bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclization of o-Alkynylisocyanobenzenes with 1,3-Dicarbonyl Compounds
Authors: Kuhakarn Chutima , La-ongthong Kannika , Sawekteeratana Natthapat , Klaysuk Jasarin , Soorukram Darunee , Leowanawat Pawaret , Reutrakul Vichai , Krobthong Sucheewin , Wongtrakoongate Patompon 
Published: March 2022

AbstractA facile and convenient reaction of o-alkynylisocyanobenzenes with various active-methylene compounds, including 1,3-diesters, 1,3-diketones, β-keto esters, and β-keto amides, under Brønsted basic conditions, has been developed. Diethyl malonate reacted smoothly with a collection of o-alkynylisocyanobenzenes to provide the corresponding 2-quinolin-2-yl malonates in excellent yields. Acetylacetone gave a mixture of quinolin-4-yl and quinolin-2-yl derivatives. Acetoacetate esters and acetoacetyl amide derivative initially gave 2-quinolin-2-yl adducts that underwent partial deacetylation under the reaction conditions.
Systemic Antiangiogenic Therapies for Bleeding in Hereditary Hemorrhagic Telangiectasia: A Practical, Evidence-Based Guide for Clinicians
Authors: Al-Samkari Hanny 
Published: March 2022

AbstractManagement of bleeding in hereditary hemorrhagic telangiectasia (HHT), the second most common hereditary bleeding disorder in the world, is currently undergoing a paradigm shift. Disease-modifying antiangiogenic therapies capable of achieving durable hemostasis via inducing telangiectasia regression have emerged as a highly effective and safe modality to treat epistaxis and gastrointestinal bleeding in HHT. While evidence to date is incomplete and additional studies are ongoing, patients presently in need are being treated with antiangiogenic agents off-label. Intravenous bevacizumab, oral pazopanib, and oral thalidomide are the three targeted primary angiogenesis inhibitors, with multiple studies describing both reassuring safety and impressive effectiveness in the treatment of moderate-to-severe HHT-associated bleeding. However, at present there is a paucity of guidance in the literature, including the published HHT guidelines, addressing the practical aspects of antiangiogenic therapy for HHT in clinical practice. This review article and practical evidence-based guide aims to fill this unaddressed need, synthesizing published data on the use of antiangiogenic agents in HHT, relevant data for their use outside of HHT, and expert guidance where evidence is lacking. After a brief review of principles of bleeding therapy in HHT, guidance on hematologic support with iron and blood products, and alternatives to antiangiogenic therapy, this article examines each of the aforementioned antiangiogenic agents in detail, including patient selection, initiation, monitoring, toxicity management, and discontinuation. With proper, educated use of antiangiogenic therapies in HHT, patients with even the most severe bleeding manifestations can achieve durable hemostasis with minimal side-effects, dramatically improving health-related quality of life and potentially altering the disease course.
High-precision background correction and artifact suppression for ultrafast spectroscopy by quasi-simultaneous measurements in a split-sample cell
Authors: Deniz E. , Löffler J. G. , Kondratiev A. , Thun A. R. , Shen Y. , Wille G. , Bredenbeck J. 
Published: March 2022

Alternating acquisition of background and sample spectra is often employed in conventional Fourier-transform infrared spectroscopy or ultraviolet–visible spectroscopy for accurate background subtraction. For example, for solvent background correction, typically a spectrum of a cuvette with solvent is measured and subtracted from a spectrum of a cuvette with solvent and solute. Ultrafast spectroscopies, though, come with many peculiarities that make the collection of well-matched, subtractable background and sample spectra challenging. Here, we present a demountable split-sample cell in combination with a modified Lissajous scanner to overcome these challenges. It allows for quasi-simultaneous measurements of background and sample spectra, mitigating the effects of drifts of the setup and maintaining the beam and sample geometry when swapping between background and sample measurements. The cell is moving between subsequent laser shots to refresh the excited sample volume. With less than 45 μl of solution for 150 μm optical thickness, sample usage is economical. Cell assembly is a key step and covered in an illustrated protocol.
Quantitative dynamics of irreversible enzyme reaction–diffusion systems
*
Authors: Braukhoff Marcel , Einav Amit , Tang Bao Quoc 
Published: March 2022

Abstract
In this work we investigate the convergence to equilibrium for mass action reaction–diffusion systems which model irreversible enzyme reactions. Using the standard entropy method in this situation is not feasible as the irreversibility of the system implies that the concentrations of the substrate and the complex decay to zero. The key idea we utilise in this work to circumvent this issue is to introduce a family of cut-off partial entropy-like functionals which, when combined with the dissipation of a mass like term of the substrate and the complex, yield an explicit exponential convergence to equilibrium. This method is also applicable in the case where the enzyme and complex molecules do not diffuse, corresponding to chemically relevant situation where these molecules are large in size.
Center manifolds without a phase space for quasilinear problems in elasticity, biology, and hydrodynamics
Authors: Chen Robin Ming , Walsh Samuel , Wheeler Miles H 
Published: March 2022

Abstract
In this paper, we present a center manifold reduction theorem for quasilinear elliptic equations posed on infinite cylinders that is done without a phase space in the sense that we avoid explicitly reformulating the PDE as an evolution problem. Under suitable hypotheses, the resulting center manifold is finite dimensional and captures all sufficiently small bounded solutions. Compared with classical methods, the reduced ODE on the manifold is more directly related to the original physical problem and also easier to compute. The analysis is conducted directly in Hölder spaces, which is often desirable for elliptic equations. We then use this machinery to construct small bounded solutions to a variety of systems. These include heteroclinic and homoclinic solutions of the anti-plane shear problem from nonlinear elasticity; exact slow moving invasion fronts in a two-dimensional Fisher–KPP equation; and hydrodynamic bores with vorticity in a channel. The last example is particularly interesting in that we find solutions with critical layers and distinctive ‘half cat’s eye’ streamline patterns.
Impact of BNT162b2 Vaccination and Isolation on SARS-CoV-2 Transmission in Israeli Households: An Observational Study
Authors: Layan Maylis , Gilboa Mayan , Gonen Tal , Goldenfeld Miki , Meltzer Lilac , Andronico Alessio , Hozé Nathanaël , Cauchemez Simon , Regev-Yochay Gili 
Published: March 2022

Abstract
Several studies have characterized the effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, estimates of their impact on transmissibility remain limited. Here, we evaluated the impact of isolation and vaccination (7 days after the second dose) on SARS-CoV-2 transmission within Israeli households. From December 2020 to April 2021, confirmed cases were identified among health-care workers of the Sheba Medical Centre and their family members. Recruited households were followed up with repeated PCR for at least 10 days after case confirmation. Data were analyzed using a data augmentation Bayesian framework. A total of 210 households with 215 index cases were enrolled; 269 out of 667 (40%) susceptible household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Compared with unvaccinated and unisolated adult/teenager (aged &gt;12 years) contacts, vaccination reduced the risk of infection among unisolated adult/teenager contacts (relative risk (RR) = 0.21, 95% credible interval (CrI): 0.08, 0.44), and isolation reduced the risk of infection among unvaccinated adult/teenager (RR = 0.12, 95% CrI: 0.06, 0.21) and child contacts (RR = 0.17, 95% CrI: 0.08, 0.32). Infectivity was reduced in vaccinated cases (RR = 0.25, 95% CrI: 0.06, 0.77). Within households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were unvaccinated, isolation also led to important reductions in the risk of transmission.
Topological ranks reveal functional knowledge encoded in biological networks: a comparative analysis
Authors: Bonomo Mariella , Giancarlo Raffaele , Greco Daniele , Rombo Simona E 
Published: March 2022

Abstract

Motivation
Biological networks topology yields important insights into biological function, occurrence of diseases and drug design. In the last few years, different types of topological measures have been introduced and applied to infer the biological relevance of network components/interactions, according to their position within the network structure. Although comparisons of such measures have been previously proposed, to what extent the topology per se may lead to the extraction of novel biological knowledge has never been critically examined nor formalized in the literature.

Results
We present a comparative analysis of nine outstanding topological measures, based on compact views obtained from the rank they induce on a given input biological network. The goal is to understand their ability in correctly positioning nodes/edges in the rank, according to the functional knowledge implicitly encoded in biological networks. To this aim, both internal and external (gold standard) validation criteria are taken into account, and six networks involving three different organisms (yeast, worm and human) are included in the comparison. The results show that a distinct handful of best-performing measures can be identified for each of the considered organisms, independently from the reference gold standard.

Availability
Input files and code for the computation of the considered topological measures and K-haus distance are available at https://gitlab.com/MaryBonomo/ranking.

Contact
simona.rombo@unipa.it

Supplementary information
Supplementary data are available at Briefings in Bioinformatics online.
Risk of malignancy in thyroid nodules selected for fine needle aspiration biopsy based on ultrasound risk stratification
Authors: de Jong Mechteld C , McNamara John , McGlashan Nicholas , Winter Lucinda , Mihai Radu 
Published: March 2022

Abstract

Aim
Risk stratification of thyroid nodules based on ultrasound scan (USS) features using the TIRADS- or U-scale has been widely adopted. However, management decisions for patients whose work-up provide conflicting information, remains challenging. The aim of this study was to assess the rate of malignancy among those with suspicious cytology after USS-evaluation.

Methods
Retrospective review of clinical, radiological and pathological data regarding patients presenting with a thyroid nodule.

Results
Between January 2018 and December 2020, a total of 214 patients underwent surgery after presenting with thyroid nodule(s) and a fine-needle aspiration (FNA) cytology report either suspicious (Thy3–4) or diagnostic (Thy5) for thyroid malignancy. The appearance on USS was stratified using the TIRADS-scale, either to select nodules needing FNA-assessment or to characterise palpable nodules.
For Thy3a-cytology, the risk of malignancy remained low, irrespective of USS-appearance (2/15 in TIRADS2-3 versus 2/9 in TIRADS 4-5). For a Thy3f-cytology, the risk of malignancy was higher if the USS-appearance was also suspicious (11/75 in TIRADS2-3 versus 17/69 in TIRADS 4-5, p=0.03).
High-risk USS-appearance (TIRADS 4-5) in the presence of suspicious/diagnostic cytology (Thy4-5) had a 95% positive predictive value (40/42) of malignancy. Future data collection should assess the risk of malignancy when USS-appearance is malignant (TIRADS 5) yet cytology is benign (Thy2).

Conclusion
The performance of USS and FNA in this cohort corroborates published data. Until genetic panels will complement the assessment of nodules with a Thy3-cytology, diagnostic thyroid lobectomy remains necessary, as the USS has limited ability to increase the yield of malignant nodules.
Reactivation of Graves’ ophthalmopathy post-thyroidectomy for Graves’ disease
Authors: Chiu Stephanie J , Putri Christine , Allahabadia Amit , Balasubramanian Saba P , Salvi Sachin M 
Published: March 2022

Abstract

Introduction
The impact of thyroidectomy for Graves’ disease (GD) on Graves’ ophthalmopathy (GO) is not well understood. It is generally accepted that thyroidectomy does not exacerbate or precipitate GO in the majority. The aim of this study was to evaluate whether prophylactic glucocorticoid use following total thyroidectomy for GD disease prevents early post-operative reactivation of GO.

Methods
A retrospective cohort study covering 5 years, studying patients undergoing total thyroidectomy for GD. Patients were divided into 3 groups. Group A (Clinical Activity Score (CAS) unknown): Patients with symptoms such as dry eyes or signs of inactive GO, as assessed by the Endocrine Surgical team; or patients seen by their local ophthalmologist, but with signs of GO not severe enough to warrant referral to the orbital team (tertiary centre). Group B (CAS=0): Patients with burnt out or no GO, as assessed by the orbital team. Group C (CAS &gt;0): Patients with active GO, as assessed by the Orbital team. All were given prophylactic glucocorticoid cover.

Results
At least one patient in group A (n=14), none in group B (n=10) and five in group C (n=10) had early post-operative reactivation of Graves’ ophthalmopathy. Post-operative worsening of Graves’ ophthalmopathy was associated with CAS &gt;0 (p=0.0325) and thyroid stimulating hormone &lt;0.02 mIU/L (p=0.0136).

Conclusion
In those receiving prophylactic steroid, six (17.6%) demonstrated worsening GO. This was associated with a CAS &gt;0 and TSH &lt;0.02 mIU/L, suggesting either optimisation of both factors prior to thyroidectomy or considering a more potent steroid regimen.
Acute Presentation of an unblocked Phaeochromocytoma with Small Bowel Ischaemia managed by Emergency Laparotomy and Adrenalectomy
Authors: Houghton Neil , Davies Brooke , Hansel Jan , Davies Douglas , Smith Paul , Brown Andrew , Perkins Karen , Krishnaprasad Karnad , Ryska Ondrej , Walls Gerard , Tomlinson Mark 
Published: March 2022

Abstract

Introduction
A 50-year-old male presented as an emergency with acute abdominal pain, reduced consciousness and blood pressure of 230/136mmHg, having felt unwell for a year. CT scans showed a 9cm right adrenal mass, a 27mm left ventricular thrombus and emboli to the distal superior mesenteric artery. Echocardiography demonstrated a reduced ejection fraction of 25%.

Methods
Our regional multidisciplinary team (Endocrinologists, Anaesthetists, Intensivists, Biochemists and Surgeons) utilised their experience to manage this challenging emergency, with supra-regional expert consultation.

Results
In ICU, intravenous phentolamine and unfractionated heparin infusions were given, attempting to avoid surgery until alpha blockade was established. The following day sepsis and peritonitis developed: surgery could no longer be deferred and had to be undertaken without blockade. After anaesthetic induction a 12 minute asystolic arrest ensued, but circulation was restored with CPR and bolus noradrenaline. Intraoperative photographs demonstrate 150cm of infarcted small bowel being resected, and sequential adrenalectomy being undertaken to avoid further catecholamine crisis and anaesthetic, as discussed with supra-regional colleagues. Post-arrest targeted temperature management was instigated alongside empirical steroid replacement. Serum metadrenaline fell from 58,495pmol/L (&lt;510pmol/L) to 174pmol/L and normetadrenaline from 78,731pmol/L (&lt;1180pmol/L) to 330pmol/L post-resection. Histological assessment confirmed phaeochromocytoma with malignant features (PASS=6 and GAPP=5). The patient made a full recovery and ejection fraction improved to 55%.

Conclusion
This case adds to the controversial equipoise regarding pre-operative blockade. An experienced multidisciplinary adrenal team was crucial in managing this life threatening combination. Noradrenaline was effective during cardiac arrest whilst the circulation was unresponsive to adrenaline.
Unmeasurable stimulated thyroglobulin before radioactive iodine ablation predicts excellent long term outcome in patients with differentiated thyroid cancer
Authors: Sia Yi , Patel Neil , De Jong Mechteld , Khan Shad , Mihai Radu 
Published: March 2022

Abstract

Aim
To determine the likelihood of reaching unmeasurable stimulated thyroglobulin (sTG) levels after surgery for differentiated thyroid cancer (DTC).

Methods
Data on consecutive patients treated for DTC in a tertiary referral centre between May 2000 and June 2019 were retrospectively collected. Radioactive iodine ablation (RIA) was done after hormone withdrawal (before 2015) or after Thyrogen stimulation (more recent patients). During the study period, the biochemical assay for TG changed from a lower limit of detectability of 5 ng/dl to 0.2 ng/dl.

Results
A total of 403 patients (F=282; M=121) were included. sTG was &lt;0.2 in 41 patients and during a median follow-up of 32 months, none had disease recurrence. sTG was 0.2–4.99 ng/dl in 104 patients and during a median follow-up of 27 months, 5 patients had evidence of either residual disease or local recurrence. sTG was reported as &gt;5 in 258 patients and during a median follow-up of 63 months, 160 patients were disease free at the time of data collection. Patients who presented with locally advanced disease requiring modified radical neck dissection (n=78) had sTG higher than in those with earlier disease (n=325) (median 11.1 vs. 5.0ng/ml). There was a large difference in cervical uptake after RIA in patients with sTG 0.2–4.99 ng/dl (n=24) compared with those with sTG &gt;20 ng/dl (n=32) (0.7% vs 1.54%).

Conclusion
Almost half of all patients with DTC achieved unmeasurable sTG after surgery. This could be due to earlier disease but can also serve as a quality control after thyroidectomy for thyroid cancer.
The use of ARTISS fibrin sealant in thyroid surgery: case series and review of the literature.
Authors: Sekyi-Djan Ntirwa , Chapple Catherine , Myuran Tharsika , Hammond-Kenny Amy , Hilger Andreas 
Published: March 2022

Abstract

Introduction
Many techniques have been described to reduce length of stay and complication rates in thyroid surgery. ARTISS is a fibrin sealant used as an adjunct to sutures or staples, whereby it simultaneously adheres and seals subcutaneous tissues. In the context of thyroid surgery, it can augment the closure of dead space beneath the strap muscles and the platysma flaps.

Methods
A single surgeon adopted this novel technique from February 2017. A retrospective audit of 72 thyroid cases using ARTISS was conducted. Data were collected on patient demographics, ASA grade, procedure, histology, drain insertion and output, length of stay and complications.

Results
71 (99%) patients had a drain inserted. Of the 57 hemithyroidectomies, 13 (23%) patients had their drain removed and were discharged on the same day, 41 (65%) the next day and 3 (6%) remained at 2 days post-operatively. Of the 41 hemithyroidectomies who stayed one night, 21 (51%) patients had been operated on in the afternoon and were discharged the following morning. Of the 15 total thyroidectomies, 9 (60%) patients had their drain removed the following day and 6 (40%) at 2 days post-operatively. There was one post-operative superficial haematoma which did not require re-operation, another which required aspiration only, and one case of suspected wound infection treated with oral antibiotics.

Conclusion
The use of ARTISS fibrin sealant in this case series has been shown to be a safe and successful technique. Most patients are discharged within 24 hours of surgery and no cases required a return to theatre.
Outcomes of Patients with High Risk Thyroid Cancer – T3b to T4
Authors: Chrysostomos Tornari , Tan Jit Kai , Simo Ricard 
Published: March 2022

Abstract

Aims
The aims of this study are to analyse the outcomes of patients with T3b, T4 thyroid cancers (TC) by examining their tumour-node-metastasis (TNM) classification at presentation, the treatments they were offered and any postoperative complications.

Methods
A retrospective analysis of 41 patients who were diagnosed and treated for T3b and T4 thyroid cancer. Comparison of categorical variables was performed using Chi-square (where n ≥ 5) or Fisher’s exact test (where n &lt; 5). Mann Whitney U tests were used to identify statistical significance between data without normal distribution. Outcome measures included perineural invasion (PNI), lymphovascular invasion (LVI), postoperative hypocalcaemia (2 weeks, 3 months and 6 months), postoperative tri-iodothyronine, postoperative thyroxine and postoperative thyroglobulin.

Results
Patients with T4 TC were shown to have an increase in risk of PNI (3.23% vs 30.00%, p = 0.013). LVI was similar in both groups (45.16% vs 50.00%, p = 0.790). T4 patients had higher rates of postoperative hypocalcaemia at 2 weeks (10.00% vs 50.00%, p = 0.006). Postoperative hypocalcaemia was similar at 3 months (9.68% vs 10.00%, p = 0.976) and 6 months (6.67% vs 0.00%, p = 0.426). Low postoperative tri-iodothyronine was more frequent in T3b patients (29.03% vs 10.00%, p = 0.376). High postoperative thyroxine was more common in T3b patients (45.16% vs 20.00%, p = 0.069).

Conclusion
Patients with T4 TC had higher rates of PNI and postoperative hypocalcaemia. Postoperative thyroid markers differed slightly but were not statistically significant. Patient demographics and presentations did not have any significant differences.
Influence of Incidental Detection of Thyroid Nodule on Thyroid Cancer Risk and Prognosis – A Systematic Review and Meta-analysis
Authors: Chooi Je Ern , Ravindiran Abiramie , Balasubramanian Saba P 
Published: March 2022

Abstract

Background
Clinically inapparent thyroid nodules discovered serendipitously on imaging for non-thyroid indications are termed as thyroid incidentalomas. It is unclear whether these incidentalomas have a lower prevalence of malignancy or slower tumour progression compared to symptomatic nodules. The aim of this systematic review were to determine the impact of incidental detection of thyroid nodules on both the risk of malignancy and on prognosis in patients with thyroid cancer.

Methods
PubMed and MEDLINE® on Web of Science databases were searched from inception to April 2021 for English language articles reporting on human studies of thyroid cancer risk and/or prognosis in incidental and non-incidental nodules.

Results
Eighteen observational studies published between 1998 and 2020 were eligible for analysis; 4 studies reported on risk, 9 on prognosis and 5 studies reported on both risk and prognosis. When comparing the incidental and non-incidental groups in the risk study, the odds ratios calculated from the case control studies (n=6) ranged from 0.64 to 2.86; the relative risks calculated from the cohort studies (n=3) ranged from 0.13 to 6.27. A meta-analysis of the eligible case control studies (n=3) showed a non-significant summated odds ratio of 1.04 (95% CI=0.63–1.70, p=0.88). In the prognosis study, five direct and thirteen indirect markers of prognosis were compared between the incidental and non-incidental groups. A meta-analysis was not possible but incidentally detected thyroid cancer had better progression-free and overall survival.

Conclusion
Current evidence suggests that investigation and management of thyroid nodules should not be influenced by the mode of detection. However, incidentally detected nodules appear to have a better prognosis.