bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining Spine Cancer Pain Syndromes: A Systematic Review and Proposed Terminology
Authors: Pahuta Markian , Laufer Ilya , Lo Sheng-fu Larry , Boriani Stefano , Fisher Charles , Dea Nicolas , Weber Michael H. , Chou Dean , Sahgal Arjun , Rhines Laurence , Reynolds Jeremy , Lazary Aron , Gasbarrinni Alessandro , Verlaan Jorrit-Jan , Gokaslan Ziya , Bettegowda Chetan , Sarraj Mohamed , Barzilai Ori ,   On behalf of the AO Spine Knowledge Forum Tumor
Published: January 2025

Study Design

Systematic Review.

Objectives

Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients.

Methods

We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists.

Results

Our literature search identified 3515 unique citations. Through title and abstract screening, 3407 citations were excluded, resulting in 54 full-text citations for review. Pain in cancer patients is typically described as nociceptive pain (somatic vs visceral), neurologic pain and treatment related pain.

Conclusions

We consolidate the terminology used in the literature and consolidated into clinically relevant nomenclature of biologic tumor pain, mechanical pain, radicular pain, neuropathic pain, and treatment related pain. This review helps standardize terminology for cancer-related pain which may help clinicians identify pain generators.
Connections and Circulation: Routes and Commodities in the British Assam–Burma Frontier
Authors: Dzüvichü Lipokmar
Published: January 2025

This article examines the significance of connections and circulation in the British Assam–Burma frontier by focusing on the complex networks and patterns of interactions between geographical areas and the routes through which people and commodities circulated within and across the frontiers of empire. It will study the forms of connections, route networks and commodities in circulation across the imperial frontiers and, in doing so, explore how these processes linked the region to the local as well as wider webs of flows. Further, it will examine how a range of experiences ensued in the frontier tracts through these complex processes. Rather than an ‘isolated’ or ‘inaccessible’ region, a focus on the routes, connections and circulation of commodities shows how the region was not only linked to various localities and spaces but also shaped by various forms of exchanges, movements and interactions at various levels and scales. For instance, as this article will highlight, a focus on the circulation of commodities such as cowries and beads suggests how these commodities not only formed important merchandises in the exchange networks. Cowries and beads were also acquired and adapted by various social groups, whereby they became important carriers and indicators of ascribing meanings, identities and social practices in the Assam–Burma frontier. In the process, these commodities became constitutive of the experiences that were entangled in the dynamic processes of community-building and cultural formation. The article will as such examine how routes and commodities formed vital components that connected people, places and exchange networks, and how these processes, in turn, historically mediated socio-cultural spaces and practices.
Brachial Plexus Birth Injury: Treatment and Interventions
Authors: O’Shea Grace , Patel Sonia S. , Mailey Brian A.
Published: January 2025

Introduction: Brachial plexus birth injury (BPBI) is a condition affecting newborns and involves damage to the nerve fibers compromising the brachial plexus during birth. Although most newborns recover spontaneously, a large subset require surgery to regain function, and others will have permanent disability despite intervention. Deciding when to pursue surgical intervention remains a challenge for clinicians treating BPBI. Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and MEDLINE databases. A total of 24 primary and secondary sources were chosen for inclusion following full-text assessments. All sources were analyzed to provide a comprehensive review on the development of BPBI treatments and interventions over time. Results: Spontaneous recovery can be achieved in many cases of BPBI, but most patients require physical therapy and other forms of treatment to avoid muscle imbalance and prevent contracture formation. In addition to physical therapy, the most common non-surgical interventions include botulinum toxin injections and splinting. In cases requiring surgery, clinicians may use several tests and diagnostic imaging to aid in decision making. Common surgical interventions for BPBI include nerve grafting, nerve transfers, and muscle and tendon transfers. Conclusion: Most newborns recover from BPBI within the first 3 months of life. However, some require treatment to restore optimal function. In general, non-surgical interventions should be the primary course of treatment, and surgery should be avoided unless the patient is deemed unable to recover with any other treatment.
Evaluation of the Soda Tax on Obesity and Diabetes in California: A Cost-Effectiveness Analysis
Authors: Zhao Fan , Gidwani Risha , Wang May C. , Chen Liwei , Nianogo Roch A.
Published: January 2025

Introduction. Consumption of sugar-sweetened beverages (SSBs) contributes to weight gain, obesity, and diabetes. Soda tax has been proposed to reduce consumption of SSBs. What remains unclear is whether the soda tax has an effect on health and health care costs. We evaluated the cost-effectiveness of a 1-cent-per-ounce soda tax on obesity and diabetes in California. Methods. A microsimulation state-transition model was used to evaluate the cost-effectiveness of the soda tax. Health outcomes were measured in quality-adjusted life-years (QALYs). Health care costs were projected from 2015 to 2035. Results. In a simulated cohort of Californian adults, the soda tax policy prevented 2.28 million cases of overweight (95% confidence interval [CI] −0.06 to 6.63) and 0.49 million cases of obesity (95% CI −0.19 to 1.18). From the health care perspective, the incremental cost-effectiveness ratio of the soda tax was $124,839 dollars per QALY (95% CI −1,151,983 to 557,660). From the health care perspective, the soda tax policy was cost-effective 80% of the time in the probabilistic sensitivity analysis using a willingness-to-pay threshold of $100,000 per QALY. Conclusions. The 1-cent-per-ounce soda tax reduced the number of obesity cases, diabetes cases, and related complications. In addition, the soda tax policy implemented in California was cost-effective most of the time.

Highlights

Question: What remains unclear is whether the soda tax has an effect on health and health care costs. Findings: The 1-cent-per-ounce soda tax reduced the number of obesity cases, diabetes, and related complications. In addition, the soda tax policy brought large amounts of revenue. Meaning: This study provides additional evidence regarding the health care costs and cost-effectiveness related to the implementation of a soda tax.
Exploring the associations between street-view green space quantity and quality, and influenza in Guangzhou, China through machine learning and spatial regression: A socio-economic equity perspective
Authors: Wang Ruoyu , Sun Ming-Kun , Yi Shengao , Grekousis George , Dong Guang-Hui
Published: January 2025

Existing studies have highlighted that green space is associated with non-communicable diseases. However, scant attention has been paid to the association between green space quantity and quality with communicable diseases. Here, we explore the relationships between green space and influenza cases in Guangzhou, China, using street-view green (SVG) space quantity and SVG-quality indicators, which offer a better assessment of urban green space than traditional remote sensing metrics. Influenza cases were collected from hospitalization records, while street-level green space was measured by street-view data and deep neural networks. The neighbourhood deprivation index (NDI) was also used as a proxy for neighbourhood-level socio-economic status. We employed the Random Effects-Eigenvector Spatial Filtering (RE-ESF) regression model because of its usefulness in handling spatial dependence. Findings showed that higher levels of SVG-quantity and quality are associated with a lower number of influenza cases, implying a negative relationship. Specifically, the marginal effects for SVG indicate that influenza may decrease by 145 cases for every unit increase in SVG-quantity, and by 11 cases for every unit increase in SVG-quality. In terms of planning, this could mean that though green quality is essential for the aesthetic part of urban life, quantity is much more critical concerning the containment of influenza. In addition, SVG-quantity and quality moderated the positive association between NDI and influenza cases. In other words, people in more deprived neighbourhoods were more influenced by SVG-quantity and quality compared to people living in less deprived areas. This means that more green space should be added to such neighbourhoods. We also observed that the association between SVG-quality and influenza cases was weaker for females, people aged between 18 and 45, and employed people. Because influenza is the most common pandemic worldwide, green space at the street level should be considered when promoting equitable public health and this study provides quantifiable evidence for the negative effect of green space quantity and quality over influenza cases.
Lower expression of BIN1's neuronal isoform in vulnerable excitatory neurons increases risk in Alzheimer's disease
Authors: Ranganathan Rajesh , Li Siwen , Sapozhnikov Georgy , Wang Shoutang , Song You-Qiang
Published: January 2025

Background: 

Neurons in Alzheimer's disease (AD) experience elevated DNA damage, with DNA repair sites enriched at enhancer regions of genes essential for neuronal survival. Excitatory neurons in the cortical superficial layers expressing CUX2 and RORB (Cux2+/Rorb+), are selectively vulnerable in AD, but their relationship to single nucleotide polymorphisms (SNPs) in AD genome-wide association studies (GWAS) is unclear.

Objective: 

This study aimed to identify and characterize functional AD-GWAS SNPs using single-nucleus RNA sequencing data, focusing on selectively vulnerable neurons and DNA repair hotspots.

Methods: 

Filters were applied to identify candidate SNPs based on overlap with repair hotspots, RNA expression, transcription factor binding, AD association, and epigenetic significance. In vitro assays and analyses of large datasets from bulk RNA-seq (n = 1894), proteomics (n = 400), and single-nucleus RNA-seq (n = 424, 1.6 M cells) were conducted.

Results: 

BIN1 SNP, rs78710909, met multiple criteria - located in an AD-GWAS locus, repair hotspot, and promoter region. rs78710909C exhibits 1.52× higher AD risk and 5.4× differential transcription factor binding. In vitro, rs78710909C shows greater enhancer activity and weaker p53 but stronger E2F1 binding. BIN1's neuronal isoform is neuroprotective, but its AD expression is lower (p < 0.01). Moreover, only in AD and Cux2+/Rorb + neurons, rs78710909C is associated with a lower average BIN1 neuronal isoform ratio (p < 0.01). The genes upregulated in neurons with lower neuronal isoform ratio were associated with the hallmarks of AD pathology.

Conclusions: 

In a disease-relevant mechanism, the BIN1 SNP rs78710909C is associated with a lower ratio of BIN1's neuronal isoform which increases the vulnerability of specific excitatory neurons in AD patients.
Sleep disturbances and their correlation with memory impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment
Authors: Cui Linyang , Wan Yahui , Lu Yunyao , Meng Meng , Zhang Nan
Published: January 2025

Background

Episodic memory impairment is the core clinical feature of patients with typical Alzheimer's disease (AD) at an early stage. Since sleep plays a very important role in memory consolidation, the relationship between memory impairment and sleep disorders in AD patients is worthy of investigation.

Objective

To investigate sleep disturbances and their correlations with memory impairment in patients with AD and amnestic mild cognitive impairment (aMCI).

Methods

Forty-three patients with AD, 43 patients with aMCI, and 43 cognitively unimpaired controls (CUCs) were recruited and subjected to memory assessment via the Hopkins Verbal Learning Test–Revised and objective sleep evaluation via polysomnography (PSG).

Results

The total sleep time and the percentages of nonrapid eye movement (NREM) sleep stage 3 (N3) and the rapid eye movement (REM) were lower, while the percentages of NREM sleep stage 2 (N2) were greater in the AD and aMCI groups than in the CUC group (all p < 0.01). Compared with the CUC group, the AD group also presented a longer sleep latency and higher NREM sleep stage 1 (N1) percentage, apnea-hypopnea index (AHI), periodic limb movements during sleep index (PLMSI), and arousal index (AI). Both total learning scores and delayed recall scores were positively correlated with the N3 sleep percentage and negatively correlated with the AHI and PLMSI (all p < 0.01). Recognition scores were positively correlated with the N3 sleep percentage and negatively correlated with the AI (all p < 0.01).

Conclusions

Our results suggest that sleep disturbance is correlated with learning and memory disability in AD and aMCI patients. PSG is useful for screening and monitoring AD.
Comparative Analysis of Spreader Grafts and Spreader Flaps on Intranasal Drug Delivery Efficiency to Posterolateral Nasal Wall
Authors: Kim Michelle H. , Martin Hannah L. , Avashia Yash J. , Sicard Ryan M. , Chiang Harry , Woodard Charles R. , Marcus Jeffrey R. , Frank-Ito Dennis O.
Published: January 2025

Background: This study compared the impact of spreader grafts (SG) and spreader flaps (SF) on the transport of intranasal drug delivery to target the posterolateral nasal wall. Method: SG and SF were each performed in sequence on two cadaveric specimens after soft tissue elevation technique. Computed tomography scans were acquired following each procedure to generate anatomic models for computational fluid dynamics simulation of intranasal sprays under the following conditions: inhalation rate (15 and 30 L/min), spray velocity (1, 5, and 10 m/s), spray released location (center, lateral, medial, top, and bottom), head position (upright, tilted-forward, tilted-backward, and supine), and particle diameter (1-100 µm). Percentage of particles deposited on the posterolateral nasal wall were calculated. Results: For Specimen 1, highest posterolateral wall depositions were Pre-Op: left = 74%, right = 74%; SF: left = 53%, right = 22%; SG: left = 60%, right = 61%. For Specimen 2, highest posterolateral wall depositions were Pre-Op: left = 25%, right = 83%; SF: left = 29%, right = 76%; SG: left = 14%, right = 72%. In general, posterolateral wall deposition was higher at 30 L/min inhalation rate and at 1 m/s spray velocity. Conclusions: Drug delivery targeting the posterolateral nasal wall appears to be dependent on many factors. However, midvault nasal reconstruction does not increase drug delivery to the posterolateral nasal wall.
Tracking the long-term outcomes of a supported employment internship programme for autistic adults without a learning disability
Authors: Ashworth Maria C , Heasman Brett , Crane Laura , Remington Anna
Published: January 2025

Supported employment initiatives with work experience (e.g. internships) can increase employment rates for autistic people. However, such initiatives (a) are often not evidence-based, (b) focus on quantitative outcomes such as employment rates and (c) examine group-level changes without considering individual variability. Considering the effects that (un)employment can have on autistic people's well-being, it is important to examine the wider impact of supported employment initiatives. This study evaluated the long-term employment and wider outcomes of autistic adults who engaged with a supported employment internship initiative at group and individual levels. Autistic adults without a learning disability ( N = 27, ‘interns’; Mage = 23.3) involved in internships across seven organisations, participated in the study. Interns reported on (a) employment-related characteristics, (b) daily living skills, (c) general self-efficacy, (d) quality of life and (e) mental health pre-internship at six and 12–24 months post-internship. The overall employment rate increased from 25.93% to 55.56% from pre- to 12–24 months post-internship, and income and number of hours worked also increased. There were improvements in daily living skills, but other wider outcome measures did not change significantly at a group level, despite individual variability. This evidence has important implications for supporting long-term outcomes for autistic people.
Prevalence and Sociodemographic Factors Associated with Overweight and Obesity Among Adults in Colombia: A Pooled Analysis
Authors: Castro-Prieto Paula Andrea , Spijker Jeroen J. A.
Published: January 2025

Given the increased prevalence of overweight and obesity in adults in Colombia, estimating the effect of sociodemographic factors on overweight and obesity is crucial for creating and implementing public health policies. A pooled analysis was performed using a multinomial logistic regression model through Colombian Nutritional Situation Surveys held in 2010 and 2015. The study included Colombian adults between 18 and 64 years old (n = 162,119). Overall, the prevalence of obesity increased from 16.47 percent in 2010 to 18.67 percent in 2015, being higher in women than in men in both surveys. Multinomial logistic regression analysis revealed that the most critical factor of being overweight and obese were older age, having a higher level of education, being engaged in household activities, and living in regions other than the country's capital. Additionally, for obesity, belonging to the Afro Colombian racial-ethnic group and being a woman were associated with an increased probability. In conclusion, these results provide more information on the sociodemographic factors related to overweight and obesity, which will help focus public health policies on higher-risk populations, such as racial-ethnic communities.
Some reflections on ‘How should we think about globalization in a postglobalization era?’
Authors: Desai Manisha
Published: January 2025

In ‘How Should We Think About Globalization in A Post Globalization Era?’, Victor Roudometof posits that since 9/11 – that is, the start of the twenty-first century – we have been living in a postglobalization era, by which he means an era marked by the breakdown of the 1990s Washington consensus of neoliberal, economic policy-oriented globalization. He then outlines ways to think about globalization for this new era via redefining integral versus interactive globalization beyond modernization and westernization. While moving away from modernization as telos and Western-centrism is a good idea, one cannot erase the colonial/modern project and its impact globally. Perhaps in the future we may see a different kind of integral and interactive globalization, but for now the modern/colonial imprint still reverberates, and dismissing it is irresponsible.
Globalization – everything, everywhere, all the time
Authors: Nederveen Pieterse Jan
Published: January 2025

Is globalization still a proper descriptor? Does globalization also include satellites and space shuttles in outer space? Recent work widens the definition of globalization: ‘Globalization is the trend of greater worldwide connectivity of people over time and the awareness of this happening.’ This shift of emphasis to connectivity as the driving force and the key point, implies that globalization is just one of the many forms this takes. Important is not the form, which changes according to circumstances, but connectivity and what it aspires and achieves. In an era of comeback of geopolitics this may be an important course adjustment.
Natural language processing to identify suicidal ideation and anhedonia in major depressive disorder
Authors: Vance L. Alexander , Way Leslie , Kulkarni Deepali , Palmer Emily O. C. , Ghosh Abhijit , Unruh Melissa , Chan Kelly M. Y. , Girdhari Amey , Sarkar Joydeep
Published: January 2025

Background

Anhedonia and suicidal ideation are symptoms of major depressive disorder (MDD) that are not regularly captured in structured scales but may be captured in unstructured clinical notes. Natural language processing (NLP) techniques may be used to extract longitudinal data on suicidal behaviors and anhedonia within unstructured clinical notes. This study assessed the accuracy of using NLP techniques on electronic health records (EHRs) to identify these symptoms among patients with MDD.

Methods

EHR-derived, de-identified data were used from the NeuroBlu Database (version 23R1), a longitudinal behavioral health real-world database. Mental health clinicians annotated instances of anhedonia and suicidal symptoms in clinical notes creating a ground truth. Interrater reliability (IRR) was calculated using Krippendorff’s alpha. A novel transformer architecture-based NLP model was trained on clinical notes to recognize linguistic patterns and contextual cues. Each sentence was categorized into one of four labels: (1) anhedonia; (2) suicidal ideation without intent or plan; (3) suicidal ideation with intent or plan; (4) absence of suicidal ideation or anhedonia. The model was assessed using positive predictive values (PPV), negative predictive values, sensitivity, specificity, F1-score, and AUROC.

Results

The model was trained, tested, and validated on 2,198, 1,247, and 1,016 distinct clinical notes, respectively. IRR was 0.80. For anhedonia, suicidal ideation with intent or plan, and suicidal ideation without intent or plan the model achieved a PPV of 0.98, 0.93, and 0.87, an F1-score of 0.98, 0.91, and 0.89 during training and a PPV of 0.99, 0.95, and 0.87 and F1-score of 0.99, 0.95, and 0.89 during validation.

Conclusions

NLP techniques can leverage contextual information in EHRs to identify anhedonia and suicidal symptoms in patients with MDD. Integrating structured and unstructured data offers a comprehensive view of MDD’s trajectory, helping healthcare providers deliver timely, effective interventions. Addressing current limitations will further enhance NLP models, enabling more accurate extraction of critical clinical features and supporting personalized, proactive mental health care.
Adaptive evolution of stress response genes in parasites aligns with host niche diversity
Authors: Cruz-Laufer Armando J. , Vanhove Maarten P. M. , Bachmann Lutz , Barson Maxwell , Bassirou Hassan , Bitja Nyom Arnold R. , Geraerts Mare , Hahn Christoph , Huyse Tine , Kasembele Gyrhaiss Kapepula , Njom Samuel , Resl Philipp , Smeets Karen , Kmentová Nikol
Published: January 2025

Background

Stress responses are key the survival of parasites and, consequently, also the evolutionary success of these organisms. Despite this importance, our understanding of the evolution of molecular pathways dealing with environmental stressors in parasitic animals remains limited. Here, we tested the link between adaptive evolution of parasite stress response genes and their ecological diversity and species richness. We comparatively investigated antioxidant, heat shock, osmoregulatory, and behaviour-related genes (foraging) in two model parasitic flatworm lineages with contrasting ecological diversity, Cichlidogyrus and Kapentagyrus (Platyhelminthes: Monopisthocotyla), through whole-genome sequencing of 11 species followed by in silico exon bait capture as well as phylogenetic and codon analyses.

Results

We assembled the sequences of 48 stress-related genes and report the first foraging (For) gene orthologs in flatworms. We found duplications of heat shock (Hsp) and oxidative stress genes in Cichlidogyrus compared to Kapentagyrus. We also observed positive selection patterns in genes related to mitochondrial protein import (H
sp) and behaviour (For) in species of Cichlidogyrus infecting East African cichlids—a host lineage under adaptive radiation. These patterns are consistent with a potential adaptation linked to a co-radiation of these parasites and their hosts. Additionally, the absence of cytochrome P450 and kappa and sigma-class glutathione S-transferases in monogenean flatworms is reported, genes considered essential for metazoan life.

Conclusions

This study potentially identifies the first molecular function linked to a flatworm radiation. Furthermore, the observed gene duplications and positive selection indicate the potentially important role of stress responses for the ecological adaptation of parasite species.
The Calicophoron daubneyi genome provides new insight into mechanisms of feeding, eggshell synthesis and parasite-microbe interactions
Authors: Clancy Shauna M. , Whitehead Mark , Oliver Nicola A. M. , Huson Kathryn M. , Kyle Jake , Demartini Daniel , Irvine Allister , Santos Fernanda Godoy , Kajugu Paul-Emile , Hanna Robert E. B. , Huws Sharon A. , Morphew Russell M. , Waite J. Herbert , Haldenby Sam , Robinson Mark W.
Published: January 2025

Background

The rumen fluke, Calicophoron daubneyi, is the major paramphistome species infecting ruminants within Europe. Adult flukes reside within the rumen where they are in direct contact with a unique collection of microorganisms. Here, we report a 1.76-Gb draft genome for C. daubneyi, the first for any paramphistome species.

Results

Several gene families have undergone specific expansion in C. daubneyi, including the peptidoglycan-recognition proteins (PGRPs) and DM9 domain-containing proteins, which function as pattern-recognition receptors, as well as the saposin-like proteins with putative antibacterial properties, and are upregulated upon arrival of the fluke in the microbe-rich rumen. We describe the first characterisation of a helminth PGRP and show that a recombinant C. daubneyi PGRP binds to the surface of bacteria, including obligate anaerobes from the rumen, via specific interaction with cell wall peptidoglycan. We reveal that C. daubneyi eggshell proteins lack L-DOPA typically required for eggshell crosslinking in trematodes and propose that C. daubneyi employs atypical eggshell crosslinking chemistry that produces eggs with greater stability. Finally, although extracellular digestion of rumen ciliates occurs within the C. daubneyi gut, unique ultrastructural and biochemical adaptations of the gastrodermal cells suggest that adult flukes also acquire nutrients via uptake of volatile fatty acids from rumen fluid.

Conclusions

Our findings suggest that unique selective pressures, associated with inhabiting a host environment so rich in microbial diversity, have driven the evolution of molecular and morphological adaptations that enable C. daubneyi to defend itself against microorganisms, feed and reproduce within the rumen.
Potential drug targets for asthma identified through mendelian randomization analysis
Authors: Chen Xingxuan , Shang Yu , Shen Danting , Shi Si , Wen Zhe , Li Lijuan , Chen Hong
Published: January 2025

Background

The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).

Methods

We utilized GWAS data from the UK Biobank (comprising 56,167 patients and 352,255 control subjects) and the FinnGen cohort (including 23,834 patients and 228,085 control subjects). Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid proteins were derived from recently published GWAS. Bidirectional Mendelian randomization analysis, Steiger filtering, colocalization, and phenotype scanning were employed for reverse causal inference detection, further substantiating the Mendelian randomization results. A protein-protein interaction network was also constructed to reveal potential associations between proteins and asthma medications.

Results

Under Bonferroni significance conditions, Mendelian randomization analysis revealed causal relationships between seven proteins and asthma. In plasma, we observed that an increase of one standard deviation in IL1R1[1.30 (95% CI 1.20–1.42)], IL7R[1.07 (95% CI 1.04–1.11)], ECM1[1.03 (95% CI 1.02–1.05)], and CD200R1[1.18 (95% CI 1.09–1.27)] were associated with an increased risk of asthma, while an increase in ADAM19 [0.87 (95% CI 0.82–0.92)] was found to be protective. In the brain, each 10-fold increase in IL-6 sRa [1.29 (95% CI 1.15–1.45)] was associated with an increased risk of asthma, while an increase in Layilin [0.61 (95% CI 0.51–0.73)] was found to be protective. None of the seven proteins exhibited a reverse causal relationship. Colocalization analysis indicated that ECM1 (coloc.abf-PPH4 = 0.953), IL-6 sRa (coloc.abf-PPH4 = 0.966), and layilin (coloc.abf-PPH4 = 0.975) shared the same genetic variation as in asthma.

Conclusion

A causal relationship exists between genetically determined protein levels of IL1R1, IL7R, ECM1, CD200R1, ADAM19, IL-6 sRa, and Layilin (LAYN) and asthma. Moreover, the identified proteins may serve as attractive drug targets for asthma, especially ECM1 and Layilin (LAYN). However, further research is required to comprehensively understand the roles of these proteins in the occurrence and progression of asthma.
Factors affecting communication time in an emergency medical communication centers
Authors: Bensoussan Melisande , Vanier Mathilde , Loeb Thomas , Boutet Jérémie , Lapostolle Frédéric , Reuter Paul-Georges
Published: January 2025

Background

Emergency Medical Communication Centres (EMCCs) play a crucial role in emergency care by ensuring timely responses through telephone triage. However, extended communication times can impede accessibility, patient triage, and decision-making. Identifying the factors influencing communication duration is essential for improving EMCC efficiency.

Objective

This study aims to identify temporal, human, and contextual factors associated with prolonged communication times in an EMCC where decision-making is conducted by physicians.

Methods

We conducted a retrospective observational study of all calls received at a French EMCC between March 1 and December 31, 2019. A total of 108,548 patient medical files were analyzed, excluding calls from medical personnel or hospitals. We examined the total communication time (from call initiation to decision) and the medical communication time (physician involvement). Bivariate and multivariate logistic regressions were used to identify factors associated with prolonged communication times.

Results

The median total communication time was 7 min [IQR 5–11], and the median medical communication time was 3 min [IQR 2–4]. Psychiatric reasons for calling (OR = 1.75) and elderly patients (OR = 1.58) were associated with longer communication times. Calls leading to medical advice (OR = 1.48) and calls during weekends or nighttime were also significant factors. Conversely, calls for trauma or from nursing homes, and those handled by emergency physicians, were associated with shorter durations.

Conclusion

Several factors influence communication times in EMCCs, including patient demographics, reason for the call, and time of day.
Suboptimal but intact integration of Bayesian components during perceptual decision-making in autism
Authors: Fazioli Laurina , Hadad Bat-Sheva , Denison Rachel N. , Yashar Amit
Published: January 2025

Background

Alterations in sensory perception, a core phenotype of autism, are attributed to imbalanced integration of sensory information and prior knowledge during perceptual statistical (Bayesian) inference. This hypothesis has gained momentum in recent years, partly because it can be implemented both at the computational level, as in Bayesian perception, and at the level of canonical neural microcircuitry, as in predictive coding. However, empirical investigations have yielded conflicting results with evidence remaining limited. Critically, previous studies did not assess the independent contributions of priors and sensory uncertainty to the inference.

Method

We addressed this gap by quantitatively assessing both the independent and interdependent contributions of priors and sensory uncertainty to perceptual decision-making in autistic and non-autistic individuals (N = 126) during an orientation categorization task.

Results

Contrary to common views, autistic individuals integrated the two Bayesian components into their decision behavior, and did so indistinguishably from non-autistic individuals. Both groups adjusted their decision criteria in a suboptimal manner.

Limitations

This study focuses on explicit priors in a perceptual categorization task and high-functioning adults. Thus, although the findings provide strong evidence against a general and basic alteration in prior integration in autism, they cannot rule out more specific cases of reduced prior effect – such as due to implicit prior learning, particular level of decision making (e.g., social), and level of functioning of the autistic person.

Conclusions

These results reveal intact inference for autistic individuals during perceptual decision-making, challenging the notion that Bayesian computations are fundamentally altered in autism.
Beyond the perception of wind only as a meteorological hazard: importance of mechanobiology for biomass allocation, forest ecology and management
Authors: Dlouhá Jana , Moulia Bruno , Fournier Meriem , Badel Eric , Constant Thiéry
Published: January 2025

Key message

Although global changes are expected to intensify the impact of wind as a hazard, recent studies have emphasized the critical role wind plays in tree growth and development. Wind-induced swaying generates strains that the tree perceives, triggering a process known as thigmomorphogenesis. This process alters the tree’s growth patterns and wood properties to enhance its mechanical stability. Thus, wind functions not only as a hazard but also as a growth factor, enabling the tree to acclimate to wind loads and reduce its mechanical risk.

Despite the significant role of thigmomorphogenesis in tree growth and carbon allocation, this process remains largely overlooked in forest ecology and management models. We strongly advocate for the integration of wind-induced strain sensing, the primary driver of thigmomorphogenesis, alongside established environmental factors in tree and forest growth models, as well as in instrumented forest stands aimed at studying the effects of environmental factors on tree growth. This crucial step is essential for a comprehensive understanding of forest growth dynamics and for informed decision-making in forest management.
Influences of freezing and thermal cyclic loading on physical and mechanical properties of marble
Authors: Faramarzi Lohrasb , Dehghani Bijan , Azhari Amin
Published: January 2025

In this study, marble specimens were used to investigate the effects of freezing and thermal cyclic loading on physical and mechanical properties. For this purpose, four types of loading were considered, including freezing-cooling (F–C), heating–cooling (H-C), freezing-cooling-heating (F–C-H) and heating–cooling-freezing (H-C-F). The changes observed in physical and mechanical properties of the marble were analyzed in temperature extend shifting from − 30 °C to 160 °C. To achieve this goal, two marble blocks with a dimension of 30 × 30 × 30 cm3 were selected. Then, compressive and shear wave velocities, uniaxial compressive strength (UCS), Young’s modulus (E) and Brazilian tensile strength (BTS) were measured and compared in different loading conditions. Results showed that the number of freezing-cooling cycles influenced the mechanical properties of the marble. With an increase in the loading cycles, both compressional and shear wave velocities of the marble decreased. The highest reduction in tensile strength was observed in heating–cooling cycles. That is to say, the thermal loading of rock specimens caused weakening, thereby increasing the micro-crack density in the marble specimens by means of thermally shocks. It was observed that the increase in the number of loading cycles, brings about a huge decline in the marble dynamic modulus. The damage index (D) is introduced to reflect the variation of the mechanical properties and ultrasonic wave velocities of the samples before and after the thermal cyclic loading. In all freezing and thermal cyclic loading conditions, the main and predominant failure mechanism was shear failure.
Combinatorial protective effect of Cinnamomum verum and Stingless Bee Honey against oxidative stress in isoproterenol-induced cardiotoxicity in Wistar rats
Authors: Padmanabhan Arul Mozhi , Doss Victor Arokia
Published: January 2025

Background

Cardiac hypertrophy (CH) is a prevalent consequence of cardiovascular disease, necessitating treatment with synthetic medications that often have adverse effects. Natural products, like Cinnamomum verum (CV) and Stingless Bee Honey (SBH), rich in phenolic compounds, hold promise as safer alternatives. In this study, we investigated the potential cardioprotective effects of CV bark and honey produced by Stingless bee in male Wistar rats. In a 7-day controlled study, rats were randomly assigned into seven treatment groups, receiving either saline (Group I), isoproterenol (ISO) (Group II) or ISO combined with drug interventions of Losartan (Group III), CV (Group IV) and SBH (Group V) along with several combined regimens (Group VI & VII). Biochemical assays were conducted to measure antioxidant enzyme activities (Superoxide Dismutase, Catalase, Glutathione Peroxidase), non-enzymatic antioxidants (Vitamin C, Vitamin E, Reduced Glutathione), inflammatory markers, and oxidative stress levels. Histopathological analysis was also performed. stress markers in cardiac tissues, shedding light on potential therapeutic interventions.

Results

ISO induces myocardial oxidative stress, characterized by reduced antioxidants, increased oxidative stress and inflammatory markers with elevated collagen content. Our results show that co-administration of CV + SBH effectively attenuated ISO-induced myocardial oxidative stress, outperforming individual CV or SBH administration in restoring antioxidant levels and normalizing oxidative stress and inflammatory markers.

Conclusions

The results from this study underscore the importance of advancing research on the combination of CV and SBH, which hold significant promise as synergistic therapeutic agents in the treatment of complex diseases, potentially informing future healthcare policies and clinical practices.
The mental health impact of repeated COVID-19 enforced lockdowns in England: evidence from the UK Household Longitudinal Study
Authors: Dhensa-Kahlon Rashpal K. , Wan Siu Tim , Coyle-Shapiro Jacqueline A.-M. , Teoh Kevin Rui-Han
Published: January 2025

Background

Research shows initial COVID-19 lockdowns increased population mental distress. Yet, the mental health impact of repeated lockdowns in England remains unknown.

Aims

To: (a) explore changes in population mental health symptoms over the COVID-19 pandemic period (March 2020 to March 2021) in England, comparing this with trends from a decade before (2009–2019) as well as after (2021–2023); (b) compare the mental health impact of each of the three lockdowns in England with periods of eased restrictions, determining who was most affected; (c) examine the impact of demographics and distinct time periods on the prevalence of mental health symptoms.

Method

A secondary analysis of a national longitudinal cohort study, utilising data from Waves 1–13 of the UK Household Longitudinal Study and from Waves 1–9 of the COVID-19 Survey. Mental health was assessed using the 12-item General Health Questionnaire. Student t-tests and logistical regressions were conducted.

Results

There was a significant increase in the prevalence of self-reported symptoms of mental health during England's pandemic period, encompassing three lockdowns, compared with the average of rates from 10 years before. Rates of reported mental health symptoms were not significantly different across each lockdown, but were significantly higher than pre-pandemic rates, declining with eased restrictions. Rates from the end of lockdown to May 2023 revealed elevated mental health symptoms compared with pre-pandemic. Elevated symptoms were observed for women, people homeworking, those with health conditions, individuals aged 30–45 years and those experiencing loneliness.

Conclusion

Repeated lockdowns in England had a substantial impact on mental health, indicating requirements for ongoing mental health support.
Phase Ib Study of BI 836880 (VEGF/Ang2 nanobody) in Combination With Ezabenlimab (anti–PD-1 antibody) in Patients With Advanced or Metastatic Solid Tumors
Authors: Girard Nicolas , Felip Enriqueta , Kim Dong-Wan , Ghiringelli Francois , Lee Jong-Seok , Pons-Tostivint Elvire , Erzen Damijan , Zhu Zheng , Jappar Dilara , Pachón Paula , Meyer Tim
Published: January 2025

PURPOSE

This phase Ib study investigated the safety and antitumor activity of BI 836880, a bispecific nanobody targeting vascular endothelial growth factor and angiopoietin-2, and ezabenlimab, an anti–PD-1 antibody, in patients with advanced or metastatic solid tumors.

METHODS

This was an open-label, multinational study (ClinicalTrials.gov identifier:
NCT03468426
) conducted in two parts. Part 1 was a dose-escalation phase to determine the recommended phase II dose (RP2D) of BI 836880 in combination with ezabenlimab in patients with metastatic non–small cell lung cancer (mNSCLC). Part 2 was an expansion phase investigating the efficacy and safety of the combination at the RP2D in eight cohorts, on the basis of tumor type. The primary end point of part 2 was objective response rate (ORR).

RESULTS

Overall, 14 patients were recruited in part 1 and 238 in part 2. In part 1, the maximum tolerated dose of the combination was not reached; the RP2D was BI 836880 720 mg plus ezabenlimab 240 mg every 3 weeks. In part 2, the ORR was 18.9% across all cohorts. In the mNSCLC cohorts, ORRs were 16.7% (after checkpoint inhibitor [CPI] monotherapy) and 7.5% (after chemotherapy + CPI). Notably higher rates were seen in patients with glioblastoma (GBM; 22.6%); hepatocellular carcinoma (HCC) who had previously received sorafenib or lenvatinib (40.0%); and previously untreated HCC (25.8%). The combination was well tolerated; the most common adverse events in part 2 were asthenia (27.3%), hypertension (21.4%), and diarrhea (20.2%).

CONCLUSION

BI 836880 combined with ezabenlimab had a positive benefit-risk ratio, with a manageable safety profile and signs of antitumor activity across a wide range of tumor types, with particularly promising activity in patients with HCC and GBM.
Rapidly Growing Thyroid Schwannoma: Diagnostic Challenges and Management Strategies
Authors: Toloza Freddy J K , Filie Armando , Raffeld Mark , Kebebew Electron , Klubo-Gwiezdzinska Joanna , Gubbi Sriram
Published: January 2025

Thyroid nodules are one of the most commonly encountered conditions in clinical endocrinology. Most thyroid nodules are of epithelial origin. However, primary thyroid mesenchymal tumors (TMTs), arising from the mesenchymal tissue, are being increasingly recognized. More than 20 different forms of benign and malignant TMTs have been described in the literature. Thyroid schwannoma is an extremely rare type of TMT, with only a few cases reported to date, accounting for less than 1% of all schwannomas. It primarily affects adults, with no significant sex predilection, and is often discovered incidentally during evaluation for thyroid nodules. Due to its rarity, the clinical presentation and natural history remain poorly understood, underscoring the importance of histopathological examination for accurate diagnosis and management. We describe a case of a patient with thyroid schwannoma who was diagnosed and managed at our center, contributing valuable insights to the limited body of knowledge on this rare entity. This is followed by a detailed description of the clinical features, diagnosis, and management of thyroid schwannomas.
Circulating Cell-Free DNA in Metabolic Diseases
Authors: Pollastri Alessio , Kovacs Peter , Keller Maria
Published: January 2025

Metabolic diseases affect a consistent part of the human population, leading to rising mortality rates. This raises the need for diagnostic tools to monitor the progress of these diseases. Lately, circulating cell-free DNA (cfDNA) has emerged as a promising biomarker for various metabolic diseases, including obesity, type 2 diabetes, and metabolic-associated fatty liver disease. CfDNA is released from apoptotic and necrotic cells into the bloodstream and other body fluids, and it retains various molecular signatures of its tissue of origin. Thus, cfDNA load and composition can reflect tissue pathologies and systemic metabolic dysfunctions. In addition to its potential as a diagnostic biomarker, interest in cfDNA derives from its recently discovered role in adipose tissue inflammation in obesity. This review discusses detection methods and clinical significance of cfDNA in metabolic diseases.
Canonical Wnt signalling from the area opaca induces and maintains the marginal zone in pre-primitive-streak stage chick embryos
Authors: Fadaili Yara , Lu Hui-Chun , Lee Hyung Chul , Ryazapova Amra , Stern Claudio D.
Published: January 2025

In chick embryos before primitive streak formation, the outermost extra-embryonic region, known as the area opaca (AO), was generally thought to act only by providing nutrients and mechanical support to the embryo. Immediately internal to the AO is a ring of epiblast called the marginal zone (MZ), separating the former from the inner area pellucida (AP) epiblast. The MZ does not contribute cells to any part of the embryo but is involved in determining the position of primitive streak formation from the adjacent AP epiblast. Recently, it was discovered that the AO can induce an MZ from AP epiblast. Here, we explore the nature of this inductive signal. We find that WNT8C is highly expressed in the AO, whereas canonical Wnt pathway targets are enriched in the MZ, along with strong nuclear β-catenin localization. Using isolation and recombination experiments combined with gain- and loss-of-function by exogenous chemical modulators of the pathway, we reveal that Wnt signalling is essential for induction and maintenance of the MZ, as well as sufficient to induce MZ properties in AP epiblast. We propose that canonical Wnt signalling is responsible for induction of the MZ by the area opaca.