bluuebunny/crossref_metadata_2025 huggingface dataset:
Agarista hispidula var. tomentosa (Ericaceae), a new variety from Minas Gerais, Brazil
Authors: DALASTRA CLAUDENICE HILDA , HEIDEN GUSTAVO
Published: January 2025

Agarista (Ericaceae) is a Neotropical genus of subshrubs, shrubs and trees in Ericaceae, highly associated with tropical mountainous environments, especially the Campos Rupestres of the Cerrado domain in the Espinhaço Range, southeast Brazil. The genus comprises 35 species and six varieties. Minas Gerais state hosts a high richness of the genus, comprising 16 species, eight of them endemic. Here we indicate two partially geographically overlapping and morphologically characterized varieties, separable primarily by the indumentum on the abaxial leaf surface. The new variety Agarista hispidula var. tomentosa from Minas Gerais state is described here, and it is readily distinguished from Agarista hispidula var. hispidula by its dense layer of unicellular hairs on the abaxial leaf surface covering the abaxial epidermis. This character state is also found in three other species and two varieties of Agarista, and it may function in avoiding water loss. A detailed description and photograph plates are provided for the new variety. A key and a distribution map to the varieties of A. hispidula is also provided.
The first review of the subgenus Ganychorus Haliday, 1835 (Hymenoptera, Braconidae, Brachistinae) in China
Authors: LU QIAN-YU , CHAI HONG-FEI , ACHTERBERG CORNELIS VAN , TANG PU , CHEN XUE-XIN
Published: January 2025

A key to twenty-five Chinese species of the subgenus Ganychorus Haliday, 1835 is presented. Fifteen new species are proposed (B. (G.) aurigineus sp. nov., B. (G.) castaneus sp. nov., B. (G.) comatoides sp. nov., B. (G.) ejuncidus sp. nov., B. (G.) fuscifemur sp. nov., B. (G.) isoruficornis sp. nov., B. (G.) latiacis sp. nov., B. (G.) longitergitus sp. nov., B. (G.) mystrus sp. nov., B. (G.) scutellatus sp. nov., B. (G.) shanxiensis sp. nov., B. (G.) shennongjiaensis sp. nov., B. (G.) signiferoides sp. nov., B. (G.) tricolor sp. nov., B. (G.) xueshanensis sp. nov.) and three species (B. (G.) diversicornis (Nees, 1835), B. (G.) kangauzi Belokobylskij, 1995, and B. (G.) sutchanicus Belokobylskij, 1995) are newly recorded from China.
A new Amazonian species, description of male of Isanopus sahlbergi Bernhauer, 1917, and a revised key to species of Isanopus Sharp, 1876 (Coleoptera: Staphylinidae)
Authors: KLEMANN-JUNIOR LOURI , CHATZIMANOLIS STYLIANOS
Published: January 2025

We describe the male of Isanopus sahlbergi, and a new species of the genus Isanopus from French Guiana, Isanopus itoupe Klemann-Junior & Chatzimanolis, sp. nov. We illustrate major diagnostic features and present a revised key to species of Isanopus.
Correlation Between Preoperative Neutrophil-to-Lymphocyte Ratio and Clinicopathological Characteristics of Papillary Thyroid Carcinomas: Toward a Preoperative Biomarker
Authors: Ben Ammar Chaima , Tbini Makram , Riahi Ines , Ben Salah Mamia
Published: January 2025

Introduction: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, with considerable variability in its clinical presentation and prognosis. Recent studies have focused on the relationship between its clinicopathological characteristics and inflammatory biomarkers, particularly the preoperative neutrophil-to-lymphocyte ratio (NLR). Our aim was to investigate the correlation between NLR and the clinicopathological features of PTC. Methods: This was a retrospective study. We involved patients who underwent surgery for PTC over a 5-year period from January 2016 to December 2021. Based on the mean NLR value, the study population was divided into 2 groups, with Group 1 corresponding to patients with an elevated NLR. Results: Our study included 102 patients aged between 20 and 83 years. All patients were euthyroid. The mean preoperative NLR was 2.01 ± 0.62, with 53% of patients classified into Group 1. On ultrasound, most nodules were classified as EU-TIRADS 5, and 38% had a Bethesda category 6 cytology. Final histopathological analysis revealed microcarcinoma in the majority of cases. PTC was multifocal in 35 cases and bilateral in 38, with an aggressive histological variant observed in 45 cases. Multivariate analysis demonstrated a statistically significant correlation between NLR and extrathyroidal invasion, lymph node metastasis, aggressive histological subtypes, and multifocality. Conclusion: NLR is a readily accessible and cost-effective preoperative biomarker. Its use could improve risk stratification and support personalized therapeutic strategies. However, prospective studies with larger, multicenter cohorts are required to validate NLR as a reliable predictive biomarker.
Employee Perceptions of Organizational Justice Amidst Threats to Civil Service Protections Through the Lens of Turnover Intention
Authors: Exmeyer Patrick C. , Jeon So Hee
Published: January 2025

Previous studies focusing on civil service reform efforts at the sub-national level have illustrated how such initiatives may adversely affect employee perceptions of organizational conditions. Despite the insights provided by existing literature, little is known as to how federal employees perceive organizational justice amidst uncertain contextual and political conditions, and how the organizational justice perceptions influence their intentions to stay or leave their organizations. Using data from the 2021 Merit Principles Survey, collected amidst deliberations regarding federal civil service reform initiatives, this study examines how federal employee perceptions of organizational justice affect their turnover intentions with different exit strategies against the backdrop of the contextual and political changes. The findings lend support to existing literature highlighting organizational justice as a key factor influencing employee intentions to remain or leave positions of federal employment. The article concludes by discussing the contributions and implications of the present research as well as its limitations.
Healthcare Experiences of Mothers of Children and Adolescents With Acute Lymphoblastic Leukemia in Mexico
Authors: Sandra Treviño-Siller , María Cecilia González-Robledo , Luz María González-Robledo , Alma Cruz Bañares
Published: January 2025

Background: In Mexico, acute lymphoblastic leukemia (ALL) is the second leading cause of death in children and adolescents aged 4–15. It is also the most frequent type of cancer in this age group. Cancer diagnosis is commonly associated with mortality and generates fear and anxiety in Mexican parents. Objective: To analyze the experiences of mothers in the care, accompaniment, and treatment adherence of children and adolescents diagnosed with ALL, including changes in their daily life and how they deal with them. Results: Health professionals at the first level of care delay to identify the symptoms of leukemia in children. ALL affects both the patient as well as the whole family and there are several changes in daily life, especially for mothers. Due to gender roles, women (mothers) are the main caregivers of sick children. Mothers often blame themselves for believing that they did not attend to their children on time or that they made some errors in children rearing. They experience fear, doubts, and confusion; these feelings diminish over the course of the disease process due to interaction with other mothers and health professionals, as well as the evolution of the disease. Conclusion: It is critical to achieve early-stage diagnosis of ALL and ensure timely treatment in children and adolescents, as well as to provide effective emotional support for mothers and foster the development of peer support networks.
A climate change talanoa: exploring creative possibilities for a hopeful future
Authors: Hollis Simon , Halapua Winston
Published: January 2025

This article explores creative possibilities for climate action through talanoa (a form of dialogue practised in the Pacific Islands). Built on inter-subjective empathy, the dignity of persons and reciprocal justice, engaging in a talanoa creates a relational space for reflecting on the profound questions of planetary life. While a talanoa is usually produced “face-to-face”, this article demonstrates how a talanoa can also be achieved across space between a political scientist in Sweden and the Archbishop emeritus of Polynesia in Fiji. Together, we reveal the value of talanoa as a powerful medium for empowering climate change action. The content of the talanoa is critical of a scientific worldview that maintains a gap between humans and nature. Instead, emphasis is placed on relationality-as-knowledge, the importance of integrity and actively listening to the voice of nature. Values are thus taken seriously as a form of transformation and a source of hope and justice.
Contesting Captions: Netflix, Fan Campaigns, and the Labor of Access
Authors: Cameron Kelsey
Published: January 2025

This article theorizes the work of deaf fans and audiences in securing streaming video captions, which it names the labor of access. While prior scholarship on captions tends to emphasize policy and regulation, streaming video lacks the legislative framework for disability access seen with televisual captions in the United States. Drawing on disability studies and fan studies, this article shifts focus to fan campaigns, which become a central site for renegotiating industry accessibility practices in the absence of regulatory oversight. Using Netflix as a case study, it chronicles how audience campaigns contribute to both the company’s initial provision of streaming captions and the ongoing work of captioning quality control. It then argues that fan-driven access victories in the era of global streaming are uneven and contingent: a successful captioning campaign in one context has no necessary impact in others.
Association between alkaline phosphatase levels and mortality in Chinese patients with colorectal cancer with liver metastases: a retrospective cohort study
Authors: Liu ZhaoXi , Zhang ZiQing , Yu GuoFang , Mo MingJiang , Xie ChuanYu , Xu DangHan , Lin JieTao , Zhang YuChen , Deng Li , Luo YiChang , Huang YingFeng , Shao Cui
Published: January 2025

Background:

Alkaline phosphatase (ALP) is a potential cancer biomarker. However, its prognostic value in patients with colorectal liver metastasis remains unclear.

Objectives:

This study aimed to investigate the association between ALP levels and mortality risk in patients with colorectal liver metastases (CRLM), providing insights for enhancing prognostic assessments.

Design:

Retrospective cohort study.

Methods:

This study included 195 patients with CRLM from a single centre in China. ALP level was the primary exposure variable, with demographic, clinical and pathological factors serving as covariates. Multivariate Cox regression analyses were used to evaluate the impact of ALP on mortality over a 4-year follow-up period. Covariates included the number of liver metastases, T stage, N stage, chemotherapy, tumour location, primary surgery, topical treatment, apolipoprotein A1, targeted therapy, tumour type, CA-199 levels, metastatic surgery, sex, Karnofsky Performance Status and age.

Results:

Of 195 enrolled patients, 134 (68.72%) were male, and 61 (31.28%) were female, with ages ranging from January 2008 to December 2019. A total of 147 patients (76.96%) were diagnosed with left hemicolon cancer and 44 (23.04%) with right hemicolon cancer. After adjusting for the covariates, elevated ALP levels were significantly associated with an increased risk of mortality (hazard ratio = 1.24, 95% confidence interval: 1.08–1.43, p = 0.0029). Sensitivity analyses confirmed the robustness of these findings, reinforcing the association across different analytical approaches.

Conclusion:

ALP level is a valuable prognostic indicator in patients with CRLM. Integrating ALP measurement into clinical practice may enhance risk stratification and patient management. Future research should explore the role of ALP in broader populations and explore its implications for treatment strategies.
Evaluation of Outcomes Following Arthroscopic Treatment of Femoroacetabular Impingement Syndrome Across Different Surgeons, Surgical Techniques, and Postoperative Protocols: A Multi-institutional Study
Authors: Spencer Andrew D. , Newby Nathan L. , Nosrat Cameron , Wong Stephanie E. , Zhang Alan L. , Hagen Mia S.
Published: January 2025

Background:

Femoroacetabular impingement syndrome (FAIS) is frequently treated arthroscopically with osteoplasty and labral repair. Surgical preferences vary in terms of equipment, technique, and postoperative protocol. Patient-reported outcome measures (PROMs) are valuable tools to assess outcomes across different institutions.

Purpose:

To compare PROMs after FAIS arthroscopy and evaluate the impact on postoperative outcomes with independent surgeons utilizing different surgical techniques and postoperative protocols.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

Prospective data were collected from patients with a 2-year follow-up after arthroscopic FAIS treatment by 2 orthopaedic surgeons from different states, each attending different sports medicine fellowships. Patients were matched according to age, sex, and body mass index. Data included patient characteristics, surgical findings, and the Hip disability and Osteoarthritis Outcome Score (HOOS) preoperatively and 2 years postoperatively. Patients with revision surgery, concomitant procedures, or incomplete pre- and postoperative data were excluded. Surgeon A utilized interportal capsulotomy, capsular repair, all-suture anchors, and a postoperative hip brace. Surgeon B employed periportal capsulotomy without repair, polyether ether ketone suture anchors, and no brace. The 2 high-volume arthroscopists (>100 hips/year) performed osteoplasty and labral repair and used a large perineal post. Cohorts were analyzed with appropriate t tests, with significance set at P < .05. The percentage of patients achieving minimal clinically important difference (MCID) was calculated using Pearson chi-square tests.

Results:

A total of 176 hips (100 women, 76 men) were included, with 88 matched patients from each institution. The mean age was 33.7 years and the body mass index was 26.3 kg/m2. Both cohorts significantly improved in all 5 HOOS subscales 2 years after surgery. When comparing the mean change in PROMs and the percentage of patients achieving the MCID, differences were only observed in the HOOS-Sports subscale (cohort A: 25.3 ± 29.7 vs cohort B: 34.3 ± 29.7; P = .048; MCID achieved in 57% of patients vs 76%; P = .01).

Conclusion:

This prospective cohort study on arthroscopic FAIS treatment indicates that matched patient cohorts from different institutions show similarly improved PROMs at 2 years. This study suggests consistent patient outcomes across sites despite geography, surgeon, training, surgical technique, implants, and postoperative protocol.
Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma
Authors: Chrisochoidou Yakinthi , Scarpino Andrea , Morales Salomon , Martin Shannon , Bird Sarah Anne , Li Yigen , Walker Brian A , Caldwell John , Le Bihan Yann-Vai , Pawlyn Charlotte
Published: January 2025

Immunomodulatory drug (IMiD) resistance is a key clinical challenge in myeloma treatment. Previous data suggests almost one third of myeloma patients acquire mutations in the key IMiD effector cereblon by the time they are pomalidomide refractory. Some events, including stop codons/frameshift mutations and copy loss, having clearly explicable effects on cereblon function. Missense mutations have also been reported throughout the length of cereblon but their functional impact has not been systematically studied. This study modelled selected missense mutations and examined their effect on cereblon function also analysing whether any mutations deleterious to IMiD action could be overcome using the novel cereblon binding agents (CELMoDs). Three patterns of response to missense mutations were apparent, mutations that led to complete loss of CRBN function for all agents, those that had no effect on CRBN function and those with agent-dependent effect on CRBN function. The latter group of 4 mutations were profiled in more detail with confirmatory experiments demonstrating an ability of the more potent CELMoDs to lead to neosubstrate degradation and cell death even though IMiDs were not active. Dynamic modelling based on a newly generated crystal structure of the DDB1/CRBN/lenalidomide complex, with greater resolution than those published to date, helped to understand the impact of these mutations. These results have important implications for the interpretation of CRBN sequencing results from patients for future therapy decisions, particularly differentiating those who may, despite relapsing on IMiDs with CRBN mutations, have the potential to still benefit from the use of CELMoD agents.
Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice
Authors: Grunenwald Anne , Peliconi Julie , Lavergne Julien , Revel Margot , Voilin Elodie , Robe-Rybkine Tania , Crambert Gilles , Dimitrov Jordan D , Blanc-Brude Olivier , Roumenina Lubka T
Published: January 2025

Sickle cell disease (SCD) is the most common genetic disease in the world and a societal challenge. SCD is characterized by multi-organ injury related to intravascular hemolysis. To understand tissue-specific responses to intravascular hemolysis and exposure to heme, we present a transcriptomic atlas in the primary target organs of HbSS vs HbAA transgenic SCD mice. We explored the transcriptomes of liver, kidney, heart, lung and bone marrow from HbAA and HbSS Townes littermates at resting state and their changes after injection of heme, assessed by RNA sequencing. Inflammation and myeloid cell signatures were omnipresent in resting HbSS organs, liver being the most affected. The injection of heme triggered a robust inflammatory response in HbAA mice. Signatures of exposure to heme in HbAA mice were downstream of TLR4 (sensor of LPS but also of heme), IL1b, IL6 and IFNg, similarly to HbSS mice at rest. Nevertheless, HbSS mice were strikingly unresponsive to heme administration, irrespective of the organ. This tolerance was driven by upregulation of the heme-detoxifying enzyme HO-1 and was abrogated by its specific inhibition. Therefore, HbSS mice develop robust protective mechanisms, which may explain how they and SCD patients survive bouts of severe hemolysis.
The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway
Authors: Fan Xing , Li Jing , Gao Yan , Li Lin , Zhang Haisong , Bi Zhaoyu
Published: January 2025

Background

Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

Methods

The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca2+/P3+, and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.

Results

Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/β-catenin pathway, which could be counteracted by repressing the Wnt/β-catenin pathway.

Conclusions

Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/β-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.
Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids
Authors: Pillay Janesh , Flikweert Antine W. , van Meurs Matijs , Grootenboers Marco J. , van der Sar-van der Brugge Simone , van der Voort Peter H. J. , Karsdal Morten A. , Sand Jannie M. B. , Leeming Diana J. , Burgess Janette K. , Moser Jill
Published: January 2025

Background

Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers.

Methods

We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers.

Results

Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX.

Conclusion

Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.
The fibronectin-targeting PEG-FUD imaging probe shows enhanced uptake during fibrogenesis in experimental lung fibrosis
Authors: Harr Thomas J. , Gupta Nikesh , Rahar Babita , Stott Kristen , Medina-Guevara Yadira , Gari Metti K. , Oler Angie T. , McDermott Ivy Sohee , Lee Hye Jin , Rasoulianboroujeni Morteza , Weichmann Ashley M. , Forati Amir , Holbert Kelsey , Langel Trevor S. , Coulter Kade W. , Burkel Brian M. , Tomasini-Johansson Bianca R. , Ponik Suzanne M. , Engle Jonathan W. , Hernandez Reinier , Kwon Glen S. , Sandbo Nathan , Bernau Ksenija
Published: January 2025

Progressive forms of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), are deadly disorders lacking non-invasive biomarkers for assessment of early disease activity, which presents a major obstacle in disease management. Excessive extracellular matrix (ECM) deposition is a hallmark of these disorders, with fibronectin being an abundant ECM glycoprotein that is highly upregulated in early fibrosis and serves as a scaffold for the deposition of other matrix proteins. Due to its role in active fibrosis, we are targeting fibronectin as a biomarker of early lung fibrosis disease activity via the PEGylated fibronectin-binding polypeptide (PEG-FUD). In this work, we demonstrate the binding of PEG-FUD to the fibrotic lung throughout the course of bleomycin-induced murine model of pulmonary fibrosis. We first analyzed the binding of radiolabeled PEG-FUD following direct incubation to precision cut lung slices from mice at different stages of experimental lung fibrosis. Then, we administered fluorescently labeled PEG-FUD subcutaneously to mice over the course of bleomycin-induced pulmonary fibrosis and assessed peptide uptake 24 h later through ex vivo tissue imaging. Using both methods, we found that peptide targeting to the fibrotic lung is increased during the fibrogenic phase of the single dose bleomycin lung fibrosis model (days 7 and 14 post-bleomycin). At these timepoints we found a correlative relationship between peptide uptake and fibrotic burden. These data suggest that PEG-FUD targets fibronectin associated with active fibrogenesis in this model, making it a promising candidate for a clinically translatable molecular imaging probe to non-invasively determine pulmonary fibrosis disease activity, enabling accelerated therapeutic decision-making.
Provocation of brachial plexus and systemic symptoms during the elevated arm stress test in individuals with myalgic encephalomyelitis/chronic fatigue syndrome or idiopathic chronic fatigue
Authors: Edwards Charles C. , Byrnes Julia M. , Broussard Camille A. , Azola Alba M. , Swope Meghan E. , Marden Colleen L. , Swope Renee L. , Lum Ying Wei , Violand Richard L. , Rowe Peter C.
Published: January 2025

Background

We have noted that some adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) report difficulty with arms-overhead activities, suggestive of brachial plexus dysfunction or thoracic outlet syndrome (TOS). In the TOS literature, diagnostic maneuvers focus on the provocation of upper limb symptoms (arm fatigue and heaviness, paresthesias, neck and upper back pain), but not on elicitation of systemic symptoms.

Objectives

To estimate the proportion of patients with fatiguing illness who experience local and systemic symptoms during a common maneuver used in evaluating TOS—the elevated arm stress test (EAST).

Methods

Patients were eligible for this retrospective study if they had been referred to the Johns Hopkins Chronic Fatigue Clinic between January 2020 and July 2023 and (a) reported difficulty maintaining arms-overhead postures, (b) were evaluated with an abbreviated one-minute EAST, and (c) had not undergone surgery in the upper limb, neck, or skull base. Modified EAST procedure: patients sat with their arms in a “hands up” or “candlestick” position while opening and closing their hands every 2–3 s repeatedly for 1 min, rather than the customary 3 min. The test was considered abnormal for local symptoms if the participant experienced pain, fatigue, heaviness, paresthesias, warmth or tremulousness in the upper limb, shoulder, neck, head, or upper back. The test was considered abnormal for systemic symptoms if the participant experienced overall fatigue, cognitive fogginess, lightheadedness, racing heart, diaphoresis, dyspnea, overall warmth, or nausea.

Results

Of 154 patients evaluated during the study period, 64 (42%) met the eligibility criteria (61/64 female, median age 18 years [range, 13 to 50]). Of the 64, 50 (78%) had ME/CFS, 13 (20%) had idiopathic chronic fatigue with associated orthostatic intolerance (OI), and one had idiopathic chronic fatigue without OI. Of the 64, 58% had evidence of joint hypermobility. Local symptoms were provoked by EAST in 62/64 (97%) within a median of 20 s. During EAST, 26/64 (41%) reported systemic symptoms (1 had only systemic but no upper limb symptoms), most commonly lightheadedness (19%) and generalized fatigue (11%).

Conclusions

Even with an abbreviated test duration, the EAST maneuver provoked local and systemic symptoms in a substantial proportion of patients with chronic fatigue, OI, and ME/CFS who had reported difficulty with arms-overhead postures. Further studies are needed to explore the prevalence of brachial plexus or TOS symptoms in unselected individuals with ME/CFS or OI, and the proportion with systemic symptoms during and after EAST.
APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology
Authors: Tran Kristine M. , Kwang Nellie E. , Butler Claire A. , Gomez-Arboledas Angela , Kawauchi Shimako , Mar Cassandra , Chao Donna , Barahona Rocio A. , Da Cunha Celia , Tsourmas Kate I. , Shi Zechuan , Wang Shuling , Collins Sherilyn , Walker Amber , Shi Kai-Xuan , Alcantara Joshua A. , Neumann Jonathan , Duong Duc M. , Seyfried Nicholas T. , Tenner Andrea J. , LaFerla Frank M. , Hohsfield Lindsay A. , Swarup Vivek , MacGregor Grant R. , Green Kim N.
Published: January 2025

Background

Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer’s Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.

Methods

We introduced the R136S variant into mouse Apoe (ApoeCh) and investigated its effect on the development of AD-related pathology using the 5xFAD model of amyloidosis and the PS19 model of tauopathy. We used immunohistochemical and biochemical analysis along with single-cell spatial omics and bulk proteomics to explore the impact of the ApoeCh variant on AD pathological development and the brain’s response to plaques and tau.

Results

In 5xFAD mice, ApoeCh enhances a Disease-Associated Microglia (DAM) phenotype in microglia surrounding plaques, and reduces plaque load, dystrophic neurites, and plasma neurofilament light chain. By contrast, in PS19 mice, ApoeCh suppresses the microglial and astrocytic responses to tau-laden neurons and does not reduce tau accumulation or phosphorylation, but partially rescues tau-induced synaptic and myelin loss. We compared how microglia responses differ between the two mouse models to elucidate the distinct DAM signatures induced by ApoeCh. We identified upregulation of antigen presentation-related genes in the DAM response in a PS19 compared to a 5xFAD background, suggesting a differential response to amyloid versus tau pathology that is modulated by the presence of ApoeCh. Bulk proteomics show upregulated mitochondrial protein abundance with ApoeCh in 5xFAD mice, but reductions in mitochondrial and translation associated proteins in PS19 mice.

Conclusions

These findings highlight the ability of the ApoeCh variant to modulate microglial responses based on the type of pathology, enhancing DAM reactivity in amyloid models and dampening neuroinflammation to promote protection in tau models. This suggests that the Christchurch variant's protective effects likely involve multiple mechanisms, including changes in receptor binding and microglial programming.

Graphical Abstract
DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations
Authors: Li Jason Sheng , Riggins Karen , Yang Li , Chen Chaorong , Castro Patricia , Alfarkh Wedad , Zarrin-Khameh Neda , Scheurer Michael E. , Creighton Chad J. , Musher Benjamin , Li Wei , Shen Lanlan
Published: January 2025

Background

The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

Results

We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL.

Conclusions

In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.
The algebraic extended atom-type graph-based model for precise ligand–receptor binding affinity prediction
Authors: Mukta Farjana Tasnim , Rana Md Masud , Meyer Avery , Ellingson Sally , Nguyen Duc D.
Published: January 2025

Accurate prediction of ligand-receptor binding affinity is crucial in structure-based drug design, significantly impacting the development of effective drugs. Recent advances in machine learning (ML)–based scoring functions have improved these predictions, yet challenges remain in modeling complex molecular interactions. This study introduces the AGL-EAT-Score, a scoring function that integrates extended atom-type multiscale weighted colored subgraphs with algebraic graph theory. This approach leverages the eigenvalues and eigenvectors of graph Laplacian and adjacency matrices to capture high-level details of specific atom pairwise interactions. Evaluated against benchmark datasets such as CASF-2016, CASF-2013, and the Cathepsin S dataset, the AGL-EAT-Score demonstrates notable accuracy, outperforming existing traditional and ML-based methods. The model’s strength lies in its comprehensive similarity analysis, examining protein sequence, ligand structure, and binding site similarities, thus ensuring minimal bias and over-representation in the training sets. The use of extended atom types in graph coloring enhances the model’s capability to capture the intricacies of protein-ligand interactions. The AGL-EAT-Score marks a significant advancement in drug design, offering a tool that could potentially refine and accelerate the drug discovery process.

Scientific Contribution

The AGL-EAT-Score presents an algebraic graph-based framework that predicts ligand-receptor binding affinity by constructing multiscale weighted colored subgraphs from the 3D structure of protein-ligand complexes. It improves prediction accuracy by modeling interactions between extended atom types, addressing challenges like dataset bias and over-representation. Benchmark evaluations demonstrate that AGL-EAT-Score outperforms existing methods, offering a robust and systematic tool for structure-based drug design.
Cell deconvolution-based integrated time-series network of whole blood transcriptome reveals systemic antiviral activities and cell-specific immunological changes against PRRSV infection
Authors: Lim Byeonghwi , Lim Chiwoong , Jang Min-Jae , Seo Young-Jun , Kim Do-Young , Tuggle Christopher K. , Lim Kyu-Sang , Kim Jun-Mo
Published: January 2025

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry. However, the molecular mechanisms behind the common and cell type-specific systemic responses during PRRS virus (PRRSV) infection are not well understood. In this study, we collected viremia data, antibody levels, and whole-blood RNA-seq data obtained from eight PRRSV-infected piglets. We utilised a cell deconvolution approach to calculate cell type enrichment, constructed a time-serial gene co-expression network with differentially expressed genes, and conducted functional annotations. Three significant modules were identified within the network. The changes associated with viremia revealed an upregulated expression of genes related to antiviral activity. In the T-cell- and NK-cell-specific modules, infection led to an increased T-cell population and upregulation of genes related to T-cell defence responses. Conversely, in the monocyte- and neutrophil-specific module, genes involved in inflammatory responses were downregulated due to a decrease in monocyte proportion. This study highlights the time-series antiviral activities associated with viremia and the transcriptomic changes associated with immune responses in specific cell types. The findings provide comprehensive insights into host responses to PRRSV infection, including diagnostic biomarkers.
Coproantigen detection and molecular identification of Cryptosporidium species among newborn and adult farm animals
Authors: Aboelsoued Dina , Toaleb Nagwa I. , Abdel Megeed Kadria N.
Published: January 2025

Cryptosporidium sp. is an obligatory intracellular apicomplexan protozoan parasite that causes a disease called cryptosporidiosis with substantial veterinary and medical importance. Therefore, this study aimed to evaluate an early diagnosis of cryptosporidiosis using the anti-Cryptosporidium parvum oocyst immunoglobulin IgG polyclonal antibodies (anti-C. parvum IgG PAbs)-based sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium oocyst antigens in fecal samples of farm animals in Egypt. Further molecular identification and sequencing were performed for the detected isolates. Eight hundred and twenty fecal samples of farm animals; 102 buffalo calves, 120 cattle calves, 100 lambs and 98 goat kids, 80 buffaloes, 60 cattle, 160 sheep and 100 goats, collected from different small-scale farms and local holders were examined for cryptosporidiosis by Modified Ziehl-Neelsen (MZN) technique. The percentage of positivity was 45.1%, 50%, 20%, 18.4%, 31.25%, 38.3%, 18.8%, and 11% in buffalo calves, cattle calves, lambs, goat kids, adult buffaloes, adult cattle, sheep, and goats, respectively. Molecular identification of Cryptosporidium samples was performed based on COWP gene, revealing the isolates: GenBank: OQ121955.1, OR029973.1 and PP316107.1 which were identical to the C. parvum and GenBank: PP316108.1 and OR029972.1 which were identical to C. hominis and C. andersoni, respectively. Then, C. parvum oocysts were used for preparation of antigens and rabbit immunization. Anti-C. parvum IgG PAbs were purified and characterized by SDS-PAGE and then labeled with horseradish peroxidase (HRP). Anti-C. parvum IgG PAbs in-house sandwich ELISA was prepared, then tested this ELISA on 820 samples and compared results with MZN microscopical examination and a commercial sandwich ELISA kit. In this study, in-house sandwich ELISA scored higher sensitivity of 98%, 100% specificity, validity 99% and relative agreement 98.6% than (92%, 90%, 91% and 91.4%) of MZN and (96%, 95%, 95.5% and 95.7%) of coproantigen commercial sandwich ELISA kit, respectively. Moreover, we used PCR to evaluate the positivity of in-house sandwich ELISA results, and the total PCR positive samples were 263 out of 268 sandwich ELISA positive samples (98.13%). In conclusion, the prepared Anti-C. parvum IgG PAbs based sandwich ELISA offered a simple and accurate diagnostic method for cryptosporidiosis in the fecal samples of different species of farm animals in Egypt with high sensitivity (98%) and specificity (100%). Further studies on this Anti-C. parvum IgG PAbs may help also in the protection against cryptosporidiosis.
Large-bore aspiration thrombectomy for the treatment of pulmonary embolism in octogenarians
Authors: Masterson Reid , Pebror Travis , Gauger Andrew , Schmitz Adam William , Butty Sabah David
Published: January 2025

Purpose

To evaluate outcomes in patients aged ≥ 80 years following large-bore aspiration thrombectomy (LBAT) for the treatment of pulmonary embolism (PE).

Materials and methods

All patients ≥ 80 years of age with PE treated via LBAT at a single center were analyzed from September 2019 – August 2024. This included the octogenarian subgroup from a recently published retrospective analysis assessing all PE patients treated with LBAT at our center between September 2019 and January 2023. The following outcomes were evaluated: technical success, change in several hemodynamic measures including pulmonary artery pressure (PAP) and right ventricle to left ventricle ratio (RV to LV ratio), length of hospital and intensive-care-unit (ICU) stay, procedure-related complications, and 7- and 30-day mortality.

Results

Forty-eight patients aged ≥ 80 years underwent LBAT procedures for PE. Technical success was achieved in 46 cases (95.8%). The mean reduction in mean PAP was 3.6 mmHg. The mean reduction in RV to LV ratio was -0.42. The mean length of postprocedural hospital and ICU stays were 5.7 ± 3.6 days and 1.0 ± 1.6 days, respectively. There were 2 procedural complications, 1 pulmonary vascular injury involving a pulmonary artery pseudoaneurysm and 1 decompensation involving hypotension requiring vasopressor support. There were no major bleeding complications or cardiac injuries. All-cause mortality was 2.1% (n = 1) at 7 days and 6.3% (n = 3) at 30 days post procedure. PE-related mortality was 2.1% (n = 1) at 30 days.

Conclusion

LBAT is a technically feasible procedure for the treatment of PE in octogenarian patients and has a favorable preliminary safety and mortality profile.
Chemical composition by PTP 1B inhibitory activity guided analysis of a plant- based antidiabetic polyherbal drug used in ethnomedical systems
Authors: Mugari Pardon , Dzomba Pamhidzai , Nyoni Stephen
Published: January 2025

Background

Due to growing resistance and continued depletion of drugs that can be used as replacements, people turn to herbal antidiabetic medicines. A polyherbal drug consisting of a mixture of two herbal plants, Zanthoxylum chalybeum and Xeroderris stuhlmannii root powder mixed in equal amounts using a tea cup, was studied to investigate its chemical composition and possible mode of action.

Methods

Phytochemicals were isolated using Column and Thin Layer Chromatography, and antidiabetic activity was ascertained using an enzyme inhibition model. Active compounds identity was established using 1HNMR, 13CNMR, HSQC-NMR, UV, FT-IR and MS spectroscopy.

Results

Results showed that the polyherbal drug consisted of two alkaloids and three anthocyanins as the major active components. PTP 1B inhibition of alkaloids was not significantly different from that of metformin with percentage inhibition of 78.6 ± 3.2 and 79.6 ± 2.3%. The anthocyanins inhibited PTP 1B enzyme significantly better than metformin with percentage inhibition of 88.2 ± 3.2, 90.3 ± 2.3 and 93.6 ± 2.9%. One new compound, an alkaloid, 1, 2-dimethoxy-12-methyl-7-(3-methylbut-2-en-1-yl)-12, 13-dihydro [1,3] benzodioxolo [5,6-c] phenanthridin-13-ol, one previously reported alkaloid berberine, IUPAC name, 9,10-dimethoxy-5,6-dihydro[1,3] dioxolo [4',5':6,7] isoquinolino [2,1-b][2] benzazin-7-ium and three anthocyanins,, malvidin 3-o-glucoside, pelargonidin-3-O-gucoside and malvidin 3, 5-O-diglucoside were identified as the active compounds in the polyherbal drug extract.

Conclusion

Presence of alkaloids and anthocyanins that have PTP 1B inhibitory activity showed that the polyherbal drug is a potential medicine for managing diabetes.
Antithrombotic therapy in adults with ectatic coronary artery disease: a systematic review and network meta-analysis
Authors: Azarboo Alireza , Daneshvar Mohammad Shahabaddin , Abroy Alireza Sattari , Assempoor Ramin , Taghvaei Aryan , Nasrollahizadeh Ali , Hajiqasemi Mohsen , Ghaseminejad-Raeini Amirhossein , Hosseini Kaveh
Published: January 2025

Background

Many studies have validated the use of antiplatelet or anticoagulant therapy in coronary artery ectasia (CAE) to reduce major adverse cardiovascular events (MACE); however, it is not completely known which group of these antithrombotic medications is more effective. The purpose of this systematic review and network meta-analysis was to evaluate the efficacy of different anti-thrombotic treatments in adult patients with CAE.

Methods

This systematic review and meta-analysis followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines as well as PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses and adhered to a registered predetermined methodology noted in the prospective register of systematic reviews (PROSPERO) protocol. Comprehensive searches were conducted until October 2024. Study selection, data extraction, and risk-of-bias assessments were independently performed by two reviewers. The pairwise meta-analysis compared the odds of MACE among patients receiving different antithrombotic therapies versus no treatment. The network meta-analysis (NMA) combined direct and indirect evidence to compare the efficacy of antithrombotic therapies for MACE.

Results

Our systematic review included 5,039 adult patients suffering from CAE. The odds of MACE were higher in patients with no treatment when compared with those on dual antiplatelet therapy (DAPT) and aspirin monotherapy; although patients on anticoagulation demonstrated a lower incidence of MACE, the difference with the no treatment group did not reach statistical significance. Among various types of interventions in NMA, DAPT was the best in the treatment of CAE.

Conclusions

Based on the surface under the cumulative ranking curve (SUCRA) value, DAPT is the most effective treatment in the prevention of MACE for CAE patients, followed by aspirin monotherapy and anticoagulant treatment.
Tuberculosis vaccines and therapeutic drug: challenges and future directions
Authors: An Yajing , Ni Ruizi , Zhuang Li , Yang Ling , Ye Zhaoyang , Li Linsheng , Parkkila Seppo , Aspatwar Ashok , Gong Wenping
Published: January 2025

Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite the deployment of the Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, the escalation of drug-resistant Mycobacterium tuberculosis strains underscores the pressing need for more efficacious vaccines and treatments. This review meticulously maps out the contemporary landscape of TB vaccine development, with a focus on antigen identification, clinical trial progress, and the obstacles and future trajectories in vaccine research. We spotlight innovative approaches, such as multi-antigen vaccines and mRNA technology platforms. Furthermore, the review delves into current TB therapeutics, particularly for multidrug-resistant tuberculosis (MDR-TB), exploring promising agents like bedaquiline (BDQ) and delamanid (DLM), as well as the potential of host-directed therapies. The hurdles in TB vaccine and therapeutic development encompass overcoming antigen diversity, enhancing vaccine effectiveness across diverse populations, and advancing novel vaccine platforms. Future initiatives emphasize combinatorial strategies, the development of anti-TB compounds targeting novel pathways, and personalized medicine for TB treatment and prevention. Despite notable advances, persistent challenges such as diagnostic failures and protracted treatment regimens continue to impede progress. This work aims to steer future research endeavors toward groundbreaking TB vaccines and therapeutic agents, providing crucial insights for enhancing TB prevention and treatment strategies.