bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in cancer outcomes across the range of eGFR
Authors: Shemilt Richard , Sullivan Michael K , Hanlon Peter , Jani Bhautesh D , De La Mata Nicole , Rosales Brenda , Elyan Benjamin M P , Hedley James A , Cutting Rachel B , Wyld Melanie , McAllister David A , Webster Angela C , Mark Patrick B , Lees Jennifer S
Published: March 2024

Background

People with chronic kidney disease (CKD) have increased incidence and mortality of most cancer types. We hypothesized that the odds of presenting with advanced cancer may vary according to differences in estimated glomerular filtration rate (eGFR), that this could contribute to increased all-cause mortality and that sex differences may exist.

Methods

Data were from Secure Anonymised Information Linkage Databank, including people with de novo cancer diagnosis (2011–17) and two kidney function tests within 2 years prior to diagnosis to determine baseline eGFR (mL/min/1.73 m2). Logistic regression models determined the odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRCr and all-cause mortality.

Results

eGFR <30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared with eGFR >75–90, eGFR <30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females [female: hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.56–1.88; male versus female comparison: HR 0.88, 95% CI 0.78–0.99].

Conclusions

Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger association with all-cause mortality in females compared with males with eGFR <30 is concerning and warrants further scrutiny.
Long non-coding RNA lung cancer-associated transcript-1 promotes glioblastoma progression by enhancing Hypoxia-inducible factor 1 alpha activity
Authors: Huang Haidong , Shah Hariti , Hao Jing , Lin Jianhong , Prayson Richard A , Xie Liangqi , Bao Shideng , Chakraborty Abhishek A , Jankowsky Eckhard , Zhao Jianjun , Yu Jennifer S
Published: March 2024

Background

Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside in hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated in GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these lncRNAs may provide new therapeutic strategies to target GSCs under hypoxia.

Methods

lncRNAs induced by hypoxia in GSCs were identified by RNA-seq. Lung cancer-associated transcript-1 (LUCAT1) expression was assessed by qPCR, RNA-seq, Northern blot, single molecule FISH in GSCs, and interrogated in IvyGAP, The Cancer Genome Atlas, and CGGA databases. LUCAT1 was depleted by shRNA, CRISPR/Cas9, and CRISPR/Cas13d. RNA-seq, Western blot, immunohistochemistry, co-IP, ChIP, ChIP-seq, RNA immunoprecipitation, and proximity ligation assay were performed to investigate mechanisms of action of LUCAT1. GSC viability, limiting dilution assay, and tumorigenic potential in orthotopic GBM xenograft models were performed to assess the functional consequences of depleting LUCAT1.

Results

A new isoform of Lucat1 is induced by Hypoxia inducible factor 1 alpha (HIF1α) and Nuclear factor erythroid 2-related factor 2 (NRF2) in GSCs under hypoxia. LUCAT1 is highly expressed in hypoxic regions in GBM. Mechanistically, LUCAT1 formed a complex with HIF1α and its co-activator CBP to regulate HIF1α target gene expression and GSC adaptation to hypoxia. Depletion of LUCAT1 impaired GSC self-renewal. Silencing LUCAT1 decreased tumor growth and prolonged mouse survival in GBM xenograft models.

Conclusions

A HIF1α-LUCAT1 axis forms a positive feedback loop to amplify HIF1α signaling in GSCs under hypoxia. LUCAT1 promotes GSC self-renewal and GBM tumor growth. LUCAT1 is a potential therapeutic target in GBM.
Proton versus photon craniospinal irradiation for adult medulloblastoma: A dosimetric, toxicity, and exploratory cost analysis
Authors: Breen William G , Geno Connie S , Waddle Mark R , Qian Jing , Harmsen William S , Burns Terry C , Sener Ugur T , Ruff Michael W , Neth Bryan J , Uhm Joon H , Routman David M , Yan Elizabeth , Kruse Jon J , Laack Nadia N , Brown Paul D , Mahajan Anita
Published: March 2024

Background

This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients.

Methods

This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients.

Results

Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18–66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54–55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P = .044) and decreased median weight loss during radiation (+1.0 versus –2.8 kg, P = .011). Weight loss was associated with acute hospitalization (P = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41–63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free.

Conclusions

This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.
Basis risk and the demand for catastrophic rainfall insurance
Authors: Negi Digvijay S , Ramaswami Bharat
Published: March 2024

Rainfall is an important source of covariate shock in developing countries. Insurance against a rainfall index has, therefore, held much promise as a formal insurance product to protect the livelihoods of poor farmers. But how good is rainfall as a measure of covariate shocks? The imperfect association between them has been flagged as a reason for low demand for index insurance. Using district crop yields and rainfall data for India, we find that tail dependence characterizes the association between aggregate crop yields and rainfall. Could this property be exploited to design catastrophic loss insurance programs that have low basis risk? Using simulations of the estimated copulas, we show that the value of index-based insurance relative to actuarial cost is higher for insurance against extreme losses (of the index) than for insurance against all losses. We conclude that index insurance could find greater acceptability if it only insured extreme losses.
Identification of early risk factors for anti-citrullinated-protein-antibody positive rheumatoid arthritis—a prospective cohort study
Authors: Cîrciumaru Alexandra , Kisten Yogan , Hansson Monika , Mathsson-Alm Linda , Joshua Vijay , Wähämaa Heidi , Loberg Haarhaus Malena , Lindqvist Joakim , Padyukov Leonid , Catrina Sergiu-Bogdan , Fei Guozhong , Vivar Nancy , Rezaei Hamed , af Klint Erik , Antovic Aleksandra , Réthi Bence , Catrina Anca I , Hensvold Aase
Published: March 2024

Objective

Individuals positive for anti-cyclic-peptide-antibodies (anti-CCP) and musculoskeletal complaints (MSK-C) are at risk for developing rheumatoid arthritis (RA). In this study we aimed to investigate factors involved in arthritis progression.

Methods

Anti-CCP2-positive individuals with MSK-C referred to a rheumatologist were recruited. Individuals lacked arthritis at clinical and ultrasound examination and were followed for ≥3 years or until clinical arthritis diagnosis. Blood samples from inclusion were analysed for nine ACPA reactivities (citrullinated α-1-enolase, fibrinogen, filaggrin, histone, vimentin and tenascin peptides); 92 inflammation-associated proteins; and HLA-shared epitope alleles. Cox regression was applied to the data to identify independent predictors in a model.

Results

Two hundred and sixty-seven individuals were included with median follow-up of 49 months (interquartile range [IQR]: 22–60); 101 (38%) developed arthritis after a median of 14 months (IQR: 6–27). The analysis identified that presence of at least one ACPA reactivity (hazard ratio [HR] 8.0; 95% CI: 2.9, 22), ultrasound-detected tenosynovitis (HR 3.4; 95% CI: 2.0, 6.0), IL-6 levels (HR 1.5; 95% CI: 1.2, 1.8) and IL-15 receptor α (IL-15Rα) levels (HR 0.6; 95% CI: 0.4, 0.9) are significant independent predictors for arthritis progression in a prediction model (Harrell’s C 0.76 [s.e. 0.02], AUC 0.82 [95% CI: 0.76, 0.89], cross-validated AUC 0.70 [95% CI: 0.56, 0.85]).

Conclusion

We propose a high RA risk phase characterized by presence of ACPA reactivity, tenosynovitis, IL-6 and IL-15Rα and suggest that these factors need to be further investigated for their biological effects and clinical values, to identify individuals at particular low risk and high risk for arthritis progression.
Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis
Authors: Khanna Dinesh , Kramer Frank , Höfler Josef , Ghadessi Mercedeh , Sandner Peter , Allanore Yannick , Denton Christopher P , Kuwana Masataka , Matucci-Cerinic Marco , Pope Janet E , Atsumi Tatsuya , Bečvář Radim , Czirják László , De Langhe Ellen , Hachulla Eric , Ishii Tomonori , Ishikawa Osamu , Johnson Sindhu R , Riccieri Valeria , Schiopu Elena , Silver Richard M , Smith Vanessa , Stagnaro Chiara , Steen Virginia , Stevens Wendy , Szücs Gabriella , Truchetet Marie-Elise , Wosnitza Melanie , Distler Oliver
Published: March 2024

Objective

To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment.

Methods

Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. α-Smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay.

Results

By week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (P = 0.004 and P = 0.008, respectively). There were no differences in skin collagen markers between the two groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies was associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively).

Conclusion

Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide–soluble guanylate cyclase–cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis.

Trial registration

Clinicaltrials.gov, NCT02283762.
Phylogenomics of Neogastropoda: The Backbone Hidden in the Bush
Authors: Fedosov Alexander E , Zaharias Paul , Lemarcis Thomas , Modica Maria Vittoria , Holford Mandë , Oliverio Marco , Kantor Yuri I , Puillandre Nicolas
Published: March 2024

The molluskan order Neogastropoda encompasses over 15,000 almost exclusively marine species playing important roles in benthic communities and in the economies of coastal countries. Neogastropoda underwent intensive cladogenesis in the early stages of diversification, generating a “bush” at the base of their evolutionary tree, which has been hard to resolve even with high throughput molecular data. In the present study to resolve the bush, we use a variety of phylogenetic inference methods and a comprehensive exon capture dataset of 1817 loci (79.6% data occupancy) comprising 112 taxa of 48 out of 60 Neogastropoda families. Our results show consistent topologies and high support in all analyses at (super)family level, supporting monophyly of Muricoidea, Mitroidea, Conoidea, and, with some reservations, Olivoidea and Buccinoidea. Volutoidea and Turbinelloidea as currently circumscribed are clearly paraphyletic. Despite our analyses consistently resolving most backbone nodes, 3 prove problematic: First, the uncertain placement of Cancellariidae, as the sister group to either a Ficoidea-Tonnoidea clade or to the rest of Neogastropoda, leaves monophyly of Neogastropoda unresolved. Second, relationships are contradictory at the base of the major “core Neogastropoda” grouping. Third, coalescence-based analyses reject monophyly of the Buccinoidea in relation to Vasidae. We analyzed phylogenetic signal of targeted loci in relation to potential biases, and we propose the most probable resolutions in the latter 2 recalcitrant nodes. The uncertain placement of Cancellariidae may be explained by orthology violations due to differential paralog loss shortly after the whole genome duplication, which should be resolved with a curated set of longer loci.
Resilience analysis of maritime transportation networks: a systematic review
Authors: Zhang Di , Tao Jiale , Wan Chengpeng , Huang Liang , Yang Ming
Published: March 2024

As supply chains in today's world become more complex and fragile, enhancing the resilience of maritime transport is increasingly imperative. The COVID-19 epidemic in 2020 exposed the vulnerability of existing supply chains, causing substantial impacts such as supply shortages, procurement constraints, logistics delays and port congestion, highlighting the need to build resilient maritime transportation networks (MTNs) and reigniting research on the resilience of maritime transport. Based on science mapping, we quantitatively analysed the domain of resilience of MTNs. We mainly study the resilience of MTNs from the following aspects: the construction of MTNs and their topological characterization, vulnerability-orientated resilience analysis of MTNs, recovery-orientated resilience analysis of MTNs, investment decision-orientated resilience analysis of MTNs, climate change-orientated resilience analysis of MTNs and pandemic-orientated resilience analysis of MTNs. This study reviews recent advances in MTN resilience research, highlighting research topics, shortcomings and future research agenda.
Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan‐cancer immunity
Authors: Liu Minghui , Zhao Huan , Peng Suming , Wu Yunfei , Liu Yanyan , Sun Wu , Zen Ke , Sun Xinlei
Published: March 2024

Zinc and ring finger 3 (ZNRF3) is a negative suppressor of Wnt signal and newly identified as an important regulator in tumorigenesis and development. However, the pan‐cancer analysis of ZNRF3 has not been reported. We found that ZNRF3 was significantly decreased in six tumors including CESC, KIRP, KIRC, SKCM, OV, and ACC, but increased in twelve tumors, namely LGG, ESCA, STES, COAD, STAD, LUSC, LIHC, THCA, READ, PAAD, TGCT, and LAML. Clinical outcomes of cancer patients were closely related to ZNRF3 expression in ESCA, GBM, KIRC, LUAD, STAD, UCEC, LGG, and SARC. The highest genetic alteration frequency of ZNRF3 occurred in ACC. Abnormal expression of ZNRF3 could be attributed to the differences of copy number variation (CNV) and DNA methylation as well as ZNRF3‐interacting proteins. Besides, ZNRF3 were strongly associated with tumor heterogeneity, tumor stemness, immune score, stromal score and ESTIMATE score in certain cancers. In terms of immune cell infiltration, ZNRF3 was positively correlated to infiltration of cancer‐associated fibroblasts in CESC, HNSC, OV, PAAD, PRAD, and THYM, but negatively associated with infiltration of CD8 T cells in HNSC, KIRC, KIRP and THYM. Moreover, ZNRF3 expression was correlated with most immune checkpoint genes in SARC, LUSC, LUAD, PRAD, THCA, UVM, TGCT, and OV, and associated with overwhelming majority of immunoregulatory genes in almost all cancers. Most RNA modification genes were also remarkably related to ZNRF3 level in KIRP, LUAD, LUSC, THYM, UVM, PRAD, and UCEC, indicating that ZNRF3 might have an important effect on cancer epigenetic regulation. Finally, we verified the expression and role of ZNRF3 in clinical specimens and cell lines of renal cancer and liver cancer. This study provides a comprehensive pan‐cancer analysis of ZNRF3 and reveals the complexity of its carcinogenic effect.
Mechanisms underlying morphological and functional changes of cilia in fibroblasts derived from patients bearing ARL3T31A and ARL3T31A/C118F mutations
Authors: Zhang Xiaoli , Yao Shun , Zhang Lujia , Yang Lin , Yang Mingzhu , Guo Qingge , Li Yan , Wang Zhongfeng , Lei Bo , Jin Xiuxiu
Published: March 2024

ARL3 is essential for cilia development, and mutations in ARL3 are closely associated with ciliopathies. In a previous study, we observed distinct phenotypes of retinal dystrophy in patients with heterozygous ARL3T31A and compound heterozygous ARL3T31A/C118F mutations, indicating that different mutation types may exert diverse effects on their functions. Here, we generated transformed immortal fibroblast cells from patients carrying heterozygous ARL3T31A and compound heterozygous ARL3T31A/C118F mutations, and systematically evaluated their cilia morphology and function, which were further validated in ARPE‐19 cells. Results showed that both ARL3T31A and ARL3T31A/C118F mutations led to a decrease in cilium formation. The ARL3T31A/C118F mutations caused significantly elongated cilia and impaired retrograde transport, whereas the ARL3T31A mutation did not induce significant changes in fibroblasts. RNA‐sequencing results indicated that compared to ARL3T31A, ARL3T31A/C118F fibroblasts exhibited a higher enrichment of biological processes related to neuron projection development, tissue morphogenesis, and extracellular matrix (ECM) organization, with noticeable alterations in pathways such as ECM‐receptor interaction, focal adhesion, and TGF‐β signaling. Similar changes were observed in the proteomic results in ARPE‐19 cells. Core regulated genes including IQUB, UNC13D, RAB3IP, and GRIP1 were specifically downregulated in the ARL3T31A/C118F group, and expressions of IQUB, NPM2, and SLC38A4 were further validated. Additionally, IQUB showed a rescuing effect on the overlong cilia observed in ARL3T31A/C118F fibroblasts. Our results not only enhance our understanding of ARL3‐related diseases but also provide new insights into the analysis of heterozygous and compound heterozygous mutations in genetics.
The Presence of Chronic Total Occlusion in Noninfarct-Related Arteries Is Associated With Higher Mortality and Worse Patient Outcomes Following Percutaneous Coronary Intervention for STEMI: A Systematic Review, Meta-Analysis and Meta-Regression
Authors: Goyal Aman , Maheshwari Surabhi , Shahbaz Haania , Shah Viraj , Shamim Urooj , Shrestha Abhigan Babu , Sulaiman Samia Aziz , Mhatre Pauras , Sohail Amir Humza , Sheikh Abu Baker , Dani Sourbha S.
Published: March 2024

Reperfusion therapy with percutaneous coronary intervention improves outcomes in patients with ST-elevation myocardial infarction. We conducted a meta-analysis to assess the impact of chronic total occlusion (CTO) in noninfarct-related artery on the outcomes of these patients. Comprehensive searches were performed using PubMed, Google Scholar, and EMBASE. The primary endpoint was the 30-day mortality rate, with secondary endpoints including all-cause mortality, repeat myocardial infarction, and stroke. Forest plots were created for the pooled analysis of the results, with statistical significance set at P < 0.05. A total of 19 studies were included in this meta-analysis, with 23,989 patients (3589 in CTO group and 20,400 in no-CTO group). The presence of CTO was associated with significantly higher odds of 30-day mortality [18.38% vs 5.74%; relative risk (RR), 3.69; 95% confidence intervals (CI), 2.68–5.07; P < 0.00001], all-cause mortality (31.00% vs 13.40%; RR, 2.79; 95% CI, 2.31–3.37; P < 0.00001), cardiovascular-related deaths (12.61% vs 4.1%; RR, 2.61; 95% CI, 1.99–3.44; P < 0.00001), and major adverse cardiovascular events (13.64% vs 9.88%; RR, 2.08; 95% CI, 1.52–2.86; P < 0.00001) than the non-CTO group. No significant differences in repeated myocardial infarction or stroke were observed between the CTO and non-CTO groups. Our findings underscore the need for further research on the benefits and risks of performing staged or simultaneous percutaneous coronary intervention for CTO in the noninfarct-related artery in patients with ST-elevation myocardial infarction.
Mpox Case Presenting With Genital Lesions and Proctitis
Authors: Alhalaseh Yazan , Modi Mitul B. , Haddad Sandra , Souchik Adam , Speiser Jodi J. , Massarani-Wafai Razan , Dahiya Madhu
Published: March 2024

Monkeypox (Mpox) is a zoonotic Orthopoxvirus of the Poxviridae family, endemic to Africa. In August 2022, the US government declared it an emergency because of the worldwide spread. Traditionally, Mpox infection spreads through contact with infected animals. However, the 2022 outbreak Centers for Disease Control and Prevention (CDC) data note that 94% of cases had recent male-to-male sexual or close intimate contact, suggesting a novel sexual transmission. In this article, we report a 39-year-old HIV-positive man presenting with a diffuse cutaneous rash, perianal pain, and bloody stool of 2-week duration. A medical history includes intravenous drug use and multiple sexual partners. Physical examination revealed umbilicated, tan-colored, crusted cutaneous papules scattered across the face, trunk, and genital regions. Perianal lesion biopsy showed an acanthotic epidermis with spongiosis, ballooning degeneration of keratinocytes, and the formation of multinucleated syncytial keratinocytes. A dermal superficial/lichenoid mixed inflammatory cell infiltrate with multinucleated giant cells was noted. Perianal lesion polymerase chain reaction (PCR) was positive for Mpox. Colonoscopy revealed a 3-cm circumferential rectal ulcer with gray exudate and necrosis. A rectal ulcer biopsy showed an ulcerated mucosa with acute proctitis and necrosis. There were scattered macrophages with intranuclear inclusion and glassy vacuolization, and Mpox infection was confirmed by immunostaining with a Mpox-specific anti-Vaccinia virus antibody.
Cellular Cutaneous Epithelioid Hemangioma Harboring the Rare GATA6::FOXO1 Gene Fusion
Authors: Tepp Jonathan A. , Agaram Narasimhan P. , Chang Jason C. , Linos Konstantinos
Published: March 2024

Epithelioid hemangioma (EH) is a benign vascular tumor displaying diverse histomorphologies. Among these, one EH subtype comprises cellular sheets of atypical epithelioid cells, posing potential challenges in distinguishing it from malignant vascular lesions. In this case report, we present a cutaneous cellular EH that carries the rare GATA6::FOXO1 gene fusion, a recent discovery. Our aim is to provide an updated insight into the evolving knowledge of EHs while delving into the histologic and molecular characteristics of the primary differential diagnoses.
Effective Collaboration in the Surgical Management of Macroglossia in Beckwith–Wiedemann Syndrome
Authors: Binhezaim Alhanouf , Al Qurashi Abdullah A. , Alissa Sami , Alyazeedi Ibtesam A.
Published: March 2024

Beckwith–Wiedemann syndrome (BWS) is a complex congenital overgrowth disorder necessitating a multidisciplinary approach for effective management. A 5-year-old Saudi girl with BWS received comprehensive care involving various specialists, including a plastic surgeon who performed a keyhole technique tongue reduction to address macroglossia. The intervention resulted in significant improvements in speech and quality of life, with no postoperative complications. Intensive speech therapy further enhanced speech development. This case report emphasizes the importance of a multidisciplinary approach and the critical role of the plastic surgeon in managing BWS patients with macroglossia to achieve optimal outcomes.
Maintaining Functionality in Temporal Skin Tumor Surgery: A Focus on Nerve Injury and Excision Margins
Authors: Al-Aswad Firas , Fernandez-Diaz Oscar F. , Abdelrazek Mohamed , Al Naser Mutaz
Published: March 2024

Background:

Operating on temporal cutaneous tumors is challenging because of the intricate facial nerve system, particularly the frontal branches, and the possibility of brow dysfunction. Surgery for deep margin clearance is difficult because of the fragile and sensitive soft tissue in the temporal region. To address this research gap, this study assessed clearance margins, types of skin tumors, and nerve injuries in this critical anatomical position. This retrospective study assessed temporal skin cancer surgery, malignancy types, and clearance margins in patients with frontal-branch facial nerve injuries.

Methods:

Forty-five patients with temporal skin carcinoma biopsies were analyzed. The deep and peripheral excision margins of skin malignancies were examined. Medical records were reviewed for clinically injured frontal nerve.

Results:

Thirty-four patients were men (75%), and basal cell carcinoma was the most prevalent histological malignancy, followed by squamous cell carcinoma. The mean age of the patients was 77.8 years (39–107 years). Two patients experienced damage to the frontal branch nerve. Twenty-six percent of the skin malignancies had inadequate deep margin excision.

Conclusions:

Removing temporal skin lesions is difficult. We discovered a 26% and 4% probability of inadequate deep margin excision and frontal branch facial nerve injury, respectively. Temporal skin lesions must be removed safely by surgeons to preserve the branches of the facial nerves. Insufficiently removed tumors require multidisciplinary teamwork and patient discussions regarding the advantages and risks to improve results.
Clinical impact of genetic testing for lipid disorders
Authors: Muzurović Emir , Borozan Sanja , Rizzo Manfredi
Published: March 2024

Purpose of review

Genetic testing is increasingly becoming a common consideration in the clinical approach of dyslipidemia patients. Advances in research in last decade and increased recognition of genetics in biological pathways modulating blood lipid levels created a gap between theoretical knowledge and its applicability in clinical practice. Therefore, it is very important to define the clinical justification of genetic testing in dyslipidemia patients.

Recent findings

Clinical indications for genetic testing for most dyslipidemias are not precisely defined and there are no clearly established guideline recommendations. In patients with severe low-density lipoprotein cholesterol (LDL-C) levels, the genetic analysis can be used to guide diagnostic and therapeutic approach, while in severe hypertriglyceridemia (HTG), clinicians can rely on triglyceride level rather than a genotype along the treatment pathway. Genetic testing increases diagnostic accuracy and risk stratification, access and adherence to specialty therapies, and cost-effectiveness of cascade testing. A shared decision-making model between the provider and the patient is essential as patient values, preferences and clinical characteristics play a very strong role.

Genetic testing for lipid disorders is currently underutilized in clinical practice. However, it should be selectively used, according to the type of dyslipidemia and when the benefits overcome costs.
Effects of bempedoic acid on markers of inflammation and Lp(a)
Authors: Reddy Sukhila , Deoker Abhizith
Published: March 2024

Purpose of review

To study the effect of bempedoic acid on markers of inflammation and lipoprotein (a) to help determine if the drug would be useful to treat patients with elevated cardiovascular risks and residual cardiovascular risk despite optimal low-density lipoprotein cholesterol (LDL-C) levels.

Recent findings

Bempedoic acid is found to cause significant reduction in LDL-C and high-sensitivity C-reactive protein (hs-CRP) in various randomized clinical trials. Multiple meta-analyses have also found that bempedoic acid therapy leads to reduction in non–high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC) and apolipoprotein B (ApoB) levels. However, it has minimal effect on lipoprotein (a) (Lp(a)) level.

Bempedoic acid is a new lipid-lowering agent that inhibits enzyme ATP-citrate lyase in the cholesterol biosynthesis pathway. Major risk of cardiovascular events and its associated morbidity and mortality are proportional to LDL-C and inflammatory markers levels. It was found that bempedoic acid significantly lowers LDL-C, hs-CRP and other inflammatory markers levels. This drug could potentially be used in patients with elevated cardiovascular risk, in patients with residual cardiovascular risk despite attaining LDL-C goal and in statin intolerant patients.
Efficacy of Endoscopic Therapy in Symptomatic Pancreatic Divisum
Authors: Malik Sheza , Ullah Hamid , Loganathan Priyadarshini , Singh Dahiya Dushyant , Chandan Saurabh , Mohan Babu P. , Adler Douglas G.
Published: March 2024

Background and Aims:

Pancreas divisum (PD) is a congenital malformation of the pancreas and is implicated as a cause of pancreatitis. The role of endotherapy has been variable in symptomatic PD indicated by recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), or chronic pancreatic-type abdominal pain (PP). The aim of this study was to analyze the pooled data to determine the success of endoscopic intervention for pancreas divisum.

Methods:

We conducted a comprehensive search of several databases (inception to July 2023) to identify studies reporting on the use of endoscopic therapy in symptomatic pancreatic divisum. The random-effects model was used to calculate the pooled rates and I
2% values were used to assess the heterogeneity.

Results:

A total of 27 studies were retrieved that reported endoscopic intervention in pancreatic divisum. The calculated pooled rate of technical success was 92% (95% CI: 87-95; I
2=63%). The calculated pooled rate of clinical success was 65% (95% CI: 60-70; I
2=60%). The rate of clinical success by PD subtypes was highest in RAP at 71% (95% CI: 65-76; I
2=24%). Available studies had significant heterogeneity in defining clinical success. The rate of adverse events was 71% (95% CI: 65-76; I
2=24%).

Conclusions:

The role of endoscopic therapy in pancreatic divisum is variable with the highest success rate in recurrent acute pancreatitis. Endoscopic intervention is associated with a higher-than-usual rate of adverse events, including post-ERCP pancreatitis.
Visualization of the Internal Thoracic Arteries in Giant Cell Arteritis on 18F-FDG Semiconductor PET/CT
Authors: Maki Takashi , Matsusaka Yohji , Egi Ryota , Seto Akira , Kuji Ichiei
Published: March 2024

A 72-year-old woman presented with the fever and the pain of skull and face for 2 weeks. 18F-FDG PET/CT equipped with semiconductor detectors revealed strong uptake not only in the temporal, cervical, subclavian arteries, and aorta, but also in the bilateral internal thoracic arteries. The diagnosis of giant cell arteritis was made. Semiconductor PET can visualize small arteries such as the internal thoracic artery. The patients with giant cell arteritis are at a high risk of ischemic heart disease, and inflammatory involvement of the internal thoracic arteries may affect the outcome of coronary artery bypass grafting.
Incidence, Risk Factors, and Outcomes of Posttransplant Erythrocytosis Among Simultaneous Pancreas-Kidney Transplant Recipients
Authors: Gibes Mina L. , Astor Brad C. , Odorico Jon , Mandelbrot Didier , Parajuli Sandesh
Published: March 2024

Background.

Posttransplant erythrocytosis (PTE) is a well-known complication of kidney transplantation. However, the risk and outcomes of PTE among simultaneous pancreas-kidney transplant (SPKT) recipients are poorly described.

Methods.

We analyzed all SPKT recipients at our center between 1998 and 2021. PTE was defined as at least 2 consecutive hematocrit levels of >51% within the first 2 y of transplant. Controls were selected at a ratio of 3:1 at the time of PTE occurrence using event density sampling. Risk factors for PTE and post-PTE graft survival were identified.

Results.

Of 887 SPKT recipients, 108 (12%) developed PTE at a median of 273 d (interquartile range, 160–393) after transplantation. The incidence rate of PTE was 7.5 per 100 person-years. Multivariate analysis found pretransplant dialysis (hazard ratio [HR]: 3.15; 95% confidence interval [CI], 1.67-5.92; P < 0.001), non-White donor (HR: 2.14; 95% CI, 1.25-3.66; P = 0.01), female donor (HR: 1.50; 95% CI, 1.0-2.26; P = 0.05), and male recipient (HR: 2.33; 95% CI, 1.43-3.70; P = 0.001) to be associated with increased risk. The 108 cases of PTE were compared with 324 controls. PTE was not associated with subsequent pancreas graft failure (HR: 1.36; 95% CI, 0.51-3.68; P = 0.53) or kidney graft failure (HR: 1.16; 95% CI, 0.40-3.42; P = 0.78).

Conclusions.

PTE is a common complication among SPKT recipients, even in the modern era of immunosuppression. PTE among SPKT recipients was not associated with adverse graft outcomes, likely due to appropriate management.
Network analysis of marmoset cortical connections reveals pFC and sensory clusters
Authors: Pailthorpe Bernard A
Published: March 2024

A new analysis is presented of the retrograde tracer measurements of connections between anatomical areas of the marmoset cortex. The original normalisation of raw data yields the fractional link weight measure, FLNe. That is re-examined to consider other possible measures that reveal the underlying in link weights. Predictions arising from both are used to examine network modules and hubs. With inclusion of the in weights the Infomap algorithm identifies eight structural modules in marmoset cortex. In and out hubs and major connector nodes are identified using module assignment and participation coefficients. Time evolving network tracing around the major hubs reveals medium sized clusters in pFC, temporal, auditory and visual areas; the most tightly coupled and significant of which is in the pFC. A complementary viewpoint is provided by examining the highest traffic links in the cortical network, and reveals parallel sensory flows to pFC and via association areas to frontal areas.
Genome-wide association study identifies new loci associated with OCD
Authors: Strom Nora I , Halvorsen Matthew W , Tian Chao , Rück Christian , Kvale Gerd , Hansen Bjarne , Bybjerg-Grauholm Jonas , Grove Jakob , Boberg Julia , Becker Nissen Judith , Damm Als Thomas , Werge Thomas , de Schipper Elles , Fundin Bengt , Hultman Christina , Höffler Kira D. , Pedersen Nancy , Sandin Sven , Bulik Cynthia , Landén Mikael , Karlsson Elinor , Hagen Kristen , Lindblad-Toh Kerstin ,   Nordic OCD and Related Disorders Consortium (NORDiC),   23andMe Research Team,   PGC TS/OCD working group, Hougaard David M. , Meier Sandra M. , Le Hellard Stéphanie , Mors Ole , Børglum Anders D. , Haavik Jan , Hinds David A. , Mataix-Cols David , Crowley James J , Mattheisen Manuel
Published: March 2024

To date, four genome-wide association studies (GWAS) of obsessive-compulsive disorder (OCD) have been published, reporting a high single-nucleotide polymorphism (SNP)-heritability of 28% but finding only one significant SNP. A sub-stantial increase in sample size will likely lead to further identification of SNPs, genes, and biological pathways mediating the susceptibility to OCD. We conducted a GWAS meta-analysis with a 2-3-fold increase in case sample size (OCD cases: N = 37,015, controls: N = 948,616) compared to the last OCD GWAS, including six previously published cohorts (OCGAS, IOCDF-GC, IOCDF-GC-trio, NORDiC-nor, NORDiC-swe, and iPSYCH) and unpublished self-report data from 23andMe Inc. We explored the genetic architecture of OCD by conducting gene-based tests, tissue and celltype enrichment analyses, and estimating heritability and genetic correlations with 74 pheno-types. To examine a potential heterogeneity in our data, we conducted multivariable GWASs with MTAG. We found support for 15 independent genome-wide significant loci (14 new) and 79 protein-coding genes. Tissue enrichment analyses implicate multiple cortical regions, the amygdala, and hypothalamus, while cell type analyses yielded 12 cell types linked to OCD (all neurons). The SNP-based heritability of OCD was estimated to be 0.08. Using MTAG we found evidence for specific genetic underpinnings characteristic of different cohort-ascertainment and identified additional significant SNPs. OCD was genetically correlated with 40 disorders or traits-positively with all psychiatric disorders and negatively with BMI, age at first birth and multiple autoimmune diseases. The GWAS meta-analysis identified several biologically informative genes as important contributors to the aetiology of OCD. Overall, we have begun laying the groundwork through which the biology of OCD will be understood and described.
Super-resolution single molecule network analysis (SuperResNET) detects changes to clathrin structure by small molecule inhibitors
Authors: Wong Timothy H. , Khater Ismail M. , Hallgrimson Christian , Li Y. Lydia , Hamarneh Ghassan , Nabi Ivan R.
Published: March 2024

Specificity of small molecules for their target molecule in the cell is critical to determine their effective use as biologics and therapeutics. Small molecule inhibitors of clathrin endocytosis, Pitstop 2, and the dynamin inhibitor Dynasore, have off-target effects and their specificity has been challenged. Here, we used SuperResNET to apply network analysis to 20 nm resolution dSTORM single-molecule localization microscopy (SMLM) to test whether Pitstop 2 and Dynasore alter the morphology of clathrin coated pits in intact cells. SuperResNET analysis of dSTORM data from HeLa and Cos7 cells identifies three classes of clathrin structures: small oligomers (Class I); pits and vesicles (Class II); and larger clusters corresponding to fused clathrin pits and clathrin plaques (Class III). SuperResNET analysis of high resolution MinFlux imaging identifies Class 1 oligomers as well as Class 2 structures including morphologically identifiable clathrin pits and vesicles. SuperResNET feature analysis of dSTORM data shows that Pitstop 2 and Dynasore induce the formation of distinct homogenous populations of clathrin structures in HeLa cells. Pitstop 2 blobs are smaller and more elongated than those induced by Dynasore, indicating that these two clathrin inhibitors arrest clathrin endocytosis at distinct stages. Pitstop 2 and Dynasore are not impacting clathrin structure via actin depolymerization as the actin depolymerizing agent latrunculin A (LatA) induced larger heterogeneous clathrin structures. Ternary analysis of SuperResNET shape features presents a distinct profile for Pitstop 2 Class II structures. The most representative Pitstop blobs align with and resemble MinFlux clathrin pits while control structures resemble Minflux clathrin vesicles. SuperResNET analysis of SMLM data is therefore a highly sensitive approach to detect the effect of small molecules on target molecule structure in situ in the cell.
Beam-based commissioning of a novel
X
-band transverse deflection structure with variable polarization
Authors: González Caminal P. , Christie F. , D’Arcy R. , Jaster-Merz S. M. , Assmann R. , Burkart F. , Conrad B. , Dinter H. , Foese M. , Herrmann J. , Hoffmann M. , Hüning M. , Jonas R. , Krebs O. , Lederer S. , Marchetti B. , Marx D. , Mueller J. , Osterhoff J. , Peperkorn I. , Reukauff M. , Schlarb H. , Schreiber S. , Tews G. , Vinatier T. , Vogt M. , de Z. Wagner A. , Wesch S. , Craievich P. , Bopp M. , Braun H.-H. , Citterio A. , Fortunati R. , Ganter R. , Kleeb T. , Marcellini F. , Pedrozzi M. , Prat E. , Reiche S. , Rolli K. , Sieber R. , Grudiev A. , Millar W. L. , Catalan-Lasheras N. , McMonagle G. , Pitman S. , del Pozo Romano V. , Szypula K. T. , Wuensch W.
Published: March 2024

Longitudinal electron-beam diagnostics play a critical role in the operation and control of x-ray free-electron lasers, which rely on parameters such as the current profile, the longitudinal phase space, or the slice emittance of the particle distribution. On the one hand, the femtosecond-scale electron bunches produced at these facilities impose stringent requirements on the resolution achievable with the diagnostics. On the other, research and development of novel accelerator technologies such as beam-driven plasma-wakefield accelerators (PWFA) demand unprecedented capabilities to resolve the centroid offsets in the full transverse plane along the longitudinal bunch coordinate. We present the beam-based commissioning of an advanced X-band transverse-deflection rf structure (TDS) system with the new feature of providing variable polarization of the deflecting force: the PolariX-TDS. By means of a comprehensive campaign of measurements conducted with the prototype, key parameters of the rf performance of the system are validated and a phase-space characterization of an electron bunch is accomplished with a time resolution of 3.3 fs. Furthermore, an analysis of second-order effects induced on the bunch from its passage through the PolariX-TDS is presented.

Published by the American Physical Society
2024
Magnetized strangelets with anomalous magnetic moment and Coulomb interactions
Authors: Chen Huai-Min , Li Xiao-Wei , Xia Cheng-Jun , Wang Jing-Tao , Peng Guang-Xiong
Published: March 2024

We study the magnetized strangelets in the baryon density-dependent quark mass model, including the effects of both confinement and lead-order perturbation interactions. The properties of magnetized strangelets are investigated under the field strength 2×1017  G, where the anisotropy caused by the strong magnetic field is insignificant and can be treated approximately as an isotropic system. The consideration of anomalous magnetic moments in the energy spectrum naturally solves the difficulty of infrared divergence encountered in integrating the density of states. The Coulomb interaction is accounted for using a self-consistent treatment. The energy per baryon, mechanically stable radius, strangeness, and electric charge of magnetized strangelets are presented, where their dependence on the field strength and parameter of confinement and perturbation are investigated.

Published by the American Physical Society
2024
Measuring scalar charge with compact binaries: High accuracy modeling with self-force
Authors: Spiers Andrew , Maselli Andrea , Sotiriou Thomas P.
Published: March 2024

Using the self-force approach, we present the premier first-post-adiabatic accuracy formalism for modeling compact binaries in theories with a massless scalar field nonminimally coupled to gravity. We limit the binary secondary to being a non-spinning compact body with no scalar dipole (we will address the spinning and scalar dipole cases in an upcoming paper). By producing an ansatz for the scalar charged point particle action, we derive first- and second-order perturbative field equations and equations of motion for the secondary compact object. Under our assumptions, implementing this formalism will produce sufficiently accurate waveform templates for precision measurements of the scalar charge of the secondary with LISA data on extreme-mass-ratio inspirals. Our formalism is consistent with almost general scalar-tensor theories of gravity. Implementing our formalism builds on self-force models in general relativity; we show the incorporation into the two-timescale formalism is straightforward. Excitingly, implementation poses no significantly more challenging barriers than computing first-post-adiabatic waveforms in general relativity.

Published by the American Physical Society
2024
Universal anomalous fluctuations in charged single-file systems
Authors: Krajnik Žiga , Schmidt Johannes , Pasquier Vincent , Prosen Tomaž , Ilievski Enej
Published: March 2024

Introducing a general class of one-dimensional single-file systems (meaning that particle crossings are prohibited) of interacting hardcore particles with internal degrees of freedom (called charge), we exhibit a dynamical universality reflected in anomalous statistical properties of macroscopic fluctuating observables such as charge transfer. We find that stringent dynamical constraints lead to universal anomalous statistics of cumulative charge currents manifested both on the timescale characteristic of typical fluctuations and also in the rate function describing rare events. By computing the full counting statistics of net transferred charge between two extended subsystems, we establish a number of unorthodox dynamical properties in an analytic fashion. Most prominently, typical fluctuations in equilibrium are governed by a universal distribution that markedly deviates from the expected Gaussian statistics, whereas large fluctuations are described by an exotic large-deviation rate function featuring an exceptional triple critical point. Far from equilibrium, competition between dynamical phases leads to dynamical phase transitions of first and second order and spontaneous breaking of fluctuation symmetry of the univariate charge large-deviation function. The rich phenomenology of the outlined dynamical universality is exemplified on an exactly solvable classical cellular automaton of charged hardcore particles. We determine the dynamical phase diagram in the framework of Lee–Yang's theory of phase transitions and exhibit a hyper-dimensional diagram of distinct dynamical regimes. Our findings lead us to conclude that the conventional classification of dynamical universality classes based on the algebraic dynamical exponents and asymptotic scaling functions that characterize hydrodynamic relaxation of the dynamical structure factor is incomplete and calls for refinement.

Published by the American Physical Society
2024