bluuebunny/crossref_metadata_2025 huggingface dataset:
HPV infection patterns and viral load distribution: implication on cervical cancer prevention in Western Kenya
Authors: Akinyi Ivy , Ouma Ogol Japheth , Ogutu Sylvester , Ogola Eric , Owenga Jane , Ayodo George , Omondi Dicken , Awandu Shehu Shagari , Vanden Broeck Davy , Redzic Nina , Pereira Ana Rita , Bogers Johannes
Published: September 2024

Human papillomavirus (HPV) coinfection remains common globally. However, its clinical significance compared to mono-infection remains controversial. Further, the epidemiology of HPV genotype combination in coinfection is not well studied in Kenya. . Between June and August 2023, a cross-sectional facility-based survey enrolled 434 women aged 16–68 years using purposive sampling strategy. Structured questionnaire was obtained from each woman regarding demographic and sexual behavior characteristics. Cervical specimen was collected from each participant and analyzed using RIATOL assay to determine HPV genotypes and viral load. Overall, HPV 52 was the most frequently detected HPV strain. The mean HPV viral load was elevated among coinfected women than those with mono-infection but there was no evidence to support differences in viral load in the two groups (P = 0.113). Mono-infection was common (58.52%). HPV 16 was noted to have a near equal presence both in mono-infection and coinfection (52.17% and 47. 83%), respectively. HPV 33 (alpha 9) and 45 (alpha 7) had the greatest preference for each other compared to all other HPV interactions. HPV 52 is the most prevalent HPV in the population supporting the need for the nonavalent HPV vaccine. Mono-infection with HPV 16 remains common corroborating the relevance of bivalent vaccine in resource limited setting where nonavalent vaccines may be unavailable. The frequent coinfection preference of HPV 33 and 45 (alpha 9 and alpha 7, respectively) pauses the need for further concurrent characterization. HPV vaccination and education on safe sexual behaviors is key in reducing HPV coinfection.
Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1-mutated oral squamous cell carcinoma
Authors: Lin Yumeng , Huang Yibo , Yang Bowen , Zhang You , Ji Ning , Li Jing , Zhou Yu , Shen Ying-Qiang , Chen Qianming
Published: September 2024

Background:

Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.

Methods:

To evaluate the efficacy of the combination of the Ca2+/calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 (FAT1)-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro. The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.

Results:

OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1-mutated OSCC cells and suppressed tumor growth in vivo. Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1-mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.

Conclusion:

Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Cerebellar involvement in Parkinson’s disease: Pathophysiology and neuroimaging
Authors: Qiu Tao , Liu Meichen , Qiu Xinhui , Li Tianbai , Le Weidong
Published: September 2024

Parkinson’s disease (PD) is a neurodegenerative disease characterized by various motor and non-motor symptoms. The complexity of its symptoms suggests that PD is a heterogeneous neurological disorder. Its pathological changes are not limited to the substantia nigra-striatal system, but gradually extending to other regions including the cerebellum. The cerebellum is connected to a wide range of central nervous system regions that form essential neural circuits affected by PD. In addition, altered dopaminergic activity and α-synuclein pathology are found in the cerebellum, further suggesting its role in the PD progression. Furthermore, an increasing evidence obtained from imaging studies has demonstrated that cerebellar structure, functional connectivity, and neural metabolism are altered in PD when compared to healthy controls, as well as among different PD subtypes. This review provides a comprehensive summary of the cerebellar pathophysiology and results from neuroimaging studies related to both motor and non-motor symptoms of PD, highlighting the potential significance of cerebellar assessment in PD diagnosis, differential diagnosis, and disease monitoring.
Omeprazole affects the expression of serotonin-1A in the brain regions and alleviates anxiety in rat model of immobilization-induced stress
Authors: Ali Sadia Basharat , Saeed Raheel , Mahmood Khalid , Haleem Darakhshan Jabeen
Published: September 2024

Omeprazole, a drug of choice for the management of gastric hyperacidity, influences serotonergic neurotransmission in brain regions and its long-term use is known to cause stress-related behavioral deficits including anxiety. Aim of the current study was to explore the effects of omeprazole treatment on immobilization-induced anxiety in rats, specifically on the role of serotonin (5-HT). In view of the role of serotonin-1A (5-HT1A) autoreceptor in the availability of 5-HT in brain regions, mRNA expression of this autoreceptor was performed in raphe nuclei. Similarly, because of the role of hippocampal 5-HT neurotransmission in anxiety-like disorders, expression of the 5-HT1A heteroreceptors was determined in this region. We found that the treatment with omeprazole reduces anxiety-like behavior in rats, increases the expression of 5-HT1A autoreceptor in the raphe and decreases the hippocampal expression of 5-HT1A heteroreceptor. This suggests a role of 5-HT1A receptor types in omeprazole-induced behavioral changes. It also indicates a potential role of omeprazole in the management of serotonergic disorders.
Jarisch–Herxheimer Reactions with artemether/lumefantrine: an uncommon side effect of anti-malarial medications
Authors: Abdallah Abdallah M. , Abbasher Hussien Mohamed Ahmed Khabab , Mohamed Malaz Tarig AbdAlla , Mohamed Imam B. , Mubarak Ismail Manasik M. El Murtada , Mosa Mohammed Hosham Mohammed , Balla Mustafa Monzer Hassan , Abdalla Mustafa Abubaker Mustafa , Abubakr Mahdi Niam Adam , Mahmmoud Fadelallah Eljack Mohammed , E. Mustafa Ahmed Ghassan
Published: September 2024

Background:

The Jarisch–Herxheimer reaction (JHR) was a nonspecific adverse effect manifested by fever, chills, headache, myalgia, and exacerbations of skin rash that’s firstly described with anti-spirochetes medications and later with fluoroquinolones, cephalosporins, meropenem, and tetracyclines but not with antiparasitic drugs. Herein we reported JHR in a young Sudanese male due to antimalarial medications with good outcomes.

Case Presentation:

A 27-year-old Sudanese man presented with malaria-like symptoms and was given an oral artemisinin combination. However, within 8 h, the patient developed high-grade fever, chills, rigors, recurrence of the headache, tachycardia, myalgia, and tachypnoea, which was diagnosed as a JHR. The drug was temporarily stopped, the patient was hydrated, and an antipyretic was given, then the drug was restarted with a good response. Viral screening and syphilis tests were negative while blood tests showed leukocytosis, lymphopenia, and left shift in granulocytes.

Discussion:

In this case, the patient received Coartem 80/480 (artemether 80 mg/lumefantrine 480 mg). Eight hours after starting treatment, his fever dropped to 37.8°C, with other symptoms improving. Surprisingly at 8 h, the patient developed a second fever of 39.4°C, with chills, headache, tachycardia, a pulse rate of 103, myalgia, and hyperventilation. This is comparable with Koefoed’s case, where the patient received Fansidar (sulfadoxine/pyrimethamine). His JHR started 10 h later, indicated by the second rise in temperature.

Conclusion:

JHR can occur with antimalarial medications, most commonly by non-specific symptoms and worsening of pre-existing skin lesions; this requires a high clinical susceptibility, particularly within the first 24 h, with treatment discontinuation and hydration as the mainstay of management, with good outcomes.
Exploring menopausal symptoms, attitudes, and behaviors among menopausal women in China: an online research perspective
Authors: You Yang , Lin Lin , Yu Qi
Published: September 2024

Objective

The number of perimenopausal women in China is rising, but the population's concept of menopausal hormone therapy (MHT) is still relatively outdated.

Methods

In this study, we used the Knowledge-Attitude-Practice (KAP) theory and collected online questionnaires from 1,100 women aged 40 to 60 years nationwide to find out their menopausal symptom profiles; to learn about their perceptions, attitudes, and behaviors toward menopause and MHT; to explore the factors influencing the acceptance of hormone treatments; and to look for better ways to promote the dissemination of menopausal knowledge.

Results

The results revealed that among women aged 40 to 60 years, 82.36% experienced possible menopausal symptoms, with hot flushes/sweating, sleep disorders, mood disorders, and fatigue being the most prevalent; 55.90% reported moderate to severe symptoms, but only 46.99% of them sought healthcare services. Among those who sought medical care, 16.00% had their first visit to climacteric clinics/gynecological endocrinology, and 5.66% accepted MHT. Furthermore, 77.82% of participants never heard of MHT or were unaware of its existence. The healthcare-seeking behavior of menopausal women in response to symptoms and their willingness to accept MHT were found to be closely associated with their level of self-care.

Conclusions

The prevalence of menopausal symptoms is higher in China than previous research findings, but due to a lack of relevant knowledge, the rate of seeking treatment from the appropriate medical department and accepting MHT is relatively low. Enhancing physicians' knowledge of the menopausal transition and using Internet tools might help improve Chinese women's knowledge of menopause and help them pass through this period smoothly.
Urinary Tract Infection in Children and the Potential Role of Pivmecillinam as a Treatment Option
Authors: Andersen Naja Lyhne , Antsupova Valeria , Boel Jonas Bredtoft , Christensen Mette Marie , Nygaard Ulrikka , Schmidt Lisbeth Samsø
Published: September 2024

We investigated the potential role of pivmecillinam in the treatment of urinary tract infections in children. Among 351 children (0–6 years) with urinary tract infections, 83% could be treated with pivmecillinam following urine culture. Resistance was highest in infants (0–3 months) caused by the high prevalence of Enterococcus faecalis. This result emphasizes the necessity for developing a pediatric oral form of pivmecillinam.
Factors Associated With Elder Abuse According to the Levels of Social Determinants in Brazil
Authors: de Araújo Monteiro Gleicy Karine Nascimento , dos Santos Renata Clemente , de Moraes Brandão Wesley Ferreira , Costa Gabriela Maria Cavalcanti , de Almeida Ana Maria , Souto Rafaella Queiroga
Published: September 2024

Objective

The aim of this study was to analyze the factors associated with elder abuse according to the levels of social determinants.

Methodology

This is a quantitative and multicentric study, with a cross-sectional cut. It was developed in two teaching hospitals in Paraíba, Brazil, with 323 older adults, from July 2019 to February 2020. Data were collected using the Hwalek–Sengstock Elder Abuse Screening Test and Conflict Tactics Scale-1 and then analyzed using descriptive and inferential statistics.

Results

There was a significant association between risk for violence and female gender (p = 0.004), residing with grandchildren (p = 0.025), and having four or more comorbidities (p < 0.00). Physical violence was associated with income (p = 0.048). A positive correlation was observed between the number of comorbidities and the risk for violence score (p < 0.001), psychological violence (p = 0.004), and physical violence (p = 0.005). The probability of presenting a risk to violence increased by 2.08 times for women, 1.03 times for those who were illiterate, and 7.03 times for those with four or more comorbidities.

Conclusion

The social determinants of health that integrate the macrosystem, such as income and number of comorbidities, correlate with situations of violence.
The safety and efficacy of Baricitinib for systemic lupus erythematosus: a systematic review and meta-analysis of randomized controlled trials
Authors: Ramadan Alaa , Gowaily Ibrahim , Saleh Othman , Abuelazm Mohamed , Ahmad Unaiza , Elzeftawy Mohammad A. , Nathan Ezie Kengo , Abdelazeem Basel
Published: September 2024

Background and objective:

Baricitinib is a JAK1 and JAK2 inhibitor approved for treating active rheumatoid arthritis and atopic dermatitis. Therefore, the authors aim to evaluate the safety and efficacy of once-daily oral Baricitinib 2 mg or 4 mg versus placebo in active SLE patients receiving standard care.

Methods:

The authors synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, and Cochrane Library until 20 March 2023. The study protocol was registered in PROSPERO.

Results:

Three RCTs with 1849 participants were included. The Baricitinib group had a significant SRI-4 response [RR: 1.11 with 95% CI (1.03, 1.21), P=0.008] and greater than or equal to 4-point SLEDAI-2K domain improvement [RR: 1.13 with 95% CI (1.02, 1.25), P=0.02] compared to the placebo group; however, there was no statistically significant difference between the two groups, regarding the secondary endpoints. For safety outcomes, Baricitinib was significantly associated with a higher incidence of Any serious adverse event [RR: 1.48 with 95% CI (1.07, 2.05), P=0.02].

Conclusion:

Baricitinib is associated with significant outcomes of SRI-4 response, greater than or equal to 4-point improvement SLEDAI-2K score, and Joint Indices. Regarding safety, there was no difference in the outcomes other than the serious adverse events.
The Impact of Nurse Residency Programs on Patient Quality and Safety Outcomes
Authors: Webb Tammy , Parker Pearman , Huett Amy , Weber Judith , Harrison Tracie , Nagel Corey
Published: September 2024

Schools of nursing are struggling to prepare registered nurses to practice in today’s complex healthcare settings. Nurse residency programs are a good solution to support the transition to practice. Nursing education leaders must be informed of the nursing quality and safety outcomes of nurse residency programs. This literature review provides insight and evaluation of the evidence related to the impact of nurse residency programs with substantial evidence of nurse outcomes and minimal patient outcomes.
Commentary
Authors: Drewnowski Adam
Published: September 2024

Quality of life (QoL) instruments fail to ask about food, diet quality, or nutritional status. Nutrition screeners, often meant for use in clinical settings, fail to ask about QoL. Arensberg and colleagues make a compelling argument for integrating these siloed and yet related concepts. Food and nutrition are among the essential components of QoL among older Americans.
Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 Fusions Expands Molecular Landscape of Adenoid Cystic Carcinoma Beyond Fusions Between MYB/MYBL1 and NFIB Genes
Authors: Skálová Alena , Klubíčková Natálie , Bradová Martina , Agaimy Abbas , Rupp Niels J. , Damjanov Ivan , Kolnikova Georgina , Martínek Petr , Šteiner Petr , Grossmann Petr , Vaněček Tomas , Michal Michal , Leivo Ilmo
Published: September 2024

Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs in all major and minor salivary gland and seromucous gland sites. AdCCs of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost consistent presence of fusion genes MYB::NFIB, or less commonly MYBL1::NFIB. We collected a cohort of 95 cases of AdCC, which were largely characterized by canonical fusions MYB::NFIB (49 cases) or MYBL1::NFIB (9 cases). In additional 11 cases of AdCC, rearrangements in MYB or NFIB genes were detected by FISH. In addition, NGS revealed novel noncanonical fusion transcripts EWSR1::MYB; ACTB::MYB; ESRRG::DNM3, MYB::TULP4, and ACTN4::MYB, each of them in 1 case. The tumors that showed noncanonical fusions had features of metatypical AdCC with a diverse architecture, lobulated multinodular growth pattern, and hypercellular peripheral palisading of nuclei (2 cases), tubular hypereosinophilia (2 cases), and pale eosinophilic to vacuolated (bubbly) cytoplasm (3 cases). Our study documented 3 cases of AdCC of salivary glands harboring novel gene fusions TULP4::MYB, ACTN4::MYB, and ACTB::MYB, in 1 case each, which have not been described before. A rare EWSR1::MYB fusion was detected in 1 case. Moreover, 1 case of sinonasal metatypical AdCC showed EWSR1 rearrangement detected by FISH. Also, 1 case with an ESRRG::DNM3 fusion of unknown significance is described in this study. These discoveries illustrate how broad molecular profiling will expand understanding of changes in known entities.
Metastatic Leiomyoma With Malignant Transformation Harboring RAB2A-PLAG1 Fusion: A Case Report and Review With Molecular Analysis
Authors: Lau Hiu Yeung , Huang Mingjie , Chang Kenneth Tou En , Kuick Chik Hong , Takano Angela
Published: September 2024

Metastasizing leiomyoma is a rare condition characterized by the development of benign-appearing smooth muscle neoplasms at extrauterine sites in patients with a history of uterine leiomyoma. These lesions occur most commonly in the lung, with the abdominopelvic and mediastinal lymph nodes being other reported sites. Malignant transformation of metastasizing leiomyoma is extremely rare, with only a few cases described in the literature. We describe a case of metastasizing leiomyoma with malignant transformation in a middle-aged Asian lady, who developed pulmonary metastatic foci 12 years after surgical excision of the original uterine leiomyomata. Molecular analysis showed a common RAB2A-PLAG1 fusion gene and identical single nucleotide variants in both tumor foci, with significantly more pronounced segmental chromosomal copy number variations in one focus showing high-grade features. A comprehensive review of the literature lends support to the hypothesis that the original leiomyomata and the metastatic foci are clonally related, with high-grade features being associated with more complex genomic signatures.
Ecologically Assessed Sleep Duration and Arterial Stiffness in Healthy Men and Women
Authors: Gaffey Allison E. , Walenczyk Kristie M. , Schwartz Joseph E. , Hall Martica H. , Burg Matthew M.
Published: September 2024

Objective

Among younger adults, to determine the associations of actigraph- and self-reported sleep duration with arterial stiffness (AS) assessed in clinic and in ecologically valid contexts, and to examine sex-specific associations.

Methods

Healthy adults (n = 282, median age = 29 years, 67% women) completed a state-of-the-art assessment of AS at rest (SphygmoCor; carotid femoral pulse wave velocity [cfPWV]; central augmentation index [cAIx]) and 7 days of actigraphy-assessed sleep with concurrent, momentary cAIx assessment for 36 hours (Oscar-2). Multivariable regressions were conducted on the full sample and sex-stratified to examine cross-sectional linear and quadratic associations of average sleep duration with resting PWV and cAIx, average cAIx while awake and asleep, and nocturnal cAIx dipping, adjusted for demographic and health covariates. Exploratory analyses included self-reported sleep duration with AS, and actigraphy and self-reported sleep duration with the ambulatory arterial stiffness index (AASI; Oscar-2).

Results

Overall and by sex, associations of average sleep duration with resting cfPWV, resting cAIx, and awake cAIx were not significant. Sleep duration showed a positive, linear association with sleep cAIx in women (95% confidence interval =1.07 to 5.86, ΔR
2 = 0.021). Among women, sleep duration was also inversely associated with cAIx dipping (95% confidence interval = −4.48 to −0.95, ΔR
2 = 0.020). Analyses with self-reported sleep duration and AASI as alternate predictors and outcomes were not significant.

Conclusions

Certain sleep duration–AS associations may be sex-specific. Assessing sleep and momentary AS in ecologically valid conditions outside the research laboratory is valuable to understand these relations. Although this investigation should be replicated, findings raise the question of whether interventions to target sleep duration also reduce AS.
Psychological Factors Modulate Quantitative Sensory Testing Measures in Fibromyalgia Patients: A Systematic Review and Meta-Regression Analysis
Authors: Carneiro Adriana Munhoz , Pacheco-Barrios Kevin , Andrade Maria Fernanda , Martinez-Magallanes Daniela , Pichardo Elly , Caumo Wolnei , Fregni Felipe
Published: September 2024

Objective

Considering the growing evidence that psychological variables might contribute to fibromyalgia syndrome (FMS), our study aims to understand the impact of psychological factors in quantitative sensory testing (QST) in FMS patients by performing a systematic review with meta-analysis.

Methods

A systematic search was carried out in PubMed/MEDLINE, EMBASE, Web of Science, and PsycINFO databases for records up until January 2024. We included 20 studies (n = 1623, 16 randomized controlled trials, and 4 nonrandomized controlled trials) with low or moderate risk of bias included.

Results

From nonrandomized evidence, our meta-analysis found a baseline relationship between anxiety, depression, and pain catastrophizing and QST measures in FMS patients. Higher pain catastrophizing levels were associated with less efficient conditioned pain modulation. Higher anxiety and depression were associated with lower pain threshold (PT). Randomized evidence showed a statistically significant increase in PT after fibromyalgia treatments (effect size = 0.29, 95% confidence interval = 0.03–0.56). The effect was not influenced by treatment type. Moreover, we found that only anxiety levels before treatment negatively influenced the PT improvements after treatment.

Conclusion

FMS patients with higher anxiety levels at baseline showed a smaller increase in PT after the intervention. Depression factor was not significant in either changes in anxiety or depression. Baseline anxiety levels should be monitored as possible confounders of QST measurements. Understanding how psychological factors and QST are related in FMS patients is critical for improving the syndrome’s management and treatment.

Protocol Registration: CRD42023429397
The Growth and Development of a Research Division in the Plastic Surgery Department of a Large Urban Academic Medical Center
Authors: James Andrew J. , Lineaweaver William C. , Yao Julia , Thayer Wesley , Perdikis Galen
Published: September 2024

Introduction

Research is a critical component of academic medicine that may or may not be prioritized in centers with high clinical volumes. The benefits of research expansion go beyond notoriety and industry partnerships, expanding into resident training and preparation of the next generation of physician-scientists. Improving a division or department's research portfolio requires a commitment to reorganizing structure, personnel, resources, and a dedication to innovative funding models. To improve research productivity and quality, our group placed several initiatives into motion beginning in August 2017 that we have outlined and evaluated in the present study. Some of these initiatives included restructuring leadership, resourcing both bench and clinical outcomes research, providing initial funding directly from clinical profits and rewarding research fiscally.

Methods

Reviews of hiring records, publications, grant allocations, and interviews with key personnel were used to generate a road map of initiatives. Average impact factor was calculated by averaging journal impact factors for all publications from the department each year, excluding any publications with greater than 5 times the raw average, and creating a corrected average that more accurately represented the work. Student t tests were used to compare mean number of publications and impact factors from 2010 to 2017 to those from 2018 to 2022.

Results

Prior to restructuring (2010–2017), the department published an average of 9 articles annually, which increased to an average of 42 articles since that time (P < 0.01). Average impact increased from 0 in 2010 to 4.02 in 2022, with the number of publications in top 10 plastic surgery journals following a similar trajectory with 1 publication in 2010 and 31 in 2023. Following an initial $1 million investment to create an institutionally directed fund in 2018, the department leveraged its research to earn $3 million in endowments, $1.25 million in industry partnerships, $3.23 million in Department of Defense funding, and $1.65 million from a multi-institutional National Institutes of Health grant.

Conclusion

Deliberate prioritization of research initiatives as noted above has led to remarkable growth in academic output.
IMPACT OF ABCC8 AND TRPM4 GENETIC VARIATION IN CENTRAL NERVOUS SYSTEM DYSFUNCTION ASSOCIATED WITH PEDIATRIC SEPSIS
Authors: Kernan Kate F. , Adkins Ashley , Jha Ruchira M. , Kochanek Patrick M. , Carcillo Joseph A. , Berg Robert A. , Wessel David , Pollack Murray M. , Meert Kathleen , Hall Mark , Newth Christopher , Lin John C. , Doctor Allan , Cornell Tim , Harrison Rick E. , Zuppa Athena F. , Notterman Daniel A. , Aneja Rajesh K.
Published: September 2024

Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. Methods: 326 children with severe sepsis underwent whole exome sequencing in an observational cohort. We compared children with and without central nervous system dysfunction (Glasgow Coma Scale <12) to assess for associations with clinical characteristics and pooled rare variants in ABCC8 and TRPM4. Sites of variation were mapped onto protein structure and assessed for phenotypic impact. Results: Pooled rare variants in either ABCC8 or TRPM4 associated with decreased odds of central nervous system dysfunction in severe pediatric sepsis (OR 0.14, 95% CI 0.003–0.87), P = 0.025). This association persisted following adjustment for race, organ failure, viral infection, and continuous renal replacement therapy (aOR 0.11, 95% CI 0.01–0.59, P = 0.038). Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4. Conclusion: This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.
Recurrence-Independent Progressive Inner-Retinal Thinning After Optic Neuritis: A Longitudinal Study
Authors: Moon Yeji , Gim Yujin , Park Kyung-Ah , Yang Hee Kyung , Kim Seong-Joon , Kim Sung-Min , Jung Jae Ho
Published: September 2024

Background:

Longitudinal changes in the inner retina in patients with optic neuritis (ON) may be helpful in monitoring patients and determining maintenance treatment. The aim of this study was to investigate longitudinal changes in the inner retina after subsiding of acute demyelinating ON and to identify the factors associated with such changes.

Methods:

In this multicenter retrospective observational study, we reviewed the medical records of 77 patients with ON, including 23 with neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4)-immunoglobulin G (IgG) (AQP4 group), 23 with myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOG group), 18 with multiple sclerosis (MS group), and 13 with idiopathic ON (iON group). We measured the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) using optical coherence tomography (OCT) at baseline and at follow-up examinations (mean follow-up duration, 29.6 ± 8.6 months; mean number of OCT, 4.2 ± 1.2) in the absence of ON recurrence.

Results:

The estimated rate of pRNFL thinning in the AQP4, MOG, MS, and iON groups was 0.66 (95% confidence interval, 0.35–0.97), 0.35 (0.04–0.66), 0.53 (0.16–0.90), and 0.25 (−0.18 to 0.68) μm/year, respectively, indicating that, in the iON group in contrast to the other groups, there was no significant decrease of pRNFL thickness. Among the AQP4, MOG, and MS groups, there was no significant difference in the rate of pRNFL thinning (P = 0.560). The rate of mGCIPL thinning in the AQP4 and MOG groups was 0.25 (0.04–0.46) μm/year and 0.38 (0.23–0.53) μm/year, respectively. Meanwhile, the rate of mGCIPL change in the MS and iON groups was 0.04 (−0.12 to 0.19) and 0.00 (−0.17 to 0.16) μm/year, respectively, which indicates that there was no significant mGCIPL thinning in the latter 2 groups. Between the AQP4 and MOG groups, meanwhile, the rate of mGCIPL change did not significantly differ (P = 0.295). Age older than 40 years was associated with significant progression of mGCIPL thinning (P = 0.005).

Conclusions:

We noted inner retina thinning progression independent of relapse activity in AQP4-ON, MOG-ON, and MS-ON. Because subclinical neuroaxonal damage continues to be incurred after an acute attack of ON subsides despite suppression of new attacks, long-term follow-up and neuroprotection should be considered to be integral to the treatment of patients with ON.
David J. Ewins. 25 March 1942—25 January 2023
Authors: Cawley FRS Peter
Published: September 2024

David Ewins was a major figure in experimental structural dynamics. He pioneered the subject that became known as modal testing, writing the seminal book on the topic which is still in use 40 years later. He did outstanding research across a wide range of topics, notably modal testing, rotating machinery vibration and the dynamics of structural joints. He was always interested in industrial applications and was a firm believer in the need for research to demonstrate impact long before it became fashionable. He was the founding director of one of the first Rolls-Royce University Technology Centres and made major contributions to the company. He loved interacting with engineers at all levels in academia and industry, and he was a passionate educator of both PhD students and engineers in industry. His influence continues to be reflected in their careers.
Generalized eigenfunction expansion and singularity expansion methods for two-dimensional acoustic time-domain wave scattering problems
Authors: Wilks B. , Meylan M. H. , Montiel F. , Wakes S.
Published: September 2024

Time-domain wave scattering in an unbounded two-dimensional acoustic medium by sound-hard scatterers is considered. Two canonical geometries, namely a split-ring resonator (SRR) and an array of cylinders, are used to highlight the theory, which generalizes to arbitrary scatterer geometries. The problem is solved using the generalized eigenfunction expansion method (GEM), which expresses the time-domain solution in terms of the frequency-domain solutions. A discrete GEM is proposed to numerically approximate the time-domain solution. It relies on quadrature approximations of continuous integrals and can be thought of as a generalization of the discrete Fourier transform. The solution then takes a simple form in terms of direct matrix multiplications. In parallel to the GEM, the singularity expansion method (SEM) is also presented and applied to the two aforementioned geometries. It expands the time-domain solution over a discrete set of unforced, complex resonant modes of the scatterer. Although the coefficients of this expansion are divergent integrals, we introduce a method of regularizing them using analytic continuation. The results show that while the SEM is usually inaccurate at

t
=
0

, it converges rapidly to the GEM solution at all spatial points in the computational domain, with the most rapid convergence occurring inside the resonant cavity.
Interactions between neural representations of the social and spatial environment
Authors: Thompson James C. , Parkinson Carolyn
Published: September 2024

Even in our highly interconnected modern world, geographic factors play an important role in human social connections. Similarly, social relationships influence how and where we travel, and how we think about our spatial world. Here, we review the growing body of neuroscience research that is revealing multiple interactions between social and spatial processes in both humans and non-human animals. We review research on the cognitive and neural representation of spatial and social information, and highlight recent findings suggesting that underlying mechanisms might be common to both. We discuss how spatial factors can influence social behaviour, and how social concepts modify representations of space. In so doing, this review elucidates not only how neural representations of social and spatial information interact but also similarities in how the brain represents and operates on analogous information about its social and spatial surroundings.

This article is part of the theme issue ‘The spatial–social interface: a theoretical and empirical integration’.
Anthropogenic impacts at the interface of animal spatial and social behaviour
Authors: Gaynor Kaitlyn M. , Abrahms Briana , Manlove Kezia R. , Oestreich William K. , Smith Justine A.
Published: September 2024

Human disturbance is contributing to widespread, global changes in the distributions and densities of wild animals. These anthropogenic impacts on wildlife arise from multiple bottom-up and top-down pathways, including habitat loss, resource provisioning, climate change, pollution, infrastructure development, hunting and our direct presence. Animal behaviour is an important mechanism linking these disturbances to population outcomes, although these behavioural pathways are often complex and can remain obscured when different aspects of behaviour are studied in isolation from one another. The spatial–social interface provides a lens for understanding how an animal’s spatial and social environments interact to determine its spatial and social phenotype (i.e. measurable characteristics of an individual), and how these phenotypes interact and feed back to reshape environments. Here, we review studies of animal behaviour at the spatial–social interface to understand and predict how human disturbance affects animal movement, distribution and intraspecific interactions, with consequences for the conservation of populations and ecosystems. By understanding the spatial–social mechanisms linking human disturbance to conservation outcomes, we can better design management interventions to mitigate undesired consequences of disturbance.

This article is part of the theme issue ‘The spatial–social interface: a theoretical and empirical integration’.
Aequorivita flava sp. nov., isolated from deep-sea sediments
Authors: Chen Xiangwei , Xia Jinmei , Fu Xiaoteng , Lai Qiliang , Wang Jianning , Du Yaping , Liu Xiupian , Li Guangyu , Tang Xixiang , Shao Zongze
Published: September 2024

Three Gram-stain-negative, aerobic, non-motile, chemoheterotrophic, short-rod-shaped bacteria, designated CDY1-MB1T, CDY2-MB3, and BDY3-MB2, were isolated from three marine sediment samples collected in the eastern Pacific Ocean. Phylogenetic analysis based on 16S rRNA gene sequences indicated that these strains were related to the genus Aequorivita and close to the type strain of Aequorivita vitellina F4716T (with similarities of 98.0–98.1%). Strain CDY1-MB1T can grow at 15–37 °C (optimum 30 °C) and in media with pH 6–9 (optimum, pH 7), and tolerate up to 10% (w/v) NaCl. The predominant cellular fatty acids of strain CDY1-MB1T were iso-C15 : 0 (20.7%) and iso-C17 : 0 3-OH (12.8%); the sole respiratory quinone was menaquinone 6; the major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and two unidentified polar lipids. The digital DNA–DNA hybridization/average nucleotide identity values between strains CDY1-MB1T, CDY2-MB3, and BDY3-MB2 and A. vitellina F4716T were 24.7%/81.6–81.7%, thereby indicating that strain CDY1-MB1T should represent a novel species of the genus Aequorivita. The genomic DNA G+C contents were 37.6 % in all three strains. Genomic analysis showed the presence of genes related to nitrogen and sulphur cycling, as well as metal reduction. The genetic traits of these strains indicate their possible roles in nutrient cycling and detoxification processes, potentially shaping the deep-sea ecosystem’s health and resilience. Based upon the consensus of phenotypic and genotypic analyses, strain CDY1-MB1T should be classified as a novel species of the genus Aequorivita, for which the name Aequorivita flava sp. nov. is proposed. The type strain is CDY1-MB1T (=MCCC 1A16935T=KCTC 102223T).
Unveiling the complexity of rifampicin drug susceptibility testing in Mycobacterium tuberculosis: comparative analysis with next-generation sequencing
Authors: Qadir Mehmood , Khan Muhammad Tahir , Khan Sajjad Ahmed , Akram Muhammad , Canseco Julio Ortiz , Faryal Rani , Wei Dong Qing , Tahseen Sabira
Published: September 2024

Graphical abstract
Temporally Corrected Dose Accumulation – Next Steps in the Biology of Reirradiation
Authors: Gopalakrishnan Vishhvaan , Feng Bezhou , Somasundaram Eashwar , Pelesko Julia , Stephans Kevin , Magnelli Anthony , Koyfman Shlomo , Videtic Gregory , Qi Peng , Yang Xiaofeng , Abbott Elliot M. , Piper Jonathan W. , Qiu Richard L.J. , Scott Jacob G.
Published: September 2024

Introduction

Treatments encompassing multiple courses of radiation are becoming increasingly common in the management of oligometastatic disease, offering opportunities to extend progression-free and overall survival. However, a major challenge in clinical practice is the lack of standardized methods to assess and mitigate toxicity risks associated with successive radiation treatments. Furthermore, normal tissue recovery post-radiation remains poorly characterized, and the absence of standardized documentation for radiotherapy history complicates large-scale research efforts. To address these limitations, we propose the development of a novel DICOM-compatible object for integration into patient medical records.

Materials and Methods

We generated software designs and bundle mathematics that demonstrate the utility of this DICOM object and how various dose forgiveness algorithms can be applied to the data. We include simple linear, exponential, logarithmic, and Gaussian recovery algorithms as well as complex non-linear algorithms based on the literature currently available.

Results

We applied the tool to an anonymized patient dataset, demonstrating the mathematical analysis applied to the data found in the new DICOM object. Noting ease and efficacy, we demonstrated that, in contrast to the current practice of gathering and structuring information distributed across electronic medical records, ready access to prior radiation courses accomplished two goals. (1) Facilitate data collection and analysis by streamlining access to comprehensive radiotherapy history, enabling researchers to conduct large-scale studies, and ultimately improve our understanding of tissue recovery. (2) Enhance clinical decision-making by enabling clinicians or software tools to leverage this data to personalize treatment plans, support clinical decision making to minimize toxicity risks during re-irradiation. For the anonymized patient, our analysis demonstrates safer delivery of re-radiation plans when viewed in the lens of dose forgiveness.

Conclusions

A novel DICOM object which keeps track of radiation treatments enables clinicians to factor tissue recovery and response into planning safer multiple radiation therapy courses and facilitates cross-institution research on re-irradiation and dose forgiveness.
Temporal Genomic Dynamics Shape Clinical Trajectory in Multiple Myeloma
Authors: Maura Francesco , Kaddoura Marcella , Poos Alexandra M. , Baughn Linda B. , Ziccheddu Bachisio , Bärtsch Marc-Andrea , Cirrincione Anthony , Maclachlan Kylee , Chojnacka Monika , Diamond Benjamin , Papadimitriou Marios , Blaney Patrick , John Lukas , Reichert Philipp , Huhn Stefanie , Gagler Dylan , Zhang Yanming , Dogan Ahmet , Lesokhin Alexander M , Davies Faith , Goldschmidt Hartmut , Fenk Roland , Weisel Katja C. , Mai Elias K. , Korde Neha , Morgan Gareth J , Rajkumar S. Vincent , Kumar Shaji , Usmani Saad , Landgren Ola , Raab Marc S. , Weinhold Niels
Published: September 2024

To comprehensively unravel the temporal relationship between initiating and driver events and its impact on clinical outcomes, we analyzed 421 whole-genome sequencing profiles from 382 patients. Using clock-like mutational signatures, we estimated a time lag of 2-4 decades between initiating events and diagnosis. In patients with hyperdiploidy, we demonstrate that trisomies of odd-numbered chromosomes can be acquired simultaneously with other chromosomal gains, such as 1q gain. We provide evidence that hyperdiploidy is acquired after canonical IGH translocation when both events are present. Finally, patients with early 1q gain had adverse outcomes similar to those with 1q amplification (>1 extra-copies), but faring worse than those with late 1q gain. This underscores that the prognostic impact of 1q gain/amp depends more on the timing of acquisition than on the number of extra copies gained. Overall, this study contributes to a better understanding of the life history of MM and may have prognostic implications.
Benchmarking Recent Computational Tools for DNA-binding Protein Identification
Authors: Luo Xizi , Yi Chi Amadeus Song , Lin Andre Huikai , Ong Tze Jet , Wong Limsoon , Rahman Chowdhury Rafeed
Published: September 2024

Identification of DNA-binding proteins (DBPs) is a crucial task in genome annotation, as it aids in understanding gene regulation, DNA replication, transcriptional control and various cellular processes. In this paper, we conduct an unbiased benchmarking of eleven state-of-the-art computational tools as well as traditional tools such as ScanProsite, BLAST, and HMMER for identifying DBPs. We highlight the data leakage issue in conventional datasets leading to inflated performance. We introduce new evaluation datasets to support further development. Through a comprehensive evaluation pipeline, we identify potential limitations in models, feature extraction techniques and training methods; and recommend solutions regarding these issues. We show that combining the predictions of the two best computational tools with BLAST based prediction significantly enhances DBP identification capability. We provide this consensus method as user-friendly software. The datasets and software are available at:https://github.com/Rafeed-bot/DNA_BP_Benchmarking.

1.

Key Points

We designed a comprehensive evaluation pipeline which systematically evaluates eleven recent machine learning (ML) based DBP identification tools.

We analyzed the test prediction mistakes made by top-performing tools identifying their potential limitations in terms of model architecture, feature extraction and class balancing.

We showed that although the best of these tools do not convincingly outperform BLAST, they still provide substantial value when integrated together with BLAST into a simple majority-voting ensemble.

We provide recommendations on more robust development & evaluation and better usability of future tools.

We provide the two best-performing ML-based tools, BLAST and the ensemble method as user-friendly software, as well as our proposed datasets, publicly available via GitHub.
Not Too Late to Intervene? A Meta-analysis of 13 Studies Evaluating the Association of Endovascular Therapy with Clinical Outcomes in Stroke Patients Presenting Beyond 24 Hours
Authors: Doheim Mohamed F , Hagrass Abdulrahman Ibrahim
Published: September 2024

Background

Association of endovascular therapy (EVT) with clinical outcomes beyond 24 hours remains unclear. We conducted a meta-analysis to answer this question.

Methods

We searched for eligible studies in PubMed from inception until June 2023. The outcomes included functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2), thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Risk ratio (RR) and 95% confidence interval (CI) were pooled.

Results

We finally included 13 studies in our meta-analysis (number of patients treated with EVT beyond 24 h=866). For single arm analysis, the pooled estimates of functional independence (mRS 0-2), sICH, and mortality were 0.342 (95% CI = 0.275 -0.410, P < 0.001), 0.062 (95% CI = 0.045 -0.078, P < 0.001), and 0.232 (95% CI = 0.164 -0.301, P < 0.001); respectively with successful reperfusion (TICI 2b-3) of 0.837 (95% CI = 0.812 -0.861, P < 0.001). Comparing EVT with medical management, the pooled analysis showed that EVT had a statistically significant advantage over medical management (RR = 2.62, 95% CI [1.38, 4.96], P = 0.003). However, our analysis showed a higher incidence of sICH in EVT group (RR = 3.58, 95% CI [1.53, 8.37], P = 0.003). When we pooled studies comparing EVT beyond 24 h with EVT within 6–24 h, the findings showed no statistically significant difference for functional independence, sICH, and 90-d Mortality.

Conclusion

EVT is associated with better clinical outcomes than medical management beyond 24 hours. These results are iconoclastic enhancing a new paradigm in which a contemporary restriction to specific time window to treat patients rather than their own clinical and imaging characteristics seems to be anecdotal. Prospective studies are needed to confirm the best eligible patients for EVT in this newly proposed window extension.