bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex- and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA vs. MIOCA
Authors: Canton Lisa , Fedele Damiano , Bergamaschi Luca , Foà Alberto , Di Iuorio Ornella , Tattilo Francesco Pio , Rinaldi Andrea , Angeli Francesco , Armillotta Matteo , Sansonetti Angelo , Stefanizzi Andrea , Amicone Sara , Impellizzeri Andrea , Suma Nicole , Bodega Francesca , Cavallo Daniele , Bertolini Davide , Ryabenko Khrystyna , Casuso Marcello , Belmonte Marta , Gallinoro Emanuele , Casella Gianni , Galiè Nazzareno , Paolisso Pasquale , Pizzi Carmine
Published: May 2023

Aims

The aim of the study is to evaluate the impact of sex on acute myocardial infarction (AMI) patients’ clinical presentation and outcomes, comparing those with non-obstructive and obstructive coronary arteries (MINOCA vs. MIOCA).

Methods and results

We enrolled 2455 patients with AMI undergoing coronary angiography from January 2017 to September 2021. Patients were divided according to the type of AMI and sex: male (n = 1593) and female (n = 607) in MIOCA and male (n = 87) and female (n = 168) in MINOCA. Each cohort was further stratified based on age (≤/> 70 years). The primary endpoint (MAE) was a composite of all-cause death, recurrent AMI, and hospitalization for heart failure (HF) at follow-up. Secondary outcomes included all-cause and cardiovascular death, recurrent AMI, HF re-hospitalization, and stroke. MINOCA patients were more likely to be females compared with MIOCA ones (P < 0.001). The median follow-up was 28 (15–41) months. The unadjusted incidence of MAE was significantly higher in females compared with males, both in MINOCA [45 (26.8%) vs. 12 (13.8%); P = 0.018] and MIOCA cohorts [203 (33.4%) vs. 428 (26.9%); P = 0.002]. Age was an independent predictor of MAE in both cohorts. Among MINOCA patients, females ≤70 years old had a higher incidence of MAE [18 (23.7%) vs. 4 (5.9%); P = 0.003] compared with male peers, mainly driven by a higher rate of re-hospitalization for HF (P = 0.045) and recurrence of AMI (P = 0.006). Only in this sub-group of MINOCA patients, female sex was an independent predictor of MAE (hazard ratio = 3.09; 95% confidence interval: 1.02–9.59; P = 0.040). MINOCA females ≤70 years old had worse outcomes than MIOCA female peers.

Conclusion

MINOCA females ≤70 years old had a significantly higher incidence of MAE, compared with males and MIOCA female peers, likely due to the different pathophysiology of the ischaemic event.

Trial registration

Data were part of the ongoing observational study ‘AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation’ (ClinicalTrials.gov Identifier: NCT03883711).
Late stent thrombosis as a complication of T and small protrusion bifurcation stenting: a case report
Authors: Offiah Gregory , McGrath Paul , Kearney Peter
Published: May 2023

Background

A case of stent thrombosis as a complication of coronary bifurcation stenting is described. We review potential complications of bifurcation stenting and established guidelines.

Case summary

A 64-year-old man presented with a non-ST segment elevation myocardial infarction. High-sensitivity troponin I peaked at 99 000 ng/L (normal <5). He previously had coronary stenting for stable angina when residing in another country 2 years previously. Coronary angiography revealed no significant stenosis with TIMI 3 flow in all vessels. Cardiac magnetic resonance imaging demonstrated a left anterior descending artery (LAD) territory regional motion abnormality, late gadolinium enhancement consistent with recent infarction, and a left ventricular apical thrombus. Repeat angiography and intravascular ultrasound (IVUS) confirmed bifurcation stenting at the junction of the LAD and second diagonal (D2) with protrusion of several millimetres of the uncrushed proximal segment of the D2 stent in the LAD vessel lumen. There was under-expansion of the LAD stent in the mid-vessel and stent malapposition in the proximal LAD, extending into the distal left main stem coronary artery and involving the ostium of the left circumflex coronary artery. Percutaneous balloon angioplasty was performed along the length of the stent, including an internal crush of the D2 stent. Coronary angiography confirmed a uniform expansion of the stented segments and TIMI 3 flow. Final IVUS confirmed full stent expansion and apposition.

Discussion

This case highlights the importance of provisional stenting as a default strategy and familiarity with procedural steps in bifurcation stenting. Furthermore, it emphasizes the benefit of intravascular imaging for lesion characterization and stent optimization.
A mimicker of constriction: a case report of a rare case of cardiac angiosarcoma
Authors: Vohra Adam S , Johannesen Justin , Jessurun Jose , Weinsaft Jonathan W , Singh Harsimran S , Cheung Jim W , Lau Christopher , Ascunce Rebecca R
Published: May 2023

Background

Cardiac angiosarcoma is an exceptionally rare primary malignant tumour with an aggressive course and typically poor prognosis. Diagnosis is difficult, and patients often present with metastatic disease. We report the rare case of a patient with cardiac angiosarcoma who presents with constrictive physiology due to tumour encasement.

Case summary

A 65-year-old female with a past medical history of Hodgkin’s lymphoma and limited scleroderma presented with progressive dyspnoea on exertion. Multimodality imaging and haemodynamics with echocardiography, cardiac magnetic resonance imaging (MRI), and cardiac catheterization showed findings of constrictive physiology. Cardiac MRI showed areas of pericardial enhancement, so she was initially started on colchicine, prednisone, and mycophenolate mofetil to treat pericardial inflammation. However, her symptoms progressed, and she underwent pericardiectomy with cardiac surgery. Pericardium was noted to be thickened and a mass-like substance was densely adherent and potentially invading the heart itself and could not be dissected free. Surgical pathology showed features consistent with epithelioid angiosarcoma. Patient had rapid progression of her disease and was started on chemotherapy. Her course, however, was complicated by acute gastrointestinal bleeding, atrial fibrillation with rapid rates, and persistent volume overload. She elected for comfort measures and passed away shortly after her diagnosis.

Discussion

Our case shows an extremely rare diagnosis, cardiac angiosarcoma, presenting with typical findings of constrictive physiology. The case shows the typical features of constrictive physiology using multimodality imaging and haemodynamics and emphasizes the need to always think broadly in creating a differential diagnosis for constriction to ensure that rare diseases are considered.
A patient with Takayasu arteritis presenting with malignant hypertension: a case report
Authors: Sierra Laura Villegas , Binzenhöfer Leonhard , Schulze-Koops Hendrik , Lackermair Korbinian , Massberg Steffen , Lüsebrink Enzo
Published: May 2023

Background

Takayasu arteritis (TA) is a rare large-vessel vasculitis primarily affecting the aorta and its proximal branches. The manifestation of TA is variable, ranging from asymptomatic cases to severe organ dysfunction secondary to vascular damage, which often delays diagnosis.

Case summary

Here, we present a 37-year-old male patient suffering from visual impairment and malignant hypertension. Emergency fundoscopy showed large left subretinal bleeding and bilateral signs of hypertensive retinopathy. Echocardiographic and magnetic resonance imaging showed mildly reduced left ventricular ejection fraction and signs of hypertensive cardiomyopathy. Evaluation for secondary causes of arterial hypertension did not reveal an underlying disease, and the patient was discharged with optimal medical therapy. He was re-admitted after 11 days with fever of unknown origin, fatigue, and elevated inflammatory markers. The diagnosis of TA was finally established using 18F-fluorodeoxyglucose positron emission computed tomography scan and sonography of carotid and subclavian arteries. Anti-inflammatory combination therapy for active, severe TA with ophthalmologic involvement was initiated using high-dose glucocorticoids and the tumour necrosis factor alpha inhibitor adalimumab to minimize drug-related risks. The patient was scheduled for multidisciplinary follow-up appointments, including specialist consultation in rheumatology, angiology, cardiology, diabetology, and ophthalmology.

Discussion

This case highlights the diversity of initial symptoms, the challenges of TA diagnosis, and the importance of comprehensive evaluation for rare secondary causes of arterial hypertension. Individualized acute and long-term care necessitates multidisciplinary management of immunosuppressive therapy, secondary organ involvement, and concomitant diseases.
Rapid daily expansion of highly mobile intracardiac calcified tissue: a case report
Authors: Sudo Yuta , Inagaki Hiroshi
Published: May 2023

Background

A calcified amorphous tumour (CAT) is a non-neoplastic mass lesion arising within the cardiac chamber. CATs are rare but are a common cause of organ embolism. In the present study, we experienced a case of an intracardiac mass with calcification that, in contrast to a typical CAT, suddenly appeared and rapidly expanded without an inflammatory response based on pathological findings.

Case summary

A 58-year-old Japanese man undergoing peritoneal haemodialysis had a high-echoic mobile mass (15 × 6 mm), which was not visible on the transthoracic echocardiography (TTE) approximately a month earlier, in the left ventricular outflow tract noted on TTE performed during a close examination for fever. Although multiple blood cultures were negative, ampicillin/sulbactam and ceftriaxone were initially administered because of suspected blood culture-negative endocarditis. The mass rapidly enlarged (22 × 5 mm) over the following days. A CAT was suspected and resected based on imaging findings with calcification; however, the pathological findings did not indicate inflammation and fibrin that are typically found in CATs. Echocardiography performed 12 months after the resection showed no recurrence.

Discussion

This intracardiac calcified tissue had several similar features to a CAT. However, the initial presentation, enlargement rate, and pathological features of the tissue differed from that of a typical CAT. Although it is unknown whether this mass is a subtype of CAT, when an intracardiac calcified tissue is detected using an imaging test, careful follow-up or early surgical resection should be considered given the possibility of rapid tissue enlargement and embolism caused by the mass.
Unveiling the spatial distribution and molecular mechanisms of terpenoid biosynthesis in Salvia miltiorrhiza and S. grandifolia using multi-omics and DESI–MSI
Authors: Xia Jie , Lou Ganggui , Zhang Lan , Huang Yanbo , Yang Jian , Guo Juan , Qi Zhechen , Li Zhenhao , Zhang Guoliang , Xu Shengchun , Song Xijiao , Zhang Xiaodan , Wei Yukun , Liang Zongsuo , Yang Dongfeng
Published: May 2023

Salvia miltiorrhiza and S. grandifolia are rich in diterpenoids and have therapeutic effects on cardiovascular diseases. In this study, the spatial distribution of diterpenoids in both species was analyzed by a combination of metabolomics and mass spectrometry imaging techniques. The results indicated that diterpenoids in S. miltiorrhiza were mainly abietane-type norditerpenoid quinones with a furan or dihydrofuran D-ring and were mainly distributed in the periderm of the roots, e.g. cryptotanshinone and tanshinone IIA. The compounds in S. grandifolia were mainly phenolic abietane-type tricyclic diterpenoids with six- or seven-membered C-rings, and were widely distributed in the periderm, phloem, and xylem of the roots, e.g. 11-hydroxy-sugiol, 11,20-dihydroxy-sugiol, and 11,20-dihydroxy-ferruginol. In addition, the leaves of S. grandifolia were rich in tanshinone biosynthesis precursors, such as 11-hydroxy-sugiol, while those of S. miltiorrhiza were rich in phenolic acids. Genes in the upstream pathway of tanshinone biosynthesis were highly expressed in the root of S. grandifolia, and genes in the downstream pathway were highly expressed in the root of S. miltiorrhiza. Here, we describe the specific tissue distributions and mechanisms of diterpenoids in two Salvia species, which will facilitate further investigations of the biosynthesis of diterpenoids in plant synthetic biology.
Functional characterization of two flavone synthase II members in citrus
Authors: Zheng Juan , Zhao Chenning , Liao Zhenkun , Liu Xiaojuan , Gong Qin , Zhou Chenwen , Liu Yilong , Wang Yue , Cao Jinping , Liu Lili , Wang Dengliang , Sun Chongde
Published: May 2023

Polymethoxylated flavones (PMFs), the main form of flavones in citrus, are derived from the flavone branch of the flavonoid biosynthesis pathway. Flavone synthases (FNSs) are enzymes that catalyze the synthesis of flavones from flavanones. However, the FNS in citrus has not been characterized yet. Here, we identified two type II FNSs, designated CitFNSII-1 and CitFNSII-2, based on phylogenetics and transcriptome analysis. Both recombinant CitFNSII-1 and CitFNSII-2 proteins directly converted naringenin, pinocembrin, and liquiritigenin to the corresponding flavones in yeast. In addition, transient overexpression of CitFNSII-1 and CitFNSII-2, respectively, in citrus peel significantly enhanced the accumulation of total PMFs, while virus-induced CitFNSII-1 and CitFNSII-2 genes silencing simultaneously significantly reduced the expression levels of both genes and total PMF content in citrus seedlings. CitFNSII-1 and CitFNSII-2 presented distinct expression patterns in different cultivars as well as different developmental stages. Methyl salicylate (MeSA) treatment reduced the CitFNSII-2 expression as well as the PMFs content in the peel of Citrus sinensis fruit but did not affect the CitFNSII-1 expression. These results indicated that both CitFNSII-1 and CitFNSII-2 participated in the flavone biosynthesis in citrus while the regulatory mechanism governing their expression might be specific. Our findings improved the understanding of the PMFs biosynthesis pathway in citrus and laid the foundation for further investigation on flavone synthesis regulation.
Characteristics ofSalvia miltiorrhizamethylome and the regulatory mechanism of DNA methylation in tanshinone biosynthesis
Authors: Li Jiang , Li Caili , Deng Yuxing , Wei Hairong , Lu Shanfa
Published: May 2023

Salvia miltiorrhiza is a model medicinal plant with significant economic and medicinal value. Its roots produce a group of diterpenoid lipophilic bioactive components, termed tanshinones. Biosynthesis and regulation of tanshinones has attracted widespread interest. However, the methylome of S. miltiorrhiza has not been analysed and the regulatory mechanism of DNA methylation in tanshinone production is largely unknown. Here we report single-base resolution DNA methylomes from roots and leaves. Comparative analysis revealed differential methylation patterns for CG, CHG, and CHH contexts and the association between DNA methylation and the expression of genes and small RNAs. Lowly methylated genes always had higher expression levels and 24-nucleotide sRNAs could be key players in the RdDM pathway in S. miltiorrhiza. DNA methylation variation analysis showed that CHH methylation contributed mostly to the difference. Go enrichment analysis showed that diterpenoid biosynthetic process was significantly enriched for genes with downstream overlapping with hypoCHHDMR in July_root when comparing with those in March_root. Tanshinone biosynthesis-related enzyme genes, such as DXS2, CMK, IDI1, HMGR2, DXR, MDS, CYP76AH1, 2OGD25, and CYP71D373, were less CHH methylated in gene promoters or downstream regions in roots collected in July than those collected in March. Consistently, gene expression was up-regulated in S. miltiorrhiza roots collected in July compared with March and the treatment of DNA methylation inhibitor 5-azacytidine significantly promoted tanshinone production. It suggests that DNA methylation plays a significant regulatory role in tanshinone biosynthesis in S. miltiorrhiza through changing the levels of CHH methylation in promoters or downstreams of key enzyme genes.
FvWRKY50 is an important gene that regulates both vegetative growth and reproductive growth in strawberry
Authors: Chen Yating , Liu Liping , Feng Qianqian , Liu Chuang , Bao Yujuan , Zhang Nan , Sun Ronghui , Yin Zhaonan , Zhong Chuanfei , Wang Yuanhua , Li Qian , Li Bingbing
Published: May 2023

The WRKY transcription factors play important roles in plant growth and resistance, but only a few members have been identified in strawberry. Here we identified a WRKY transcription factor, FvWRKY50, in diploid strawberry which played essential roles in strawberry vegetative growth, and reproductive growth. Knocking out FvWRKY50 by genome editing accelerated flowering time and leaf senescence but delayed anthocyanin accumulation in fruit. Further analysis showed that FvWRKY50 acted as a transcriptional repressor to negatively regulate the expression of flowering- and leaf senescence-related genes, including FvFT2, FvCO, FvFT3, and FvSAUR36. Notably, FvWRKY50 directly upregulated the expression of FvCHI and FvDFR by binding their promoter under normal conditions, but at low temperature FvWRKY50 was phosphorylated by FvMAPK3 and then induced protein degradation by ubiquitination, delaying anthocyanin accumulation. In addition, the homozygous mutant of FvWRKY50 was smaller while the biallelic mutant showed normal size. These new findings provide important clues for us to further reveal the regulatory mechanisms of strawberry growth and fruit ripening
The Conditional Association Between Populism, Ideological Extremity, and Affective Polarization
Authors: Stefanelli Alberto
Published: May 2023

In recent years there has been an increasing interest in whether populism is related to opinion extremity. Yet, research on the topic offers little direct evidence on whether and under which conditions populist ideas at the individual level are related to policy extremity and inter-party dislike. This article aims to fill this gap by focusing on the reasons populist individuals hold more or less extreme opinions. Using data from the 2016 American National Electoral Study, I find that populist attitudes are a strong correlate of both ideological extremity and affective polarization, yet this association is conditional on respondent’s party affiliation. Populism is related to higher levels of ideological extremity among Democrats and stronger negative leader evaluations among Republicans. This finding indicates that the relationship between populism and citizens’ political judgements varies depending on the ability of populist leaders to make certain dimensions of the competition salient (i.e., ideological or affective) and exploit pre-existing ideological and partisan rivalries (i.e., party identity).
Genomic Analyses of Longitudinal Mycobacterium abscessus Isolates in a Multicenter Cohort Reveal Parallel Signatures of In-Host Adaptation
Authors: Choi JooHee , Keen Eric C , Wallace Meghan A , Fishbein Skye , Prusa Jerome , Zimbric Madsen , Mejia-Chew Carlos R , Mehta Shail B , Bailey Thomas C , Caverly Lindsay J , Burnham Carey-Ann D , Dantas Gautam
Published: May 2023

Background

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective.

Methods

We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays.

Results

We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds.

Conclusions

We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.
Serial Casting as an Effective Method for Burn Scar Contracture Rehabilitation: A Case Series
Authors: Schetzsle Stephanie , Lin Weber Wei Chiang , Purushothaman Prabhu , Ding Jie , Kwan Peter , Tredget Edward E
Published: May 2023

Guidelines and protocols for orthoses in burn scar contracture rehabilitation are limited. The current study aims to determine the optimal frequency of casting, potentially facilitating the development of a serial casting protocol. Previous literature supporting casting has low generalizability due to methodology limitations. Seven patients with burn scar contracted joints, who did not respond to traditional therapy, were recruited in this study. Patients were serially casted once, three times, or five times a week. Joint range of motion was maximized with stretching and exercise techniques before every new cast application. Across all patients, active range of motion increased from 65.8 ± 27.8° to 108.1 ± 23.3° with casting; or from 57.8 ± 16.2% to 96.7 ± 2.9% of normal. Similarly, scars improved from 9.5 ± 1.5 to 4.9 ± 1.4 on the Modified Vancouver Scar Scale score. This therapeutic effect was achieved within an average of 8.5 ± 3.7 d and 4.0 ± 2.2 new cast applications. Given the study findings, the procedures outlined could be used to develop a standardized serial casting protocol for burn scar contracture rehabilitation.
The bacterial effector SidN/Lpg1083 promotes cell death by targeting Lamin-B2
Authors: Gao Jiajia , Xu Wenwen , Tang Feng , Xu Minrui , Zhou Qin , Yang Xingyuan , Zhang Nannan , Ma Jinming , Yang Qi , Chen Xiaofang , Qin Ximing , Ge Honghua
Published: May 2023

To facilitate survival, replication, and dissemination, the intracellular pathogen Legionella pneumophila relies on its unique type IVB secretion system (T4SS) to deliver over 330 effectors to hijack host cell pathways in a spatiotemporal manner. The effectors and their host targets are largely unexplored due to their low sequence identity to the known proteins and functional redundancy. The T4SS effector SidN (Lpg1083) is secreted into host cells during the late infection period. However, to the best of our knowledge, the molecular characterization of SidN has not been studied. Herein, we identified SidN as a nuclear envelope-localized effector. Its structure adopts a novel fold, and the N-terminal domain is crucial for its specific subcellular localization. Furthermore, we found that SidN is transported by eukaryotic karyopherin Importin-13 into the nucleus, where it attaches to the N-terminal region of Lamin-B2 to interfere with the integrity of the nuclear envelope, causing nuclear membrane disruption and eventually cell death. Our work provides new insights into the structure and function of an L. pneumophila effector protein, and suggests a potential strategy utilized by the pathogen to promote host cell death and then escape from the host for secondary infection.
Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting
Authors: Singh Simron , Hope Thomas A , Bergsland Emily B , Bodei Lisa , Bushnell David L , Chan Jennifer A , Chasen Beth R , Chauhan Aman , Das Satya , Dasari Arvind , Del Rivero Jaydira , El-Haddad Ghassan , Goodman Karyn A , Halperin Daniel M , Lewis Mark A , Lindwasser O Wolf , Myrehaug Sten , Raj Nitya P , Reidy-Lagunes Diane L , Soares Heloisa P , Strosberg Jonathan R , Kohn Elise C , Kunz Pamela L ,   NET CTPM participants, Bergsland Emily , Beveridge Tom , Bodei Lisa , Borek Anita , Brockman Michelle , Bushnell David , Capala Jacek , Chan Jennifer , Chasen Beth , Chauhan Aman , Das Satya (Nanu) , Arvind Dasari N , Davies-Venn Cynthia , Del Rivero Jaydira , Demaria Sandra , Donoghue Martha , Eads Jennifer , El-Haddad Ghassan , Fielman Natalie , Fishbein Lauren , Gericke Germo , Goodman Karyn , Halperin Daniel , Hendifar Andrew , Hicks Rodney , Hobbs Robert , Hobday Timothy , Hope Thomas , Iyer Renuka , Jaffe Deborah , Kennedy Andrew , Kohn Elise , Kulke Matthew , Kunos Charles , Kunz Pamela L , Lewis Mark , Lin Frank , Lindwasser Wolf , Mailman Josh , McDonald Michael , McEwan Sandy , Myrehaug Sten , Nakasato Antonio , Nothwehr Steve , Ou Fang-Shu , Padda Sukhmani , Pavel Marianne , Pilowa Anthony , Raj Nitya , Ramnaraign Brian , Reidy-Lagunes Diane , Rubinstein Larry , Saletan Stephen , Shah Manisha , Singh Simron , Soares Heloisa , Soulen Michael , Strosberg Jonathan , Untch Brian , Wahba Mona , Wong Rebecca , Yao James
Published: May 2023

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.
A Method for Epicuticular Wax and Contaminant Removal from Herbarium Specimens for Scanning Electron Microscopy
Authors: Dai Guang-Yi , Qin Qiao-Mei , Deng Ru-Fang , Hu Xiao-Ying
Published: May 2023

We describe a method for cleaning leaf epicuticular wax and contaminants from herbarium specimens in preparation for scanning electron microscopy. Specimens are rinsed in chloroform, heated at 50°C for 8 hrs, ultrasonicated in 70% ethanol, and subjected to critical-point drying. This method helps preserve and reveal the surface details of specimens that are heavily covered with epicuticular wax and contaminants, making many morphologically and functionally important details readily visible. We tested our method by using it to clean herbarium specimens and comparing the results with those obtained using three other chemicals: acetone, xylene, and 1:1 acetone:xylene, confirming that chloroform treatment was the most effective.
Assessing Common Content and Responsiveness of the QoR-15 and the SF-8 in the Context of Recovery from Regional Anesthesia for Joint Replacement
Authors: Aloziem Okechukwu U , Williams Brian A , Mikolic Joseph M , Boudreaux-Kelly Monique Y , Faruque Saurab , Piva Sara R , Ibinson James W , Switzer Galen E
Published: May 2023

Purpose

There is no consensus regarding how best to measure postoperative quality of recovery after anesthesia/surgery (e.g., using 24-hour survey instruments) in veterans or active military. Our goals were to (1) describe health-related quality-of-life (HRQoL) and recovery across time in veterans, (2) examine the commonality between the quality of recovery (QoR-15) and short-form (SF) surveys (including the SF-8, 24-hour version), and (3) examine the responsiveness of these surveys.

Materials and Methods

This study was approved by the Institutional Review Boards from the University of Pittsburgh, the VA Pittsburgh, and the Human Research Protection Office of the Department of Defense. Secondary analyses of data were executed based on a randomized trial dataset of knee/hip arthroplasty patients, the study having recruited 135 total veterans. QoR-15 and HRQoL SF surveys were completed and self-reported before surgery (pre-op), on postoperative day 2 (PO-D2), and 6 weeks postoperatively. Descriptive statistics were used to examine scores across time. Common content was examined using Pearson’s r. Responsiveness was examined using distribution-based methods.

Results

Average veteran age was 67 year, 89% were male, 88% white, and average body mass index was 33 kg∙m−2. QoR-15 scores declined from pre-op to PO-D2 but were higher than pre-op at 6 weeks. SF physical component summary (PCS) scores were low both pre-op and PO-D2, but were elevated over baseline at 6 weeks. SF mental component summary (MCS) scores declined from baseline to PO-D2 but were higher than pre-op at 6 weeks. Associations of the QoR-15 total score and PCS/MCS were medium/large and statistically significant at P ≤ .01. Both instruments were responsive to changes.

Conclusion

QoR-15 and SF-8 have high content commonality and performed similarly in veterans across time. SF-8 has added benefits of (1) brevity, (2) assessment of physical and mental health components, and (3) being normed to the general population. The SF-8, if used without the QoR-15 in tandem in future study of anesthesia-related outcomes, would need to be supplemented by separate questions addressing postoperative nausea/vomiting (a frequent outcome after anesthesia that is relevant to same-day and next-day mobilization after elective joint replacement surgery).
DIANA-miRPath v4.0: expanding target-based miRNA functional analysis in cell-type and tissue contexts
Authors: Tastsoglou Spyros , Skoufos Giorgos , Miliotis Marios , Karagkouni Dimitra , Koutsoukos Ioannis , Karavangeli Anna , Kardaras Filippos S , Hatzigeorgiou Artemis G
Published: May 2023

DIANA-miRPath is an online miRNA analysis platform harnessing predicted or experimentally supported miRNA interactions towards the exploration of combined miRNA effects. In its latest version (v4.0, http://www.microrna.gr/miRPathv4), DIANA-miRPath breaks new ground by introducing the capacity to tailor its target-based miRNA functional analysis engine to specific biological and/or experimental contexts. Via a redesigned modular interface with rich interaction, annotation and parameterization options, users can now perform enrichment analysis on Gene Ontology (GO) terms, KEGG and REACTOME pathways, sets from Molecular Signatures Database (MSigDB) and PFAM. Included miRNA interaction sets are derived from state-of-the-art resources of experimentally supported (DIANA-TarBase v8.0, miRTarBase and microCLIP cell-type-specific interactions) or from in silico miRNA–target interactions (updated DIANA-microT-CDS and TargetScan predictions). Bulk and single-cell expression datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression project (GTEx) and adult/fetal single-cell atlases are integrated and can be used to assess the expression of enriched term components across a wide range of states. A discrete module enabling enrichment analyses using CRISPR knock-out screen datasets enables the detection of selected miRNAs with potentially crucial roles within conditions under study. Notably, the option to upload custom interaction, term, expression and screen sets further expands the versatility of miRPath webserver.
Efficient gene activation in plants by the MoonTag programmable transcriptional activator
Authors: Casas-Mollano J Armando , Zinselmeier Matthew H , Sychla Adam , Smanski Michael J
Published: May 2023

CRISPR/Cas-based transcriptional activators have been developed to induce gene expression in eukaryotic and prokaryotic organisms. The main advantages of CRISPR/Cas-based systems is that they can achieve high levels of transcriptional activation and are very easy to program via pairing between the guide RNA and the DNA target strand. SunTag is a second-generation system that activates transcription by recruiting multiple copies of an activation domain (AD) to its target promoters. SunTag is a strong activator; however, in some species it is difficult to stably express. To overcome this problem, we designed MoonTag, a new activator that works on the same basic principle as SunTag, but whose components are better tolerated when stably expressed in transgenic plants. We demonstrate that MoonTag is capable of inducing high levels of transcription in all plants tested. In Setaria, MoonTag is capable of inducing high levels of transcription of reporter genes as well as of endogenous genes. More important, MoonTag components are expressed in transgenic plants to high levels without any deleterious effects. MoonTag is also able to efficiently activate genes in eudicotyledonous species such as Arabidopsis and tomato. Finally, we show that MoonTag activation is functional across a range of temperatures, which is promising for potential field applications.
Constitutional Review in the European Legal Space: A Political Science Perspective
Authors: Landfried Christine
Published: May 2023

In this contribution, I present the hypothesis that constitutional review in both the democratic nation-state and the European legal space allows for a method of reflecting on social problems that differs from the mode of politics and, precisely because of the difference between judicial and political decision-making, increases the capacity for legitimate and effective governance. There are six conditions for such a positive potential of constitutional review for democracies. First, citizens must trust constitutional courts and law should be rooted in socially accepted values. Second, democratic, transparent, and diversity-oriented procedures for the selection and election of constitutional court judges are necessary for legitimate constitutional review. Third, constitutional review requires independent courts and a specific way of judicial decision-making that differs from politics. Fourth, a division of labour between constitutional courts and parliaments, linked to the functions of both institutions, ensures the effective protection of the constitution. Fifth, complying with the principle of subsidiarity is crucial because supranational and international courts have insufficient knowledge of national law and, vice versa, national constitutional courts have insufficient knowledge of European law. And finally, the sixth condition is to develop a European understanding of the legal norms of the European Union and the Council of Europe while respecting cultural, legal, and political differences between nation-states. After describing these normative conditions, I will empirically examine whether and to what extent these conditions for the legitimacy and problem-solving capacity of constitutional review are actually met in the European legal space.
New treatment for osteoarthritis: Gene therapy
Authors: Li Xinyu , Shen Leyao , Deng Zhenghan , Huang Zeyu
Published: May 2023

Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.
The Generation of Eocene Mafic Dike Swarms During the Exhumation of a Core Complex, Biarjmand Area, NE Iran
Authors: Azizi Hossein , Daneshvar Narges , Asahara Yoshihiro , Minami Masayo , Anma Ryo
Published: May 2023

Several swarms of parallel E–W dikes cuts late Neoproterozoic- to early Paleozoic (540 Ma) basement in the Biarjmand area, NE Iran. The microgabbroic to doleritic dike are several hundred meters long and 0.5 to 3 meters wide. U–Pb dating of their zircon grains yields a crystallization age of 46.0 ± 7.1 Ma for the dike swarms. The dikes have SiO2 contents of 46.0–49.3 wt%, and Fe2O3 contents of 9.80–14.8 wt% with variable MgO (4.92–9.16 wt%), TiO2 (1.47–2.65 wt%), and K2O contents (0.33–1.13 wt%). The dikes have low contents of high field strength elements (HFSEs), and have some similarities to transitional mid-ocean ridge basalts (T-MORB) based on their chemical composition. Positive ${\varepsilon}_{Nd}(t)$ values of +5.2 to +6.0 for the dike samples imply that the basaltic magma was generated from depleted lithospheric mantle. After the closure of the Sabzevar ocean and obduction of the large mantle peridotite body over the continental crust in the late Cretaceous-Paleocene, the gravitational instability in the central Iran/Eurasia plate collision zone triggered exhumation of old basement coeval with injection of the mafic magma. During exhumation, mylonitic deformation with brittle-ductile structures affected the basement metagranite and the host rocks. The metagranite and dike swarms cut the Cretaceous Sabzevar ophiolite, and the disparting of ophiolite members probably occurred during basement exhumation in the Cenozoic. The similar ages of the mafic dike swarms and other Eocene magmatic rocks of the Urumiah (Urmia) Dokhtar magmatic arc (UDMA), western Iran, is consistent with a rapid extensional regime over the Sabzevar suture zone on an earlier collision zone in NE Iran. This process provided a suitable setting for the exhumation of the old basement, the emplacement of the parallel dike swarm, and the development of shallow basins in this area.
Hyper-anti-freezing bionic functional surface to −90°C
Authors: Wang Zhaolong , Xie Mingzhu , Guo Qing , Liao Yibo , Zhang Ce , Chen Yongping , Dong Zhichao , Duan Huigao
Published: May 2023

Freezing phenomenon has troubled people for centuries, and efforts have been made to lower the liquid freezing temperature, raise the surface temperature, or mechanical deicing. Inspired by the elytra of beetle, we demonstrate a novel functional surface for directional penetration of liquid to reduce icing. The bionic functional surface is fabricated by projection microstereolithography (PµSL) based three dimensional printing technique with the wettability on its two sides tailored by TiO2 nanoparticle sizing agent. A water droplet penetrates from the hydrophobic side to the superhydrophilic side of such a bionic functional surface within 20 ms, but it is blocked in the opposite direction. Most significantly, the penetration time of a water droplet through such a bionic functional surface is much shorter than the freezing time on it, even though the temperature is as low as −90°C. This work opens a gate for the development of functional devices for liquid collection, condensation, especially for hyperantifogging/freezing.
Coupling sum rules and oblique corrections in gauge-Higgs unification
Authors: Hosotani Yutaka , Funatsu Shuichiro , Hatanaka Hisaki , Orikasa Yuta , Yamatsu Naoki
Published: May 2023

In grand-unified-theory-inspired SO(5) × U(1)X × SU(3)C gauge-Higgs unification (GHU) in the Randall–Sundrum warped spacetime, the W- and Z-couplings of all 4D fermion modes become nontrivial. The W- and Z-couplings of zero-mode quarks and leptons slightly deviate from those in the SM, and the couplings take the matrix form in the space of Kaluza–Klein (KK) states. In particular, the 4D couplings and mass spectra in the KK states depend on the Aharonov–Bohm phase θH in the fifth dimension. Nevertheless there emerge three astonishing sum rules among those coupling matrices, which guarantees the finiteness of certain combinations of corrections to vacuum polarization tensors. We confirm by numerical evaluation that the equality in the sum rules holds with 5- to 7-digit accuracy. Based on the sum rules we propose improved oblique parameters in GHU. Oblique corrections due to fermion 1-loop diagrams are found to be small.
Is parental unemployment associated with increased risk of adverse childhood experiences? A systematic review and meta-analysis
Authors: Judd Natasha , Hughes Karen , Bellis Mark A , Hardcastle Katie , Amos Rebekah
Published: May 2023

Background

Unemployment has adverse consequences for families and can put children at risk of harm. This study presents a systematic review and meta-analysis of global evidence on associations between parental unemployment and adverse childhood experiences (ACEs).

Methods

Systematic literature searches across four databases identified cross-sectional, cohort or case–control studies measuring associations between parental employment and individual or cumulative ACEs in children. Available risk estimates were extracted and pooled odds ratios calculated using random-effects models.

Results

Of 60 included studies, 37 provided risk estimates suitable for pooling across seven ACE types. Paternal/any parental unemployment was associated with a 29% increased risk of sexual abuse, 54% increased risk of neglect, 60% increased risk of physical abuse and around 90% increased risk of child maltreatment and parental mental illness. No associations were found between maternal unemployment and ACEs. Pooling estimates from representative general population studies also identified increased risk of child maltreatment with paternal/any parental unemployment (82%) but not maternal unemployment.

Conclusions

Children who grow up with parental unemployment can be at increased risk of ACEs. A combination of socioeconomic measures to increase employment opportunities and parental support targeting fathers and mothers may help break multigenerational cycles of abuse and deprivation.
Optimal Capital Structure and Risk Management Policies of Banks That Use CoCo Futures to Hedge Financial-Sector Risk
Authors: Goldstein Robert S , Yang Fan
Published: May 2023

We investigate the joint optimal risk management and capital structure decisions of banks when they use contingent-convertible (CoCo) futures contracts to hedge financial-sector risk. In spite of banks choosing significantly higher leverage ratios, their default probabilities drop appreciably while their equity values increase, allowing banks to compete more favorably with the shadow-banking system. Banks’ value-maximizing decision to hedge financial-sector risk unintentionally leads to an economy with extremely low aggregate bank default rates across all future states of nature. Thus, CoCo futures offer a powerful microprudential and macroprudential policy tool. That banks choose not to hedge financial-sector risk in practice is consistent with managers internalizing bank bailouts.
Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study
Authors: Kim Tae-Joon , Kim Min Hye , Kim Jung Hwan , Jun Jin-Sun , Byun Jung-Ick , Sunwoo Jun-Sang , Shin Jung-Won , Gho Sung-Min , Sohn Chul-Ho , Jung Ki-Young
Published: May 2023

Study Objectives

The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM).

Methods

We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method.

Results

RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and −0.466, respectively).

Conclusions

Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.
PhyloCoalSimulations: A Simulator for Network Multispecies Coalescent Models, Including a New Extension for the Inheritance of Gene Flow
Authors: Fogg John , Allman Elizabeth S , Ané Cécile
Published: May 2023

We consider the evolution of phylogenetic gene trees along phylogenetic species networks, according to the network multispecies coalescent process, and introduce a new network coalescent model with correlated inheritance of gene flow. This model generalizes two traditional versions of the network coalescent: with independent or common inheritance. At each reticulation, multiple lineages of a given locus are inherited from parental populations chosen at random, either independently across lineages or with positive correlation according to a Dirichlet process. This process may account for locus-specific probabilities of inheritance, for example. We implemented the simulation of gene trees under these network coalescent models in the Julia package PhyloCoalSimulations, which depends on PhyloNetworks and its powerful network manipulation tools. Input species phylogenies can be read in extended Newick format, either in numbers of generations or in coalescent units. Simulated gene trees can be written in Newick format, and in a way that preserves information about their embedding within the species network. This embedding can be used for downstream purposes, such as to simulate species-specific processes like rate variation across species, or for other scenarios as illustrated in this note. This package should be useful for simulation studies and simulation-based inference methods. The software is available open source with documentation and a tutorial at https://github.com/cecileane/PhyloCoalSimulations.jl.