bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mpox: emergence following smallpox eradication, ongoing outbreaks and strategies for prevention
Authors: Bryant Amy E. , Shulman Stanford T. 
Published: January 2025

Purpose of review
This review focuses on the temporal relationship between the discontinuation of the global smallpox eradication effort with the rise of mpox in Africa and worldwide. It also discusses the global 2022 clade II mpox epidemic and the current 2024 clade I mpox outbreak. Newer findings on viral evolution and pathogenesis, plus current and future strategies for disease prevention, are reviewed.

Recent findings
The temporal association between the incidence of mpox and the World Health Organization's Global Smallpox Eradication Program (GSEP) is presented. The 2022 global mpox epidemic is discussed. Recent data show that clade IIb monkeypox virus (MPXV)-2022 has novel genetic features supporting a greater propensity for mutations that may be responsible for enhanced human-to-human transmissibility, increased disease severity and accelerated viral evolution. In 2023, another outbreak of mpox began in Africa, this time due to the potentially more virulent MPXV clade Ib strains. This outbreak remains ongoing in Africa, and clade Ib mpox cases have recently been reported elsewhere including the United States and Great Britain. The World Health Organization has deemed mpox to be a global public health emergency. Two smallpox vaccines are approved for mpox prevention in the United States; a third smallpox vaccine and an improved diagnostic test have recently received WHO Emergency Use authorization. Newer mRNA-based vaccines for evolving orthopoxvirus infections are discussed.

Summary
Vaccination to prevent smallpox provides immunologic cross-protection against infection with other members of genus Orthopoxvirus, including mpox. Discontinuation of the global smallpox eradication program in the 1980s and the subsequent waning of herd immunity contributed to the 2022 multinational epidemic of human clade IIb mpox infections. A second multinational outbreak with clade Ib MPXV is ongoing. Vaccination against smallpox remains the gold standard for mpox prevention, however newer multiepitope mRNA-based vaccines are in development and hold promise for prevention of mpox and other orthopoxvirus outbreaks.
Effect of Saline Sealing After CT-Guided Lung Biopsy on Pneumothorax and Hemoptysis
Authors: Zhang Xiaoxia , An Jianli , Wu Jingpeng , Jing Xiuxiu , Lu Hongzhi , Tian Ye 
Published: January 2025

Objective:
To confirm that saline sealing of the needle trace after computed tomography (CT)-guided lung biopsy reduces the incidence of pneumothorax and chest tube insertion, and to observe its effects on pulmonary hemorrhage and hemoptysis.

Materials and Methods:
Patients who underwent CT-guided lung biopsy at our hospital between January 2018 and January 2024 were included in the study. Patients were divided into 2 groups according to whether the needle trace was sealed with saline after tissue sampling. Patient baseline characteristics, lung lesion factors, procedural factors, pneumothorax rates, chest tube insertion rates, pulmonary hemorrhage rates, and hemoptysis rates were recorded.

Results:
The incidence of pneumothorax was 28.9% (38/132) and 15.8% (15/95) in groups A (control) and B (with sealed traces), respectively (P=0.002). The incidence of pneumothorax requiring chest tube insertion was significantly lower in group B than in group A (1.1% vs. 6.8%; P=0.048). The incidence of pulmonary hemorrhage was similar between the 2 groups (38.6% vs. 42.1%; P=0.599). No significant difference was observed in the hemoptysis of patients in groups A and B (6.8% vs. 10.5%; P=0.320). In the binary logistic regression analysis, significant risk factors for pneumothorax included lack of saline sealing, smaller lesion size, multiple passes through the pleura, and the lateral decubitus position. Smaller lesions and longer biopsy trace lengths were independent risk factors for hemoptysis.

Conclusions:
Sealing the needle trace with saline significantly reduced the incidences of pneumothorax and chest tube insertion due to pneumothorax. Moreover, it did not significantly increase the incidence of pulmonary hemorrhage or hemoptysis. This technique is recommended for use in CT-guided lung biopsies.
Refractory Psychosis as a Red Flag for End of Life in Individuals With Dementia With Lewy Bodies
Authors: Armstrong Melissa J. , Galvin James E. , Manning Carol , Boeve Bradley F. , Pontone Gregory M. , Taylor Angela S. , Patel Bhavana , Fleisher Jori E. , Maixner Susan M. 
Published: January 2025

Objectives:
Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life.

Methods:
We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death. We reviewed codebooks and quotes from 3 studies regarding end-of-life experiences in DLB to identify experiences that aligned with this phenotype.

Results:
In addition to the 4 cases, family caregivers in prior studies described prominent worsening of psychosis before death in some individuals with DLB. The worsening often occurred several months before death and was sometimes associated with rapid deterioration. Worsening psychosis was the prominent symptom and was not initially accompanied by cognitive or physical decline. In many cases, the refractory psychosis resulted in inpatient psychiatric hospitalization or residential care, but these scenarios were challenging because of the individual’s behavior.

Conclusion:
Refractory psychosis in DLB, particularly out of proportion to other symptoms, may be a signal of approaching the end of life. More research is needed to understand this phenomenon and to develop effective and safe treatments for psychosis in DLB.
Language Mapping With rTMS in Healthy Pediatric Patients
Authors: Vedala Kishore , Kadis Darren S. , Vannest Jennifer , Sino Sara , Horn Paul S. , Maue Ellen , Williamson Brady , Mangano Francesco T. , Leach James L. , Greiner Hansel M. 
Published: January 2025

Purpose:
Repetitive transcranial magnetic stimulation (rTMS) is a potentially effective, noninvasive tool for language mapping. However, there is a paucity of data in pediatric patients. In this study, we aimed to map language sites in healthy pediatric participants with navigated rTMS.

Methods:
Children aged 5 to 18 years underwent bilateral language mapping. Stimulation was delivered at 5 Hz during visual-naming and auditory verb-generation tasks in 1 to 2 second bursts. We targeted 33 standardized sites per hemisphere. In total, 34 participants completed the visual-naming task, and 27 participants completed the verb-generation task. Lateralization index (LI) and Wilcoxon signed-rank test were used to assess language lateralization. A difference of least squares means model was developed to determine the prevalence of visual-naming and verb-generation errors within lobar and hemispheric regions.

Results:
Weak left lateralization was observed for visual naming (LI 0.14; p = 0.038), and no lateralization was observed for verb generation (LI 0.08; p = 0.269). Using multiple least squares regression, left hemisphere errors were more likely to occur than right hemisphere errors for visual naming (OR 1.23; 95% CI 1.06–1.44), but no lateralization effect was observed for verb-generation errors (OR 1.11; 95% CI 0.93–1.27).

Conclusions:
rTMS is likely to identify bilateral or weakly left-lateralized language sites in pediatric patients during language tasks. Although rTMS can be a useful noninvasive method for identifying potential language-positive sites, our results in healthy controls suggest that it cannot be used as a singular method for language mapping in the preoperative setting.
Evaluation of p16/Ki- 67 cytology as triage test for high-risk HPV-positive women in a “see and treat strategy”
Authors: Onyango Calleb George , Ogonda Lilian , Guyah Bernard 
Published: January 2025

AbstractBackgroundAlthough high risk human papilloma virus DNA (hr-HPV-DNA) test is the primary tool for cervical cancer screening, with visual inspection with acetic acid (VIA) serving as a triage test where Pap cytology is not available, the low intra-observer agreement associated with VIA means its reliability is limited and a more efficient test is still required. The aim of this study was to compare the performance of p16/Ki-67 cytology with VIA in the detection of cervical precancer and the feasibility as an alternative triage in the “see and treat strategy”.MethodsIn a hospital-based cross-sectional study, we utilized stored provider-collected specimens from a previous study of women referred with cervical abnormalities to a tertiary hospital in Kisumu County, Kenya from February 2021 to November 2023. Specimens were tested with both Xpert and p16/ki-67 Immunostain. All hr-HPV positive women with cervical lesions were triaged using VIA and p16/Ki- 67 cytology. CIN2 or worse (≥CIN2) were defined as the clinical end points.ResultsThe p16/ Ki- 67 Immunostaining showed a statistically significant higher sensitivity (84.6% vs. 59.0%%), specificity (44.0% vs. 62.0%), positive predictive value (28.2% vs. 28.8%) and negative predictive value (91.7% vs. 85.3%) compared to VIA examination.ConclusionThe p16/Ki-67 immunostaining for the detection of ≥CIN2 has shown high sensitivity and high negative predictive value in our study, which is comparable to several previous findings; implying that the assay is superior to VIA in identifying ≥CIN2 and can serve as an alternative tool for triaging primary HPV-positive women in the current “see and treat” strategy.
The Association between Mental Health and Cognitive Ability: Evidence from The UK Household Longitudinal Study
Authors: Iqbal Syka , Waqas Muhammad , Yong Min Hooi , McGarrigle Ronan , Vaportzis Eleftheria 
Published: January 2025

AbstractThe relationship between poor mental health and cognitive impairments in older age is well- established. Social engagement also influences cognitive ability; however much of the research on this relationship has not accounted for the impact of mental health and demographic factors. This study examined the associations between cognitive ability and mental health in older adults, controlling for social interaction and socio-demographic factors. In total, 7,685 individuals aged 65 or older were drawn from the UK Household Longitudinal Study Understanding Society (1). Cognitive abilities were assessed using self-reports and performance on five tasks (immediate and delayed word recall, subtraction, number series and numerical ability). Mental health scores were derived from the General Health Questionnaire (GHQ-12). We controlled for social interaction, gender, ethnicity, educational background, marital status, number of children, and geographic location. We found positive relationships between mental health and all measures of cognitive ability except performance on subtraction and number series tasks. These relationships remained after controlling for social interaction. Demographic factors that contributed to the relationship between mental health and cognitive ability included being White, having higher education, being male for numerical tasks only, and being female, married or divorced for verbal memory tasks only. Overall, our results suggest that the relationship between mental health and cognitive abilities persists when controlling for social interaction alongside socio- demographic factors in older adults, underscoring the importance of addressing these factors in policies and interventions for healthy ageing.
How Users of Different Ages Rate a Mobile App for Self-Testing of Hearing
Authors: Pastucha Małgorzata , Gos Elżbieta , Kochanek Krzysztof , Skarżyński Henryk , Jedrzejczak W. Wiktor 
Published: January 2025

AbstractIntroductionTraditional diagnostic methods of hearing assessment, such as pure tone audiometry, may not be equally accessible to everyone due to geographical or mobility limitations. Utilizing a mobile application (app) for self-assessment of hearing is a promising alternative. However, the effectiveness of apps, as well as their usability across different age groups, remains largely unexplored. The objective of the present study was to assess, across different age groups, the usability of the “Hearing Test” app which allows self-testing of hearing on a mobile phone.Materials and methodsThe study was conducted on 77 participants from three age groups (16–39 years, 40–59 years, 60 years and older) who self-tested their hearing thresholds using the mobile app and who later underwent pure tone audiometry with an audiologist. The usability of the app was evaluated using a questionnaire based on the Mobile App Rating Scale (MARS), which was complemented by participant observation and interview.ResultsThe app generally yielded results comparable to pure tone audiometry. However, older age groups tended to report higher levels of difficulty across several usability dimensions. Specifically, the oldest group rated the app lower in terms of functionality (M = 2.30; SD = 1.27) and engagement-customization (M = 2.11; SD = 1.28). For the oldest participants, the greatest difficulties related to installation (48%), and interpretation of results (26%). None of the participants aged 60 or older were able to complete the test independently, in contrast to 67% of the youngest participants and 28% of the middle-aged who did not require assistance. All age groups expressed a preference for a conventional hearing test over an app-based assessment, although the youngest group showed the greatest openness to using mobile apps.ConclusionsThe “Hearing Test” app has demonstrated its potential as a tool for initial hearing assessment, particularly among younger users. However, older individuals often encounter difficulties with installation, interpretation of results, and overall usability. Adapting the interface to meet the specific needs of older users, including user-friendly tutorials and clear presentation of results, is crucial for enhancing its usability.
Systematic identification of context-dependent gene-essentiality in Glioblastoma: The GBM-CoDE platform
Authors: Foster Mitchell T , Ewing Ailith , Frame Margaret , Brennan Paul M , Khamseh Ava , Beentjes Sjoerd V , Carragher Neil O , Semple Colin A 
Published: January 2025

AbstractGlioblastoma (GBM) is a heterogeneous and aggressive brain tumour that is invariably fatal despite maximal treatment. Genetic or transcriptomic ‘biomarkers’ could be used to stratify patients for treatments, however, pairing biomarkers with appropriate therapeutic ‘targets’ is challenging. Consequently, therapeutics have not yet been optimised for specific GBM patient subsets. Here we integrate genome-wide CRISPR/Cas9 knockout screening and genetic-annotation data for 60 distinct patient-derived, IDHwildtype, adult GBM cell lines, quantifying the essentiality of 15,145 genes. We describe a novel method using Targeted Learning, to estimate the effect size of GBM-relevant biomarkers on context-dependent gene essentiality (GBM-CoDE). We derive multiple target-biomarker pair hypotheses, which we release in an accessible platform to accelerate translation to biomarker-stratified clinical trials. Two of these (WWTR1 with EGFR mutation/amplification, and VRK1 with VRK2 expression suppression) have been validated in GBM, implying that our additional novel findings may be valid. Our method is readily translatable to other cancers of unmet need.
RIG-I Stimulation Enhances Effector Function and Proliferation of Primary Human CD8 T Cells
Authors: Mohamed Adham Abuelola , Wallerath Christina , Hunkler Charlotte , Hartmann Gunther , Stankovic Sanda , Brooks Andrew G , Schlee Martin 
Published: January 2025

AbstractCytotoxic CD8 T lymphocytes (CTL) are crucial in antiviral immune responses. However, their recruitment to infection sites renders them at risk of viral infection that could modulate their effector activity. CTL express RIG-I that detects cytosolic viral RNA and subsequently induce antiviral gene expression. Here, we investigated how influenza A virus (IAV) infection influence TCR-dependent effector responses. IAV infection of CTL stimulated RIG-I, and activated downstream pathways including TBK1 and NF-⍰B, resulting in type-I interferon secretion. Transfection of CTL with a pure RIG-I ligand, tri-phosphorylated double stranded RNA(3p-dsRNA), not only stimulated these pathways but also enhanced CTL proliferationin vitroand protected them from IAV infection. Analogous with a positive effect on CD8 effector function, both IAV infection and RIG-I ligand transfection enhanced CTL degranulation and cytokine secretion. Conversely, activation of CTL via CD3/CD28-crosslinking increased their susceptibility to IAV infection. Altogether, RIG-I stimulation either by IAV infection or 3p-dsRNA transfection promoted cell intrinsic antiviral pathways and enhanced CD8 effector functions. These findings suggest that RIG-I agonists could enhance and prolong CTL effector function in immunotherapy.
FastCCC: A permutation-free framework for scalable, robust, and reference-based cell-cell communication analysis in single cell transcriptomics studies
Authors: Hou Siyu , Ma Wenjing , Zhou Xiang 
Published: January 2025

AbstractDetecting cell-cell communications (CCCs) in single-cell transcriptomics studies is fundamental for understanding the function of multicellular organisms. Here, we introduce FastCCC, a permutation-free framework that enables scalable, robust, and reference-based analysis for identifying critical CCCs and uncovering biological insights. FastCCC relies on fast Fourier transformation-based convolution to computep-values analytically without permutations, introduces a modular algebraic operation framework to capture a broad spectrum of CCC patterns, and can leverage atlas-scale single cell references to enhance CCC analysis on user-collected datasets. To support routine reference-based CCC analysis, we constructed the first human CCC reference panel, encompassing 19 distinct tissue types, over 450 unique cell types, and approximately 16 million cells. We demonstrate the advantages of FastCCC across multiple datasets, most of which exceed the analytical capabilities of existing CCC methods. In real datasets, FastCCC reliably captures biologically meaningful CCCs, even in highly complex tissue environments, including differential interactions between endothelial and immune cells linked to COVID-19 severity, dynamic communications in thymic tissue during T-cell development, as well as distinct interactions in reference-based CCC analysis.
Metabolic Adaptations Rewire CD4 T Cells in a Subset-Specific Manner in Human Critical Illness with and without Sepsis
Authors: Stier Matthew T. , Sewell Allison E. , Mwizerwa Erin L. , Sim Chooi Ying , Tanner Samantha M. , Nichols Casey M. , Durai Heather H. , Jennings Erin Q. , Lindau Paul , Wilfong Erin M. , Newcomb Dawn C. , Bastarache Julie A. , Ware Lorraine B. , Rathmell Jeffrey C. 
Published: January 2025

ABSTRACTHost immunity in sepsis has features of hyperinflammation together with progressive immunosuppression, particularly among CD4 T cells, that can predispose to secondary infections and ineffectual organ recovery. Metabolic and immunologic dysfunction are archetypal findings in critically ill patients with sepsis, but whether these factors are mechanistically linked remains incompletely defined. We characterized functional metabolic properties of human CD4 T cells from critically ill patients with and without sepsis and healthy adults. CD4 T cells in critical illness showed increased subset-specific metabolic plasticity, with regulatory T cells (Tregs) acquiring glycolytic capacity that stabilized suppressive markers FOXP3 and TIGIT and correlated with clinical illness severity. Single-cell transcriptomics identified differential kynurenine metabolism in Tregs, which was validatedex vivoas a mechanism of Treg glycolytic adaptation and suppressive rewiring. These findings underscore immunometabolic dysfunction as a driver of CD4 T cell remodeling in sepsis and suggest therapeutic avenues to restore an effective immune response.
Kinesin-8/Kip3 requires beta tubulin tail for depolymerase activity
Authors: Alemany Kaitlin , Johnson Samantha , Moore Jeffrey K. 
Published: January 2025

AbstractCarboxy-terminal tails (CTTs) of tubulin proteins are sites of regulating microtubule function. We previously conducted a genetic interaction screen and identified Kip3, a kinesin-8 motor, as potentially requiring the β-tubulin CTT (β-CTT) for function. Here we use budding yeast to define how β-CTT promotes Kip3 function and the features of β-CTT that are important for this mechanism. We find that β-CTT is necessary for Kip3 depolymerase activity, but not for microtubule binding and motility. Mutant yeast cells lacking β-CTT show increased accumulation of Kip3 at plus ends and along microtubules, but no increase in catastrophe when Kip3 is overexpressed.In vitroexperiments show that the β-CTT is necessary for Kip3 to form a tight complex with soluble tubulin but is unnecessary for Kip3 to bind tubulin in the microtubule lattice. These results suggest a model in which β-CTT promotes Kip3 depolymerase activity by supporting a Kip3-tubulin binding state that is only accessible at the microtubule plus end or in solution.
Incident Stroke in Pediatric Sickle cell Anemia Despite Overall Improved Transcranial Doppler Velocity in a Ugandan Hydroxyurea Trial: Antecedent and ongoing risks
Authors: Wambaka Bill , Mpungu Amiirah , Mboizi Vincent , Kalibbala Dennis , Nambatya Grace , Murungi Susan , Kabatabaazi Maxencia , Nakafeero Maria , Kasirye Phillip , Munube Deogratias , Namazzi Ruth , Idro Richard , Green Nancy S. 
Published: January 2025

AbstractIntroductionTranscranial doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher-resource regions, targeting interventions for highest velocity (“abnormal”). We sought to identify additional stroke risk factors in Uganda.MethodsWe conducted a 30-month open-label single-arm Ugandan hydroxyurea trial, dose-escalated to maximum tolerated dose, aimed to test brain protection for children aged 3-9 years with SCA. Study procedures included history, clinical stroke examination and prospective TCD and laboratory assessments.ResultsOverall, 264 children received study HU, mean age 5.6±1.7, hemoglobin 7.8±1.2g/dL, fetal hemoglobin (HbF) 11.9±8.1%, enrolment TCD maximum velocity 148.4±29.3cm/second; 15 (5.7%) had abnormal TCD. Mean TAMV at trial completion was131.9±SD25.7 cm/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person years); Two had enrolment HbF ≤3.1%, 2 had low oxygen saturation (90%), 1 had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis or uncertain cause. At trial completion, 8 additional participants had a higher risk TCD category than at enrolment.ConclusionEffectiveness of TCD screening for stroke prevention may vary by region, as no participant with incident stroke was at highest risk. Antecedent and/or ongoing SCA-related risks of anemia, low HbF, hypoxemia, infections and/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify highest stroke risk in the region, and need for primary stroke prevention from early and continuous hydroxyurea therapy.