bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations
Authors: Jago Matthew J. , Soley Jake K. , Denisov Stepan , Walsh Calum J. , Gifford Danna R. , Howden Benjamin P. , Lagator Mato 
Published: January 2025

Abstract
A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique – Quantitative Mutational Scan sequencing (QMS-seq) – that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E. coli strains exposed to ciprofloxacin, cycloserine, or nitrofurantoin and identify 812 resistance mutations, many in genes and regulatory regions not previously associated with resistance. We find that multi-drug and antibiotic-specific resistance are acquired through categorically different types of mutations, and that minor genotypic differences significantly influence evolutionary routes to resistance. By quantifying mutation frequency with single base pair resolution, QMS-seq informs about the underlying mechanisms of resistance and identifies mutational hotspots within genes. Our method provides a way to rapidly screen for resistance mutations while assessing the impact of multiple confounding factors.
α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia
Authors: Olari Lia-Raluca , Liu Sichen , Arnold Franziska , Kühlwein Julia , Gil Miró Marta , Updahaya Ajeet Rijal , Stürzel Christina , Thal Dietmar Rudolf , Walther Paul , Sparrer Konstantin M. J. , Danzer Karin M. , Münch Jan , Kirchhoff Frank 
Published: January 2025

Abstract
HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies show that α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.
Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome
Authors: Horti-Oravecz Klaudia , Bozsik Anikó , Pócza Tímea , Vereczkey Ildikó , Strausz Tamás , Tóth Erika , Sedlackova Tatiana , Rusnakova Diana , Szemes Tomas , Likó István , Oláh Edit , Butz Henriett , Patócs Attila , Papp János , Grolmusz Vince Kornél 
Published: January 2025

Abstract
Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its’ pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS.
Stability indicating RP-HPLC technique for simultaneous estimation of nirmatrelvir and ritonavir in their new copackaged dosage form for COVID-19 treatment
Authors: Yassin Mohamed G. , Roshdy Aya , Marie Aya A. 
Published: January 2025

Abstract
RP-HPLC technique was developed and optimized for simultaneous identification and estimation of nirmatrelvir (NIR) and ritonavir (RIT) in their new copackaged tablet. Stability of nirmatrelvir (NIR) was studied after exposure to different five stress conditions; alkali, acid, heat, photo and oxidation degradation. The chromatographic separation was achieved using VDSpher PUR 100 ODS (4.6-mm x 15-mm), 3.5 μm column and mixture of 0.03 M potassium di-hydrogen phosphate buffer pH 4 and acetonitrile (45:55, v/v) as mobile phase. The column temperature was set at 40 °C, flow rate at 1mL/min and UV detection at 215 nm. The NIR and RIT retention times were 3.94 ± 0.08 min and 9.08 ± 0.1 min, respectively. Linear relationship was established in range of (1.5–105 µg/mL) for NIR and (1–70 µg/mL) for RIT with good reproducibility. The found mean percentage recoveries of nirmatrelvir (NIR) and ritonavir (RIT) were 100.03% and 99.85%, respectively. The developed method shows very good sensitivity as the LOQ and LOD were found to be 3.001 & 0.990 µg/mL, respectively for NIR and 2.765 & 0.912 µg/mL, respectively for RIT. The developed approach was validated concerning to ICH guidelines and applied successfully for the simultaneous estimation of NIR and RIT in their new copackaged dosage from. The results of assay using the proposed approach were compared statistically to the results found by applying the published one with good agreement.
Understanding pectin cross-linking in plant cell walls
Authors: Obomighie Irabonosi , Prentice Iain J. , Lewin-Jones Peter , Bachtiger Fabienne , Ramsay Nathan , Kishi-Itakura Chieko , Goldberg Martin W. , Hawkins Tim J. , Sprittles James E. , Knight Heather , Sosso Gabriele C. 
Published: January 2025

Abstract
Pectin is a major component of plant cells walls. The extent to which pectin chains crosslink with one another determines crucial properties including cell wall strength, porosity, and the ability of small, biologically significant molecules to access the cell. Despite its importance, significant gaps remain in our comprehension, at the molecular level, of how pectin cross-links influence the mechanical and physical properties of cell walls. This study employs a multidisciplinary approach, combining molecular dynamics simulations, experimental investigations, and mathematical modelling, to elucidate the mechanism of pectin cross-linking and its effect on cell wall porosity. The computational aspects of this work challenge the prevailing egg-box model, favoring instead a zipper model for pectin cross-linking, whilst our experimental work highlights the significant impact of pectin cross-linking on cell wall porosity. This work advances our fundamental understanding of the biochemistry underpinning the structure and function of the plant cell wall. This knowledge has important implications for agricultural biotechnology, informing us about the chemical properties of plant pectins that are best suited for improving crop resilience and amenability to biofuel extraction by modifying the cell wall.
Traumatic Brain Injury in College Students: Exploring Associations Between Social–Emotional Functioning and Fatigue
Authors: Riccardi Jessica Salley , Bradfield Lydia 
Published: January 2025

Purpose:
The purpose of this research study was to explore the associations between social–emotional functioning and fatigue for college students with a likely history of traumatic brain injury (TBI).

Method:

Twenty college students (
n
= 13 with a likely history of TBI) completed the online survey measures for this study. Participants completed questions related to demographic and injury characteristics, friendship, emotional support, emotional and behavioral dyscontrol, and fatigue.

Results:
For all domains, participants in the TBI and no-TBI groups reported functioning near the population mean, with no significant differences in functioning based on group. When analyzing only participants with TBI, greater fatigue was significantly correlated with less emotional support and greater emotional and behavioral dyscontrol. Friendship was not significantly correlated to emotional support or fatigue.

Conclusions:
The results provide unique insights into functioning during college for individuals who experienced their TBI as a teenager. These findings can inform future research that investigates emotional support as a management strategy to reduce fatigue and emotional and behavioral dyscontrol in larger samples of students in the chronic stages of recovery from TBI.
Yield management for the cinema industry
Authors: Bär Sören , Rasch Teresa , Strohmenger Michael , Kurscheidt Markus 
Published: January 2025

Abstract
Cinema operators have so far behaved more conservatively in terms of their price management. In the course of the digital transformation, there are many opportunities for price innovations. The implementation of yield management strategies in the cinema industry would have a positive impact on revenue and capacity utilization and can both strengthen the competitive situation of cinemas and contribute to increasing profitability. It is essential to determine what the number or proportion of discounted tickets should be and how many tickets can be sold at the regular price. This can be calculated using the critical fractile method, which assumes that the demand follows the normal distribution in a certain period and the distribution parameters are known. In this paper, the number of tickets to be offered at the regular price is calculated based on the evaluation of statistical data on visitor numbers, occupancy rates and prices of the German cinema industry and a leading German cinema chain.
Vortex-induced vibration energy harvesting with tandem square bluff bodies: Spacing ratio effects
Authors: Chen Yuansheng , Qi Zheng , Ji Hongli , Du Jianzhou , Zhao Pengcheng , Li Longting 
Published: January 2025

The horizontal (L/D) and vertical H/D) spacing ratios of square bluff bodies are critical parameters influencing the efficiency of vortex-induced vibration (VIV) wind energy harvesting. This study investigates a tandem stationary square bluff body (SSBB) and a vibrating square bluff body under various spacing configurations using ANSYS/FLUENT simulations. The results show that without SSBB, the root-mean-square (RMS) voltage generated by the piezoelectric patches increases consistently with wind speed. However, with SSBB, RMS voltage initially decreases and then increases as L/D rises, reaching a minimum at L/D = 4.5. At optimal configurations (L/D = 6.5, H/D = 0.5) and a wind speed of 9 m/s, the RMS voltage achieves a maximum value, improving by 34.43% compared to the configuration without SSBB. Experimental validation confirms the simulation results. This finding will be a significant fundamental for future design of VIV wind energy harvesting devices.
Advancements in flow control using plasma actuators: a comprehensive review
Authors: Karthikeyan K V , Harish R 
Published: January 2025

Abstract
The practical challenges related to aerodynamics, such as transition delay, drag reduction, lift enhancement, turbulence management, and flow separation delay, have led to an increasing the application of plasma actuators in aeronautics for flow control. The significance of plasma actuators in these applications arises from their unique characteristics, including the absence of moving parts, lower mass compared to traditional devices like vortex generators, slats, and flaps, and rapid response. For over a decade, the term ‘plasma’ actuator has played a crucial role in discussions regarding flow control in fluid dynamics. In particular, mechanisms utilizing Dielectric Barrier Discharge (DBD) have demonstrated effectiveness in controlling airflow at atmospheric pressure. These actuators produce a vector field of body force that interacts with the momentum of the external flow, enabling effective flow control. With advanced designs and an improved understanding of the underlying physics, plasma actuators demonstrate effectiveness not only at low speeds but also at supersonic, transonic, and high subsonic Mach numbers. Considering these advancements, a thorough review of plasma actuator models was conducted, formulating governing equations with insights drawn from existing literature. The assessment of the effectiveness of DBD plasma actuator involved discussions exploring its performance in both streamline and bluff body applications. Additionally, deliberations included an exploration of the most suitable mode for transonic and supersonic flow, particularly in the context of nanosecond dielectric barrier discharge plasma actuators. The review extended to cutting-edge plasma actuators, including plasma synthetic jet actuators, plasma flaps, and plasma vortex generators, providing insights into their advancements and applications.
Exploring photo-excited states of aromatic sulfones for efficient near-infrared-activated photothermal cancer therapy
Authors: Yoshida Kazuya , Suzuki Toshiaki , Osakada Yasuko , Fujitsuka Mamoru , Miyatake Yukiko , Biju Vasudevanpillai , Takano Yuta 
Published: January 2025

Abstract
Near-infrared light activation enhances phototherapeutic efficacy due to deep-tissue penetration and minimal invasion. While near-infrared-phototherapeutic agents are widely studied, conventional designs often increase molecular size, affecting pharmacokinetics. This study elucidates the photo-excited states of sulfone-containing aromatic compounds as efficient near-infrared-activated photothermal agents for cancer therapy. We synthesized sulfone-rosamine compounds (3 and 4) exhibiting strong optical absorption around 700 nm, attributed to a unique orbital in the LUMO. Compound 4, 35% smaller than conventional near-infrared-dye molecules, such as Cy5.5 (0.86 nm3/molecule), enhances intracellular mobility. Upon photoexcitation, 4 undergoes rapid non-radiative relaxation, resulting in remarkable photothermal effects and photostability. Transient absorption spectroscopy and density functional theory calculations revealed a mechanism involving rapid non-radiative deactivation after illumination, efficiently converting light to heat. The near-infrared-induced photothermal effect effectively killed various cancer cell lines, including HeLa, MDA-MB-231, and PCI-55. This study provides guidelines for designing novel photodrugs with improved intracellular mobility, near-infrared light responsiveness, and photostability, and introduces the advancement of cancer treatment.
Heart-breaking Tumours- A Case Series of Malignant Pericardial Effusion
Authors: Wan Muhamad Hatta Syarifah Syafiqah , Mirza Abdur Rahman , Sunni Nadia , Bashir Ahmed 
Published: January 2025

Abstract

Background
Malignant pericardial effusions are often linked to metastases from solid tumours, such as those in the lung or breast, or haematological diseases. Primary cardiac tumours are rare, occurring in only 0.02% of cases, with pericardial tumours comprising 6.7% to 12.8% of all primary cardiac tumours.

Case Summary
Case 1: A 49-year-old Black African male presented with chest pain and breathlessness after a COVID-19 vaccine. Initially treated for pericarditis, he returned with worsening symptoms. Echocardiography revealed pericardial effusion and cardiac tamponade. Imaging confirmed a right atrial mass diagnosed as malignant biphasic mesothelioma. He died four months after diagnosis.
Case 2: A 43-year-old Caucasian male developed breathlessness and fever post-COVID-19 vaccine. Imaging identified a large posterior pericardial mass, later diagnosed as synovial sarcoma. Chemotherapy yielded minor tumour reduction, but he succumbed to his illness, spending his final days in a hospice.

Discussion
Initial clinical signs are critical in determining the origin of pericardial effusion. Malignancy should be suspected in cases with cardiac tamponade, unexplained haemorrhagic pericardial fluid, or recurrent symptoms. Negative cytology warrants further investigation with advanced imaging or biopsy to improve diagnostic sensitivity.
Diagnosing rare tumours involves multiple imaging modalities, fluid analysis, biopsies, and an interdisciplinary approach, with pathological analysis being the gold standard. Treatment remains challenging due to the rapid progression of these tumours, with surgery often not feasible. A multi-pronged diagnostic approach is crucial, and clinicians must maintain suspicion for malignancy in persistent pericardial effusion cases, even in the context of other potential confounding factors.
Ages at coronary heart disease and death in familial hypercholesterolaemia: a Danish nationwide study spanning 44 years
Authors: Reeh Jacob , Afzal Shoaib , Wulff Anders Berg , Nordestgaard Børge G 
Published: January 2025

Abstract

Background and Aims
Familial hypercholesterolaemia leads to lifelong elevated low-density lipoprotein cholesterol with increased risk of coronary heart disease and pre-mature death. It is unknown whether the prognosis for individuals with familial hypercholesterolaemia has improved over the past four decades as registration of this condition has been limited worldwide. However, in Danish nationwide registries, modified ICD coding has allowed such registration since 1978. This study tested the hypothesis that age at death and coronary heart disease has improved from 1978 to 2021 in individuals with vs. those without familial hypercholesterolaemia.

Methods
From nationwide registries, all Danish residents were included in a retrospective cohort study. Inclusion and follow-up were from 1978 to 2021. Individuals diagnosed with familial hypercholesterolaemia were identified, and trends over time were examined for age at death and age at coronary heart disease.

Results
During follow-up for those with (n = 10 199) and without (n = 9 174 926) familial hypercholesterolaemia, 27% and 27% died and 34% and 9% experienced coronary heart disease. Age at death was 22 years younger in 1978 (P &lt; .001) but similar in 2021 (P = .16) in individuals with vs. without familial hypercholesterolaemia. Although the corresponding age at coronary heart disease was 20 years younger in 1978 (P &lt; .001), it was still 7 years younger in 2021 (P &lt; .001) in individuals with vs. without familial hypercholesterolaemia. These results were similar in women and men and in a 1:100 matched analysis by sex, ethnicity, and time of birth.

Conclusions
Nationwide from 1978 to 2021 in Denmark, normalization of age at death but not age at coronary heart disease was observed for individuals diagnosed with familial hypercholesterolaemia.
Neighbourhood characteristics and loneliness in later life: The role of ‘person-environment fit’
Authors: Lam Jack , Baxter Janeen 
Published: January 2025

Abstract

Background and Objectives
There is increasing acknowledgment that loneliness is associated with neighbourhood characteristics in addition to individual characteristics. We use four waves of geocoded data to examine longitudinal associations between neighbourhood characteristics and loneliness of older adults.

Research Design and Methods
We draw on ‘person-environment fit’ theory, utilizing individual assessments of neighbourhoods, but also create aggregate assessments of neighbourhood by combining responses from other respondents from the same geographic area to test associations with loneliness.

Results
Random-effects models demonstrate individual and aggregate assessments of neighbourhoods are related to loneliness, though in models inclusive of control variables, the associations between aggregate assessments of neighbourhood and loneliness were attenuated. Fixed-effects models show only individual assessments of the neighbourhood are associated with variations in loneliness.

Discussion and Implications
Consistent with the ‘person-environment fit’ theory, loneliness appears more sensitive to individual assessments of neighbourhood, irrespective of others’ assessments. Our findings point to the subjective nature of loneliness and suggest that measures to improve loneliness should focus on understanding and addressing individual perceptions of neighbourhoods, highlighting the importance of promoting age-friendly environments.
Characteristics and antimicrobial susceptibility of bacteria causing acute otitis media in children at Vietnam National Children’s Hospital: a cross-sectional study
Authors: Đỗ Hồng Điệp , Trần Minh Điển , Nguyễn Tuyết Xương , Thủy Phùng Thị Bích , Ngọc Hoàng Thị Bích , Liên Phạm Thị Lan , Nguyen Minh , DeAngelis Elena , Thân Hữu Tiệp , Nguyễn Khắc Trưởng , Guzman-Holst Adriana 
Published: January 2025

Abstract

Background
Acute otitis media (AOM) is a leading cause of healthcare visits, antibiotic prescription and complications in children aged under 5 years. Following the introduction of pneumococcal conjugate vaccines (PCVs), non-typeable Haemophilus influenzae (NTHi) has become the most common causative agent for AOM, followed by Streptococcus pneumoniae and Moraxella catarrhalis. PCVs are not yet included in the National Immunization Program in Vietnam.

Objectives
To determine the frequency and characteristics of the pathogens related to AOM in Vietnam in children ≤5 years old.

Methods
This was a cross-sectional study performed at the Vietnam National Children’s Hospital from October 2021 to December 2023 in children ≤5 years old diagnosed with acute suppurative otitis media. Clinical features of the children were described. Pathogens of interest were identified by culture or real-time PCR (rtPCR). The antibiotic susceptibility profiles of H. influenzae and S. pneumoniae isolates were determined.

Results
In total, 482 children ≤5 years old were included, of which 70.8% were ≤2 years old and 61% had an history of AOM. The most frequent bacteria isolated were H. influenzae (52.1%, 99.6% of which were NTHi) and S. pneumoniae (41.1%). Most S. pneumoniae isolates were resistant to azithromycin, clarithromycin and cefuroxime. Most H. influenzae isolates were resistant to amoxicillin, cefixime, cefuroxime, azithromycin and clarithromycin.

Conclusions
The pathogens most frequently associated with AOM in this study were in line with previous findings. Many isolates were resistant to commonly given oral antibiotics. These results can inform decision-making on AOM prevention and treatment strategies in Vietnam.
Geographic profiling of psychosis prevalence by ethnic group: an application of ecological inference to London neighbourhoods
Authors: Congdon Peter 
Published: January 2025

Abstract
In view of ethnic and geographic heterogeneity in psychosis, establishing varying psychosis prevalence both by neighbourhood, and by ethnic group, is important for mental health needs assessment and service planning. This paper uses an ecological inference framework to estimate neighbourhood psychosis rates by ethnic group, when the available information is limited to totals of diagnosed psychosis by neighbourhood. To assess sensitivity in inferences, and possible spatial confounding, alternative models for ethnic-area psychosis rates are used. In an application to 4,835 micro-neighbourhoods across London, the highest psychosis rates are among Black ethnic groups, with a rate ratio averaging 2.35 compared with prevalence among Whites. There is evidence for an ethnic density effect: lower psychosis rates than expected in neighbourhoods with high non-White ethnic concentration.