bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease
Authors: Liao Wupeng , Lim Albert Y. H. , Tan W. S. Daniel , Abisheganaden John , Wong W. S. Fred 
Published: April 2020

Background and PurposeCorticosteroid resistance poses a major barrier to an effective anti‐inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re‐sensitization actions of andrographolide, a bioactive molecule from the herb Andrographis paniculata, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients.Experimental ApproachCorticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS‐induced IL‐8 production, in the presence and absence of andrographolide. The mechanisms of corticosteroid re‐sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)‐induced acute lung injury model.Key ResultsImpaired inhibition of IL‐8 production by dexamethasone was detected in PBMCs from COPD patients and in CSE‐exposed U937 cells, together with reduced levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and histone deacetylase‐2 (HDAC2). In both PBMCs and CSE‐exposed U937 cells, andrographolide restored dexamethasone inhibition of IL‐8 production, accompanied by the up‐regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE‐induced Akt and reduce the level of c‐Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS‐exposed mice.Conclusion and ImplicationsWe report here for the first time a novel corticosteroid re‐sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.
Central nervous system lupus presenting as rhombencephalitis responding to aggressive immunotherapy: A unique case
Authors: Kaur Harleen , Mittal Gaurav K. , Singhdev Jennifer 
Published: April 2020

AbstractBackgroundSystemic lupus erythematosus (SLE) is the prototypic autoimmune connective tissue disorder (CTD) usually affecting young females. Central nervous system lupus is a serious complication encountered in SLE cases. Predominant involvement of rhombencephalon in patients of SLE at the first contact with health care professional has not been seen and described frequently in the literature. It still remains a diagnostic and therapeutic challenge.Case presentationThis paper describes a case of SLE in an adolescent female who was diagnosed as having rhombencephalitis, which is a rare presentation of SLE.ConclusionsCentral nervous system lupus should be included in the provisional diagnosis of any young female patient presenting with complicated neurologic manifestations over the background of joint pain or fever or headache or confusion or psychosis, to avoid misdiagnosis and aid in timely institution of aggressive immunotherapy.
Enhancing Māori and Pasifika graduate interest in ophthalmology surgical training in New Zealand/Aotearoa: Barriers and opportunities
Authors: Freundlich Simone E. N. , Connell Charlotte J. W. , McGhee Charles N. J. , Cunningham William J. , Bedggood Antony , Poole Phillippa 
Published: April 2020

AbstractImportanceImproving the representation of indigenous ophthalmologists in New Zealand.BackgroundMāori, indigenous to New Zealand/Aotearoa and Pacific Peoples indigenous to Pacific Island Nations living in New Zealand, experience poorer health outcomes across several ophthalmic conditions. The Royal Australian and New Zealand College of Ophthalmologists have identified indigenous workforce development as a priority.DesignMixed‐methods study, utilizing retrospective analysis of Medical Schools Outcomes Database and Longitudinal Tracking Project responses, and prospective interviews with Māori/Pasifika medical graduates.ParticipantsThis study involved 64 medical graduates from the University of Auckland (UoA) and the University of Otago, and six Māori/Pasifika medical postgraduates in New Zealand.MethodsRetrospective analysis of medical graduate responses who ranked ophthalmology among their top‐three preferred specialties in the Medical Schools Outcomes Database and Longitudinal Tracking Project. Prospective semi‐structured interviews with Māori/Pasifika medical postgraduates.Main Outcome MeasuresSpecialty training influencing factors and prevocational ophthalmology experience.ResultsA total of 64 (6.7%) out of 954 medical graduates from the UoA and University of Otago ranked ophthalmology among their top‐three preferred training specialties (2012‐2017). Of the 64 graduates, six (9.3%) identified as Māori/Pasifika. No significant difference in influencing factors between Māori/Pasifika and non‐Māori/Pasifika students was identified. Both groups ranked intellectual content, procedural skills, specialty exposure and mentorship as highly influential. Qualitative interviews with Māori/Pasifika graduates highlighted positive experiences in ophthalmology but limited exposure overall. Negative anecdotes and unclear training pathways discouraged Māori/Pasifika interest in Ophthalmology training.Conclusions and RelevanceMāori/Pasifika graduate interest in ophthalmology training was relatively low. Valuable insights include enhancing specialty exposure, mentor development, promoting Māori/Pasifika connections and clarifying training pathways for future graduates.
Deletions of specific exons of FHOD3 detected by next‐generation sequencing are associated with hypertrophic cardiomyopathy
Authors: Ochoa Juan P. , Lopes Luis R. , Perez‐Barbeito Marlene , Cazón‐Varela Laura , de la Torre‐Carpente Maria M. , Sonicheva‐Paterson Natalia , De Uña‐Iglesias David , Quinn Ellen , Kuzmina‐Krutetskaya Svetlana , Garrote José A. , Elliott Perry M. , Monserrat Lorenzo 
Published: April 2020

AbstractDespite new strategies, such as evaluating deep intronic variants and new genes in whole‐genome‐sequencing studies, the diagnostic yield of genetic testing in hypertrophic cardiomyopathy (HCM) is still around 50%. FHOD3 has emerged as a novel disease‐causing gene for this phenotype, but the relevance and clinical implication of copy‐number variations (CNVs) have not been determined. In this study, CNVs were evaluated using a comparative depth‐of‐coverage strategy by next‐generation sequencing (NGS) in 5493 HCM probands and 2973 disease‐controls. We detected three symmetrical deletions in FHOD3 that involved exons 15 and 16 in three HCM families (no CNVs were detected in the control group). These exons are part of the diaphanous inhibitory domain of FHOD3 protein, considered a cluster of mutations for HCM. The clinical characteristics of the affected carriers were consistent with those reported in FHOD3 in previous studies. This study highlights the importance of performing CNV analysis systematically in NGS genetic testing panels for HCM, and reinforces the relevance of the FHOD3 gene in the disease.
Next‐generation sequencing approaches and challenges in the diagnosis of developmental anomalies and intellectual disability
Authors: Bruel Ange‐Line , Vitobello Antonio , Tran Mau‐Them Frédéric , Nambot Sophie , Sorlin Arthur , Denommé‐Pichon Anne‐Sophie , Delanne Julian , Moutton Sébastien , Callier Patrick , Duffourd Yannis , Philippe Christophe , Faivre Laurence , Thauvin‐Robinet Christel 
Published: April 2020

AbstractRecent advances in next‐generation sequencing (NGS) technologies have revolutionized the field of human genetics. Alongside a broad panel of bioinformatics tools and databases, NGS technologies have unprecedentedly improved the molecular diagnosis rate and the identification of new genes associated with rare disorders. However, about 50% of patients remain without a final diagnosis. Here, we highlight the utility of NGS applications in developmental anomalies and intellectual disability, illustrating their main advantages and pitfalls. Through specific examples, we suggest novel strategies and tools for identifying the molecular bases in the remaining patients, and we outline future challenges.
HNRNPH1‐related syndromic intellectual disability: Seven additional cases suggestive of a distinct syndromic neurodevelopmental syndrome
Authors: Reichert Sara C. , Li Rachel , A. Turner Scott , van Jaarsveld Richard H. , Massink Maarten P.G. , van den Boogaard Marie‐José H. , del Toro Mireia , Rodríguez‐Palmero Agustí , Fourcade Stéphane , Schlüter Agatha , Planas‐Serra Laura , Pujol Aurora , Iascone Maria , Maitz Silvia , Loong Lucy , Stewart Helen , De Franco Elisa , Ellard Sian , Frank Julie , Lewandowski Raymond 
Published: April 2020

AbstractPathogenic variants in HNRNPH1 were first reported in 2018. The reported individual, a 13 year old boy with a c.616C>T (p.R206W) variant in the HNRNPH1 gene, was noted to have overlapping symptoms with those observed in HNRNPH2‐related X‐linked intellectual disability, Bain type (MRXSB), specifically intellectual disability and dysmorphic features. While HNRNPH1 variants were initially proposed to represent an autosomal cause of MRXSB, we report an additional seven cases which identify phenotypic differences from MRXSB. Patients with HNRNPH1 pathogenic variants diagnosed via WES were identified using clinical networks and GeneMatcher. Features unique to individuals with HNRNPH1 variants include distinctive dysmorphic facial features; an increased incidence of congenital anomalies including cranial and brain abnormalities, genitourinary malformations, and palate abnormalities; increased incidence of ophthalmologic abnormalities; and a decreased incidence of epilepsy and cardiac defects compared to those with MRXSB. This suggests that pathogenic variants in HNRNPH1 result in a related, but distinct syndromic cause of intellectual disability from MRXSB, which we refer to as HNRNPH1‐related syndromic intellectual disability.
The Otology Questionnaire Amsterdam: A generic patient‐reported outcome measure about the severity and impact of ear complaints. Validation, reliability and responsiveness
Authors: Kraak Jeroen T. , van Dam Tom F. , van Leeuwen Lisette M. , Kramer Sophia E. , Merkus Paul 
Published: April 2020

AbstractObjectiveTo examine the construct validity, reliability and responsiveness of the Otology Questionnaire Amsterdam (OQUA).DesignMulticentre, longitudinal study in 2 separate cohorts of patients visiting an ENT surgeon via an online survey programme.SettingTertiary ENT clinics.ParticipantsCohort 1 consisted of patients at their first visit at an ENT outpatient clinic with an ear complaint. Cohort 2 consisted of patients who underwent surgery, with a 3‐month follow‐up post‐surgery.Main outcome measuresConstruct validity: Hypothesis testing, internal consistency and inter‐item correlation. Reliability: Test‐retest reliability. The construct approach was used for assessing responsiveness. Hypotheses were formulated based on the association between the OQUA and Glasgow Health Status Inventory (GHSI) or Global Rating Scale (GRS).ResultsConstruct validity: The correlation between the individual items in the impact domain ranged from 0.424 to 0.737. Confirmatory factor analysis showed a good fit. As expected, the OQUA impact showed strong relationships with GHSI total and general scale.Reliability: The test‐retest reliability coefficient ranged from 0.541 to 0.838.Responsiveness: All hypotheses were conformed. As expected, the change score of the OQUA showed good correlation between OQUA impact and GHSI and moderate correlation between the GRS and OQUA complaints.ConclusionThe OQUA has 8 complaint domains (earache, pressure sensation, itching, tinnitus, hearing loss, ear discharge, loss of taste and dizziness) and 1 impact domain. Each domain results in one score of 0‐100. The OQUA shows good results for construct validity, (test‐retest) reliability and responsiveness, supporting the potential benefit for the patient with an ear complaint visiting the ENT surgeon. The extensive validation furthermore confirms a certified generic otology PROM with an impact and a complaints' part, to be used in different types of otologic interventions and patient groups.
Clinical management of 52 consecutive retro‐rectal tumours treated at a tertiary referral centre
Authors: Carpelan‐Holmström M. , Koskenvuo L. , Haapamäki C. , Renkonen‐Sinisalo L. , Lepistö A. 
Published: April 2020

AbstractAimThe aim of this single‐institution study was to analyse the diagnostic methods, preoperative work‐up and outcomes of 52 retro‐rectal tumours.MethodAll patients treated for retro‐rectal tumours from 2012 to 2017 were included.ResultsOut of 52 patients, 40 (77%) were women. The median age of patients at the time of surgery was 43 (19–76) years, and 30 (58%) were asymptomatic at the time of diagnosis. All tumours were visible on magnetic resonance imaging (MRI) prior to surgery. The sensitivity and specificity for predicting malignancy on preoperative imaging for retro‐rectal tumours were 25% and 98%, respectively. Forty‐four procedures (85%) were performed using the perineal approach. The median hospital stay was 3 (1–18) days. There was no 30‐day postoperative mortality. Eleven (21%) patients developed postoperative complications, mostly surgical site infections. Twenty‐nine tumours (56%) were benign tailgut cysts. Four (8%) tumours were malignant and were considered to be removed with a tumour‐free resection margin. Local recurrent disease was detected on MRI in 14 (27%) patients at a median of 1.05 (range 0.78–1.77) years after primary surgery. Only the multi‐lobular shape of the tumour was found to be an independent risk factor for recurrence (P = 0.030).ConclusionA preoperative MRI is mandatory in order to plan the surgical strategy for retro‐rectal tumours. Symptomatic, solid, large tumours should be removed because of the risk of malignancy. Minor cystic lesions with thin walls as well as asymptomatic recurrences of benign tumours are suitable to be followed conservatively.
Robotic vs laparoscopic total mesorectal excision for rectal cancers: has a paradigm change occurred? A systematic review by updated meta‐analysis
Authors: Gavriilidis P. , Wheeler J. , Spinelli A. , de‘Angelis N. , Simopoulos C. , Di Saverio S. 
Published: April 2020

AbstractAimThe debate about the oncological adequacy, safety and efficiency of robotic vs laparoscopic total mesorectal excision for rectal cancers continues. Therefore, an updated, traditional and cumulative meta‐analysis was performed with the aim of assessing the new evidence on this topic.MethodA systematic search of the literature for data pertaining to the last 25 years was performed. Fixed‐ and random‐effects models were used to cumulatively assess the accumulation of evidence over time.ResultsPatients with a significantly higher body mass index (BMI), tumours located approximately 1 cm further distally and more patients undergoing neoadjuvant therapy were included in the robotic total mesorectal excision (RTME) cohort compared with those in the laparoscopic total mesorectal excision (LTME) cohort [RTME, mean difference (MD) = 0.22 (0.07, 0.36), P = 0.005; LTME, MD = −0.97 (−1.57, 0.36), P < 0.002; OR = 1.47 (1.11, 1.93), P = 0.006]. Significantly lower conversion rates to open surgery were observed in the RTME cohort than in the LTME cohort [OR = 0.33 (0.24, 0.46), P < 0.001]. Operative time in the LTME cohort was significantly reduced (by 50 min) compared with the RTME cohort. Subgroup analysis of the three randomized controlled trials (RCTs) challenged all the significant results of the main analysis and demonstrated nonsignificant differences between the RTME cohort and LTME cohort.ConclusionAlthough the RTME cohort included patients with a significantly higher BMI, more distal tumours and more patients undergoing neoadjuvant therapy, this cohort demonstrated lower conversion rates to open surgery when compared with the LTME cohort. However, subgroup analysis of the RCTs demonstrated nonsignificant differences between the two procedures.
Small donor size does not negatively impact outcomes after deceased‐donor renal transplantation
Authors: Giffen Zane C. , Siddique Abu Bakkar , Koizumi Naoru , Ortiz Jorge 
Published: April 2020

AbstractHigher body mass index (BMI) of deceased‐donors is associated with poorer outcomes in transplant recipients. The effect of low donor BMI on recipient graft function is not clear. Scientific Registry of Transplant Recipients data on recipients of deceased‐donor kidneys from 2000 to 2019 were categorized by donor BMI (donor BMI < 18, 18‐27, and >27). Primary outcome was death‐censored graft survival. The impact of multiple recipient and donor variables, including low donor BMI and the difference between donor and recipient BMI, was evaluated using a multivariate Cox proportional‐hazards model. Low BMI donors (LBD) were more likely to be younger, female, and white (all P < .05). LBD were less likely to be Hispanic, diabetic, or have hypertension (all P < .001). LBD recipients were more likely to be younger and female (both P < .001). Low donor BMI was not significantly associated with recipient graft survival. Donor‐recipient BMI difference did not correlate with an increased risk of graft failure. Similar results were obtained when donors were classified using body surface area (BSA). Small donor size in terms of BMI or BSA or a large discrepancy between donor and recipient size should not necessarily preclude transplantation of an otherwise acceptable kidney.
An unusual case of cutaneous Waldenström macroglobulinemia with the MYD88 L265P mutation
Authors: Minzenmayer Andrew N. , Miranda Roberto N. , Powell Priscilla R. , Parekh Palak K. 
Published: April 2020

AbstractWaldenström macroglobulinemia is a lymphoplasmacytic lymphoma with bone marrow involvement and a monoclonal IgM gammopathy. Infiltration of the skin by neoplastic cells is very rare, and it can be difficult to distinguish from marginal zone lymphoma. The MYD88 L265P mutation is strongly associated with Waldenström macroglobulinemia, and it may be helpful in differentiating the two disorders, although the presence of this mutation is not specific, and other factors must be considered when making the final diagnosis. We present a diagnostically challenging case of cutaneous Waldenström macroglobulinemia in which the MYD88 L265P mutation was identified in the skin but not in the bone marrow, due to a low tumor burden.
In vivo cutaneous antinuclear antibody positivity in palisaded neutrophilic and granulomatous dermatitis
Authors: Dong Jinhong , Zubkov Micaella , Weston Gillian , Storonsky Michael , Murphy Michael 
Published: April 2020

AbstractPalisaded neutrophilic and granulomatous dermatitis (PNGD) is commonly associated with underlying systemic inflammatory and neoplastic diseases, infections, and drug reactions. In vivo cutaneous antinuclear antibodies (ANA) have been described in skin biopsies from patients with known autoimmune disorders, but not previously reported in the setting of PNGD. We present two patients with systemic lupus erythematosus (SLE) and histopathologically confirmed PNGD. Direct immunofluorescence (DIF) studies revealed in vivo cutaneous ANA positivity in both patients. DIF findings in the skin mirrored serum autoantibody results. ANA positivity in skin specimens is reported as highly predictive of systemic connective tissue diseases (SCTD), although specific testing is not currently recommended as part of the laboratory work‐up or diagnostic criteria for these disorders. In this case report, positive ANA results in skin biopsies of PNGD reflect the serological findings and clinical evidence of SLE in both patients. In vivo cutaneous ANA positivity is an interesting and supportive finding in PNGD in the setting of SCTD.
Differences in cytopathologist thyroid nodule malignancy rate
Authors: Ronen Ohad , Cohen Hector , Sela Eyal , Abu Mor 
Published: April 2020

AbstractObjectives:The accuracy of a cytological diagnosis obtained by fine needle aspiration is influenced by several factors including the technique used and the experience of both the aspirator as well as the cytologist. In this project we planned to evaluate the interobserver differences of thyroid nodule cytopathology in our medical centre.Methods:The study was conducted using retrospective pathology reports from a single academic centre from August 2013 to September 2017. We compared the sensitivity, specificity, negative and positive predictive values, malignancy rates, and accuracy of two cytopathologists who evaluated thyroid nodules.Results:We included 287 fine needle aspirations of thyroid nodules in the study. Approximately one fifth (18.5%) of patients had surgery and the rate of malignancy was 40%. There was a similar frequency of use of all thyroid Bethesda system (TBS) categories with the exception of TBS 3 (8.0% and 21.2%, P = .01). As a consequence, the malignancy rate was different in TBS 3 category (40% vs 17%, P = .545).Conclusions:There are interobserver differences in the evaluation of thyroid nodules. Clinicians should be aware of such differences because they affect the malignancy rate in each TBS category.
Dental and maxillofacial injuries associated with electric‐powered bikes and scooters in Israel: A report for 2014‐2019
Authors: Lin Shaul , Goldman Sharon , Peleg Kobi , Levin Liran ,   With support of the Israel Trauma Group
Published: April 2020

AbstractBackground/AimsElectric‐Powered Bikes and powered scooters present a new method of transportation and are becoming commonly used worldwide. However, the reports on traumatic dental injuries related to their use are scarce. The aim of this study was to report the frequency and severity of dental and maxillofacial injuries associated with electric‐powered bikes and scooters in Israel between the years 2014 and 2019.MethodsThis was a retrospective cohort study based on data from the Israeli National Trauma Registry (INTR). The INTR provides comprehensive data on hospitalized patients from all six Level I trauma centers (TC) and 15 of the 20 Level II TCs in Israel. All injured patients who were hospitalized due to a traffic collision between 2014 and 2019 were identified. The data for those hospitalized due to an e‐bike or motorized scooter accident were extracted as well as for pedestrians who were injured as a result of a crash with these vehicles.ResultsA total of 3,686 hospital admissions were related to electric‐powered bikes and scooters. Of those, 378 (10.3%) were oral and maxillofacial injuries. Most of the oral and maxillofacial injuries were attributed to powered bikes (321 out of 378; 84.92%) and the rest to powered scooters. There was a constant increase in general as well as the oral and maxillofacial injuries during the study years. Almost 20% of the cases involved injuries to the teeth. Overall, 291 pedestrians were reported to be injured due to electric‐powered bikes and scooters; 29 (9.97%) of them, suffered from oral and maxillofacial injuries. Most of those were children aged 0‐15 years (41.38%) and elders older than 60 years (37.39%).ConclusionsTrauma related to electric‐powered bikes and scooters is an increasing concern. Dental professionals should be actively involved in educational and legislative efforts focusing on the prevention of e‐bike and scooter‐related injuries, in general, and specifically maxillofacial injuries.