bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the Lateral Orbital “C-Angle” With Calcium Hydroxylapatite: An Anatomic and Clinical Study
Authors: Alghoul Mohammed S , Vaca Elbert E , Bricker Jonathan T , Mioton Lauren M
Published: July 2020

Background

Deliberate injection of specific facial subunits may improve aesthetic outcomes in facial rejuvenation. We contend that the lateral orbital area (LOA) is a key anatomic subunit in the perception of eye attractiveness, with a C-shaped distribution of fat contributing to the formation of a distinct angle in the lateral orbit.

Objectives

The aim of this study was to describe the anatomy of the LOA that constitutes the C-shaped angle and to investigate the safety and cosmetic outcomes of nonsurgical enhancement of that area with calcium hydroxylapatite (CaHA).

Methods

Four injected fresh-frozen cadaver heads were dissected. Twenty patients were enrolled in a prospective clinical study. Participants were seen on the day of injection, and at 2 weeks and 3 months postinjection. Two-dimensional and 3D photographs were analyzed to quantify the volumetric changes between pretreatment and postinjection time points. Secondary outcomes included Global Aesthetic Improvement Scale score and subject satisfaction at 3 months.

Results

Cadaver dissections revealed distinct fat compartments and a zone of adhesion forming the C-shaped area around the lateral orbit. In the clinical study, a mean of 1.88 mL of CaHA was injected into each lateral periorbital region. There was 97% and 76% volume retention at 2 weeks and 3 months, respectively, with 70% of patients being “very satisfied” at 3 months. The average Global Aesthetic Improvement Scale rating at 3 months was 3.95. There were no complications.

Conclusions

The LOA is a distinct facial subunit that can be enhanced safely by CaHA injection with good cosmetic outcomes. Focusing on the C-angle can improve periorbital aesthetics.

Level of Evidence: 4
“Myocardial inflammatory changes before and after antiretroviral therapy initiation in people with advanced HIV disease”
Authors: Piñeirua-Menéndez A , Flores-Miranda R , Sánchez-Nava D , Ortega-Pérez R , Belaunzaran-Zamudio P F , Pérez-Patrigeon S , Cárdenas-Ochoa A , Oseguera-Moguel J , Galindo-Uribe J , Orihuela-Sandoval C , Vázquez-Ortiz Z , Vázquez-Lamadrid J , Morelos-Guzmán M , Rosales-Uvera S , Crabtree-Ramírez B , Sierra-Madero J
Published: July 2020

Because high frequency and late presentation of HIV disease in our population, we decided to explore the presence of myocarditis among people with HIV-infection and advanced immunosuppression (less than 200 CD4+ cells/μL), and to describe the inflammatory changes observed after combined antiretroviral therapy (cART) initiation in an observational, longitudinal, prospective cohort performing cardiovascular MRI (cMRI) and doppler trans-thoracic echocardiogram (TTE).
Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV
Authors: Danesh Ali , Ren Yanqin , Brad Jones R.
Published: July 2020

Purpose of review

‘Broadly neutralizing antibodies’ (bNAbs), are rare HIV-specific antibodies which exhibit the atypical ability to potently neutralize diverse viral isolates. While efforts to elicit bNAbs through vaccination have yet to succeed, recent years have seen remarkable preclinical and clinical advancements of passive immunization approaches targeting both HIV prevention and cure. We focus here on the potential to build upon this success by moving beyond neutralization to additionally harness the diverse effector functionalities available to antibodies via fragment crystallizable-effector (Fc) functions.

Recent findings

Recent studies have leveraged the ability to engineer bNAb Fc domains to either enhance or abrogate particular effector functions to demonstrate that activities such as antibody-dependent cell-mediated cytotoxicity contribute substantially to in-vivo antiviral activity. Intriguingly, recent studies in both nonhuman primates and in humans have suggested that passive bNAb infusion can lead to durable immunity by enhancing virus-specific T-cell responses through a ‘vaccinal effect’.

The combination of antibody engineering strategies designed to enhance effector functions, with the broad and potent antigen recognition profile of bNAbs, has the potential to give rise to powerful new therapeutics for HIV. We aim to provide a timely review of recent advances to catalyze this development.
Galectin-3, IL-1A, IL-6, and EGF Levels in Corneal Epithelium of Patients With Recurrent Corneal Erosion Syndrome
Authors: Candar Tuba , Asena Leyla , Alkayid Husamadden , Altınörs Dilek D.
Published: July 2020

Purpose:

To determine the galectin-3 (Gal3), interleukin-1 (IL-1), interleukin-6 (IL-6), and epidermal growth factor (EGF) levels in corneal epithelium of patients with recurrent corneal erosion (RCE) syndrome and compare them with healthy controls.

Methods:

In this prospective interventional case control study, 32 eyes of 32 patients with RCE syndrome who had corneal epithelial erosions and 28 eyes of 28 healthy participants scheduled for photorefractive keratectomy (control group) were included. Exclusion criteria included corneal dystrophies, ectasia, dry eye, previous ocular surgery or topical medications, and systemic diseases. Epithelial samples were obtained during epithelial debridement in the study group and mechanical epithelial keratectomy in the control group. Galectin-3 levels were studied by the chemiluminescent microparticle immunoassay method. IL-1, IL-6, and EGF levels were determined using corresponding ELISA kits.

Results:

The median Gal3 levels were 132.25 ng/mL in the study group and 106.50 ng/mL in the control group. The median IL-1 and IL-6 levels were 6.24 pg/mL and 10.16 pg/mL, respectively, in the study group which were higher than that in the control group. The median EGF level in the study group was lower than that the control group with 1.30 pg/mL versus 2.67 pg/mL. In the control group, there was a significant positive correlation between EGF and IL-6 (r = 0.554; P = 0.040). A similar correlation was not observed in patients with RCE (r = −0.071; P = 0.794).

Conclusions:

The lack of increased EGF expression and the imbalance between growth factors, adhesion molecules, and interleukins may be the reason for the impaired wound healing response in RCE syndrome.
Complications and Management of Prestripped Descemet Membrane Endothelial Keratoplasty Grafts
Authors: Gadhvi Kunal A. , Pagano Luca , Parekh Mohit , Levis Hannah J. , Romano Vito
Published: July 2020

Prestripped Descemet membrane endothelial keratoplasty is a relatively new technique that offers advantages in reduced surgical time and reduced tissue wastage compared with surgeon-stripped graft. Here, we report the following 2 types of prestripped Descemet membrane endothelial keratoplasty graft complications and their management: 1 free floating in the transport media and the other graft mispositioned.
Diagnostic Criteria for Terrien Marginal Degeneration: Nordic Terrien Degeneration Study
Authors: Ruutila Minna , Fagerholm Per , Lagali Neil , Hjortdal Jesper , Bram Thue , Moilanen Jukka , Kivelä Tero T.
Published: July 2020

Purpose:

To refine the diagnostic criteria for Terrien marginal degeneration (TMD) based on experience in 3 Nordic countries.

Methods:

This is a retrospective, multicenter, hospital-based cross-sectional study of 49 eyes of 29 white patients in tertiary referral centers in Finland, Sweden, and Denmark from 1998 to January 2018. The median follow-up was 3 years. Symptoms, best corrected visual acuity, astigmatism, corneal thickness, curvature and cavities, stage, and progression were analyzed.

Results:

TMD was diagnosed equally likely between 15 and 86 years of age (median, 47 years). Twenty patients (69%) had bilateral disease, and 62% were men. Seventeen patients (59%) had symptoms including blurred vision and ocular surface disease symptoms without inflammatory signs. Eight patients (28%) had slightly reduced corneal sensitivity. Median best corrected visual acuity was 20/25 (range, 20/16–20/200) and astigmatism was 2.6 diopters (D) (range, 0–10) with a mean progression of 0.41 D per year (range, 0–5.4). Age and astigmatism were not correlated. All eyes had peripheral vascularization, lipid deposits, and hyperreflectivity throughout thinned peripheral stroma and its anterior edge. The thinning progressed in 15 patients (52%). Of 26 patients, 8 (31%) had single or confluent paralimbal intrastromal cavities, most commonly superiorly. By Süveges classification, the stage was 2 (92%) or 3 (8%). Minimum corneal thickness and corneal curvature were loosely associated, leading to different stages in Wang classification in 34 eyes (69%).

Conclusions:

TMD is defined by peripheral corneal thinning, superficial neovascularization, lipid deposition at the leading edge, absence of ulceration and inflammation, and frequently cavitation. The most sensitive way to follow its progression is anterior segment optical coherence tomography.
Assessment of Long-Term Anterior and Posterior Topographic Changes in the Cornea After Ptosis Surgery Using Fourier Harmonic Analysis
Authors: Yamamoto Risako , Ono Takashi , Toyono Tetsuya , Shirakawa Rika , Noda Mika , Yoshida Junko , Miyai Takashi
Published: July 2020

Purpose:

We aimed to assess the corneal refractive changes induced by ptosis surgery in patients with acquired ptosis using Fourier harmonic analysis.

Methods:

This retrospective observational study enrolled consecutive patients who underwent levator aponeurotic surgery for acquired ptosis at the Department of Ophthalmology in the University of Tokyo Hospital from May 2016 to January 2018. Best corrected visual acuity, central corneal thickness, average keratometric corneal power (AvgK), corneal astigmatism, and topographic data using Fourier analysis were analyzed preoperatively and 6 months postoperatively.

Results:

Thirty-two eyes of 32 patients (age, 72.6 ± 8.5 years) were included in this study. There were no significant differences in best corrected visual acuity and central corneal thickness. However, there were significant decreases in anterior AvgK, anterior corneal astigmatism, and posterior corneal astigmatism 6 months postoperatively (all, P < 0.001). Fourier harmonic analysis showed that the anterior spherical component significantly decreased 6 months postoperatively (P < 0.001). There were no significant differences in other components of the anterior and posterior cornea. There was a significant negative correlation between preoperative posterior AvgK and changes in posterior AvgK (r = −0.891, P < 0.001) and between preoperative posterior corneal astigmatism and changes in posterior corneal astigmatism at 6 months (r = −0.858, P < 0.001).

Conclusions:

Anterior and posterior corneal keratometry and posterior corneal astigmatism significantly changed 6 months after ptosis surgery for acquired ptosis.
The Effect of the Coronavirus Pandemic on Physician Assistant Educators
Authors: Neary Stephanie , Van Rhee James , Roman Christopher
Published: July 2020

Purpose

The coronavirus (COVID-19) pandemic has presented physician assistant (PA) educators with unprecedented challenges in delivering content remotely with minimal time to develop new pedagogical strategies. We surveyed faculty about their experience during the early weeks of adapting to these new instructional techniques.

Methods

An anonymous quantitative and qualitative survey was distributed to all individuals registered by programs as Physician Assistant Education Association members.

Results

The survey response rate was 22.3% (667/2991) with 32% of program directors (PD), and 23.7% of faculty reporting they had taught online synchronous content prior to COVID-19 adaptations. Prior experience with technology was associated with significantly lower levels of faculty stress during the pivot to online instruction. A majority of the respondents felt educational quality had remained consistent despite the transition to online teaching, and a majority of both faculty and program directors anticipate only minor changes to program structure once they are able to return to traditional classroom learning. Concerns about technology were most commonly cited as stressors and as causes of decreased quality of instruction.

Conclusion

Educational challenges and stress during the pandemic were most prominently associated with unfamiliar technology. It remains to be seen what changes persist when the pandemic subsides.
Recent advances in the treatment of uremic pruritus
Authors: Trachtenberg Aaron J. , Collister David , Rigatto Claudio
Published: July 2020

Purpose of review

This article provides a focused update on uremic pruritus, highlighting the latest evidence concerning the epidemiology, pathophysiology, and treatment options for this common and bothersome condition.

Recent findings

Half of dialysis patients and a quarter of those with nondialysis chronic kidney disease experience bothersome itch that reduces quality of life and is increasingly recognized to be associated with poor outcomes including mortality. The KALM-1 trial, which reported effective symptomatic relief with difelikefalin, has bolstered support for the role of an imbalance of μ and κ-opioid receptor activity in pruritogenesis. The role of a chronic inflammatory state, increased cytokine levels and altered immune signaling in pruritogenic nerve activation continues to be elucidated with basic science, which paves the wave for future novel therapeutics. In the meantime, gabapentin appears to be the most evidence-based widely available uremic pruritus treatment, as long as care is taken with dosing and monitoring of side-effects.

Uremic pruritus remains a top research priority. Patients with uremic pruritus may be able to look forward to a new decade of understanding, knowledge, and novel treatment options for this burdensome condition. As difelikefalin and other potential agents come to market, cost-effectiveness assessments of these interventions will help determine if the widespread use of them is feasible amongst renal programs.
Molecular and functional characteristics of megakaryocytes and platelets in aging
Authors: Esparza Orlando , Higa Kelly , Davizon-Castillo Pavel
Published: July 2020

Purpose of review

Advances in medical care and preventive measures have contributed to increasing life expectancy. Therefore, it is critical to expand our understanding of the physiological and pathophysiological adaptations of the hematological system in aging. We highlight and review the findings from recent investigations aimed at understanding the effects of aging on megakaryocytes and platelets.

Recent findings

Biochemical and transcriptomic studies of megakaryocytes and platelets from older humans and mice have advanced our understanding of the molecular and functional characteristics of megakaryocytes and platelets during aging. These studies have led to the identification of metabolic and inflammatory pathways associated with the generation of hyperreactive platelets that may significantly contribute to the high incidence of thrombosis in aging.

By increasing our research efforts to understand and identify the characteristics of megakaryocytes and platelets in aging, we will increase our potential to develop novel therapies aimed at decreasing the incidence of aging-associated thrombosis. These efforts will also serve as a foundation to better understand the role of megakaryocytes and platelets in other age-related hematological conditions with high thrombotic risk such as clonal hematopoiesis of indeterminate potential and myeloproliferative neoplasms.
Insurance Denials in Reduction Mammaplasty: How Can We Serve Our Patients Better?
Authors: Boukovalas Stefanos , Boson Alexis L. , Padilla Pablo L. , Sljivich Michaela , Tran Jacquelynn P. , Spratt Heidi , Phillips Linda G.
Published: July 2020

Background:

Reduction mammaplasty is the standard of care for symptomatic macromastia. The process of requesting insurance coverage for reduction mammaplasty is cumbersome and potentially controversial, and insurance policies vary significantly. The goal of our analysis is to identify trends in insurance coverage rates, assess for the presence of disparities, and propose ways to increase chances of successful preauthorization.

Methods:

The authors performed a retrospective review of preauthorizations for reduction mammaplasty at a single institution from 2012 to 2017. Insurance company names were deidentified. Preauthorization denial rates were assessed by year, insurance carrier, and reason for denial. Multiple regression analysis was performed to identify predictors for predetermination denial by insurance companies.

Results:

Among 295 preauthorizations, 212 were approved (72 percent) and 83 were denied (28 percent), among which 18 were appealed, 13 successfully. Rates of insurance denials have been increasing steadily, from 18 percent to 41 percent. Medicaid had the lowest denial rates (9.3 percent), whereas private carriers denials ranged from 21.4 to 62.1 percent. In terms of reason for denial, 30 percent were because of contract exclusion, 39 percent were because of inadequate documentation or not meeting medical criteria, and 12 percent were because of inadequate predicted resection weight. Certain private insurance carriers were the only independent predictors of predetermination denial.

Conclusions:

Rate of preauthorization denials is high and has been increasing steadily. Insurance criteria remain arbitrary. A proper documentation and appeal process by the plastic surgeon may improve rates of insurance approval. Although resection weight does not correlate with symptom relief, predicted breast tissue resection weight continues to be critical for insurance approval.
Oncologic Safety and Surveillance of Autologous Fat Grafting following Breast Conservation Therapy
Authors: Hanson Summer E. , Kapur Sahil K. , Garvey Patrick B. , Hernandez Mike , Clemens Mark W. , Hwang Rosa F. , Dryden Mark J. , Butler Charles E.
Published: July 2020

Background:

Autologous fat grafting is a useful adjunct following breast reconstruction. The impact of autologous fat grafting on oncologic safety and surveillance remains questionable, particularly following breast conservation therapy.

Methods:

The authors performed a retrospective review of patients who underwent delayed fat grafting following breast conservation therapy between 2006 and 2016. A control group of conservatively managed patients without grafting was matched for cancer stage, age, body mass index, and follow-up. Outcomes included locoregional recurrence and oncologic surveillance.

Results:

Seventy-two patients were identified per cohort. There were no differences in median age (50 years versus 51 years; p = 0.87), body mass index (28.2 kg/m2 versus 27.2 kg/m2; p = 0.38), or length of follow-up (61.9 months versus 66.8 months; p = 0.144) between controls and grafted patients, respectively. Overall, four patients in each cohort experienced recurrence (5.6 percent; p = 1.00) with similar cumulative incidence estimates observed (log-rank test, p = 0.534). There were no significant differences in palpable mass (9.7 percent versus 19.4 percent; p = 0.1), fat necrosis (34.7 percent versus 33.3 percent; p = 0.86), calcifications (37.5 percent versus 34.7 percent; p = 0.73), or indication for breast biopsy (15.3 percent versus 22.2 percent; p = 0.23) between breast conservation and breast conservation therapy plus autologous fat grafting cohorts, respectively.

Conclusions:

Overall, the authors found no difference in recurrence rates after breast conservation with or without delayed fat grafting. Furthermore, there were no differences in the rates of fat necrosis, palpable mass, and abnormal radiographic findings. This study represents the longest follow-up to date in in a large matched study of autologous fat grafting with breast conservation therapy demonstrating oncologic safety and no interference with follow-up surveillance.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Male Aesthetics for the Gluteal Area: Anatomy and Algorithm for Surgical Approach for Dynamic Definition Body Contouring
Authors: Hoyos Alfredo E. , Perez Mauricio E. , Domínguez-Millán Rodrigo
Published: July 2020

Background:

Gluteal prominence is a unique characteristic that is widely acknowledged in female contouring but ignored in the male population. This study focuses on male gluteal aesthetics based on a muscular anatomical approach.

Methods:

A retrospective review of gluteal contouring in men from January of 2012 to September of 2019 was conducted. Male body sculpting surgery in the gluteal area was performed in most cases. Patients were included according to preoperative assessment and the American Heart Association risk analysis. The gluteal area was divided into four main anatomical contouring zones and classified according to the procedure type. The follow-up period of 3 months to 6 years was included with photographs and medical assessment data. A nonstandardized satisfaction survey was performed postoperatively.

Results:

The analysis included data from 374 consecutive gluteal dynamic definition liposculptures performed in men (mean age, 38.2 years; range, 20 to 66 years). Patients were treated according to the authors’ new classification of deformities. Fat extraction, liposhifting, and fat grafting were performed on a regular basis to enhance and define the gluteal area. A satisfaction index of 92.5 percent was reported. Minor complications were reported: seroma, 0.2 percent; prolonged bruising, 1.3 percent; and swelling, 1.8 percent. No necrosis, burns, or infections were reported.

Conclusions:

Men have been increasingly requesting improvement and definition of the buttocks, and our novel algorithm allows for a reliable method in this regard. The high satisfaction index supports the natural and athletic results accomplished with our new approach.
Individual Variation in Pain Sensitivity and Implicit Negative Bias Toward Pain
Authors: Ye Qian , Li Xiaoyun , Peng Weiwei
Published: July 2020

Objective

Although previous studies have shown the linkage between pain sensitivity and pain-related cognitions, this study investigated whether individual variation in pain sensitivity is related to implicit negative bias toward pain.

Methods

Two groups of participants with low (LPS) or high (HPS) pain sensitivity (LPS group:n= 33; HPS group:n= 31) were recruited based on their scores on pain sensitivity questionnaires. This categorization was later confirmed via pain ratings to electrical stimulations. Implicit negative bias toward pain was assessed using the Implicit Association Test (IAT) involving target (pain and nonpain) and attribute (negative and neutral-affect) concept words. Behavioral and event-related potential responses for congruent and incongruent pairings during the IAT were compared between the LPS and HPS groups.

Results

Relative to the LPS group, participants in the HPS group exhibited greater D-score (Cohen’sd= 0.364,p= .004). Event-related potential results showed that, although P3 amplitudes to congruent and incongruent pairings differed significantly for the HPS group (Cohen’sd= 0.757,p< .001), this difference was not observed for the LPS group (Cohen’sd= 0.089,p= .29). Mediation analysis further revealed that the IAT effect on P3 responses accounted for 17.58% of the association between pain sensitivity and D-score (confidence interval = [0.009–0.051]).

Conclusions

Individual variation in pain sensitivity relates to implicit negative bias. This linkage is partially accounted for by the electrophysiological response that has been related to cognitive process of stimulus evaluation and categorization. Pain treatment might benefit from techniques designed to alter implicit bias.
Emergency Department Management of Recent-Onset Atrial Fibrillation
Authors: Weant Kyle A. , Matuskowitz Andrew J. , Gregory Haili , Caporossi Jeffrey , Hall Gregory A.
Published: July 2020

Atrial fibrillation (AF) is the most common tachyarrhythmia managed in the emergency department (ED). Visits to the ED for a presentation of AF have been increasing in recent years, with an admission rate that exceeds 60% in the United States and contributes substantially to health care costs. Recent-onset AF—defined as symptom onset less than 48 hr—is a common ED presentation for which rate control or acute electrical or pharmacological cardioversion may be appropriate treatment modalities depending on patient-specific circumstances. The focus of this review is to discuss the current recommendations regarding the management of recent-onset nonvalvular AF in the ED, discuss medication administration considerations, and identify implementation strategies in the ED to optimize throughput and reduce hospital admissions.
Collaboration during a crisis – the Lighthouse Lab volunteers
Authors: Ulhuq Fatima R. , Berry Sophia K. , Kelly Lucy , Stansfield Ben , Deal Anna , Lester Harriet
Published: July 2020

As a group of early-career researchers, we recount our experiences of volunteering at one of the national Lighthouse Labs based at the UK Biocentre in Milton Keynes. We worked together as part of a multidisciplinary team to support the large-scale processing of coronavirus disease 2019 (COVID-19) swabs from across the whole of the UK.
Three-Dimensional Label-Free Imaging and Quantification of Migrating Cells during Wound Healing
Authors: Lee A. J. , Hugonnet H. , Park W.S. , Park Y.K.
Published: July 2020

The wound healing assay provides essential information about collective cell migration and cell-to-cell interactions. It is a simple, effective, and widely used tool for observing the effect of numerous chemical treatments on wound healing speed. To perform and analyze a wound healing assay, various imaging techniques have been utilized. However, image acquisition and analysis are often limited in two-dimensional space or require the use of exogenous labeling agents. Here, we present a method for imaging large-scale wound healing assays in a label-free and volumetric manner using optical diffraction tomography (ODT). We performed quantitative high-resolution three-dimensional (3D) analysis of cell migration over a long period without difficulties such as photobleaching or phototoxicity. ODT enables the reconstruction of the refractive index (RI) tomogram of unlabeled cells, which provides both structural and biochemical information about the individual cell at subcellular resolution. Stitching multiple RI tomograms enables long-term (24 h) and large field-of-view imaging (> 800 × 400 μm2) with a lateral resolution of 110 nm. We demonstrated the thickness changes of leading cells and studied the effects of cytochalasin D. The 3D RI tomogram also revealed increased RI values in leading cells compared to lagging cells, suggesting the formation of a highly concentrated subcellular structure.

STATEMENT OF SIGNIFICANCE

The wound healing assay is a simple but effective tool for studying collective cell migration (CCM) that is widely used in biophysical studies and high-throughput screening. However, conventional imaging and analysis methods only address two-dimensional properties in a wound healing assay, such as gap closure rate. This is unfortunate because biological cells are complex 3D structures, and their dynamics provide significant information about cell physiology. Here, we presented three-dimensional (3D) label-free imaging for wound healing assays and investigated the 3D dynamics of CCM. High-resolution subcellular structures as well as their collective dynamics were imaged and analyzed quantitatively. Our label-free quantitative 3D analysis method provides a unique opportunity to study the behavior of migrating cells during the wound healing process.
Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naïve Children: Results from the ABCD Study
Authors: Hatoum Alexander S. , Johnson Emma C. , Baranger David A.A. , Paul Sarah E. , Agrawal Arpana , Bogdan Ryan
Published: July 2020

In substance naïve children (n=3,013), polygenic risk score (PRS) for problematic alcohol use was associated with lower volume of the frontal pole and greater cortical thickness of the supramarginal gyrus. Several other areas showed nominal significance. These associations suggest that genetic liability to alcohol involvement may manifest as variability in brain structure prior to consumption of the first alcoholic drink and alter brain morphometry during the start of adolescence.
An antibody-dependent enhancement (ADE) activity eliminated neutralizing antibody with potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys
Authors: Wang Shuang , Peng Yun , Wang Rongjuan , Jiao Shasha , Wang Min , Huang Weijin , Shan Chao , Jiang Wen , Li Zepeng , Gu Chunying , Chen Ben , Hu Xue , Yao Yanfeng , Min Juan , Zhang Huajun , Chen Ying , Gao Ge , Tang Peipei , Li Gang , Wang An , Wang Lan , Chen Shuo , Gui Xun , Zhang Jinchao , Yuan Zhiming , Liu Datao
Published: July 2020

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, showing high SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity was eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Most importantly, potent prophylactic and therapeutic effects against SARS-CoV-2 were observed in rhesus monkeys. A single dose of MW05/LALA completely blocked the infection of SARS-CoV-2 in a study of its prophylactic effect and totally cleared SARS-CoV-2 in three days in a treatment setting. These results pave the way for the development of MW05/LALA as an effective strategy for combating COVID-19.
Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection
Authors: Liu Yaobin , Mukherjee Rukmini , Bonn Florian , Colby Thomas , Matic Ivan , Glogger Marius , Heilemann Mike , Dikic Ivan
Published: July 2020

SidE family ofLegionellaeffectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) of host proteins during bacterial infection. SdeA localizes predominantly to ER and partially to the Golgi apparatus, and mediates serine ubiquitination of multiple ER and Golgi proteins. Here we show that SdeA causes disruption of Golgi integrity due to its ubiquitin ligase activity. The Golgi linking proteins GRASP55 and GRASP65 are PR-ubiquitinated on multiple serine residues, thus preventing their ability to cluster and form oligomeric structures. In addition, we found that the functional consequence of Golgi disruption is not linked to the recruitment of Golgi membranes to the growingLegionella-containing vacuoles. Instead, it affects the secretory pathway, including cytokine release in cells. Taken together, our study sheds light on the Golgi manipulation strategy by whichLegionellahijacks the secretory pathway and promotes bacterial infection.
Ebselen Exhibits Antimicrobial Activity AgainstClostridioides difficileBy Disrupting Redox Associated Metabolism
Authors: Marreddy Ravi K.R. , Olaitan Abiola O. , May Jordan N. , Dong Min , Hurdle Julian G.
Published: July 2020

High recurrence rates and spread of antibiotic-resistant strains necessitate the need for alternative therapeutics forClostridioides difficileinfections (CDIs). Ebselen, a reactive organoselenium compound inhibitsC. difficilevirulence toxins TcdA and TcdB, by covalently binding to their cysteine protease domains. Ebselen is thought to lack antibacterial activity againstC. difficilecells and its anti-toxin action is suggested to be solely responsible for its efficacy. However,C. difficilehas several essential cysteine-containing enzymes that could be potential sites for covalent modification by ebselen; hence, we re-evaluated its anti-C. difficileproperties. In BHI agar, ebselen inhibited almost allC. difficilestrains (MICs of 2-8 µg/ml), with ribotype 078 being intrinsically resistant (MIC>64 µg/ml). Wilkins-Chalgren and Brucella agars are recommended media for anaerobic susceptibility testing. Ebselen was either slightly attenuated by pyruvate found in Wilkins-Chalgren agar or obliterated by blood in Brucella agars. Transcriptome analysis showed ebselen altered redox-associated processes, cysteine metabolism and significantly enhanced the expression of Stickland proline metabolism to likely regenerate NAD+from NADH. Intracellularly cells increased the uptake of cysteines, depleted non-protein thiols and disrupted NAD+/NADH redox ratio. Growth inhibitory concentrations of ebselen also reduced toxin and spore production. Taken together, ebselen has bactericidal activity againstC. difficile, with multiple mechanisms of action that negatively impacts toxin production and sporulation. To harness the polypharmacological properties of ebselen, chemical optimization is warranted, especially to obtain derivatives that could be effective in severe CDI, where intestinal bleeding could occur.
Impact of lossy compression of X-ray projections onto reconstructed tomographic slices
Authors: Marone Federica , Vogel Jakob , Stampanoni Marco
Published: July 2020

Modern detectors used at synchrotron tomographic microscopy beamlines typically have sensors with more than 4–5 mega-pixels and are capable of acquiring 100–1000 frames per second at full frame. As a consequence, a data rate of a few TB per day can easily be exceeded, reaching peaks of a few tens of TB per day for time-resolved tomographic experiments. This data needs to be post-processed, analysed, stored and possibly transferred, imposing a significant burden onto the IT infrastructure. Compression of tomographic data, as routinely done for diffraction experiments, is therefore highly desirable. This study considers a set of representative datasets and investigates the effect of lossy compression of the original X-ray projections onto the final tomographic reconstructions. It demonstrates that a compression factor of at least three to four times does not generally impact the reconstruction quality. Potentially, compression with this factor could therefore be used in a transparent way to the user community, for instance, prior to data archiving. Higher factors (six to eight times) can be achieved for tomographic volumes with a high signal-to-noise ratio as it is the case for phase-retrieved datasets. Although a relationship between the dataset signal-to-noise ratio and a safe compression factor exists, this is not simple and, even considering additional dataset characteristics such as image entropy and high-frequency content variation, the automatic optimization of the compression factor for each single dataset, beyond the conservative factor of three to four, is not straightforward.
Crystal structure of the FYCO1 RUN domain suggests possible interfaces with small GTPases
Authors: Sakurai Shunya , Shimizu Toshiyuki , Ohto Umeharu
Published: July 2020

FYCO1 is a multidomain adaptor protein that plays an important role in autophagy by mediating the kinesin-dependent microtubule plus-end-directed transport of autophagosomes. FYCO1 contains a RUN domain, which is hypothesized to function as a specific effector for members of the Ras superfamily of small GTPases, but its role has not been well characterized and its interaction partner(s) have not been identified. Here, the crystal structure of the FYCO1 RUN domain was determined at 1.3 Å resolution. The overall structure of the FYCO1 RUN domain was similar to those of previously reported RUN domains. Detailed structural comparisons with other RUN domains and docking studies suggested a possible interaction interface of the FYCO1 RUN domain with small GTPases of the Ras superfamily.
Adoption of principle-based IFRS and intercompany comparability of operating performance
Authors: Ghosh Protap Kumar , Bairagi Ranajit Kumar , Mondal Abinash
Published: July 2020

Purpose

The study aims to investigate whether the adoption of IFRS could ensure ultimate intercompany comparability of operating performance in terms of uniformity in the application of accounting methods and reporting style.

Design/methodology/approach

Using content analysis on 125 annual financial statements of 25 companies from five industries listed on the Dhaka Stock Exchange in Bangladesh, this study reports that only the sole adoption and application of principle based IFRS cannot ensure ultimate intercompany comparability of financial reports.

Findings

The findings document that the adoption of IFRS cannot ensure the application of same accounting methods as well as way of presentations which is a precondition of greater comparability of operating performance of competitive firms. The methodological and reporting direction through local regulatory agencies alongside maximum compliance with principle based IFRS can enhance intercompany comparability of financial reports in the same industry.

Originality/value

This study tries to manifest that sole adoption cum implementation of IFRS could not ensure ultimate intercompany comparability of operating performance within the same industry and urges to conduct further research to find out the ways to do so.
Moderation-mediation framework connecting internal branding, affective commitment, employee engagement and job satisfaction: an empirical study of BPO employees in Indian context
Authors: Kaur Prabhjot , Malhotra Keshav , Sharma Sanjeev K.
Published: July 2020

Purpose

Taking an evidence from social exchange theory, this research examines the mediating role of affective commitment in the correlation between internal branding, employee engagement and job satisfaction. The moderating role of work environment on the link between internal branding and affective commitment is also studied in this research.

Design/methodology/approach

The data were collected by using well-structured research measures from 215 employees working in the BPO sector of India (Punjab and Chandigarh). The hypotheses were developed, and the conceptual model was validated by applying structural equation modeling. The data were analyzed by using two statistical packages, namely SPSS and AMOS.

Findings

The findings suggest that internal branding has a significant positive relationship with employee engagement, job satisfaction and affective commitment. The mediating effect of affective commitment on the relationship between internal branding and employee engagement was full, whereas on the relationship between internal branding and job satisfaction, it was partial. Work environment also moderated the relationship of internal branding with affective commitment.

Research limitations/implications

The current study offers significant lessons to management thinkers, human resource (HR), organizational branding and marketing manager. However, BPO sector should be aware about the critical role played by internal branding to enhance affective commitment, employee engagement and job satisfaction of the employees. The role of affective commitment is also taken into account to study the effect of internal branding on employee engagement and employee's job satisfaction. For itself, internal branding cannot be considered as in isolation and is doubtful to be efficacious if the work environment is not encouraging to an employee as well as to the brand values.

Practical implications

This study offers significant lessons to management thinkers, HR, organizational branding and marketing manager. However, BPO sector should be aware about the critical role played by internal branding to enhance employee engagement, job satisfaction and affective commitment of the employees. An important role of affective commitment is also taken into account to study the effect of internal branding on employee engagement and employee's job satisfaction. For itself, internal branding cannot be considered as in isolation and is doubtful to be efficacious if employees are not provided an encouraging work environment.

Originality/value

Existing researches on internal branding are theoretical in nature and overlook the empirical impact of internal branding on employee engagement, job satisfaction and affective commitment from the BPO employees' perspective. The study also offers an empirical examination of potential mediator and moderator for internal branding.
Land contributions to the supernormal development of infrastructure in China
Authors: Yang Ge , Cen Shutian
Published: July 2020

Purpose

Over the past 20 years, China's infrastructure has developed at an extraordinary speed. The current literature mainly focuses on the effects of political incentives on the infrastructure. However, this paper indicates that the structural change of China's land regime is an important clue and that the supernormal development of China's infrastructure is an explicable result for that.

Design/methodology/approach

This paper theoretically proves that in a politically centralized and economically decentralized economic entity with a public land-ownership regime, the self-financing mechanism formed by local officials through regulation of the land-grant price is the primary factor that influences the optimal supply volume of infrastructure in a region, in addition to political and economic incentives, and whether the self-financing mechanism can be formed or not depends on the structure of a country's land regime, which can help to explain the difference between the development of infrastructure in China and that in other developing countries from a theoretical angle.

Findings

The paper suggests that the mode is facing an important transformation toward land reform and new-type urbanization construction, and the replication and promotion of China's experience in infrastructure construction are of further significance under the Belt and Road Initiative as it provides a method for helping developing countries to eliminate infrastructure bottlenecks.

Originality/value

Through the test of multinational panel data, the paper indicates that the structural change of China's land regime around 1990 had an overall effect on the supernormal development of infrastructure in China. The paper indicates that the “land-based development mode” of China's infrastructure indeed contributed to the supernormal development of infrastructure in China, but there are still some shortcomings in this mode.
South Africa’s COVID-19 lockdown dilemma
Authors: Ward Michael
Published: July 2020

Learning outcomes

The case presents a significant amount of information on the outbreak of COVID-19 and the expected impact on the economy. Although the case is necessarily concise, several links are given to the online articles and video material on which the case is based. This allows participants to deepen their knowledge of the virus and their understanding of its likely economic impact. To frame the discussion, several philosophies, ranging from Libertarianism to Marxism, are lightly expounded. Readers will need to consider divergent ideas; the sanctity of human life versus the monetary value of a life; the hysteria evoked by COVID-19 deaths versus the placid acceptance of an annual 66,000 deaths by another disease – TB; and the differential economic impact of the virus across extremes of inequality. Perhaps, the key issue relates to the skewness in the death rate: Should young people’s livelihood be sacrificed for a few old people about to die anyway? The case also illustrates the essence of a dilemma – a situation in which a difficult choice has to be made between two or more alternatives, especially ones that are equally undesirable.

Case overview/synopsis

In March 2020, South African President Cyril Ramaposa ordered a 21-day national “lockdown” to enable and enforce social distancing in an effort to slow the spread of the COVID-19. Many other countries had already taken similar steps, but in a country with 43,000 murders annually, South Africa’s response to only 11 COVID-19 deaths and 1,071 cases was both rapid and harsh. Schools, businesses, social areas and parks were closed. Medical emergencies, essential services and weekly grocery shopping were the only permissible activities. Two weeks after lockdown, there were 1,845 cases and 18 deaths, a far cry from the predicted 30,000 cases and 300 deaths, estimated on the basis of the three-day doubling rate at the start of lockdown. Many businesses, pulverised by closure, daily wage earners and those fearful of losing jobs were hopeful that the lockdown would not be extended. In a country with immense inequality, how would the masses under the age of 65 years, already in poverty and now with their lives pulled apart by an imported disease of the wealthy, respond to extended social and economic deprivation followed by bailouts for business?

Complexity academic level

MBA and Executive Education

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS: 11 Strategy.
Eskom’s COVID-19 force majeure
Authors: Ward Michael
Published: July 2020

Learning outcomes

The case describes the fall of Eskom, which in 2001 was named the Financial Times’ Power Company of the Year, but by 2019 was suffering from “systemic corruption, malfeasance, fraud and state capture” that had “compromised the credibility of the organisation and eroded investor confidence”. Eskom’s incompetent management lays the ground for reasonable doubt as to whether the force majeure notice was indeed irresistible. The case suggests several methods available in financial markets to hedge risk – but to what extent are these relevant and appropriate? The main objective of the case, however, is to examine and assess the criteria required to claim force majeure. Two aspects are questionable: Was the virus unforeseeable and was it irresistible? Eskom is “bleeding” R2.5m per month because of significantly reduced electricity demand, and while it clearly benefits Eskom to break their supply contract, the consequences for Exxaro are far more dire. And, if carried to conclusion, how would such actions impact the entire economy?

Case overview/synopsis

In April 2020 South Africa’s stated-owned electricity utility Eskom sent a pre-cautionary force-majeure notification to Exxaro Limited’s Grootegeluk Coal Mine. The notification, citing COVID-19 as an unforeseeable, external and irresistible event, would have disastrous consequences for the mine’s 25 m tonnes pa coal contract to supply Eskom’s Medupi power station. Not only was the legality of the force-majeure questionable, it was unethical, and not in the spirit of President Ramaposa’s call to businesses to continue paying contractors. The case briefly describes Eskom’s troubled history following South Africa’s 1994 democratic election. It examines the force majeure clause common in contracts, and questions whether COVID-19 meets the criteria of an “unforeseeable, external and irresistible” event.

Complexity academic level

MBA and Executive Education

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 7: Management Science.