bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome
Authors: Fukami-Gartner Abi , Baburamani Ana A , Dimitrova Ralica , Patkee Prachi A , Ojinaga-Alfageme Olatz , Bonthrone Alexandra F , Cromb Daniel , Uus Alena U , Counsell Serena J , Hajnal Joseph V , O’Muircheartaigh Jonathan , Rutherford Mary A 
Published: May 2023

Abstract
Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.
Impact of Point-of-Care Rapid Diagnostic Tests on Antibiotic Prescription Among Patients Aged &lt;18 Years in Primary Healthcare Settings in 2 Peri-Urban Districts in Ghana: Randomized Controlled Trial Results
Authors: Adjei Alexander , Kukula Vida , Narh Clement Tetteh , Odopey Selase , Arthur Emmanuel , Odonkor Gabriel , Mensah Michael Matey , Olliaro Piero , Horgan Philip , Dittrich Sabine , Moore Catrin E , Salami Olawale , Awini Elizabeth , Nkeramahame Juvenal , Williams John , Baiden Rita 
Published: May 2023

Abstract

Background
Inappropriate antibiotic prescriptions are a known driver of antimicrobial resistance in settings with limited diagnostic capacity. This study aimed to assess the impact of diagnostic algorithms incorporating rapid diagnostic tests on clinical outcomes and antibiotic prescriptions compared with standard-of-care practices, of acute febrile illness cases at outpatient clinics in Shai-Osudoku and Prampram districts in Ghana.

Methods
This was an open-label, centrally randomized controlled trial in 4 health facilities. Participants aged 6 months to &lt;18 years of both sexes with acute febrile illness were randomized to receive a package of interventions to guide antibiotic prescriptions or standard care. Clinical outcomes were assessed on day 7.

Results
In total, 1512 patients were randomized to either the intervention (n = 761) or control (n = 751) group. Majority were children aged &lt;5 years (1154 of 1512, 76.3%) and male (809 of 1512, 53.5%). There was 11% relative risk reduction of antibiotic prescription in intervention group (RR, 0.89; 95% CI, .79 to 1.01); 14% in children aged &lt;5 years (RR, 0.86; 95% CI, .75 to .98), 15% in nonmalaria patients (RR, 0.85; 95% CI, .75 to .96), and 16% in patients with respiratory symptoms (RR, 0.84; 95% CI, .73 to .96). Almost all participants had favorable outcomes (759 of 761, 99.7% vs 747 of 751, 99.4%).

Conclusions
In low- and middle-income countries, the combination of point-of-care diagnostics, diagnostic algorithms, and communication training can be used at the primary healthcare level to reduce antibiotic prescriptions among children with acute febrile illness, patients with nonmalarial fevers, and respiratory symptoms.

Clinical Trials Registration
NCT04081051.
Understanding the Decline of Incident, Active Tuberculosis in People With Human Immunodeficiency Virus in Switzerland
Authors: Zeeb Marius , Tepekule Burcu , Kusejko Katharina , Reiber Claudine , Kälin Marisa , Bartl Lena , Notter Julia , Furrer Hansjakob , Hoffmann Matthias , Hirsch Hans H , Calmy Alexandra , Cavassini Matthias , Labhardt Niklaus D , Bernasconi Enos , Braun Dominique L , Günthard Huldrych F , Kouyos Roger D , Nemeth Johannes ,   the Swiss HIV Cohort Study, Meier Jan , Schäfer Yves , Follonier Océane , Perraudin Danièle , Amstad Marianne 
Published: May 2023

Abstract

Background
People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear.

Methods
We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures.

Results
In 21 528 PWH, LTBI prevalence declined from 15.1% in 2001% to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (hazard ratio [HR] 9.8, 5.8–16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease.

Conclusions
TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.
First report on the serum chemistry and haematology of free-ranging dusky (Carcharhinus obscurus) and sandbar (Carcharhinus plumbeus) sharks in the eastern Mediterranean Sea
Authors: Starostinetsky-Malonek Tal , Scheinin Aviad , Aroch Itamar , Davidovich Nadav , Bigal Eyal , Livne Leigh , Hauser-Davis Rachel Ann , Wosnick Natascha , Tchernov Dan , Morick Danny 
Published: May 2023

Abstract
Shark assessments in the Mediterranean Sea are still scarce, and serum chemistry and haematological data have yet to be reported for wild dusky (Carcharhinus obscurus) or sandbar (Carcharhinus plumbeus) shark populations in the Mediterranean Sea. Herein, blood samples were obtained from adult dusky (n = 23) and sandbar (n = 14) sharks from an aggregation site near the Hadera power and desalination plants in Israel in the winters of 2016–20. Several serum chemistry analytes were characterized with relation to stress, body size and environmental conditions. Glucose concentrations were higher, while total cholesterol concentrations were lower in dusky sharks than in sandbar sharks, potentially due to distinct metabolic pathways utilized during the capture-related activity by both species. However, differences in sex and size are noted and should be considered. The blood cell morphology of both species was consistent with previous findings for sandbar sharks. Atypical monocytes were noted in one dusky shark. Preliminary and exploratory reference intervals for female dusky sharks were calculated for glucose, triglycerides, total cholesterol, total protein and creatine kinase. These data must be viewed with caution due to the potential influence of capture-related stress on analyte concentrations and activities and the fact that only females were employed in the calculations. Moreover, the sampling site is adjacent to coastal power and desalination plants, which may significantly affect shark physiology. Although limited, this novel database on dusky and sandbar shark serum chemistry and haematology aspects is essential as a first attempt to obtain data on these species in the eastern Mediterranean Sea and for future conservation and long-term biomonitoring efforts.
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

Abstract

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 (≤/&gt; 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 &lt; 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

Abstract

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 &lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

AbstractPolymethoxylated 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.