bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theobroma cacaoimproves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia
Authors: Martin L. , Kaci N. , Benoist-Lasselin C. , Mondoloni M. , Decaudaveine S. , Estibals V. , Cornille M. , Loisay L. , Flipo J. , Demuynck B. , de la Luz Cádiz-Gurrea M. , Barbault F. , Fernández-Arroyo S. , Schibler L. , Segura-Carretero A. , Dambroise E. , Legeai-Mallet L. 
Published: February 2021

AbstractA gain-of-function mutation in the fibroblast growth factor receptor 3 gene (FGFR3) results in achondroplasia (ACH), the most frequent form of dwarfism. The constitutive activation of FGFR3 impaired bone formation and elongation and many signaling transduction pathways. Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH. Natural plant compounds are the prime sources of drug candidates. Here, we found that the phenol compound (-)-epicatechin isolated fromTheobroma cacaoeffectively inhibits FGFR3’s downstream signaling pathways. Transcriptomic analysis inFgfr3mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways. (-)-Epicatechin is able to rescue impairments in the expression of these mRNA that control both the structural organization of the primary cilium and ciliogenesis-related genes. In femurs isolated from a mouse model (Fgfr3Y367C/+) of ACH, we showed that (-)-epicatechin countered the bone growth impairment during 6 days ofex vivocultures. We confirmedin vivothat daily subcutaneous injections of (-)-epicatechin inFgfr3Y367C/+mice increased bone elongation and rescued the primary cilium defect observed in chondrocytes. This modification of the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation. The results of the present proof-of-principle study illustrated (-)-epicatechin’s ability may facilitate the development of (-)-epicatechin as a treatment for patients with ACH.
Urban tourism performance index over the COVID-19 pandemic
Authors: Anguera-Torrell Oriol , Vives-Perez Jordi , Aznar-Alarcón Juan Pedro 
Published: February 2021

Purpose
This study aims to propose and estimate the urban tourism performance index (UTPI), an index that can measure and track the month-by-month tourism performance on main tourism cities since the initial outbreak of the COVID-19 pandemic. The UTPI is estimated for the following urban destinations: Bangkok, Paris, London, Dubai, Singapore, Kuala Lumpur, New York, Istanbul, Tokyo, Seoul, Osaka, Phuket, Milan, Barcelona, Bali and Hong Kong.

Design/methodology/approach
Monthly based data measuring the tourism industry’s performance for these urban destinations has been collected. This data includes airlines’ and hotels’ performance, as well as potential tourists’ online searches. The obtained data has been combined using a principal component analysis, generating the UTPI.

Findings
The UTPI shows that all urban areas analyzed in this study experienced a devastating negative impact because of the COVID-19 pandemic outbreak. However, the tourism recovery evolution follows heterogeneous patterns.

Research limitations/implications
The proposed index can be estimated using additional variables. Moreover, the index is only estimated for 16 tourism cities. Future studies can reproduce the methodology by incorporating further variables and amplifying the geographical coverage.

Practical implications
The UTPI might be useful for researchers and policymakers interested in using a measure of tourism performance during the COVID-19 pandemic in some of the most important urban destinations. Likewise, the UTPI index may serve as a suitable aggregated measure of tourism performance in a post-COVID-19 era or to monitor tourism during future crises.

Originality/value
This study analyzes the tourism performance during the COVID-19 pandemic from an urban perspective.
Ude Jones Udeogu v FRN & Ors no SC. 622C/2019: its implication on fighting financial crime and the way forward
Authors: Yakubu Sirajo 
Published: February 2021

Purpose
The purpose of this paper is to show how fighting financial crime suffered a setback in Nigeria as a result of the Supreme Court ruling in an appeal case – Ude Jones Udeogu v FRN and Ors no SC. 622C/2019.

Design/methodology/approach
This paper is a critical analysis of the implication of Supreme Courts’ ruling in Ude Udeogu Jones, its implication to law enforcement’s effort in fighting financial crime and the way to get around the ruling. The paper adopts qualitative methods. It is conducted through the analysis of the ruling and the relevant laws.

Findings
Due to the ruling in UdeUdeogu Jones, Section 396(7) of the Administration of Criminal Justice Act 2015 is no longer good law. Federal High Court judges elevated to the Court of Appeal no longer have special dispensation to conclude criminal cases they part heard. Furthermore, the ruling is a serious setback on the law enforcement’s efforts in fighting corruption. However, the drastic effect of the ruling can be mitigated by amending Section 396(7).

Research limitations/implications
Because the ruling is very recent, analysis is based on the relevant enactments and case laws including recent decisions of the Court of Appeal and the Supreme Court.

Originality/value
There is no comprehensive work on this ruling. Therefore, this paper adds value to knowledge as it makes clear the background of the appeal case, as well as the impact of the ruling of the Supreme Court on fighting financial crime in Nigeria and the way to get around the ruling.
Ethical behavior is the antidote to toxic culture
Authors: Meidav Neta 
Published: February 2021

Purpose
In this paper, the author sought to explain why ethical behavior is the antidote to toxic workplace culture at a time where employees are forced to take their complaints through external channels when internal procedures fall short.

Design/methodology/approach
The author draws upon recent discussions around employer responsibilities in the wake of #MeToo and the Black Lives Matter movements, using relevant case studies to outline where employers have failed to offer adequate protection for their employees.

Findings
The author found that by promoting a healthy speak-up culture within the workplace, employees are more likely to feel that their concerns are heard, and the issues can be dealt with internally, to the benefit of both individuals and their organizations.

Originality/value
HR departments will be able to access the merits of shifting workplace culture to a more transparent model that bridges the trust gap between employees and their organizations.
Do dimethyl fumarate and nicotinic acid elicit common, potentially HCA2‐mediated adverse reactions? A combined epidemiological‐experimental approach
Authors: Dubrall Diana , Pflock René , Kosinska Joanna , Schmid Matthias , Bleich Markus , Himmerkus Nina , Offermanns Stefan , Schwaninger Markus , Sachs Bernhardt 
Published: February 2021

AimDimethyl fumarate and nicotinic acid activate the hydroxy‐carboxylic acid receptor 2 (HCA2) and induce flushing. It is not known whether HCA2 mediates other adverse drug reactions (ADRs) to these two substances. This study aims to compare ADRs associated with dimethyl fumarate and nicotinic acid, and to discuss whether they are HCA2‐mediated.MethodsWe identified spontaneous reports of suspected ADRs to dimethyl fumarate and nicotinic acid in the European Adverse Drug Reaction Database (EudraVigilance). These reports were analysed at different hierarchical levels of the Medical Dictionary for Regulatory Activities (MedDRA). In addition, we screened murine organs for HCA2 expression.ResultsSimilarities in the ADR profile of dimethyl fumarate and nicotinic acid included “gastrointestinal signs and symptoms” (odds ratio [OR] 0.8 [0.6‐1.1]), “hepatobiliary investigations” (OR 1.3 [0.7‐2.5]) and “anxiety disorders and symptoms” (OR 0.9 [0.3‐2.2]) in High Level Group Terms; “diarrhoea (excluding infective)” (OR 1.2 [0.7‐1.8]) and “liver function analyses” (OR 1.3 [0.7‐2.6]) in High Level Terms; and “diarrhoea” (OR 1.2 [0.7‐2.0]) and “vomiting” (OR 0.9 [0.4‐1.7]) in Preferred Terms. In analogy, HCA2 was expressed in the gastrointestinal tract, liver and central nervous system (CNS) of murine organs. A discrepant ADR profile was seen for “lymphopenia” (n = 777) at the preferred term level (only reported for dimethyl fumarate) and “blood glucose increased” (more often reported for nicotinic acid; OR 0.1 [0.0‐0.5]).ConclusionThe gastrointestinal ADRs common to both substances may be mediated by HCA2. Other ADRs not common to both substances are compound or indication‐specific reactions and likely do not involve HCA2.
‘Maturing Out’ as dilemmatic: Transitions towards relatively light drinking practices among UK University students
Authors: Conroy Dominic , Morton Charlotte , Griffin Christine 
Published: February 2021

ObjectivesUniversity students in the UK engage in relatively high alcohol consumption levels, yet young adults, including students, now drink less than previously and abstain more. Against this cultural backdrop, our objective was to further understanding of ‘maturing out’ of excessive drinking practices among students by focusing on drinking transitions that had taken place during university years.DesignA qualitative interview study.MethodsSemi‐structured interviews were conducted with ten 18‐ to 27‐year‐old UK undergraduate university students who self‐identified as light or non‐drinkers. Interviews were audio‐recorded, and anonymized interview transcripts were subjected to an experience‐focused application of thematic analysis.ResultsParticipants reported dilemmas involved in transitions from relatively high to low levels of alcohol consumption. One dilemma was characterized by managing to drink less (or nothing) without cutting off social options with university friends/peers. A second dilemma concerned not wishing to fully abandon the pleasures and increased social confidence that alcohol consumption could afford. Results also demonstrated that self‐reported drinking could contradict participants’ self‐defined ‘light drinker’ status.ConclusionsThis study reinforces the view that ‘maturing out’ involves more than simply having gained new responsibilities during young adulthood. Recognition of these dilemmatic features of drinking transitions could be drawn on in novel campus‐based interventions. Such interventions may help strengthen realistic and sustainable moderate drinking by guiding students to anticipate potential difficulties involved in planned reductions in personal drinking but may also help foster students’ ability to view drinking choices as in transition rather than as permanent and enduring.
Medical treatment of recurrent ischaemic priapism: a review of current molecular therapeutics and a new clinical management paradigm
Authors: Joice Gregory A. , Liu James L. , Burnett Arthur L. 
Published: February 2021

ObjectivesTo examine the current molecular therapeutics in the medical treatment of recurrent ischemic priapism (RIP). To propose a stepwise clinical management paradigm for the treatment of RIP.MethodsWe performed a literature search using the PubMed database for the terms ‘recurrent ischemic priapism’ and ‘stuttering priapism’ up until December 2020. We assessed pre‐clinical and clinical studies regarding medical management of RIP and molecular pathophysiology. Case series and randomized trials were evaluated by study quality and patient outcomes to determine a potential clinical management scheme.ResultsRecent research has fostered an improved understanding of the underlying molecular pathophysiology of RIP that has paved the way forward for developing new therapeutic agents. Medications targeting neurovascular, hormonal and haematological mechanisms associated with RIP show great promise towards remedying this condition. A host of therapeutic agents operating across different mechanistic directions may be implemented according to a clinical management scheme to potentially optimize RIP outcomes.ConclusionRIP remains a medically neglected condition with current management focused on treating the acute condition rather than modulating the course of disease. Continued research into the molecular mechanisms of RIP and standardized clinical pathways can improve the quality of care for patients suffering from this condition.
Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients
Authors: Aibara N , Ohyama K , Nakamura M , Nakamura H , Tamai M , Kishikawa N , Kawakami A , Tsukamoto K , Nakashima M , Kuroda N 
Published: February 2021

Summary
Primary biliary cholangitis (PBC) is characterized by the presence of serum anti-mitochondrial autoantibodies (AMAs). To date, four antigens among the 2-oxo-acid dehydrogenase complex family, which commonly have lipoyl domains as an epitope, have been identified as AMA-corresponding antigens (AMA-antigens). It has recently been reported that AMAs react more strongly with certain chemically modified mimics than with the native lipoyl domains in AMA-antigens. Moreover, high concentrations of circulating immune complexes (ICs) in PBC patients have been reported. However, the existence of ICs formed by AMAs and their antigens has not been reported to date. We hypothesized that AMAs and their antigens formed ICs in PBC sera, and analyzed sera of PBC and four autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic scleroderma, and rheumatoid arthritis) using immune complexome analysis, in which ICs are separated from serum and are identified by nano-liquid chromatography-tandem mass spectrometry. To correctly assign MS/MS spectra to peptide sequences, we used a protein-search algorithm that including lipoylation and certain xenobiotic modifications. We found three AMA-antigens, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the E2 subunit of the 2-oxo-glutarate dehydrogenase complex (OGDC-E2) and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation and xenobiotic modifications from PBC sera. Although the lipoylated sites of these peptides were different from the well-known sites, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs. Further investigation of the lipoylated sites, xenobiotic modifications, and IC formation will lead to deepen our understanding of PBC pathogenesis.
Atypical glandular cells in Papanicolaou test: Which is more important in the detection of malignancy, architectural or nuclear features?
Authors: Yucel Polat Aysegul , Tepeoglu Merih , Tunca Muzeyyen Zeynep , Ayva Ebru Sebnem , Ozen Ozlem 
Published: February 2021

AbstractObjectiveAtypical glandular cells (AGCs) in Pap (Papanicolaou) smears are uncommon but may represent various benign and malignant lesions. The aim of this study was to evaluate the AGC incidence in Pap smears, analyse the relationship between AGC and malignancy, and reveal the importance of architectural and nuclear features observed cytologically in malignancies.MethodsPatients diagnosed with AGC on the basis of cervicovaginal cytology between May 2011 and July 2018 were included in this study. All slides were retrospectively reviewed and subclassified according to the Bethesda 2001 classification system. The cytomorphological features observed in the smears were recorded. Cytohistological correlations were evaluated, and the significant clinicopathological findings for malignancy were determined.ResultsOf 87 536 Pap smears, 195 (0.22%) had AGC results and 156 had tissue follow‐up. Among the 156 smears with AGC, 80 (51.3%) were diagnosed as AGC‐NOS (atypical glandular cells, not otherwise specified) and 76 (48.7%) as AGC‐FN (atypical glandular cells, favour neoplastic). Follow‐up biopsies revealed benign pathologies in 49 cases (31.4%) and malignant pathologies in 107 (68.6%). The rate of malignancy observed in AGC‐FN cases (89.5%) was higher than the rate of malignancy in AGC‐NOS cases (48.8%). Among the cytomorphological features, nuclear irregularity, presence of macronucleoli, feathering, loss of polarity, papillary pattern, and three‐dimensional formation were found to be significant indicators of malignancy.ConclusionAs AGC in Pap smear was associated with a clinically significant diagnosis in 68.6% of the cases in our study, we suggest that all patients with AGC should undergo further clinical assessment.
DLBCL of bilateral submandibular glands and MALToma of thyroid—A rare coexistence
Authors: Kushwaha Pritika , Singh Meeta , Mandal Shramna , Dhingra Shruti , Jain Shyama 
Published: February 2021

AbstractInvolvement of the bilateral submandibular glands and thyroid by the same lymphoma simultaneously has been reported in the literature. However, two different types of lymphomas presenting simultaneously at different sites have never been reported. This case report highlights this rare occurrence. A 65‐year‐old female, a known case of Hashimoto’s thyroiditis with raised anti‐TPO antibodies, presented with thyroid swelling for 1 year and bilateral submandibular swelling for 3 years. FNAC and flow cytometry showed features of mucosa‐associated lymphoid tissue lymphoma in the thyroid gland, whereas the bilateral submandibular glands showed features of diffuse large B cell lymphoma. Histopathology and immunohistochemistry from the submandibular swelling led to similar diagnoses as the flow cytometry.
Cost‐effectiveness of rapid on‐site evaluation of endoscopic ultrasound fine needle aspiration in gastrointestinal lesions
Authors: Khoury Tawfik , Sbeit Wisam 
Published: February 2021

AbstractBackground and aimRapid on‐site evaluation (ROSE) can improve adequacy rates of fine needle aspiration (FNA) and thus save operational costs. Our aim was to assess the cost‐efficacy of ROSE performed during endoscopic ultrasound (EUS)‐FNA of gastrointestinal lesions.MethodThis was a retrospective cohort study of 156 patients who underwent EUS‐FNA for pancreatic, submucosal upper gastrointestinal, and adjacent lesions at Galilee Medical Center between 2012 and 2017. The patient cohort was divided into group A (62 patients, 39.7%) who underwent EUS‐FNA with ROSE, and group B (94 patients, 60.3%) without ROSE. Cost analysis was based on the additional expenditure of repeated EUS‐FNA sessions needed to reach accurate and final diagnosis in the two groups.ResultsThe overall cost was significantly higher in group B ($121 422) as compared to group A ($72 861), including the ROSE cost. Additional EUS‐FNA sessions were needed in 11.3% and 23.4% in groups A and B, respectively. The additional cost to achieve final pathological diagnosis was $7203 and $24 696 in groups A and B, respectively (P = .02), yielding a savings of $252 per EUS‐FNA case by adding ROSE. Notably, adding ROSE to the EUS‐FNA exam for gastrointestinal non‐pancreatic lesions resulted in even higher savings per case ($682.40). Moreover, adding ROSE improved specimen adequacy to achieve final pathological diagnosis (odds ratio = 7.13, P = .0005).ConclusionsEUS‐FNA with ROSE was cost‐effective. Incorporating ROSE into the clinical practice of EUS‐FNA saves costs and improves specimen adequacy.
Intraoperative consultation in the diagnosis of posterior fossa brain tumors following the 2016 WHO update
Authors: Gupta Kirti , Kapatia Gargi , Salunke Pravin , Ahuja Chirag K , Singh Vikram 
Published: February 2021

AbstractObjectiveIntraoperative crush/squash smear or frozen section consultation is routinely performed at several centers and offers rapid onsite assessment of tumor type and provides invaluable information to the neurosurgeons. The WHO classification of central nervous system neoplasms underwent a paradigm shift in 2016 with the incorporation of molecular data with the morphological features, such that several new entities came to be distinctly defined. With this paper, we present our experience at intraoperative consultation of brain tumors arising in posterior fossa and aim to apprise the pathologists with the spectrum of cytomorphologic appearances that can occur during such consultation and highlight the diagnostic dilemmas and pitfalls encountered in this setting.MethodsThis is a retrospective observational study illustrating the salient morphological features of commonly encountered brain tumors arising in the posterior fossa (prototype example of each type) reported at our institute over a period of seven years. Both squash smears and rapid snap frozen section were prepared and stained with Toluidine blue and rapid hematoxylin and eosin (H&E) stains.Results and conclusionsWhile the majority of tumors at this location comprise of pilocytic astrocytoma, ependymoma, and medulloblastoma, some rare examples may also arise; common differentials must be considered and prudently excluded to arrive at the diagnosis which is crucial in guiding the neurosurgeon. Both squash smears and rapid frozen section should be prepared and complement each other for rapid on‐site evaluation.
The combination of ACR‐Thyroid Imaging Reporting and Data system and The Bethesda System for Reporting Thyroid Cytopathology in the evaluation of thyroid nodules—An institutional experience
Authors: Sakthisankari Shanmugasundaram , Vidhyalakshmi Sreenivasan , Shanthakumari Sivanandam , Devanand Balalakshmoji , Nagul Udayasankar 
Published: February 2021

AbstractBackgroundThe Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is widely utilised by cytopathologists. The American College of Radiology (ACR) has also proposed a thyroid imaging reporting and data system (TIRADS) to classify thyroid nodules and guide their selection for fine needle aspiration (FNA). The current study aimed to analyse the usefulness of TBSRTC in thyroid cytology reporting, to examine its histological correlation with TIRADS, and to compare the management of lesions in each cytological category in our institute to the TBSRTC recommendations.Materials and methodsA retrospective study was performed on all thyroid FNAs from a 2‐year period at a tertiary care centre. Histological correlations of TBSRTC and ACR TIRADS were examined for cases with surgical follow‐up, and the risk of malignancy in each TBSRTC category, and sensitivity and specificity of FNA and TIRADS, were calculated.ResultsA total of 337 thyroid FNAs were examined, with histological follow‐up in 99 cases. Risk of malignancy in categories I‐VI was 9.5%, 2.3%, 0.0, 8%, 87.5% and 100.0%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of FNA were 60.0%, 99.0%, 85.7%, and 97.5%, respectively, while those values for thyroid ultrasound were 90.3%, 72.2%, 92.9% and 65%, respectively.ConclusionThe study substantiates the usefulness of TBSRTC in arriving at a more precise diagnosis. Hurthle cell lesions with atypia were the common cause of misdiagnosis. The combination of TIRADS and TBSRTC aids in better stratification of thyroid nodules and in decision making for management of lesions.