPH, characterised by blood loss of at least 1500 ml requiring the administration of sulprostone. The shock index, defined as the ratio of heart rate to SBP, was recorded at two time points: at the start of sulprostone infusion (T0) and at the time of the most severe symptoms after enrolment but before the occurrence of refractory PPH (T1). Refractory PPH was defined by the need for four or more blood products, interventional radiology, or laparotomy (excluding caesarean section).

THE MAIN OUTCOME

The predictive ability of the shock index was assessed using univariate and multivariate logistic regression and area under the receiver operating characteristic curve (AUROC).

RESULTS

From November 2014 to November 2016, 332 patients experienced severe PPH, of which 316 were included in the final analysis. The prevalence of refractory PPH was 35.4% (112/316). We found that high shock index levels at T0 were independently associated with the occurrence of refractory PPH: odds ratio (OR) 3.07 [95% confidence interval (CI), 1.22 to 7.89, P = 0.017]. In addition, high shock index levels at T1 were also independently associated with the occurrence of refractory PPH: OR 5.28 (95% CI, 2.25 to 12.8), P < 0.001. The AUROC of shock index levels measured at T0 and T1 were 0.614 (95% CI, 0.549 to 0.678) and 0.681 (95% CI, 0.616 to 0.746), respectively.

CONCLUSION

The shock index measured at the start of sulprostone infusion and at the worst time after enrolment, has poor discriminative power to predict this event.
Spatial single-cell proteomics landscape decodes the tumor microenvironmental ecosystem of intrahepatic cholangiocarcinoma
Authors: Hong Libing , Mei Jie , Sun Xuqi , Wu Yifan , Dong Zhen , Jin Yuzhi , Gao Liaoliao , Cheng Jinlin , Tian Weihong , Liu Chuan , Li Bin , Hu Pingping , Liu Lulu , Xin Shan , Dai Xiaomeng , Zhao Peng , Guo Rongping , Chen Minshan , Yun Jingping , Lin Bo , Wei Wei , Fang Weijia , Bao Xuanwen
Published: February 2025

Background & Aims

The prognoses and therapeutic responses of patients with intrahepatic cholangiocarcinoma (iCCA) depend on spatial interactions among tumor microenvironment (TME) components. However, the spatial TME characteristics of iCCA remain poorly understood. The aim of this study was to generate a comprehensive spatial atlas of iCCA using artificial intelligence-assisted spatial multiomics patterns and to identify spatial features associated with prognosis and immunotherapy.

Approach & Results:

Spatial multiomics, including imaging mass cytometry (IMC, n=155 in-house), spatial proteomics (n=155 in-house), spatial transcriptomics (n=4 in-house), multiplex immunofluorescence (mIF, n=20 in-house), single-cell RNA sequencing (scRNA-seq, n=9 in-house and n=34 public), bulk RNA-seq (n=244 public), and bulk proteomics (n=110 in-house and n=214 public), were employed to elucidate the spatial TME of iCCA. More than 1.06 million cells were resolved, and the findings revealed that spatial topology, including cellular deposition patterns, cellular communities, and intercellular communications, profoundly correlates with the prognosis of iCCA patients. Specifically, CD163hi M2-like resident-tissue macrophages suppress anti-tumor immunity by directly interacting with CD8+ T cells, resulting in poorer patient survival. Additionally, five spatial subtypes with distinct prognoses were identified, and potential therapeutic options were generated for these subtypes. Furthermore, a spatial TME deep learning system was developed to predict the prognosis of iCCA patients with high accuracy from a single 1-mm2 tumor sample.

Conclusions:

This study offers preliminary insights into the spatial TME ecosystem of iCCA, providing valuable foundations for precise patient classification and the development of personalized treatment strategies.
Traumatic Encephalopathy Syndrome: Head Impact Exposure and Blood Biomarkers in Professional Combat Athletes
Authors: Kleven Brooke D. Conway , Chien Lung-Chang , Cross Chad L. , Labus Brian , Bernick Charles
Published: February 2025

Objective: This study aimed to (1) determine whether there was an association between a diagnosis of traumatic encephalopathy syndrome (TES) and changes in three specific serum biomarkers, and (2) determine head impact exposure thresholds among both TES+ and TES− groups. Setting: Data were collected from Cleveland Clinic’s Professional Athletes Brain Health Study (PABHS). Participants: This study included 192 professional combat athletes, 35 years of age and older. Athletes must be actively fighting or retired with a minimum of 10 professional fights over their careers. Design/Intervention: This was a retrospective observational study of the PABHS longitudinal cohort. Main Measures: The generalized linear model with the generalized estimating equation for repeated measurements was used to compare various biomarkers between both active and retired TES− and TES+ groups. Results: The odds ratio for TES diagnosis was 5.44 (95% CI = 2.48, 11.94; P < .0001) among active fighters and 10.75 (95% CI = 3.52, 32.85; P < .0001) among retired fighters, indicating the odds for a TES diagnosis were over 5 times greater for active fighters with every fight completed at or beyond 30 professional fights. Retired fighters had 10 times greater odds of TES diagnosis with every fight completed at or beyond 15 professional fights. Likewise, the odds of a TES diagnosis were 2.0% (95% CI = 0.3, 3.1; P = 0.0039) greater with each pg/mL increase of glial fibrillary acidic protein (GFAP). No relationship was observed between a TES diagnosis and neurofilament light chain or P-tau231. Conclusion: This study provides preliminary evidence that progressively elevated levels of the GFAP blood biomarker increase the odds of a TES diagnosis among retired professional fighters. Further evaluation is required to improve clarity and understanding of the relationship between progressive changes in the GFAP blood biomarker and a TES diagnosis, specifically evaluating the duration of chronicity and exposure thresholds.
Plasma Microbial Cell-free DNA Sequencing for the Detection of Kingella kingae Pediatric Spinal Infections
Authors: Ahmed Asim A. , Park Sarah Y. , Smollin Matthew J. , Lindner Martin S. , Sarmiento Clemente Adriana , Del Valle Penella Ana , Laufer P. Marcelo , Sanchez-Vegas Carolina , Cotilla Manuel R. , Melish Marian E. , Trieu Connie , Kabani Nazia A. , Cooper Joshua , Lloyd Audrey R. , Kimberlin David W. , Arnold John C. , Jordan-Villegas Alejandro , Patterson Lori E. , Foster Catherine E. , Yagupsky Pablo
Published: February 2025

Background:

Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe’s fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae.

Methods:

Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age <18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results:

Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11–23 months). All case-patients had vertebral osteomyelitis with 9 having spondylodiscitis. Compared with usual care tests, mcfDNA sequencing was significantly more sensitive (McNemar’s test 6.25, 2-tailed P = 0.0133). It was the only method of microbiological diagnosis in 9 patients, providing results in a median of 2.5 days (range 2–5 days) from sample collection. K. kingae mcfDNA was detected despite antibiotic pretreatment in 5/5 case-patients. Pathogen-tailoring of antimicrobial coverage was undertaken in 9 children.

Conclusion:

Plasma mcfDNA sequencing offers a rapid, noninvasive method of detecting K. kingae causing pediatric spinal infections. This culture-independent approach may facilitate diagnosis, despite antibiotic pretreatment and subsequently targeted therapy and potentially obviate the need for biopsy.
Comparative evaluation of clinical results and patient-reported outcomes of enhanced monofocal and conventional monofocal intraocular lenses
Authors: Kabura Ryota , Takeshita Tetsuji , Furushima Kyoka , Iwasaki Rumi , Fukuda Rikako , Amikawa Hinako , Oshika Tetsuro
Published: February 2025

Purpose:

To evaluate and compare visual performance of two enhanced monofocal intraocular lenses (IOLs), XY1-EM (Vivinex Impress, Hoya) and DIB00V (TECNIS Eyhance, Johnson & Johnson) with that of a conventional monofocal IOL, XY-1 (Vivinex, Hoya).

Setting:

Kamiamakusa General Hospital, Kumamoto, Japan.

Methods:

A retrospective analysis was conducted on 130 eyes from 75 patients, including 46 eyes (27 patients) implanted with XY1-EM, 47 eyes (26 patients) with DIB00V, and 37 eyes (22 patients) with XY-1.

Results:

Corrected-distance visual acuity was comparable across all three groups. Both enhanced monofocal IOLs (XY1-EM and DIB00V) demonstrated significantly superior distance-corrected visual acuity at 70 cm and 50 cm compared to the conventional monofocal IOL (XY1). The rates of spectacle independence were also significantly higher in the enhanced monofocal IOL groups. In a direct comparison between the two enhanced monofocal IOLs, XY1-EM exhibited a significantly better defocus curve at -1.5D than DIB00V. Patients reported higher subjective satisfaction for "reading a newspaper" and "speed of adaptation to daily vision" in the XY-1 group compared to the DIB00V group.

Conclusions:

The new enhanced monofocal IOL, Vivinex Impress XY1-EM, demonstrated significantly improved intermediate visual acuity compared to the conventional monofocal IOL. It also showed slightly superior intermediate visual acuity and higher subjective satisfaction compared to the other enhanced monofocal IOL evaluated in this study.
Females Have a Higher Prevalence of Severe and Dysplastic Fundic Gland Polyposis
Authors: Altfillisch Charles , Meyer Chase , Yuquimpo Kyle , Jackson Katy , Saha Souvik , Montgomery Robert , Madan Rashna , Buckles Daniel , Bansal Ajay
Published: February 2025

Goals:

The purpose of this study was to determine risk factors associated with the development of Fundic Gland Polyps (FGP) and its association with gastric cancer.

Background:

Gastric cancer incidence is increasing and may be linked to PPIs. FGP﻿ are ﻿ common and a possible intermediary between PPI use and the risk of gastric cancer.

Study:

This single-center retrospective case-control study compared multiple risk factors between cases with FGP﻿ and controls between January 1, 2021 and December 31, 2021. Severe FGP was defined by innumerable, diffuse, or >50 polyps by endoscopic reporting and dysplasia by histopathology. Patient outcomes with severe polyposis and dysplasia were reviewed. Gastrectomy specimens and endoscopic reports were reviewed for FGP in an independent cohort of patients with known gastric cancer. Univariate and multivariate models using logistic regression were constructed.

Results:

The main logistic regression model included 591 participants (330 cases and 261 controls). Increasing age [OR: 1.02 (1.01 to 1.03)] and >2 years of PPI use [OR: 2.76 (1.72 to 4.47)] were associated with increased risk of FGP whereas smoking was protective [OR: 5.41 (2.58 to 12.24)]. Most patients with severe FGP (87.5%), low-grade (77%), and high-grade dysplasia (80%) were females. No patients developed gastric cancer on follow-up (mean: 13.9 mo). None of the patients within an independent cohort of gastric cancers diagnosed between January 1, 2021 and December 31, 2021 had FGP.

Conclusions:

Although FGP are equally common among sexes, severe and dysplastic FGP are more common among females, but none progressed to cancer. These data could be useful to counsel patients with FGP.
The Role of Artificial Intelligence Combined With Digital Cholangioscopy for Indeterminant and Malignant Biliary Strictures
Authors: McCarty Thomas R. , Shah Raj , Allencherril Ronan P. , Moon Nabeel , Njei Basile
Published: February 2025

Background:

Current endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopic-based diagnostic sampling for indeterminant biliary strictures remain suboptimal. Artificial intelligence (AI)-based algorithms by means of computer vision in machine learning have been applied to cholangioscopy in an effort to improve diagnostic yield. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic performance of AI-based diagnostic performance of AI-associated cholangioscopic diagnosis of indeterminant or malignant biliary strictures.

Methods:

Individualized searches were developed in accordance with PRISMA and MOOSE guidelines, and meta-analysis according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve (SROC).

Results:

Five studies (n=675 lesions; a total of 2,685,674 cholangioscopic images) were included. All but one study analyzed a deep learning AI-based system using a convoluted neural network (CNN) with an average image processing speed of 30 to 60 frames per second. The pooled sensitivity and specificity were 95% (95% CI: 85-98) and 88% (95% CI: 76-94), with a diagnostic accuracy (SROC) of 97% (95% CI: 95-98). Sensitivity analysis of CNN studies (4 studies, 538 patients) demonstrated a pooled sensitivity, specificity, and accuracy (SROC) of 95% (95% CI: 82-99), 88% (95% CI: 72-95), and 97% (95% CI: 95-98), respectively.

Conclusions:

Artificial intelligence-based machine learning of cholangioscopy images appears to be a promising modality for the diagnosis of indeterminant and malignant biliary strictures.
Taking the Guess Work Out of Endoscopic Polyp Measurement
Authors: Kerbage Anthony , Souaid Tarek , Singh Kailash , Burke Carol A.
Published: February 2025

Colonoscopy is a crucial tool for evaluating lower gastrointestinal disease, monitoring high-risk patients for colorectal neoplasia, and screening for colorectal cancer. In the United States, over 14 million colonoscopies are performed annually, with a significant portion dedicated to post-polypectomy follow-up. Accurate measurement of colorectal polyp size during colonoscopy is essential, as it influences patient management, including the determination of surveillance intervals, resection strategies, and the assessment of malignancy risk. Despite its importance, many endoscopists typically rely on visual estimation alone, which is often imprecise due to technological and human biases, frequently leading to overestimations of polyp size and unnecessarily shortened surveillance intervals. To address these challenges, multiple tools and technologies have been developed to enhance the accuracy of polyp size estimation.

The review examines the evolution of polyp measurement techniques, ranging from through-the-scope tools to computer-based and artificial intelligence-assisted technologies.
Glucagon like peptide-1 receptor agonists as a promising therapeutic option of metabolic dysfunction associated steatotic liver disease and obesity: hitting two targets with one shot
Authors: Kaya Eda , Syn Wing-Kin , Manka Paul
Published: February 2025

Purpose of review

Obesity and type 2 diabetes mellitus (T2DM) are significant global health challenges, closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in treating T2DM and obesity, but their potential for managing MASLD is still being explored. This review aims to examine the current progress in using GLP-1RAs for MASLD treatment and evaluate emerging dual and triple hormonal agonists as future therapeutic options.

Recent findings

GLP-1RAs have been effective in controlling blood sugar levels, promoting weight loss, and improving cardiovascular and kidney function. Furthermore, they have shown potential benefits for liver function in patients with MASLD. GLP-1, a key incretin hormone, influences glucose metabolism, appetite, and insulin sensitivity while affecting gastric emptying and potentially reducing fat deposition in the liver. Recent developments in GLP-1RAs include various formulations with different administration and dosing options, expanding their therapeutic use.

GLP-1RAs have become central to the management of T2DM, obesity, and possibly MASLD due to their ability to lower HbA1c, aid in weight reduction, and provide cardiovascular protection. As research continues, dual and triple hormonal agonists are emerging as the next evolution of incretin-based therapies, offering promising new strategies for addressing MASLD in the future.
The role of gluten and wheat in irritable bowel syndrome and noncoeliac gluten or wheat sensitivity
Authors: van Gils Tom , Simrén Magnus
Published: February 2025

Purpose of review

The role of gluten and wheat in irritable bowel syndrome (IBS) is unclear, whereas it plays a key-role in the diagnosis and treatment of noncoeliac gluten or wheat sensitivity (NCGWS). This review aims to provide the most recent insights in pathophysiological mechanisms and to summarize the evidence for a gluten- or wheat-free diet in IBS and NCGWS.

Recent findings

The exact role of gluten and wheat in IBS and NCGWS pathophysiological mechanisms remains complex. However, recent findings suggest a role for antigliadin antibodies to identify those IBS patients who may benefit from a gluten-free diet and low levels of fecal calprotectin to differentiate IBS and NCGWS. The importance of gut-brain interactions in self-reported gluten sensitive individuals was shown by a strong nocebo effect, although a role of gluten could not be excluded. Evidence for a gluten-free diet remains debatable in both conditions, whereas a wheat-free diet may have more potential, especially in NCGWS.

IBS and NCGWS are two closely related conditions with a complex and largely unrevealed pathophysiology. The role of gluten may have been overestimated in the past, but it is likely that certain wheat components, along with gut-brain interactions, play a role in both conditions.
Measuring kidney stone volume – practical considerations and current evidence from the EAU endourology section
Authors: Grossmann Nico C. , Panthier Frederic , Afferi Luca , Kallidonis Panagiotis , Somani Bhaskar K.
Published: February 2025

Purpose of review

This narrative review provides an overview of the use, differences, and clinical impact of current methods for kidney stone volume assessment.

Recent findings

The different approaches to volume measurement are based on noncontrast computed tomography (NCCT). While volume measurement using formulas is sufficient for smaller stones, it tends to overestimate volume for larger or irregularly shaped calculi. In contrast, software-based segmentation significantly improves accuracy and reproducibility, and artificial intelligence based volumetry additionally shows excellent agreement with reference standards while reducing observer variability and measurement time. Moreover, specific CT preparation protocols may further enhance image quality and thus improve measurement accuracy. Clinically, stone volume has proven to be a superior predictor of stone-related events during follow-up, spontaneous stone passage under conservative management, and stone-free rates after shockwave lithotripsy (SWL) and ureteroscopy (URS) compared to linear measurements.

Although manual measurement remains practical, its accuracy diminishes for complex or larger stones. Software-based segmentation and volumetry offer higher precision and efficiency but require established standards and broader access to dedicated software for routine clinical use.
The Association Between Quality and Safety of Nursing Care: A Correlational Study
Authors: Bartoníčková Daniela , Kohanová Dominika , Mazalová Lenka , Holušová Lucie , Lorencová Nikola , Fišerová Anna , Greaves P. Jane
Published: February 2025

Background:

Patient safety culture is critical for ensuring quality nursing care, yet its role is not fully understood in various health care settings.

Purpose:

To explore the association between patient safety culture and nurses’ perceptions of the quality of nursing care provided in hospitals in the Czech Republic.

Methods:

A correlation study was conducted with 535 nurses from 6 hospitals using the questionnaires Hospital Survey on Patient Safety Culture 2.0 and Scale of Perception of Nursing Activities that Contribute to Nursing Care Quality.

Results:

Significant associations were found between nursing care quality and dimensions of patient safety culture. Supervisor, manager, or clinical leader support; reporting patient safety events; and handoffs and information exchange were important predictors for improving nursing care quality (P < .05).

Conclusions:

Management support, adverse events, effective communication, and teamwork are essential for improving patient safety and have a significant impact on the quality of nursing care provided and must be properly supported.