bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Head Impulse Test With and Without Optokinetic Stimulation in Subjects With Persistent Postural Perceptual Dizziness (PPPD): Preliminary Report
Authors: Teggi Roberto , Gatti Omar , Cangiano Jacopo , Fornasari Francesco , Bussi Mario 
Published: November 2019

Objective:
Persistent postural perceptual dizziness (PPPD) is a clinical condition characterized by unsteadiness present on most days for a period of at least 3 months. The aim of our work was to assess vestibular function, the role of anxiety, and possible interactions between visual and vestibular systems in patients with PPPD.

Study Design:
Cross-sectional prospective study.

Setting:
Tertiary referral center.

Patients:
Twenty-five PPPD patients.

Interventions:
Clinical history was collected before examination; vestibular function was assessed through bedside examination, video and functional head impulse test (video-HIT, f-HIT). The latter test was based on having the patient identify an optotype displayed on a computer screen during passive head rotations. The test was repeated while optokinetic stimulation (OKS) was given on the screen. Results were compared with those of 25 controls. State and trait anxiety levels were measured with the State-Trait Anxiety Inventory (STAI) questionnaire. Anxiety before and after vestibular examination was assessed using a VAS scale.

Main Outcome Measure:
Results of video and functional HIT with and without OKS.

Results:
Video-HIT and f-HIT showed normal values in all subjects. f-HIT with OKS provoked more reading errors in patients than in controls. The interaction of group per time detected different decreasing trends between the two groups (p = 0.0002).
Patients presented a reduction in anxiety levels after examination. Nine patients fulfilled diagnostic criteria for vestibular migraine, eight of whom presented nystagmus either to positional tests or vibration test. Only anxiety levels before testing were predictive of worsening of f-HIT with optokinetic stimulation (p = 0.0007).

Conclusions:
Our data support the hypothesis that increased anxiety may play a role in visuo-vestibular interactions; moreover, they are not inconsistent with the hypothesis that OKS might provoke a “threatening effect,” leading to gaze bias during examination.
Inner Ear Proteins as Potential Biomarkers
Authors: Mulry Erin , Parham Kourosh 
Published: November 2019

Objective:
The purpose of this manuscript is to identify proteins exclusive to the inner ear based on published research to identify potential candidate biomarkers and guide future inner ear research.

Data Sources:
Literature on inner ear proteins published on Pubmed, Google Scholar, and Scopus was reviewed using key words such as “inner ear molecule,” “inner ear exclusive protein,” and several specific protein searches such as “prestin” based on findings from the initial searches.

Study Selections:
Studies were selected for abstract review based on title relevance, and full text was chosen for review based on abstract relevance. Several related studies cited in initially reviewed literature were also chosen to compile more detailed information on specific molecules with the goal of at least two to three published articles for each protein.

Data Extraction & Synthesis:
Proteins that were cited to have only been found within the inner ear were included in this review, including some proteins that were later identified outside the inner ear. Information regarding their size, location, function, and clinical significance was recorded.

Conclusions:
Based on this literature search, eight proteins exclusive to the inner ear were identified including otolin-1, otoconin 90/95, prestin, otoancorin, otogelin, α-tectorin, β-tectorin, and cochlin. Proteins initially found to be exclusive to the inner ear though later identified outside of the inner ear included oncomodulin, otospiralin, and otoraplin. This literature review may serve as a focused guide for future research on proteins exclusive to the inner ear as potential biomarkers for diseases of the inner ear.
Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery
Authors: Sherry Alexander D. , Khattab Mohamed H. , Totten Douglas J. , Wharton David M. , Luo Guozhen , Manzoor Nauman F. , Rivas Alejandro , Chambless Lola B. , Davis Larry T. , Attia Albert , Cmelak Anthony J. 
Published: November 2019

Objective:
Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance.

Study Design:
Retrospective cohort study.

Setting:
Tertiary referral center.

Patients:
We evaluated 54 patients with vestibular schwannoma before and after SRS.

Intervention(s):
Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist.

Main Outcome Measure(s):
Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland–Altman method evaluated reproducibility. Linear regression evaluated predictors of model error.

Results:
All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS.

Conclusions:
The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.
HBeAg Negativity Is Associated With More Advanced Liver Fibrosis in Patients With Chronic Hepatitis B
Authors: Wang Jian , Wu Weihua , Yan Xiaomin , Wei Jie , Yao Kefang , Yang Yue , Xiong Yali , Xia Juan , Liu Yong , Chen Yuxin , Jia Bei , Zhang Zhaoping , Ding Weimao , Huang Rui , Wu Chao 
Published: November 2019

Background:
Serum hepatitis B e antigen (HBeAg) status is associated with the progression of chronic hepatitis B (CHB). The authors aimed to investigate the relationship between HBeAg status and liver pathology in CHB patients.

Methods:
A total of 683 treatment-naive CHB patients who had undergone liver biopsy were retrospectively enrolled from 2 medical centers. Propensity score-matching (PSM) method was performed to adjust the imbalance of baseline confounders between HBeAg-positive and HBeAg-negative CHB patients.

Results:
HBeAg-negative CHB patients (n=338) exhibited more advanced liver fibrosis than HBeAg-positive CHB patients (n=345) before PSM (P<0.001). However, there were no significant differences in the distribution of inflammation grades between HBeAg-positive and HBeAg-negative CHB patients (P=0.051). Of these 683 CHB patients, 123 patients were included in each group after PSM. HBeAg-negative CHB patients still showed significantly advanced liver fibrosis as compared with HBeAg-positive CHB patients (P=0.03) after PSM. Furthermore, the distribution of liver inflammation grades in the HBeAg-negative CHB patients was also more severe than patients with HBeAg-positive (P=0.037). HBeAg-negative status was identified as an independent risk factor of significant liver fibrosis (P=0.011) by multivariate analysis.

Conclusions:
HBeAg negativity is associated with more advanced liver fibrosis in CHB patients.
Molecular imaging and radionuclide therapy of neuroendocrine tumors
Authors: Haider Mintallah , Al-Toubah Taymeyah , El-Haddad Ghassan , Strosberg Jonathan 
Published: November 2019

Purpose of review
Neuroendocrine tumors are heterogeneous neoplasms with variable prognoses and clinical behaviors. The majority of well differentiated NETs express somatostatin receptors. Identification of these receptors has contributed to advancements in molecular and targeted radiotherapies.

Recent findings
Molecular scans provide important diagnostic, staging, and prognostic data. Somatostatin-receptor imaging aids in selection of patients who are eligible for somatostatin-receptor-targeting therapies. Peptide receptor radionuclide therapy has recently demonstrated robust efficacy in a phase III study of progressive midgut NETs. Current studies are investigating novel receptor agonists and antagonists, new classes of radioactive isotopes, and radiosensitizing combination treatments.

Summary
The sophistication of molecular imaging is improving and its importance is increasing as a diagnostic, predictive, and prognostic tool. Theranostics, the coupling of molecular imaging with receptor-targeted therapy, represents a novel approach to cancer treatment.
Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn’s Disease: Case Report and Review of Literature
Authors: Shayowitz Michelle , Bressler Moshe , Ricardo Alison P. , Grudnikoff Eugene 
Published: November 2019

Introduction:
Infliximab, an anti-inflammatory agent, is used to treat various autoimmune disorders. There are at least 3 reports of severe psychiatric adverse effects of the drug, including suicidal behaviors in adults and psychosis in adult and adolescent patients. We report a case of an adolescent who developed depression and suicidal behaviors shortly after beginning infliximab. Although there have been reports of adolescents developing acute psychosis shortly after starting infliximab, this is, to our knowledge, the first report of adolescent suicidal behavior in the setting of infliximab treatment.

Methods:
We describe a patient’s presentation and clinical course, as well as existing reports of adverse psychiatric effects of infliximab.

Results:
A 16-year-old male with a 2-year history of disabling symptoms and complications of Crohn’s disease was initiated on a trial of infliximab. Within days of the first infliximab infusion, he experienced symptoms of depression, which intensified over weeks and resulted in a serious suicide attempt. The patient was treated with fluoxetine, melatonin, and psychotherapy, which effectively managed his infliximab-induced depressive disorder with suicidal thoughts and behaviors. Posttreatment, he tolerated additional infliximab infusions without the recurrence of psychiatric symptoms.

Conclusions:
Treatment with infliximab may rarely and suddenly cause severe and potentially life-threatening psychiatric symptoms. Therefore, youth with chronic illnesses considered for infliximab treatment should be screened for preexisting, as well as for a family history of, psychiatric disorders and suicidal behavior.
Putting Together the Pieces: Development and Validation of a Risk-Assessment Model for Nipple-Sparing Mastectomy
Authors: Frey Jordan D. , Salibian Ara A. , Choi Mihye , Karp Nolan S. 
Published: November 2019

Background:
Optimizing outcomes and assessing appropriate candidates for breast reconstruction after nipple-sparing mastectomy is an ongoing goal for plastic surgeons.

Methods:
All patients undergoing nipple-sparing mastectomy from 2006 to June of 2018 were reviewed and randomly divided into test and validation groups. A logistic regression model calculating the odds ratio for any complication from 12 risk factors was derived from the test group, whereas the validation group was used to validate this model.

Results:
The test group was composed of 537 nipple-sparing mastectomies (50.2 percent), with an overall complication rate of 27.2 percent (146 nipple-sparing mastectomies). The validation group was composed of 533 nipple-sparing mastectomies (49.8 percent), with an overall complication rate of 22.9 percent (122 nipple-sparing mastectomies). A logistic regression model predicting overall complications was derived from the test group. Nipple-sparing mastectomies in the test group were divided into deciles based on predicted risk in the model. Risk increased with probability decile; decile 1 was significantly protective, whereas deciles 9 and 10 were significantly predictive for complications (p < 0.0001). The relative risk in decile 1 was significantly decreased (0.39; p = 0.006); the relative risk in deciles 9 and 10 was significantly increased (2.71; p < 0.0001). In the validation group, the relative risk of any complication in decile 1 was decreased at 0.55 (p = 0.057); the relative risk in deciles 9 and 10 was significantly increased (1.89; p < 0.0001). In a receiver operating characteristic curve analysis, the area under the curve was 0.668 (p < 0.0001), demonstrating diagnostic meaningfulness of the model.

Conclusion:
The authors establish and validate a predictive risk model and calculator for nipple-sparing mastectomy with far-reaching impact for surgeons and patients alike.
Follow-Up Study: One-Step Salvage of Infected Prosthetic Breast Reconstructions Using Antibiotic-Impregnated Polymethylmethacrylate Plates and Concurrent Tissue Expander Exchange
Authors: Xue Amy S. , Volk Angela S. , DeGregorio Valerie L. , Jubbal Kevin T. , Bullocks Jamal M. , Izaddoost Shayan A. 
Published: November 2019

Background:
Periprosthetic infections represent major complications in breast reconstruction, frequently leading to expander-implant loss. No consensus regarding a management algorithm for attempted salvage currently exists. This study assessed outcomes of the authors’ salvage protocol using an antibiotic-impregnated polymethylmethacrylate implant with expander device exchange.

Methods:
A retrospective chart review identified infected implant-based breast reconstruction cases treated between 2009 and 2017. Of 626 cases initially identified, a total of 62 cases had severe prosthetic infections, and underwent either prosthetic salvage (n = 45) or immediate explantation (n = 17). All the prosthetic salvage patients received intravenous antibiotics followed by surgical débridement, insertion of polymethylmethacrylate plates, device exchange, and postoperative antibiotics. After clinical resolution of infection, tissue expansion was performed, with the polymethylmethacrylate plates remaining in situ until exchanged for permanent implants.

Results:
The authors’ study demonstrated a primary infection clearance rate of 82.2 percent (n = 37). Compared to the traditional explantation group, a significantly higher percentage of the salvage patients completed final reconstruction (84.4 percent versus 35.3 percent; p < 0.001). Fewer patients abandoned reconstruction efforts after infection clearance (2.2 percent versus 58.8 percent; p < 0.001). The majority of cases (78.8 percent) that succeeded the salvage protocol ultimately received implant-based reconstruction; 62.5 percent that failed the salvage protocol still went on to receive autologous tissue reconstruction.

Conclusions:
Sustained local antibiotic delivery using polymethylmethacrylate implants and expander device exchange can successfully salvage an infected breast expander/implant. Compared with the traditional explantation approach, more patients complete final reconstruction. Other benefits include preserved skin envelope integrity and possibly improved long-term aesthetic outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Updates in trichomonas treatment including persistent infection and 5-nitroimidazole hypersensitivity
Authors: Muzny Christina A. , Van Gerwen Olivia T. , Kissinger Patricia 
Published: November 2019

Purpose of review
The purpose of this review is to update information on treatment of Trichomonas vaginalis. T. vaginalis is estimated to be the most common treatable sexually transmitted infection. In the world and is associated with poor birth outcomes, cervical cancer, sperm motility and morphology issues, and HIV acquisition and transmission.

Recent findings
The efficacy of the recommended 2-g oral single-dose metronidazole (MTZ) for the treatment of T. vaginalis in women has recently been challenged. Two recent multicentered randomized trials and a meta-analysis have demonstrated that the 7-day dose of MTZ 500 mg twice daily was nearly two times more efficacious at clearing infection compared with the 2-g dose. Partner treatment is also essential, since up to 70% of male sexual partners can be infected and rescreening of treated women at 3 months is also recommended given the high repeat infection rates. Future studies should examine the importance of treating asymptomatic T. vaginalis, best treatment for men, the influence of the microbiome on treatment efficacy and different formulations of intravaginal treatments for hypersensitivity.

Summary
7-day 500 mg twice daily MTZ should be used as the first line treatment for T. vaginalis-infected women.
Muscle Recurrence of a Primarily Nodal Follicular Lymphoma Studied by Contrast-Enhanced 18F-FDG PET/CT
Authors: Belmonte Gianfranco , Caldarella Carmelo , Hohaus Stefan , Manfredi Riccardo , Minordi Laura Maria 
Published: November 2019

Abstract
We report the case of a 52-year-old woman with follicular lymphoma localized in the left inguinal region without any extranodal involvement and achieving a complete response after radiotherapy. After a 3-year disease-free interval, muscular recurrence at the left arm was shown by contrast-enhanced 18F-FDG PET/CT. Contrast-enhanced 18F-FDG PET/CT performed after immunochemotherapy documented complete disease remission. Lymphoid tissue is usually not present in the skeletal muscle, making muscular lymphomatous involvement quite unusual; muscular relapse of a primarily nodal lymphoma is even rarer.
Unraveling the Enigma of Nonarteritic Anterior Ischemic Optic Neuropathy
Authors: Rizzo Joseph F. 
Published: November 2019

Abstract:
Non-arteritic anterior ischemic optic neuropathy (NAON) is the second most common optic neuropathy in adults. Despite extensive study, the etiology of NAION is not definitively known. The best evidence suggests that NAION is caused by an infarction in the region of the optic nerve head (ONH), which is perfused by paraoptic short posterior ciliary arteries (sPCAs) and their branches. To examine the gaps in knowledge that defies our understanding of NAION, a historical review was performed both of anatomical investigations of the ONH and its relevant blood vessels and the evolution of clinical understanding of NAION. Notably, almost all of the in vitro vascular research was performed prior our current understanding of NAION, which has largely precluded a hypothesis-based laboratory approach to study the etiological conundrum of NAION. More recent investigative techniques, like fluorescein angiography, have provided valuable insight into vascular physiology, but such light-based techniques have not been able to image blood vessels located within or behind the dense connective tissue of the sclera and laminar cribrosa, sites that are likely culpable in NAION. The lingering gaps in knowledge clarify investigative paths that might be taken to uncover the pathogenesis of NAION and possibly glaucoma, the most common optic neuropathy for which evidence of a vascular pathology also exists.
Spatial enrichment of phosphoinositide metabolism is a molecular switch to promote metastasis
Authors: Nacke Marisa , Sandilands Emma , Nikolatou Konstantina , Román-Fernández Álvaro , Mason Susan , Patel Rachana , Lilla Sergio , Yelland Tamas , Galbraith Laura , McGarry Lynn , Morton Jennifer P. , Shanks Emma , Leung Hing , Zanivan Sara , Ismail Shehab , Markert Elke , Blyth Karen , Bryant David M. 
Published: November 2019

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. We developed 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by spatially enriching cortical phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants restrict PI(3,4,5)P3 production to discrete cortical domains to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PIP3-signalling, and predicts long-term poor outcome across multiple cancers. Spatial enrichment of phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.HighlightsSpatial enrichment of PI(3,4,5)P3 is a molecular switch to promote invasion.IQSEC1 is a GEF for ARF5/6, promoting PIP5K-dependent PI(3,4,5)P3 production downstream of the HGF receptor Met.Pro-invasive IQSEC1 variants restrict cortical PI(3,4,5)P3 production to subdomains that convert into invasive protrusions.IQSEC1 inhibition attenuates in vitro invasion and metastasis in vivo.IQSEC1 module is associated with poor outcome across tumour types.
2’3’-cGAMP triggers a STING and NF-κB dependent broad antiviral response in Drosophila
Authors: Cai Hua , Holleufer Andreas , Simonsen Bine , Schneider Juliette , Lemoine Aurélie , Gad Hans-Henrik , Huang Jingxian , Huang Jieqing , Chen Di , Peng Tao , Marques João T. , Hartmann Rune , Martins Nelson , Imler Jean-Luc 
Published: November 2019

AbstractWe recently reported that an orthologue of STING regulates infection by picorna-like viruses in drosophila. In mammals, STING is activated by the cyclic dinucleotide 2’3’-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we show that injection of flies with 2’3’-cGAMP can induce expression of dSTING-regulated genes. Co-injection of 2’3’-cGAMP with a panel of RNA or DNA viruses results in significant reduction of viral replication. This 2’3’-cGAMP-mediated protection is still observed in flies mutant for the genes Atg7 and AGO2, which encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, it is abrogated in flies mutant for the NF-κB transcription factor Relish. Analysis of the transcriptome of 2’3’-cGAMP injected flies reveals a complex pattern of response, with early and late induced genes. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program, which predates the emergence of Interferon Regulatory Factors and interferons in vertebrates.