bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity Associated with Low Lean Mass and Low Bone Density Has Higher Impact on General Health in Middle-Aged and Older Adults
Authors: de França Natasha A. G. , Peters Barbara S. E. , dos Santos Elizabete A. , Lima Marcela M. S. , Fisberg Regina M. , Martini Ligia Araújo
Published: December 2020

It is believed that the phenomenon of simultaneous changes in body composition could have a higher negative impact on general health. Thus, we aimed to investigate the prevalence of concomitant body composition disturbances and evaluate the association with dietary intake, sedentary behaviour, muscle strength, and performance. This is a cross-sectional study with 218 community-dwelling adults, aged 63 (59–69) years, both sexes (52% female) recruited from the Health Survey of the City of São Paulo. Assessments include appendicular lean mass (LM), fat mass and bone mineral density (BMD) by DXA, grip strength, time spent sitting, and dietary intake. Subjects were clustered into 8 groups: (1) normal, (2) osteopenia (OP), (3) low LM, (4) obesity, (5) OP + low LM, (6) obesity + OP, (7) obesity + low LM, and (8) obesity + OP + low LM. Statistical analyses include ANCOVA, the chi-square test, and linear regression models. 52 (23%) individuals presented obesity associated with another body composition change, with 14 (6%) having the combination of the 3 conditions (obesity + OP + low LM). All groups with obesity showed lower protein intake (

p
≤
0.001

); however, those with obesity or obesity + low LM spent more time in a sitting position (

p
=
0.002

), and the group with obesity + OP + low LM had the lowest grip strength. The combination of obesity with low LM and OP presented the aggravating factor of being associated with lower grip strength. In a context of demographic and nutrition transition, the findings represent a demand for longitudinal investigations.
From Radiological Manifestations to Pulmonary Pathogenesis of COVID-19: A Bench to Bedside Review
Authors: Saburi Amin , Schoepf U. Joseph , Ulversoy Kyle A. , Jafari Ramezan , Eghbal Fatemeh , Ghanei Mostafa
Published: December 2020

In this review, we aim to assess previous radiologic studies in COVID-19 and suggest a pulmonary pathogenesis based on radiologic findings. Although radiologic features are not specific and there is heterogeneity in symptoms and radiologic and clinical manifestation, we suggest that the dominant pattern of computed tomography is consistent with limited pneumonia, followed by interstitial pneumonitis and organizing pneumonia.
An Incidental Finding of Gastric Mucosa-Associated Lymphoma (MALToma) in a Sleeve Gastrectomy with Literature Review
Authors: Mai Brenda , Friscia Michaelangelo , Younes Pamela , Thomas-Ogunniyi Jaiyeola , Chen Lei
Published: December 2020

Mucosal-associated lymphoid tissue (MALT) lymphoma can typically be identified as a mass lesion or nodularity endoscopically and macroscopically. We report an incidental finding of a Helicobacter pylori gastric mucosal-associated lymphoid tissue (MALT) lymphoma in a sleeve gastrectomy specimen with no gross examination findings.
Modified Fracture Mechanics Approach for Hydraulic Fracturing Stress Measurements
Authors: Gao Guiyun , Wang Chenghu , Zhou Hao , Wang Pu
Published: December 2020

Hydraulic fracturing (HF) test has been widely used to determine in situ stress. The use of a conventional continuum method for this purpose has raised considerable controversies concerning field tests, particularly in the determination of the maximum horizontal principal stress under preexisting fractures. Fracture mechanics methods are very promising when considering preexisting cracks. However, most fracture mechanics methods do not include the effects of confinement on fracture parameters that depend on confining stress. In the present paper, we proposed a modified approach based on fracture mechanics for stress determination considering the relation between fracture toughness and confining stress based on the Rummel and Abou-Sayed methods. Then, we conducted true triaxial hydraulic fracturing tests under different stress ratios for granite and sandstone specimens to verify the proposed approach. The observed typical pressure-time curves indicate that in the conducted hydraulic fracturing tests, the steady fracture growth was attained. Moreover, we demonstrated that the stress ratios influence crack orientations. The horizontal maximum principal stresses determined using the modified Rummel method achieve the lowest relative error compared with other considered stress estimation approaches. This modified fracture mechanics method could be used as a potential alternative approach to obtain a considerably more precise estimation of the maximum horizontal stress in hydraulic fracturing stress determination.
Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia
Authors: Bhatnagar Bhavana , Kohlschmidt Jessica , Mrózek Krzysztof , Zhao Qiuhong , Fisher James L. , Nicolet Deedra , Walker Christopher J. , Mims Alice S. , Oakes Christopher , Giacopelli Brian , Orwick Shelley , Boateng Isaiah , Blachly James S. , Maharry Sophia E. , Carroll Andrew J. , Powell Bayard L. , Kolitz Jonathan E. , Stone Richard M. , Byrd John C. , Paskett Electra D. , de la Chapelle Albert , Garzon Ramiro , Eisfeld Ann-Kathrin
Published: December 2020

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with cytogenetic and molecular factors and patient demographics (e.g., age and race). We compared survival of 25,523 non-Hispanic Black and White adults with AML using Surveillance Epidemiology and End Results (SEER) Program data and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols. Black patients had shorter survival than White patients, both in SEER and in the setting of Alliance clinical trials. The disparity was especially pronounced in Black patients <60 years, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival. Gene mutation profiles showed fewer NPM1 and more IDH2 mutations in younger Black patients. Overall survival of younger Black patients was adversely affected by IDH2 mutations and FLT3-ITD, but, in contrast to White patients, was not improved by NPM1 mutations.

Significance:

We show that young Black patients have not benefited as much as White patients from recent progress in AML treatment in the United States. Our data suggest that both socioeconomic factors and differences in disease biology contribute to the survival disparity and need to be urgently addressed.

See related commentary by Vyas, p. 540.

This article is highlighted in the In This Issue feature, p. 521
Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of Panobinostat in Combination with Bortezomib and Dexamethasone in Japanese Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma
Authors: Suzuki Kenshi , Sunami Kazutaka , Matsumoto Morio , Maki Akio , Shimada Fumika , Suzuki Kazuyuki , Shimizu Kazuyuki
Published: December 2020

Introduction: Panobinostat, bortezomib, and dexamethasone combination therapy demonstrated progression-free survival (PFS) benefit over bortezomib and dexamethasone alone in the PANORAMA-1 study in relapsed/refractory multiple myeloma (MM). Here, we present data from a phase II study (NCT02290431) of this combination in Japanese patients with relapsed or relapsed-and-refractory MM. Methods: Patients received 3-week cycles of 20-mg oral panobinostat (weeks 1 and 2), 1.3-mg/m2 subcutaneous bortezomib (days 1, 4, 8, and 11), and 20-mg oral dexamethasone (day of and the day following bortezomib administration) for a total of 8 cycles (24 weeks; treatment phase 1). Patients with treatment benefit had an option to enter the extension phase to receive 6-week (42-day) cycles of panobinostat (weeks 1, 2, 4, and 5) plus bortezomib (days 1, 8, 22, and 29) and dexamethasone (day of and the day following bortezomib treatment) for 24 weeks. The primary objective was complete response (CR) + near CR (nCR) rate after treatment phase 1 as per the modified European Society for Blood and Marrow Transplantation criteria. Results: Of the 31 patients, 4 (12.9%) completed the treatment and 27 (87.1%) discontinued; 17 (54.8%) entered the extension phase. In total, 24 patients (77.4%) entered the survival follow-up phase and followed until study closure when the last patient was treated for 1 year after treatment phase 1. The CR + nCR rate was 48.4% (90% CI: 33.6–63.2). The overall response rate (CR + nCR + partial response) was 80.6%. The median PFS, duration of response, time to response, and time to progression were 15.3, 22.7, 1.4, and 15.3 months, respectively. All patients experienced adverse events (AEs), with diarrhea (80.6%), decreased appetite (58.1%), and thrombocytopenia (54.8%) being the most frequent, regardless of relationship to the study treatment. Thrombocytopenia (48.4%), fatigue (25.8%), diarrhea (22.6%), neutrophil count decrease (22.6%), platelet count decrease (22.6%), and lymphocyte count decrease (22.6%) were the most frequent grade 3/4 AEs. Conclusion: The study met the primary objective with 48.4% CR + nCR rate. The AEs associated with the combination treatment were safely managed using the existing AE management guidelines, including dose interruption/modification and/or supportive medical intervention. This treatment regimen is an effective option with a favorable benefit/risk profile for Japanese patients with relapsed/refractory MM.
Prevalence of Amblyopia and Associated Risk Factors in Tibetan Grade One Children
Authors: Meng Zhaojun , Fu Jing , Chen Weiwei , Li Lei , Su Han , Dai Wei , Yao Yao
Published: December 2020

Introduction: Amblyopia is an important public health problem and standard screening is quite necessary for early diagnosis and treatment especially for the remote areas. As the place of the largest Tibetan population, the Tibetan Plateau has special geographical characteristics such as high altitude, time zone, and ethnic composition, where very little information is available about the prevalence of amblyopia and other ocular diseases. The article aims to determine the prevalence of amblyopia and associated factors in grade 1 Tibetan children, living in Lhasa, Tibet Autonomous Region. Methods: A cross-sectional study was conducted. All the participants were scheduled for comprehensive eye examinations including visual acuity testing, ocular deviation and movement evaluation, cycloplegic refraction and examinations of the external eye, anterior segment, media, and fundus. Amblyopia was assessed in the children according to the standard definition. Results: A total of 1,856 students participated in the examinations (97.58% response rate). 1,852 students completed all the related examinations, and 34 of them were diagnosed as amblyopia with the prevalence of 1.84% (95% confidence interval [CI]: 1.22–2.45%). Unilateral amblyopia was diagnosed in 23 students (1.24%, 95% CI: 0.74–1.75%), including 16 anisometropic, 4 strabismic, 1 visual deprivational, and 2 mixed. Other 11 students were diagnosed as bilateral amblyopia (0.59%, 95% CI: 0.24–0.94%), including 9 ametropic, 1 deprivational, and 1 with nystagmus. The mean cylinder refraction and absolute value of the spherical equivalent refraction of amblyopic eyes was respectively −2.15 ± 1.52 D and 2.70 ± 2.33 D. Amblyopia was significantly associated with hyperopia (≥+2.00 D, odds ratio [OR] 8.22, 95% CI 3.42–19.72), astigmatism (≤−2.00 D, OR 6.76, 95% CI 2.56–17.85), and anisometropia (≥+0.50 to <+1.00 D, OR 3.95, 95% CI 1.44–10.79; ≥+1.00 D, OR 21.90, 95% CI 8.24–58.18). Conclusions: The prevalence of amblyopia in grade 1 students of Lhasa is relatively higher than that of many other ethnic populations in China previously reported. Refractive errors including anisometropia, hyperopia, and astigmatism are the major risk factors of amblyopia.
The Influence of Surface Electromyography Visual and Clinician Verbal Feedback on Swallow Effort Ratio at Different Bolus Volumes in a Healthy Population
Authors: Galek Kristine E. , Bice Ed M.
Published: December 2020

Background/Aims: The effortful swallow is a common treatment intervention requiring increased intensity to facilitate adaptations and modify swallow kinematics. The type of feedback and bolus volume provided may influence the intensity of the effortful swallow. To determine the increased effortful swallow intensity, a clinician can collect the peak amplitude of an effortful swallow and a typical swallow and compute a “swallow effort ratio” (SER). Dividing the effortful swallow surface electromyography (sEMG) peak amplitude by the typical swallow sEMG peak amplitude derives the SER. A higher SER suggests increased intensity. An increase in the SER may have clinical relevance in swallowing therapy as a threshold of intensity is required to elicit neuroplastic change. The purpose of this investigation was to determine whether sEMG visual and clinician verbal feedback increases the SER. Additionally, the investigation examined whether the SER is influenced by different liquid bolus volumes. Methods: Eighty-two nondysphagic, healthy adults were assigned at random to 2 groups. One group received no feedback, and the other received verbal and visual feedback while performing typical and effortful swallows at 3 liquid volumes. Results: An analysis of covariance compared the typical and effortful peak swallow amplitudes among 3 volumes in the 2 feedback groups. There was a significant effect on the peak amplitude values by feedback group F(2, 79) = 22.82, p < 0.001. There were no differences in peak amplitude by volume regardless of feedback F(2, 78) = 0.413, p = 0.663. Conclusion: It appears that sEMG visual and clinician verbal feedback increases the SER, which may be a surrogate for intensity. An increased SER may have a positive effect on swallow intervention as intensity is known to influence outcomes of exercise and elicit neuroplastic change.
The Role of the Albumin-Bilirubin Score for Predicting the Outcomes in Japanese Patients with Advanced Hepatocellular Carcinoma Treated with Ramucirumab: A Real-World Study
Authors: Hatanaka Takeshi , Naganuma Atsushi , Shibasaki Mitsuhiko , Kohga Tatsuya , Arai Yosuke , Nagashima Tamon , Ueno Takashi , Namikawa Masashi , Saito Shuichi , Hoshino Takashi , Takizawa Daichi , Arai Hirotaka , Makita Fujio , Kakizaki Satoru , Harimoto Norifumi , Shirabe Ken , Uraoka Toshio
Published: December 2020

Aim: The aim of this retrospective study was to investigate the efficacy and safety of ramucirumab treatment under real-world conditions and to clarify the role of albumin-bilirubin (ALBI) score in predicting outcomes. Methods: Between June 2019 and May 2020, a total of 16 patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab in Gunma Saiseikai Maebashi Hospital and its affiliated hospitals was included. Results: The median age was 71 (interquartile range [IQR] 65–74) years old, and 12 patients (75.0%) were male. The modified ALBI (mALBI) grade was 1, 2a, and 2b at baseline in 4 (25.0%), 3 (18.8%), and 9 patients (56.3%), respectively. The Barcelona Clinic Liver Cancer stage was intermediate and advanced stage in 1 (6.3%) and 15 patients (93.8%), respectively. The serum α-fetoprotein at baseline was 4,911 (IQR 2,091–17,377) ng/mL. The disease control rate in patients with mALBI grade1 + 2a was significantly higher than in those with mALBI grade 2b (100 vs. 28.6%, p = 0.028). The patients with mALBI grade 1 + 2a had a significantly better overall survival (OS) and longer progression-free survival (PFS) than those with mALBI grade 2b (median OS 6.7 vs. 3.0 months; p = 0.036, median PFS 7.5 vs. 1.4 months; p = 0.002). The number of cycles of ramucirumab treatment was significantly correlated with the ALBI score (r = −0.452, p = 0.030). The patients with mALBI grade 1 + 2a showed a low incidence of adverse events (AEs) and discontinuation due to AEs. Conclusions: Advanced HCC patients with mALBI grade 1 + 2a may be a good indication for ramucirumab treatment.
Neuroepidemiology: Perspectives from Africa
Authors: Owolabi Joshua O.
Published: December 2020

Neuroepidemiology is an important field that deserves critical attention globally and more specifically on the African continent. The African continent currently has less than adequate and reliable data on mental health generally or neurological disorders. Only few prevalence and incidence studies’ reports are available. Africa is affected by diverse neurological problems that deserve epidemiological attention ranging from chronic neurological disorders to outbreaks of epidemics of neurological importance, including konzo, lead poisoning, and infectious diseases of neurological importance. The current effort is an attempt to report perspectives about neuroepidemiology from Africa and to critically appraise the current scenarios toward deciphering the factors that have limited the development and advancements of the field in Africa. This article highlights specific points on needs as found and provides suggestions and recommendations on the way forward. The study was conducted in Nigeria through a network named ANDEN. Questionnaires were administered through all neuroscience-related platforms. Ninety-two respondents completed the questionnaires properly. Most respondents were young scientists with bachelors’ and master’s level of training and were almost equally divided between males and females. Their responses were analysed and presented as descriptive statistics and thematic summary of free responses. The interest of these African neuroscientists in neuroepidemiology ranked between high and very high. A good proportion rated the likelihood of a career path in neuroepidemiology between high and very high. The importance and relevance of the field to the advancement of mental health was also rated very high. The current attention and commitment of research efforts and funding to neuroepidemiology was, however, rated low. Many potential African neuroscientists would agree that their current greatest need is the knowledge of the subject and field of neuroepidemiology. By implication, there is a great need for them to be educated in this area. The findings showed that neuroepidemiology is a relatively neglected aspect of neurology and neuroscience research on the continent. The interest of respondents in this field underscores the critical and urgent need to develop the field, promote training and research funding toward developing capacities, and carrying out cutting edge research.
ERBB2 Pathway in Biliary Tract Carcinoma: Clinical Implications of a Targetable Pathway
Authors: Jacobi Oded , Ross Jeffrey S. , Goshen-Lago Tal , Haddad Riad , Moore Assaf , Sulkes Aaron , Brenner Baruch , Ben-Aharon Irit
Published: December 2020

Background/Aims: Current chemotherapy regimens for cholangiocarcinoma (CCA) yield poor outcomes, with a median overall survival of <12 months. Recent data on the genomic landscape of CCAs have created opportunities for targeted therapy. Yet, data regarding its efficacy are scarce. We aimed to describe the genomic landscape of a CCA patient cohort using next-generation sequencing (NGS), focusing on the ERBB/EFGR pathway and assessing response to anti-HER2 agents. Methods: Tissue samples of intrahepatic CCA (IHCC) and extrahepatic CCA (EHCC) underwent NGS for somatic aberrations. The clinical outcomes for patients treated with anti-HER2 agents were evaluated. Results: A total of 1,863 CCA cases (1,615 IHCCs and 248 EHCCs) underwent NGS, and they revealed a high prevalence of ERBB alterations (IHCC, 4.2%; EHCC, 9.7%). Among these, 23.8% of the IHCCs and 53.6% of the EHCCs had a point mutation in ERBB2, and 66.6% of the IHCCs and 41.2% of the EHCCs had ERBB copy number amplification. Three EHCC patients were diagnosed at our institute with ERBB/EGFR aberrations; 2 patients were treated with neratinib and 1 patient with a chemotherapy-trastuzumab combination. All 3 achieved disease stabilization and a clinical benefit. One patient underwent a liquid biopsy before and after 3 months of treatment, demonstrating disappearance of the ERBB2 clone and emergence of a Myc-mutated clone after treatment. Conclusions: The genomic landscape of CCAs may harbor targetable alterations, especially in the ERBB/EGFR pathway. These alterations may have clinical significance in everyday practice.
Pedunculopontine Nucleus Deep Brain Stimulation for Parkinsonian Disorders: A Case Series
Authors: Dayal Viswas , Rajabian Ali , Jahanshahi Marjan , Aviles-Olmos Iciar , Cowie Dorothy , Peters Amy , Day Brian , Hyam Jonathan , Akram Harith , Limousin Patricia , Hariz Marwan , Zrinzo Ludvic , Foltynie Thomas
Published: December 2020

Background: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. Objectives: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. Materials and Methods: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson’s disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20–30 Hz and optimized in an iterative manner. Results: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. Conclusions: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.
Emerging Adults in Inpatient Substance Use Treatment: A Prospective Cohort Study of Patient Characteristics and Treatment Outcomes
Authors: Andersson Helle Wessel , Lauvsnes Anders D. Forsmo , Nordfjærn Trond
Published: December 2020

Introduction: Compared to older adults, emerging adults treated for substance use disorders (SUDs) are more likely to have unfavorable outcomes. However, few studies have investigated the baseline characteristics and treatment outcomes of emerging adults in inpatient SUD treatment. Aims: This study investigated differences in demographic and clinical characteristics and treatment outcomes (relapse or treatment discontinuation) among emerging adult and adult inpatients. Prospective associations between baseline characteristics and unfavorable treatment outcomes were also analyzed across both patient groups. Methods: A prospective cohort study was conducted among inpatients (n = 499) at 4 SUD treatment centers in Norway. The sample included emerging adult patients aged 18–25 years (n = 149) and adult patients above 25 years (n = 350). Medical records provided data on sociodemographic variables, substance use characteristics, diagnoses, and treatment completion status. Self-reported measures, including age of onset of substance use, motivation, and mental distress, were completed within 2 weeks of admission to treatment. A telephone interview 3 months after discharge provided information about relapses. Results: Emerging adults had a more adverse risk profile in terms of demographic characteristics, clinical variables, and treatment outcomes. Multivariable results showed that polysubstance use and an attention deficit hyperactivity disorder (ADHD) diagnosis were the strongest predictors of unfavorable treatment outcomes for emerging adults. For older adults, only baseline mental distress was a significant predictor of unfavorable treatment outcomes. Conclusions: Treatment and follow-up initiatives could be better tailored for emerging adults. Identification of treatment needs among emerging adults manifesting polysubstance use and ADHD may reduce the likelihood of unfavorable treatment outcomes in this patient group.
Explicit Diagnostic Criteria for Transient Ischemic Attacks Used in the Emergency Department Are Highly Sensitive and Specific
Authors: Göbel Carl H. , Karstedt Sarah C. , Münte Thomas F. , Göbel Hartmut , Wolfrum Sebastian , Lebedeva Elena R. , Olesen Jes , Royl Georg
Published: December 2020

Background: Making a correct diagnosis of a transient ischemic attack (TIA) is prone to errors because numerous TIA mimics exist and there is a shortage of evidence-based diagnostic criteria for TIAs. In this study, we applied for the first time the recently proposed explicit diagnostic criteria for transient ischemic attacks (EDCT) to a group of patients presenting to the emergency department of a large German tertiary care hospital with a suspected TIA. The aim was to determine the sensitivity and specificity of the EDCT in its clinical application. Methods: A total of 128 patients consecutively presenting to the emergency department of the University Hospital of Lübeck, Germany, under the suspicion of a TIA were prospectively interviewed about their clinical symptoms at the time of presentation. The diagnosis resulting from applying the EDCT was compared to the diagnosis made independently by the senior physicians performing the usual diagnostic work-up (“gold standard”), allowing calculation of sensitivity and specificity of the EDCT. Results: EDCT achieved a sensitivity of 96% and a specificity of 88%. When adding the additional criterion F (“the symptoms may not be better explained by another medical or mental disorder”), specificity significantly increased to 98%. Conclusions: The data show that the EDCT in its modified version as proposed by us are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA.
Detecting Apoptosis as a Clinical Endpoint for Proof of a Clinical Principle
Authors: Zollet Piero , Yap Timothy E. , Cordeiro M. Francesca
Published: December 2020

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarise the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase.
One-Year Anatomical and Functional Outcomes of the Argus II Implantation in Korean Patients with Late-Stage Retinitis Pigmentosa: A Prospective Case Series Study
Authors: Yoon Young Hee , Humayun Mark S. , Kim Yoon Jeon
Published: December 2020

Purpose: To report the anatomical and functional outcomes of Argus II retinal prosthesis implantation in Korean patients. Methods: We included 5 consecutive patients with end-stage retinitis pigmentosa (RP) who underwent Argus II retinal prosthesis implantation and were followed for at least 12 months. The transcorneal electrical evoked response was utilized for patient selection. We used intraoperative optical coherence tomography (OCT) for optimal placement of the array and provided specialized vision rehabilitation training. A morphological evaluation using SD-OCT and a functional evaluation using computer-based visual function tests, a letter-reading ability test, and the Functional Low-Vision Observer Rated Assessment (FLORA) were conducted. Results: Postoperatively, the array was completely apposed to the retinal surface in all eyes, except for one eye which had a preexisting macular concavity. Fibrosis-like tissues of ≥50-μm thickness developed at the interface in 2 eyes. All of the patients showed improvement in computer-based visual function tests and could read ETDRS letters at a distance of 50 cm. Three patients could read Korean words. FLORA was improved in all patients, mainly in tasks of visual mobility, daily activities, and social interactions. Conclusions: Along with good anatomical outcomes and specialized rehabilitation practices, recipients of the Argus II implant showed profound improvements in functional vision and mobility.
Risk of Coronary Obstruction and Feasibility of Coronary Access After Repeat Transcatheter Aortic Valve Replacement With the Self-Expanding Evolut Valve
Authors: Forrestal Brian J. , Case Brian C. , Yerasi Charan , Shea Corey , Torguson Rebecca , Zhang Cheng , Ben-Dor Itsik , Deksissa Teshome , Ali Syed , Satler Lowell F. , Shults Christian , Weissman Gaby , Wang John C. , Khan Jaffar M. , Waksman Ron , Rogers Toby
Published: December 2020

Background:

The supra-annular leaflet position and tall stent frame of the self-expanding Evolut PRO or Evolut PRO+ transcatheter heart valves (THVs) may cause coronary occlusion during transcatheter aortic valve replacement (TAVR)-in-TAVR and present challenges for future coronary access. We sought to evaluate the risk of TAVR-in-TAVR with Evolut PRO or Evolut PRO+ THVs and the feasibility of future coronary access.

Methods:

The CoreValve Evolut PRO Prospective Registry (EPROMPT; NCT03423459) prospectively enrolled patients with symptomatic severe aortic stenosis to undergo TAVR using a commercially available latest generation self-expanding THV at 2 centers in the United States. Computed tomography was performed 30 days after TAVR, which we used to simulate TAVR-in-TAVR with a second Evolut PRO or Evolut PRO+ THV and evaluate for risk of coronary obstruction and feasibility of future coronary access.

Results:

Eighty-one patients enrolled with interpretable computed tomography are reported herein. Computed tomography simulation predicted sinus of Valsalva sequestration and resultant coronary obstruction during future TAVR-in-TAVR in up to 23% of patients. Computed tomography simulation predicted that the position of the pinned THV leaflets would hinder future coronary access in up to 78% of patients after TAVR-in-TAVR.

Conclusions:

Further THV design improvements and leaflet modification strategies are needed to mitigate the risk of coronary obstruction during TAVR-in-TAVR with self-expanding THVs and to facilitate future coronary access.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03423459.
Lipid Profiles and Heart Failure Risk
Authors: Wittenbecher Clemens , Eichelmann Fabian , Toledo Estefanía , Guasch-Ferré Marta , Ruiz-Canela Miguel , Li Jun , Arós Fernando , Lee Chih-Hao , Liang Liming , Salas-Salvadó Jordi , Clish Clary B. , Schulze Matthias B. , Martínez-González Miguel Ángel , Hu Frank B.
Published: December 2020

Rationale:

Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF.

Objective:

We aimed to link single lipid metabolites and lipidomics networks to the risk of developing HF.

Methods and Results:

Discovery analyses were based on 216 targeted lipids in a case-control study (331 incident HF cases and 507 controls, matched by age, sex, and study center), nested within the PREDIMED (Prevención con Dieta Mediterránea) study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multistep workflow, including machine learning–based identification of the HF-related network clusters, and regression-based discovery of the HF-related lipid patterns within these clusters. If available, significant findings were externally validated in a subsample of the EPIC-Potsdam cohort (2414 at-risk participants, including 87 incident HF cases). After confounder-adjustments, 2 lipids were significantly associated with HF risk in both cohorts: CER (ceramide) 16:0 (relative risk [RR] per SD in PREDIMED, 1.28 [95% CI, 1.13–1.47]) and phosphatidylcholine 32_0 (RR per SD in PREDIMED, 1.23 [95% CI, 1.08–1.41]). Additionally, lipid patterns in several network clusters were associated with HF risk in PREDIMED. Adjusted for standard risk factors, an internally cross-validated score based on the significant HF-related lipids that were identified in the network analysis in PREDIMED was associated with a higher HF risk (20 lipids, RR per SD, 2.33 [95% CI, 1.93%–2.81%). Moreover, a lipid score restricted to the externally available lipids was significantly associated with HF incidence in both cohorts (6 lipids, RRs per SD, 1.30 [95% CI, 1.14–1.47] in PREDIMED, and 1.46 [95% CI, 1.17–1.82] in EPIC-Potsdam).

Conclusions:

Our study identified and validated 2 lipid metabolites and several lipidomics patterns as potential novel biomarkers of HF risk. Lipid profiling may capture preclinical molecular alterations that predispose for incident HF.

Registration:

URL:
https://www.isrctn.com/ISRCTN35739639
; Unique identifier: ISRCTN35739639.
Endothelial Cell Indoleamine 2, 3-Dioxygenase 1 Alters Cardiac Function After Myocardial Infarction Through Kynurenine
Authors: Melhem Nada Joe , Chajadine Mouna , Gomez Ingrid , Howangyin Kiave-Yune , Bouvet Marion , Knosp Camille , Sun Yanyi , Rouanet Marie , Laurans Ludivine , Cazorla Olivier , Lemitre Mathilde , Vilar José , Mallat Ziad , Tedgui Alain , Ait-Oufella Hafid , Hulot Jean-Sébastien , Callebert Jacques , Launay Jean-Marie , Fauconnier Jeremy , Silvestre Jean-Sébastien , Taleb Soraya
Published: December 2020

Background:

Ischemic cardiovascular diseases, particularly acute myocardial infarction (MI), is one of the leading causes of mortality worldwide. Indoleamine 2, 3-dioxygenase 1 (IDO) catalyzes 1 rate-limiting step of L-tryptophan metabolism, and emerges as an important regulator of many pathological conditions. We hypothesized that IDO could play a key role to locally regulate cardiac homeostasis after MI.

Methods:

Cardiac repair was analyzed in mice harboring specific endothelial or smooth muscle cells or cardiomyocyte or myeloid cell deficiency of IDO and challenged with acute myocardial infarction.

Results:

We show that kynurenine generation through IDO is markedly induced after MI in mice. Total genetic deletion or pharmacological inhibition of IDO limits cardiac injury and cardiac dysfunction after MI. Distinct loss of function of IDO in smooth muscle cells, inflammatory cells, or cardiomyocytes does not affect cardiac function and remodeling in infarcted mice. In sharp contrast, mice harboring endothelial cell–specific deletion of IDO show an improvement of cardiac function as well as cardiomyocyte contractility and reduction in adverse ventricular remodeling. In vivo kynurenine supplementation in IDO-deficient mice abrogates the protective effects of IDO deletion. Kynurenine precipitates cardiomyocyte apoptosis through reactive oxygen species production in an aryl hydrocarbon receptor–dependent mechanism.

Conclusions:

These data suggest that IDO could constitute a new therapeutic target during acute MI.
Impact of Sleep Apnea on Cardioembolic Risk in Patients With Atrial Fibrillation
Authors: Pengo Martino F. , Faini Andrea , Grote Ludger , Ludka Ondrej , Joppa Pavol , Pataka Athanasia , Dogas Zoran , Mihaicuta Stefan , Hein Holger , Anttalainen Ulla , Ryan Silke , Lombardi Carolina , Parati Gianfranco ,   on behalf of the ESADA Working Group
Published: December 2020

Background and Purpose:

An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF.

Methods:

We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Sp
o
2
and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA
2
DS
2
-VASc score.

Results:

From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA
2
DS
2
-VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Sp
o
2
81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively,
P
<0.05).

Conclusions:

These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.
Severity of Nonalcoholic Fatty Liver Disease and Risk of Future Ischemic Stroke Events
Authors: Xu Jie , Dai Liye , Zhang Yijun , Wang Anxin , Li Hao , Wang Yilong , Meng Xia , Wu Shouling , Wang Yongjun
Published: December 2020

Background and Purpose:

We assessed prospectively whether nonalcoholic fatty liver disease (NAFLD) and its severity predict future ischemic stroke (IS) events in a community-based cohort.

Methods:

From the Kailuan study, participants free of history of stroke, cancer, or myocardial infarction were enrolled after excluding alcohol abuse and other liver diseases. NAFLD was evaluated through ultrasonography. Participants with NAFLD were further stratified into mild, moderate, and severe groups. The outcome was the first occurrence of IS. The secondary outcomes included myocardial infarction and combined vascular events. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of incident IS according to presence and severity of NAFLD, adjusting for age, sex, physical activity, body mass index, smoker, history of hypertension, diabetes, hypercholesterolemia, lipid-lowering medication, HDL (high-density lipoprotein), triglyceride, hsCRP (high-sensitivity C-reactive protein), and fasting blood glucose.

Results:

During a median of 10.34 years of follow-up, we documented 3490 incident stroke cases among 79 905 participants. NAFLD was found in 24 874 (31.18%) participants. Relative to participants without NAFLD at the baseline, those with NAFLD had a 16% higher risk (95% CI, 1.07–1.26) of developing ischemic stroke, after adjusted for confounding variables. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.15 (95% CI, 1.05–1.25), 1.19 (95% CI, 1.06–1.34), and 1.21 (95% CI, 1.08–1.50), respectively.

Conclusions:

The severity of NAFLD is associated with a higher risk of future ischemic stroke events.
Mapping Working-Class Activism in Reconstruction St. Louis
Authors: Belanger Elizabeth
Published: December 2020

Blending the tools of micro-history with historical Geographical Information Systems (GIS) permits us to chart the social networks and everyday journeys of black working-class women activists and the middle-class men with whom they came into contact in Reconstruction St. Louis. Social and spatial ties shaped the activism of St. Louis’ working-class women; mapping these ties reveals the links between everyday acts of resistance and organized efforts of African Americans to carve out a space for themselves in the restructuring city and make visible a collective activism that crossed class and racial boundaries.
History and the Study of Inequality
Authors: Klein Herbert S.
Published: December 2020

Economic inequality has become one of the most important themes in the social sciences. The debate has revolved around two basic models. Was Kuznets correct in his prediction that inequality declines with economic growth, or was Piketty, along with others in the Berkeley/Paris/Oxford group, correct to counter that capitalism without severe constraints inevitably leads to increasing inequality? The resolution will depend on long-term historical analysis. In Global Inequality, Milanovic proposed new models to analyze the social, economic, political, and historical factors that influence changes in inequality over time and space. In Capitalism, Alone, he changes direction to examine what patterns of capitalism and inequality will look like in the twenty-first century and beyond, as well as how inequality might be reduced without violence.
SEEC: Photography at the Speed of Light
Authors: de Dios Rodríguez Enar , Klopfer Brannon B. , Haslinger Philipp , Juffmann Thomas
Published: December 2020

SEEC photography is a project at the intersection of art and science. It uses modern technology to record the motion of light, to see c, that is, the universal physical constant for the speed of light and the inspiration for the project name SEEC. In order to familiarize the general public with this physical phenomenon, SEEC records light moving across familiar objects, with visual scenes paying homage to iconic images from the history of photography. Exposure times shorter than 0.3 nanoseconds allow the authors to capture light (Greek: phos) in the process of writing (Greek: graphein) an image.
Sonifying Data: For the Art, for the Science and for What Lies Between
Authors: Ballora Mark
Published: December 2020

To explore intersections of art and science is to acknowledge that there are differing degrees of knowing, understanding and experience. This article describes three data sonification projects the author worked on using datasets from researchers. The sonifications were created to be used within scientifically informed musical performances by Grateful Dead percussionist Mickey Hart. The projects posed particular design challenges for the author as he sought to create “data art” that had “sonification integrity.”
Memory Machines: Infrastructural Performance as an Art Method
Authors: Bhowmik Samir , Parikka Jussi
Published: December 2020

Through the Memory Machines performance tour conducted in a public library, the authors analyze multisensory methods including immersive performance and walking tours as probes into cultural infrastructures. Combining discussions of media theory and artistic practice, including collaboration with the 00100 Ensemble, the authors present infrastructural performance as an art method for creative infrastructural research.
Breaking the Circuit: Encountering Media’s Entanglements with Environment and Behavior through an Energy Art Practice
Authors: Bhowmik Samir
Published: December 2020

Uncovering and exhibiting digital media’s entanglements with energy, behavior and environment through artistic practice has been a decade-long quest for the author. Through three art projects the author describes his experiments with the energy consumption of media, lithium battery recycling, the Cloud and network connectivity. Arguing for critical artistic approaches, the author examines concerns of ecology and behavior as investigated by installation, by workshop, and by community participation, together forming an energy art practice.
Crypto Art: A Decentralized View
Authors: Franceschet Massimo , Colavizza Giovanni , Smith T’ai , Finucane Blake , Ostachowski Martin Lukas , Scalet Sergio , Perkins Jonathan , Morgan James , Hernández Sebastián
Published: December 2020

Crypto art is limited-edition digital art, cryptographically registered with a token on a blockchain. Tokens represent a transparent, auditable origin and provenance for a piece of digital art. Blockchain technology allows tokens to be held and securely traded without the involvement of third parties. Crypto art draws its origins from conceptual art—sharing the immaterial and distributive nature of artworks, the tight blending of artworks with currency and the rejection of conventional art markets and institutions. The authors propose a collection of viewpoints on crypto art from different actors within the system: artists, collectors, gallerists, art historians and data scientists. A set of emerging themes and open challenges surfaces.
A Neural Network Looks at Leonardo’s(?) Salvator
Mundi
Authors: Frank Steven J. , Frank Andrea M.
Published: December 2020

The authors use convolutional neural networks (CNNs) to analyze authorship questions surrounding the works of Leonardo da Vinci—in particular, Salvator Mundi, the world’s most expensive painting and among the most controversial. Trained on the works of an artist under study and visually comparable works of other artists, the authors’ system can identify likely forgeries and shed light on attribution controversies. Leonardo’s few extant paintings test the limits of the system and require corroborative techniques of testing and analysis.
Is There a Place in Human Consciousness Where Surveillance Cannot Go?Noor: A Brain Opera
Authors: Pearlman Ellen
Published: December 2020

Noor: A Brain Opera is the first fully interactive, immersive brainwave opera, in which a performer wearing a wireless EEG brainwave headset touches, gazes and walks around audience members in a 360° theater while a story is narrated. Her measured emotional states trigger videos, sound and a prerecorded libretto as her emotions are displayed as live time-colored bubbles. The opera rhetorically asks: “Is there a place in human consciousness where surveillance cannot go?” This article discusses the rationale and implementation of the brainwave opera.
Tracking the Loving Gaze
Authors: Stylianou-Lambert Theopisti , Panayides Omiros
Published: December 2020

Tracking the Loving Gaze is a futile attempt to follow, map and capture the way cherished personal photographs are viewed. The authors asked 30 survey subjects to use an eye tracker while looking at a preselected photograph that held a special meaning for them. The raw visual data from this process—heat maps, focus maps and scan paths—became the foundation of a body of work that includes darkroom prints, short videos and a limited-edition artist book. Apart from exploring the invisible viewing processes of personal photography, this article introduces the concepts of the detached and the invested viewer as well as the corresponding concepts of the cold and the loving gaze.
The Missing Female Homunculus
Authors: Wright Haven , Foerder Preston
Published: December 2020

The somatosensory homunculus shows an exaggerated human figure that illustrates the proportion of the brain devoted to the sense of touch in each part of the body. Originally based on Wilder Penfield’s brain mapping, it has been presented as a drawing of a human figure along the somatosensory cortex, an independent human figure and a sculpted figure. Until recently, these homunculi have been male due to the lack of information on the female somatosensory cortex. A few female homunculi have been drawn. Based on more current brain research, the authors present, to their knowledge, the first sculpted 3D female somatosensory homunculus.