bluuebunny/crossref_metadata_2025 huggingface dataset:
Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022
Authors: Shan Qijun , Ma Xudong , Chen Yujie , Zhou Guanghua , Gao Sifa , Sun Jialu , Guo Fuping , Zhang Feng , Ma Dandan , Sun Guoqiang , Zhu Wen , Meng Xiaoyang , Ruan Guiren , Zhang Yuelun , Tan Xutong , Liu Dawei , Wang Yi , Yin Chang , Zhou Xiang ,   On behalf of Children Hepatitis in China, China National Critical Care Quality Control Center Group and National Quality Control Center for Medical Record Management
Published: January 2024

Background:

Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.

Methods:

Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis.

Results:

The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0).

Conclusion:

The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.
Development of a standard set of data variables and a database platform for panvascular disease
Authors: Yang Jing , Su Xi , Dong Zhihui , Yang Pengfei , Shi Xiaoming , Wang Jiangang , Zheng Xueying , Tong Zhu , Zhang Hongjian , Hu Hao , Luo Sihui , Sun Wen , Sun Xiaotong , Zhang Yingmei , Ge Junbo ,   on behalf of the Panvascular Medicine Expert Committee
Published: January 2024

Panvascular disease has emerged as a growing disease burden worldwide, highlighting the requirement of advanced research based on a holistic perspective. Establishing a standard set of data variables for clinical research on epidemiology, risk evaluation, diagnostic strategy, the efficacy of therapeutics, and care quality monitoring is paramount. A multidisciplinary working group consisting of 12 experts developed a standardized data variables and definitions through a systemic review and analysis of major domestic and international guidelines, clinical research articles, and standard terminologies in conjunction with data on Chinese clinical treatment and practice and research needs. A total of 555 data variables were included, among which 129 were mandatory. The key domains based on the timeline of care delivery are as follows: (1) demographics, (2) patient characteristics and comorbidities, (3) presentation details, (4) laboratory testing, (5) non-invasive tests, (6) invasive procedures/operations, (7) pre-discharge review, (8) risk assessment, and (9) follow-up. Patients with atherosclerotic cardiovascular disease, subclinical atherosclerosis, and high-risk factors are eligible for enrollment into the database. As of March 31, 2023, a total of 20 participating hospitals have started collecting patient data. A total of 2,106 patients have been enrolled.
Low-density lipoprotein cholesterol reduction is associated with computed tomography angiography signs of regression and stabilization of coronary plaque: from the TARGET trial
Authors: Guo Ziqiang , Chen Guanxi , Ding Yipu , Wang Xi , Shan Dongkai , Liu Zinuan , Jing Jing , Chen Yundai , Yang Junjie
Published: January 2024

Background and purpose:

The effectiveness of low-density lipoprotein cholesterol (LDL-C) lowering therapy in patients with higher baseline LDL-C levels has been extensively studied in Western populations. However, it remains uncertain whether the standard low-to-moderate lipid-lowering therapy practiced in Chinese individuals can lead to coronary plaque regression. Our objective is to explore the connections between plaque regression/stabilization, baseline LDL-C levels, and the extent of LDL-C reduction.

Methods:

This study constitutes a post hoc analysis derived from the TARGET trial, which initially recruited patients diagnosed with stable coronary artery disease (CAD) exhibiting an intermediate stenosis range of 30% to 90% as detected through coronary computed tomographic angiography (CCTA). Eligible participants for this analysis had undergone both baseline CCTA and a minimum 1-year follow-up. Patients were categorized into four groups based on their LDL-C levels and the degree of LDL-C reduction during the follow-up period. The assessment of coronary plaque regression within each group was conducted through the analysis of CCTA images, examining parameters such as total plaque (TP), percent atheroma volume (PAV), non-calcified plaque (NCP), low-attenuation plaque (LAP), and calcified plaque (CP).

Results:

Among the participants analyzed, totaling 287 individuals with an average age of 59.7 ± 7.1 years, comprising 69.7% men, the median duration between the initial and subsequent scans stood at 21 months (Q1–Q3, 15–29 months). Among these, 76 patients (26.5%) had been receiving statin therapy consistently before the baseline scan (defined as continued statin treatment), while 179 patients (62.3%) had commenced statin therapy after the baseline scan but before the follow-up scan (classified as new statin therapy). Notably, plaque regression was observed in 79 patients (28%), notably more frequent in those with higher baseline LDL-C levels and individuals who achieved a >25% reduction in LDL-C (P < 0.001). The median annual progression of TP was 1.9 (interquartile range [IQR] = −3.6 to 11.8), while for NCP, it was 1.5 (IQR = −4.6 to 11.0). In a multivariate logistic regression analysis, plaque regression demonstrated independent associations with LDL-C reduction exceeding 25% (odds ratio [OR] = 2.103, 95% confidence interval [95% CI] = 1.408–3.836) and baseline LDL-C levels (OR = 1.024, 95% CI = 1.004–1.044).

Conclusions:

Modest LDL-C reduction was associated with computed tomography angiography (CTA) evidence of coronary plaque regression and stabilization. The plaque regression is particularly marked in patients with a high baseline LDL-C level and LDL-C reduction of >25%.
Pitavastatin in the Prevention of Cardiovascular Disease in People Living with HIV: A Review
Authors: Whiteson Harris Z. , Drogy Maddison , Eickel Grant , Frishman William H.
Published: January 2024

HIV is associated with a wide array of pathophysiologic mechanisms that ultimately contribute to mortality. While HIV is traditionally known as a disease that attacks the immune system, it is now established that infection with HIV can cause cardiovascular disease (CVD). Through inflammation, atherogenesis, interactions with antiretroviral therapy/highly-active antiretroviral therapy (ART/HAART), and other mechanisms, HIV is an independent risk factor for the development of CVD. The treatment of the CVD risks associated with HIV is complicated, especially due to interactions with hyperlipidemic drugs and ART/HAART. There is a prompt need for a drug (or drug class) that is known to reduce the risk of CVD, specifically in people living with HIV. Recently, the randomized trial to prevent vascular events in HIV trial evaluated the usage of pitavastatin in preventing major cardiac events in people with HIV, showing a significant reduction in cardiac events among those taking the therapeutic. In this review, we evaluate the mechanisms by which HIV contributes to CVD, and the randomized trial to prevent vascular events in HIV trial, and postulate about future directions of the drug in treating people living with HIV.
An update on the current indications for in vitro maturation
Authors: Ho Vu N-A. , Ho Tuong M. , Vuong Lan N. , García-Velasco Juan
Published: January 2024

Purpose of review

In vitro maturation has become a significant component of modern assisted reproductive techniques. Published data have been supported for the safety and effectiveness of in vitro maturation treatment. In recent years, potential indications for in vitro maturation (IVM) have been a topic of interest and investigation.

Recent findings

Significant improvements in technique enhancement and data publication for evaluating the efficacy of IVM have been achieved. Recent studies have shown that IVM could offer several advantages over in vitro fertilization. Currently, there are growing indications for IVM beyond the commonly mentioned indication of infertile women with polycystic ovary syndrome. Additionally, some potential candidates might have significant advantages for IVM, such as women diagnosed with gonadotropin resistance ovary syndrome or those seeking fertility preservation. With a better understanding of IVM, from basic science to clinical practice, it can be applied safely, effectively, and affordably to a broader range of patients, making it a more accessible and patient-friendly option.

Despite the possibly acknowledged limitations, the potential of in vitro maturation cannot be denied. As this technique becomes increasingly accessible to patients and more continuous efforts are dedicated to advancing this technique, the impact of in vitro maturation is expected.
Beyond Weight Loss: the Emerging Role of Incretin-Based Treatments in Cardiometabolic HFpEF
Authors: Capone Federico , Nambiar Natasha , Schiattarella Gabriele G.
Published: January 2024

Purpose of review

Incretin-based drugs are potent weight-lowering agents, emerging as potential breakthrough therapy for the treatment of obesity-related phenotype of heart failure with preserved ejection fraction (HFpEF). In this review article, we will discuss the contribution of weight loss as part of the benefits of incretin-based medications in obese patients with HFpEF. Furthermore, we will describe the potential effects of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists on the heart, particularly in relation to HFpEF pathophysiology.

Recent findings

In the STEP-HFpEF trial, the GLP-1 receptor agonist semaglutide significantly improved quality of life outcomes in obese HFpEF patients. Whether the beneficial effects of semaglutide in obese patients with HFpEF are merely a consequence of body weight reduction is unclear. Considering the availability of other weight loss strategies (e.g., caloric restriction, exercise training, bariatric surgery) to be used in obese HFpEF patients, answering this question is crucial to provide tailored therapeutic options in these subjects.

Incretin-based drugs may represent a milestone in the treatment of obesity in HFpEF. Elucidating the contribution of weight loss in the overall benefit observed with these drugs is critical in the management of obese HFpEF patients, considering that other weight-lowering strategies are available and might represent potential alternative options for these patients.
Levamisole-Adulterated Cocaine-Induced Mucous Membrane Pemphigoid: Case Reports and Literature Review
Authors: Thijs Elke , Hurley Daire , Cummings Brendan , Elewaut Dirk , Verougstraete Nick , Claerhout Ilse , Murphy Conor C. , Power William , Roels Dimitri
Published: January 2024

Purpose:

The aim of this study was to report 2 cases of levamisole-adulterated cocaine-induced mucous membrane pemphigoid.

Methods:

This study is a review of case reports and literature.

Results:

Two patients presented with bilateral severe purulent conjunctivitis, corneal ulceration, and rapidly progressive forniceal shortening. Both patients were active cocaine users. A complete blood analysis showed a positive antineutrophil cytoplasmic antibody immunofluorescence with a mixed perinuclear antineutrophil cytoplasmic antibody and cytoplasmic-staining antineutrophil cytoplasmic antibody pattern. Direct immunofluorescence examination of conjunctival tissue showed linear deposition of component 3 and immunoglobulins at the basal membrane. A diagnosis of levamisole-adulterated cocaine-induced mucous membrane pemphigoid was made. In case 1, this suspicion was confirmed by investigating remnants of cocaine on the patient's debit card using mass spectrometry, which contained traces of levamisole. In both cases, aggressive immunosuppressive therapy combining systemic corticosteroids and rituximab was able to control the disease. However, by the time these therapies were initiated, significant corneal injury had occurred requiring corneal grafts in both patients.

Conclusions:

Given the rising abuse of cocaine, it is important that ophthalmologists are made aware of its association with severe atypical cicatricial conjunctivitis. To the best of our knowledge, we present the first case proving the causal relationship between levamisole and ocular cicatricial pemphigoid.
Weight loss, bariatric surgery, and novel antidiabetic drugs effects on diabetic retinopathy: a review
Authors: Perez Alejandro M. , Neag Emily , Sridhar Jayanth , Williams Basil K.
Published: January 2024

Purpose of review

Diabetic retinopathy (DR) is a leading cause of visual impairment, and the increasing prevalence of diabetes and obesity will impact rates of visual impairment moving forward. Our review aims to synthesize the current body of evidence regarding the impact of lifestyle interventions, such as weight loss, bariatric surgery, and novel antidiabetic drugs, on DR.

Recent findings

Literature review revealed insufficient evidence regarding the impact of weight loss on DR. Preoperative DR patients undergoing bariatric surgery were found to have similar short-term chances of improvement or worsening DR. Progression of DR with glucagon-like peptide 1 receptor agonists treatments appears unrelated to specific drugs and was also observed with traditional antidiabetic medications.

Rapidly correcting HbA1c levels (≥2%) can paradoxically lead to early worsening DR. Patients considering weight loss, bariatric surgery, and novel antidiabetic drugs should be aware of the potential for DR progression, but they should not be discouraged, as achieving glycemic control is essential for reducing long-term morbidity and mortality from other diabetes-related complications. It is advisable to conduct a baseline retinal examination before treatment and continue monitoring during therapy. Further research is needed to understand the long-term effects of these treatments on DR.
Implementing mobile text messaging on glycemic control in patients with diabetes mellitus
Authors: Tuzon Jan , Mulkey David C.
Published: January 2024

Background:

Uncontrolled blood glucose may lead to serious complications in patients with type two diabetes mellitus (T2DM). Patients may not have the support, motivation, or encouragement to adhere to the lifestyle changes necessary to control their T2DM.

Local problem:

More than 75% of the primary care clinic's patients are diagnosed with T2DM, with most patients at the practice site having an average hemoglobin A1c (HbA1c) level of 8.5%. The primary care clinic did not use text messaging to disseminate diabetes self-management education and support (DSMES) as outlined in Standard 4 of the American Diabetic Association's (ADA) clinical practice guideline.

Methods:

This evidence-based quality improvement project was conducted in a rural outpatient primary care clinic to determine whether implementing the ADA's 2022 National Standards for DSMES using text messaging would affect HbA1C levels among adult patients with T2DM.

Interventions:

Patients were sent weekly text messages over a 12-week period. Text messages contained information promoting self-care, tips about healthy diet, exercise reminders, instructions about proper blood glucose monitoring, and reminders about medication adherence.

Results:

A total of 160 patients were included. A paired-sample t-test showed a reduction in HbA1c levels after the intervention from baseline (M = 7.53, SD = 1.72) to postimplementation (M = 6.91, SD = 0.89), t (159) = 11.88, p = .001.

Conclusion:

Based on the results, implementing the ADA's National Standards for DSMES Standard 4 may affect HbA1c levels in this population.
Racial Disparities in Pelvic Floor Disorders
Authors: Sarzo Carlotta , Nurmahomed Nur , Ralston Charlotte , Igbedioh Carlene , Schizas Alexis , Hainsworth Alison , Ferrari Linda
Published: January 2024

Objective:

To investigate the impact of racial disparities and socioeconomic status on pelvic floor disorder (PFD) care.

Background:

Racial disparities in colorectal PFD remain uninvestigated, despite prior research in urogynecology.

Methods:

This retrospective study was conducted at Guy’s and St. Thomas’ Hospital of London in 2023. Patients with colorectal PFD from 2013 to 2018 were evaluated. Patients were classified according to the Index of Multiple Deprivation (IMD) scores and divided into quintiles. The lowest quintile represents the most deprived, whereas the higher quintile represents the least deprived. Assessed variables are: patient complaints, symptoms, consultant and biofeedback referrals, investigations, multidisciplinary meeting (MDM) discussions, treatment, and follow-up appointments.

Results:

A total of 2001 patients were considered. A total of 1126 patients were initially analyzed, and 875 patients were excluded owing to incomplete data. Eight ethnic groups were identified in this study. Constipation was the most common complaint across ethnic groups (P = 0.03). Diagnostics, MDM discussions, and conservative treatment did not vary among ethnicities. White British and Asian patients were significantly more likely to be seen by a consultant (P = 0.001) and undergo surgery (P = 0.002). In the second part of the study, the IMD was calculated for 1992 patients who were categorized into quintiles. Diagnostic tests, discussion in MDM, consultant review, and surgical treatments were significantly lower in the 2 lowest quintiles (P < 0.001, P < 0.001, P = 0.02, and P = 0.02, respectively). Conservative treatment did not vary between the IMD groups.

Conclusions:

Disparities in the diagnosis and treatment of colorectal PFD exist among ethnic minorities and patients of low socioeconomic status. This study allows for the replication of service provision frameworks in other affected areas to minimize inequalities.
“I Have a Different Perspective as I Am Working Through This”
Authors: DeThorne Laura S. , Pierce Kelli , Rang Mariesa , Schafer Sabrina , VanRyswyk Karli , Angulo-Jiménez Henry
Published: January 2024

Purpose:

Whereas the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) characterizes autism as a neurological disorder typified by impairment in social communication and restricted interests/repetitive behaviors (American Psychiatric Association, 2013), the neurodiversity paradigm focuses on autism as a form of neurological diversity that may be central to a person's identity. The purpose of this study was to pilot the Autism Understanding Tool for Introspection and Evaluation (AUTIE) as a means to encourage and examine speech–language pathologists' (SLPs) reflections on autism.

Methods:

We utilized purposeful maximum variation sampling to recruit nine SLPs (one being a graduate student) and administered a “think aloud” procedure with video conferencing to elicit their reflections while taking the AUTIE. Participant reflections were analyzed using three sequential phases of inductive thematic analysis.

Results:

The analysis of 270 self-reflective comments led to eight key themes that were each associated with comments from four or more of the nine participating SLPs: (a) acknowledgment of divergent perspectives, (b) specification of environmental barriers, (c) importance of autistic identity, (d) questioning the concept of normality, (e) resolving tensions through person-centered care, (f) integrating multiple forms of expertise, (g) parallels with other marginalized identities, and (h) changes in views over time. We contextualized the themes by embedding examples within analytic narratives from two autistic SLP participants

Conclusion:

Results supported use of the AUTIE as a tool to elicit meaningful reflection about the divergent and evolving views of autism. Implications focused on the need to address this complex landscape both within our individualized clinical practice and our professional field at large.
Comparison of sensitivity among dynamic balance measures during walking with different tasks
Authors: Yamagata Shunsuke , Yamaguchi Takeshi , Shinya Masahiro , Milosevic Matija , Masani Kei
Published: January 2024

Although various measures have been proposed to evaluate dynamic balance during walking, it is currently unclear which measures are most sensitive to dynamic balance. We aimed to investigate which dynamic balance measure is most sensitive to detecting differences in dynamic balance during walking across various gait parameters, including short- and long-term Lyapunov exponents (
λ
s
and
λ
l
), margin of stability (MOS), distance between the desired and measured centre of pressure (dCOP–mCOP) and whole-body angular momentum (WBAM). A total of 10 healthy young adults were asked to walk on a treadmill under three different conditions (normal walking, dual-task walking with a Stroop task as an unstable walking condition, and arm-restricted walking with arms restricted in front of the chest as another unstable walking condition) that were expected to have different dynamic balance properties. Overall, we found that
λ
s
of the centre of mass velocity,
λ
s
of the trunk velocity,
λ
s
of the hip joint angle, and the magnitude of the mediolateral dCOP–mCOP at heel contact can identify differences between tasks with a high sensitivity. Our findings provide new insights into the selection of sensitive dynamic balance measures during human walking.
Optofluidic passive parity-time-symmetric systems
Authors: Assogba Onanga Franck , Chandrahalim Hengky
Published: January 2024

This research introduces a novel methodology of harnessing liquids to facilitate the realization of parity-time (
PT
)-symmetric optical waveguides on highly integrated microscale platforms. Additionally, we propose a realistic and detailed fabrication process flow, demonstrating the practical feasibility of fabricating our optofluidic system, thereby bridging the gap between theoretical design and actual implementation. Extensive research has been conducted over the past two decades on
PT
-symmetric systems across various fields, given their potential to foster a new generation of compact, power-efficient sensors and signal processors with enhanced performance. Passive
PT
-symmetry in optics can be achieved by evanescently coupling two optical waveguides and incorporating an optically lossy material into one of the waveguides. The essential coupling distance between two optical waveguides in air is usually less than 500 nm for near-infrared wavelengths and under 100 nm for ultraviolet wavelengths. This necessitates the construction of the coupling region via expensive and time-consuming electron beam lithography, posing a significant manufacturing challenge for the mass production of
PT
-symmetric optical systems. We propose a solution to this fabrication challenge by introducing liquids capable of dynamic flow between optical waveguides. This technique allows the attainment of evanescent wave coupling with coupling gap dimensions compatible with standard photolithography processes. Consequently, this paves the way for the cost-effective, rapid and large-scale production of
PT
-symmetric optofluidic systems, applicable across a wide range of fields.
Optimal entropic properties of SARS-CoV-2 RNA sequences
Authors: Formentin Marco , Chignola Roberto , Favretti Marco
Published: January 2024

The reaction of the scientific community against the COVID-19 pandemic has generated a huge (approx. 10
6
entries) dataset of genome sequences collected worldwide and spanning a relatively short time window. These unprecedented conditions together with the certain identification of the reference viral genome sequence allow for an original statistical study of mutations in the virus genome. In this paper, we compute the Shannon entropy of every sequence in the dataset as well as the relative entropy and the mutual information between the reference sequence and the mutated ones. These functions, originally developed in information theory, measure the information content of a sequence and allows us to study the random character of mutation mechanism in terms of its entropy and information gain or loss. We show that this approach allows us to set in new format known features of the SARS-CoV-2 mutation mechanism like the CT bias, but also to discover new optimal entropic properties of the mutation process in the sense that the virus mutation mechanism track closely theoretically computable lower bounds for the entropy decrease and the information transfer.
The skeletal completeness of the Palaeozoic chondrichthyan fossil record
Authors: Schnetz Lisa , Butler Richard J. , Coates Michael I. , Sansom Ivan J.
Published: January 2024

Chondrichthyes (sharks, rays, ratfish and their extinct relatives) originated and diversified in the Palaeozoic but are rarely preserved as articulated or partly articulated remains because of their predominantly cartilaginous endoskeletons. Consequently, their evolutionary history is perceived to be documented predominantly by isolated teeth, scales and fin spines. Here, we aim to capture and analyse the quality of the Palaeozoic chondrichthyan fossil record by using a variation of the skeletal completeness metric, which calculates how complete the skeletons of individuals are compared to estimates of their original entirety. Notably, chondrichthyan completeness is significantly lower than any published vertebrate group: low throughout the Silurian and Permian but peaking in the Devonian and Carboniferous. Scores increase to a range similar to pelycosaurs and parareptiles only when taxa identified solely from isolated teeth, scales and spines are excluded. We argue that environmental influences probably played an important role in chondrichthyan completeness. Sea level significantly negatively correlates with chondrichthyan completeness records and resembles patterns already evident in records of ichthyosaurs, plesiosaurs and sauropodomorphs. Such observed variations in completeness highlight the impact of different sampling biases on the chondrichthyan fossil record and the need to acknowledge these when inferring patterns of chondrichthyan macroevolution.
An equivariant Reeb–Beltrami correspondence and the Kepler–Euler flow
Authors: Fontana-McNally Josep , Miranda Eva , Peralta-Salas Daniel
Published: January 2024

We prove that the correspondence between Reeb and Beltrami vector fields presented in Etnyre & Ghrist (Etnyre, Ghrist 2000Nonlinearity13, 441–458 (doi:10.1088/0951-7715/13/2/306)) can be made equivariant whenever additional symmetries of the underlying geometric structures are considered. As a corollary of this correspondence, we show that energy levels above the maximum of the potential energy of mechanical Hamiltonian systems can be viewed as stationary fluid flows, though the metric is not prescribed. In particular, we showcase the emblematic example of then-body problem and focus on the Kepler problem. We explicitly construct a compatible Riemannian metric that makes the Kepler problem of celestial mechanics a stationary fluid flow (of Beltrami type) on a suitable manifold, theKepler–Euler flow.
Rapid divergent evolution of internal female genitalia and the coevolution of male genital morphology revealed by micro-computed tomography
Authors: Sloan Nadia S. , Harvey Mark S. , Huey Joel A. , Simmons Leigh W.
Published: January 2024

Animal genitalia are thought to evolve rapidly and divergently in response to sexual selection. Studies of genital evolution have focused largely on male genitalia. The paucity of work on female genital morphology is probably due to problems faced in quantifying shape variation, due to their composition and accessibility. Here we use a combination of micro-computed tomography, landmark free shape quantification and phylogenetic analysis to quantify the rate of female genital shape evolution among 29 species ofAntichiropusmillipedes, and their coevolution with male genitalia. We found significant variation in female and male genital shape among species. Male genital shape showed a stronger phylogenetic signal than female genital shape, although the phylogenetic signal effect sizes did not differ significantly. Male genital shape was found to be evolving 1.2 times faster than female genital shape. Female and male genital shape exhibited strong correlated evolution, indicating that genital shape changes in one sex are associated with corresponding changes in the genital shape of the other sex. This study adds novel insight into our growing understanding of how female genitalia can evolve rapidly and divergently, and highlights the advantages of three-dimensional techniques and multivariate analyses in studies of female genital evolution.
Lack of detection of SARS-CoV-2 in wildlife from Kerala, India in 2020–21
Authors: Zachariah Arun , Krishnankutty Sajesh P. , Manazhi Jishnu , Omanakuttan Vishnu , Santosh Sam , Blanchard Adam , Tarlinton Rachael
Published: January 2024

Spillover of SARS-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white-tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), six Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus (Common Palm Civet), five Viverricula indica (Small Indian Civet), four Herpestes edwardsii (Common Mongoose), ten Panthera tigris (Bengal Tiger), eight Panthera pardus fusca (Indian Leopard), four Prionailurus bengalensis (Leopard cats), two Felis chaus (Jungle cats), two Cuon alpinus (Wild dogs) and one Melursus ursinus (sloth bear).
Using unsupervised topic modeling to uncover document hierarchy and latent topics in prostate cancer clinical texts
Authors: Denti Tuulia , Sun Wei , Ji Shaoxiong , Moen Hans , Kerro Oleg , Rannikko Antti , Marttinen Pekka , Koskinen Miika
Published: January 2024

Objective

Medical records reflect patients’ health status and journey through healthcare services and medical specialties. As a result, document collections contain various text types, even about one patient, which makes medical texts unique. Our aim was to take advantage of the implicit document hierarchy of medical records to evaluate contextualized neural topic modeling as a tool to gain insight into a mixed set of notes related to prostate cancer treatment, i.e., to uncover document types, their contents, and relations.

Materials and Methods

We collected clinical text documents from 21,872 prostate cancer patients and organized the documents into a hierarchy using the document metadata. We trained neural topic models without the metadata to index the document collections, performed rigorous numerical evaluations of topic and clustering quality to optimize the topic count, visualized the latent representation of the models, and evaluated the topic clusters with respect to document metadata.

Results

Topic clusters reflected the structure of the document hierarchy and provided information about the contents of different text types. The determination of the optimal number of topics required complementary information by topic and clustering quality metrics.

Discussion

The topic modeling was found useful in visualizing and indexing large document collections, in providing an understanding of document contents, and in revealing document organization comparable to metadata-based hierarchy.

Conclusion

Hospital databases contain masses of text documents, and topic modeling can provide means for analysts and researchers to group documents into discernable and explainable classes.
RNA G-quadruplex dynamic steers the crosstalk between protein synthesis and energy metabolism
Authors: Dumas Leïla , Shin Sauyeun , Rigaud Quentin , Cargnello Marie , Hernández-Suárez Beatriz , Herviou Pauline , Saint-Laurent Nathalie , Leduc Marjorie , Le Gall Morgane , Monchaud David , Dassi Erik , Cammas Anne , Millevoi Stefania
Published: January 2024

Cancer cells rely on mitochondria for their bioenergetic supply and macromolecule synthesis. Central to mitochondrial function is the regulation of mitochondrial protein synthesis, which primarily depends on the cytoplasmic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing evidence that mitochondrial protein synthesis contributes to the onset and progression of cancer, and can thus offer new opportunities for cancer therapy, knowledge of the underlying molecular mechanisms remains limited. Here, we show that RNA G-quadruplexes (RG4s) regulate mitochondrial function by modulating cytoplasmic mRNA translation of nuclear-encoded mitochondrial proteins. Our data support a model whereby the RG4 folding dynamics, under the control of oncogenic signaling and modulated by small molecule ligands or RG4-binding proteins, modifies mitochondria-localized cytoplasmic protein synthesis. Ultimately, this impairs mitochondrial functions, affecting energy metabolism and consequently cancer cell proliferation.
A Simple and Rapid Protocol for the Isolation of Murine Bone Marrow Suitable for the Differentiation of Dendritic Cells
Authors: Song Runqiu , Bafit Mariam , Tullett Kirsteen M. , Tan Peck Szee , Lahoud Mireille H. , O’Keeffe Meredith , Purcell Anthony W. , Braun Asolina
Published: January 2024

The generation of bone marrow-derived dendritic cells is a widely used approach in immunological research to study antigen processing and presentation as well as T cell activation responses. However, the initial step of isolating the bone marrow can be time-consuming, especially when larger numbers of precursor cells are required. Here, we assessed whether an accelerated bone marrow isolation method using centrifugation is suitable for the differentiation of FMS-like tyrosine kinase 3 ligand-driven dendritic cells. Compared to the conventional flushing method, the centrifugation-based isolation method resulted in a similar bone marrow cell yield on day 0, increased cell numbers by day 8, similar proportions of dendritic cell subsets, and consequently a higher number of type 1 conventional dendritic cells (cDC1) from the culture. Although the primary purpose of the method optimization was to improve experimental efficiency and increase the output of cDC1s, the protocol is also compatible with the differentiation of other dendritic cell subsets such as cDC2 and plasmacytoid dendritic cells, with an improved output cell count and a consistent phenotype.
Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection
Authors: Hao Qinggang , Shen Junling , Sang Lei , Bai Yan , Sun Jianwei
Published: January 2024

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds ofin vivoscreening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improve our understanding of the metastasis mechanisms, but also provide potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.
IL-2 immunotherapy rescues irradiation-induced T cell exhaustionin vivo
Authors: Yong Carmen S. M. , Telarovic Irma , Gregor Lisa , Raeber Miro E. , Pruschy Martin , Boyman Onur
Published: January 2024

Radiotherapy (RT) can stimulate anti-cancer T cell responses that target primary and distant tumors. In addition to antigen-mediated stimulation of effector T cells, signals from stimulatory cytokines, notably interleukin-2 (IL-2), are necessary for optimal T cell function and memory. However, timing and IL-2 receptor (IL-2R) bias of such signals are ill-defined. Using image-guided RT in a mouse colon cancer model, we observed that single high-dose (1 x 20 Gy) RT transiently upregulated IL-2Rα (CD25) on effector CD8+T cells, facilitating the use of CD25-biased IL-2 immunotherapy. Timed administration of CD25-biased IL-2 treatment after RT favored the expansion of tumor-infiltrating CD8+T cells over regulatory T cells and IL-2Rβ (CD122)highCD8+T cells, which resulted in comparable anti-tumor effects as with RT plus CD122-biased IL-2 immunotherapy. Moreover, intratumoral CD8+T cells from animals receiving combined IL-2R-biased IL-2 and RT showed reduced signatures of T cell exhaustion. Finally, these combination treatments affected both primary irradiated and distant non-irradiated tumors, achieving durable responses. We demonstrate that timed and IL-2R subunit-biased IL-2 immunotherapy synergized with single high-dose RT to achieve potent anti-cancer immunity.
An LPS-dephosphorylating alkaline phosphatase of PhoA family from the marine bacteriumCobetia amphilectiKMM 296 and multiplicity of alkaline phosphatase families inCobetiaspp
Authors: Balabanova Larissa , Bakholdina Svetlana , Buinovskaya Nina , Noskova Yulia , Kolpakova Oksana , Vlasova Vanessa , Bondarev Georgii , Seitkalieva Aleksandra , Son Oksana , Tekutyeva Liudmila
Published: January 2024

A highly active alkaline phosphatase (ALP) from the mollusk strain of the marine bacteriumCobetia amphilectiKMM 296 (CmAP) was found to remove phosphorus from theEscherichia colilipopolysaccharides (LPS). Phylogenetic analysis of the amino acid sequences of ALPs found in 36 availableCobetiagenomes revealed that CmAP and its homologues from nine strains clustered together with the human and squid LPS-detoxifying enzymes. Each strain of the genusCobetiahas a variety of ALPs mostly of the PhoD and PhoX families. The PhoA gene encoding for the CmAP-like ALP is characteristic for the subspeciesC. amphilecti, with a complete set of four ALP families, including PafA and two PhoD structures (5 genes). However, a single strain of the speciesCobetia crustatorumJO1Tfrom fermented shrimp, phylogenetically distant fromC. amphilectiandC. marina, among four ALPs contains a CmAP homologue carrying an inactive mutation. Apparently, the multiplicity of ALPs in bacteria of the genusCobetiais a trait of incredible adaptation to a phosphorus-depleted environment and a specialty of organophosphate destructor in eco-niches to which they once emerged, includingZosteraspp. roots. The ALP clusterization and an identity level of the genus-specific biosynthetic genes encoding for ectoine and polyketide cluster T1PKS, responsible for sulfated extracellular polysaccharide synthesis, coincide with a new whole genome-based taxonomic classification of the genusCobetia. The LPS-dephosphorylating property of the PhoA familyC. amphilectiALP CmAP may be used in the development of anti-inflammatory drugs.
Metagenomic Insights Reveal Unrecognized Diversity of Entotheonella in JapaneseTheonellaSponges
Authors: Yamabe Sota , Yoshitake Kazutoshi , Ninomiya Akihiro , Piel Jörn , Takeyama Haruko , Matsunaga Shigeki , Takada Kentaro
Published: January 2024

Numerous biologically active natural products have been discovered from marine sponges, particularly fromTheonella swinhoei, which is known to be a prolific source of natural products such as polyketides and peptides. Recent studies have revealed that many of these natural products are biosynthesized byCandidatusEntotheonella phylotypes, which are uncultivated symbionts withinT. swinhoei. Consequently, Entotheonella is considered an untapped biochemical resource. In this study, we conducted metagenomic analyses to assess the diversity of Entotheonella in fourT. swinhoeiindividuals (two each of chemotypes Y and W), after separating filamentous bacteria using density gradient centrifugation. We obtained five Entotheonella genomes from filamentous bacteria-enriched fractions. Notably, one of these genomes is significantly different from previously reported Entotheonella variants. Additionally, we identified closely related Entotheonella members present across different chemotypes ofT. swinhoei. Thus, our metagenomic insights reveal that the diversity of Entotheonella withinTheonellasponges is greater than previously recognized.
High-throughput single-cell, single-mitochondrial DNA assay using hydrogel droplet microfluidics
Authors: Park Juhwan , Kadam Parnika S. , Atiyas Yasemin , Chhay Bonirath , Tsourkas Andrew , Eberwine James H. , Issadore David A.
Published: January 2024

There is growing interest in understanding the biological implications of single cell heterogeneity and intracellular heteroplasmy of mtDNA, but current methodologies for single-cell mtDNA analysis limit the scale of analysis to small cell populations. Although droplet microfluidics have increased the throughput of single-cell genomic, RNA, and protein analysis, their application to sub-cellular organelle analysis has remained a largely unsolved challenge. Here, we introduce an agarose-based droplet microfluidic approach for single-cell, single-mtDNA analysis, which allows simultaneous processing of hundreds of individual mtDNA molecules within >10,000 individual cells. Our microfluidic chip encapsulates individual cells in agarose beads, designed to have a sufficiently dense hydrogel network to retain mtDNA after lysis and provide a robust scaffold for subsequent multi-step processing and analysis. To mitigate the impact of the high viscosity of agarose required for mtDNA retention on the throughput of microfluidics, we developed a parallelized device, successfully achieving ~95% mtDNA retention from single cells within our microbeads at >700,000 drops/minute. To demonstrate utility, we analyzed specific regions of the single mtDNA using a multiplexed rolling circle amplification (RCA) assay. We demonstrated compatibility with both microscopy, for digital counting of individual RCA products, and flow cytometry for higher throughput analysis.
Convergence for Inactivation of TGFβ Signaling Is a Common Feature of Advanced Pancreatic Cancer
Authors: Hong Jungeui , Kohutek Zachary , Zhang Haochen , Karnoub Elias-Ramzey , Kappagantula Rajya , Wood Laura D. , Iacobuzio-Donahue Christine
Published: January 2024

We performed WES of 250 unique tumor tissues from 30 multiregion sampled pancreatic cancer research autopsies from patients diagnosed with advanced stage disease. We find that most genetic alterations in PDAC occur in a subclonal manner, and some genes occurred in a subclonal manner exclusively. Convergent evolution within the TGFβ pathway was also identified as a common feature of advanced stage disease, withSMAD4inactivation more common among metastatic PDACs compared to inactivation of TGFβ surface receptors that was more common in locally advanced tumors. The mode of clinical management (radiation versus chemotherapy) contributed distinct mutational signatures yet these mutations are not predicted to have functional relevance to tumor progression. Overall, these findings provide a first definition of the genetic features that distinguish among patients with locally advanced versus metastatic PDAC. These findings may have clinical relevance in upfront clinical decision making for the optimal candidates for neoadjuvant therapy.
Urolithin A improves Alzheimer’s disease cognition and restores mitophagy and lysosomal functions
Authors: Hou Yujun , Chu Xixia , Park Jae-Hyeon , Zhu Qing , Hussain Mansoor , Li Zhiquan , Madsen Helena Borland , Yang Beimeng , Wei Yong , Wang Yue , Fang Evandro F. , Croteau Deborah L. , Bohr Vilhelm A.
Published: January 2024

Background

Compromised autophagy, including impaired mitophagy and lysosomal function, is thought to play a pivotal role in Alzheimer’s disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of early and/or long-term treatment, as well as more detailed mechanisms of action, are not known.

Methods

We addressed these questions in three mouse models of AD, and behavioral, electrophysiological and biochemistry assays were performed.

Results

Long-term UA treatment significantly improved learning, memory and olfactory function in different AD transgenic mice. UA also reduced Aβ and Tau pathologies, and improved long-term potentiation. We found that UA activated autophagy/mitophagy via increasing lysosomal functions. At the cellular level, UA improved lysosomal function and normalized lysosomal cathepsins, especially targeting cathepsin Z, to restore lysosomal function in AD, indicating the important role of cathepsins in UA-induced therapeutic effects of AD.

Conclusions

Collectively, our study highlights the importance of lysosomal dysfunction in AD etiology, and points to the high translational potential of UA.