bluuebunny/crossref_metadata_2025 huggingface dataset:
The Profile and Role of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: An Immunohistochemical Study
Authors: El-Rebey Hala S. , Abdou Asmaa G. , Sultan Mervat M. , Ibrahim Shymaa H. , Holah Nanis S.
Published: August 2020

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Tumor-infiltrating lymphocytes (TILs) are a class of cells that form the tumor microenvironment and thus have an effect on carcinogenesis. The aim of this study was to investigate the immunohistochemical expression of CD8, CD4, cytotoxic T lymphocyte–associated protein-4 (CTLA-4), and granzyme B in HCC and their correlation with clinicopathologic parameters and prognosis. This study was carried out on 112 cases of HCC. High percentage of CD8+ TILs was associated with large tumors and adjacent noncirrhotic liver. High percentage of CD4+ TILs and high CD4 to CD8 ratio were associated with nonviral etiology, low alpha fetoprotein, and direct acting antiviral treatment. High percentage of CTLA-4-positive TILs tended to be associated with high-grade HCC, while a high percentage of CTLA-4 in tumor cells was associated with multiple lesions and low tumor grade. High percentage of granzyme B+ TILs was associated with low grade, early stage, and absence of tumor recurrence. High CD4 percentage and high CD4/CD8 ratio affected patients’ overall survival. There is a dynamic interaction between the different subsets of lymphocytes in the environment of HCC manifested by coparallel expression of CD4 and CD8 augmenting the expression of CTLA-4, and only CD8 augments the expression of granzyme B. This opens the gate for the beneficial role of immunotherapy in the management of HCC, reducing recurrence and improving survival.
Characteristics of Patients With Congenital Heart Disease Requiring ICU Admission From Japanese Emergency Departments*
Authors: Haga Taiki
Published: August 2020

Objectives:

To evaluate the characteristics of patients with congenital heart disease requiring ICU admission from emergency departments and determine the associations between the reasons for emergency department visits and specific congenital heart disease types or cardiac procedures.

Design:

Retrospective observational study using data from a Japanese multicenter database.

Setting:

Twelve PICUs and 11 general ICUs in Japan.

Patients:

All patients requiring ICU admission from an emergency department during 2013–2018, divided into two groups: with congenital heart disease and without congenital heart disease groups.

Interventions:

None for this analysis.

Measurements and Main Results:

Of the 297 patients with congenital heart disease (9.2% of a total of 3,240 patients), more than half had moderate-to-high complexity congenital heart disease; most of them were pediatric patients who had visited specialized congenital heart disease centers. All the patients’ clinical outcomes were similar. Regarding the reasons for emergency department admission, seizure was significantly associated with a single ventricle anatomy (odds ratio, 3.3; 95% CI, 1.1–10.0), post-Glenn shunt placement (odds ratio, 5.6; 95% CI, 1.1–29.4), and a Fontan-type operation status (odds ratio, 6.3; 95% CI, 1.5–25.5). Sepsis and gastrointestinal bleeding were associated with asplenia (odds ratio, 21.1; 95% CI, 4.3–104 and odds ratio, 21.0; 95% CI, 3.1–141, respectively); gastrointestinal bleeding was also associated with systemic-to-pulmonary artery shunt placement (odds ratio, 18.8; 95% CI, 2.8–125) and a Fontan-type operation status (odds ratio, 17.0; 95% CI, 2.6–112). Arrhythmia was associated with a single ventricle anatomy (odds ratio, 21.0; 95% CI, 3.1–141), systemic-to-pulmonary artery shunt placement (odds ratio, 18.8; 95% CI, 2.8–125), and a Fontan-type operation status (odds ratio, 17.0; 95% CI, 2.6–112).

Conclusions:

Classification of the reasons for emergency department admission by congenital heart disease type and surgical stage may guide clinicians in the selection of appropriate treatments in such settings.
Point-of-Care Ultrasound to Assess Gastric Content in Pediatric Emergency Department Procedural Sedation Patients
Authors: Moake Matthew M. , Presley Bradley C. , Hill Jeanne G. , Wolf Bethany J. , Kane Ian D. , Busch Carrie E. , Jackson Benjamin F.
Published: August 2020

Objectives

There is debate regarding the timing of procedural sedation and analgesia (PSA) in relation to fasting status. Point-of-care ultrasound (POCUS) provides the ability to measure gastric content and is being used as a surrogate for aspiration risk in anesthesia. We sought to evaluate the gastric content of pediatric emergency department (PED) patients undergoing PSA using POCUS.

Methods

We performed a prospective observational study using a convenience sample of pediatric patients undergoing PSA between July 1, 2018, and June 30, 2019. Following a brief history, gastric content was measured using POCUS in both supine and right lateral decubitus positions at 2-hour intervals until the time of PSA. Qualitative content and calculated volume were classified based on the Perlas Model of anesthesia “Risk” assessment.

Results

Ninety-three patients were enrolled with 61.3% male and mean age of 6.5 years. Gastric content was determined in 92 patients. There were 79.3% that had “high risk” content at the time of PSA, with a median fasting time of 6.25 hours and no serious adverse events. Fasting duration had a weak to moderate ability to predict “risk” category (area under the curve = 0.73), with no patient (n = 17) who underwent multiple evaluations awaiting PSA progressing from “high” to “low risk.”

Conclusions

The majority of PED patients undergoing PSA at our institution had “high risk” gastric content with no clinically significant change occurring during serial evaluations. This calls into question the utility of delaying PSA based upon fasting status and lends support to a more comprehensive risk-benefit approach when planning pediatric PSA.
Fat gain differs by sex and hormonal status in persons living with suppressed HIV switched to raltegravir/etravirine
Authors: Assoumou Lambert , Racine Chrystèle , Fellahi Soraya , Lamaziere Antonin , Farabos Dominique , Beniguel Lydie , Bastard Jean-Philippe , Feve Bruno , Gibowski Séverine , Katlama Christine , Costagliola Dominique , Capeau Jacqueline
Published: August 2020

Fat gain is reported in integrase strand transfer inhibitors exposed persons living with HIV. We investigated in 165 persons living with HIV (117 men/48 women), included in the 96-week ANRS-163-ETRAL trial and switched to raltegravir/etravirine, the impact of sex, menopausal status and ovarian reserve (detectable anti-Müllerian hormone). From baseline to 48/96 weeks, women with ovarian reserve were protected from raltegravir/etravirine-induced weight/fat gain and associated insulin-resistance while peri/postmenopausal women increased weight, fat and insulin resistance as did men. The functional ovarian status could protect against raltegravir/etravirine-induced weight gain.
Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection
Authors: Gay Cynthia L. , Neo Dayna T. , Devanathan Aaron S. , Kuruc Joann D. , McGee Kara S. , Schmitz John L. , Sebastian Joe , Shaheen Nicholas J. , Ferrari Guido , McKellar Mehri , Fiscus Susan A. , Hicks Charles B. , Robertson Kevin , Kashuba Angela D.M. , Eron Joseph J. , Margolis David M.
Published: August 2020

Objectives:

The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI).

Design:

Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis.

Methods:

Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0–4, 12, 48), cerebrospinal fluid (CSF) (weeks 2–4, 24 and 48) and endoscopic biopsies (weeks 4–12 and 36–48). Neuropsychological performance was assessed at weeks 0, 24 and 48.

Results:

Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure.

Conclusion:

NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment.

ClinicalTrials.gov:

NCT00855413
Incidence, clearance, persistence and factors related with high-risk anal HPV persistence in South-East Asian MSM and transgender women
Authors: Yunihastuti Evy , Teeratakulpisarn Nipat , Jeo Wifanto Saditya , Nilasari Hanny , Rachmadi Lisnawati , Somia I Ketut Agus , Sukmawati Made Dewi Dian , Amijaya Komang Agus Trisna , Yee Ilias A. , Hairunisa Nany , Hongchookiat Piranun , Trachunthong Deondara , Pankam Tippawan , Nonenoy Siriporn , Ramautarsing Reshmie , Azwa Iskandar , Merati Tuti P. , Phanuphak Praphan , Phanuphak Nittaya , Palefsky Joel M.
Published: August 2020

Objectives:

Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence.

Design:

Prospective cohort study.

Methods:

MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence.

Results:

Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1–0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47–5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22–11.19) and Bali (aOR 3.39; 95% CI 1.07–10.75), being employed/freelance (aOR 3.99; 95% CI 1.48–10.77), and not being circumcised (aOR 2.29; 95% CI 1.07–4.88) were independently associated with anal HR-HPV persistence.

Conclusion:

HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.
Tailoring Contrast Media Protocols to Varying Tube Voltages in Vascular and Parenchymal CT Imaging
Authors: Martens Bibi , Hendriks Babs M.F. , Mihl Casper , Wildberger Joachim E.
Published: August 2020

The latest technical developments in CT have created the possibility for individualized scan protocols at variable kV settings. Lowering tube voltages closer to the K-edge of iodine increases attenuation. However, the latter is also influenced by patient characteristics such as total body weight. To maintain a robust contrast enhancement throughout the patient population in both vascular and parenchymal CT scans, one must adapt the contrast media administration protocols to both the selected kV setting and patient body habitus. This article proposes a simple rule of thumb for how to adapt the contrast media protocol to any kV setting: the 10-to-10 rule.
Remote Ischemic Conditioning Reduced Acute Lung Injury After Traumatic Brain Injury in the Mouse
Authors: Saber Maha , Rice Amanda D. , Christie Immaculate , Roberts Rebecca G. , Knox Kenneth S. , Nakaji Peter , Rowe Rachel K. , Wang Ting , Lifshitz Jonathan
Published: August 2020

Traumatic brain injury (TBI) can induce acute lung injury (ALI). The exact pathomechanism of TBI-induced ALI is poorly understood, limiting treatment options. Remote ischemic conditioning (RIC) can mitigate detrimental outcomes following transplants, cardiac arrests, and neurological injuries. In this study, we hypothesized that RIC would reduce TBI-induced ALI by regulating the sphingosine-1-phosphate (S1P)-dependent pathway, a central regulator of endothelial barrier integrity, lymphocyte, and myokine trafficking. Male mice were subjected to either diffuse TBI by midline fluid percussion or control sham injury and randomly assigned among four groups: sham, TBI, sham RIC, or TBI RIC; RIC was performed 1 h prior to TBI. Mice were euthanized at 1-h postinjury or 7 days post-injury (DPI) and lung tissue, bronchoalveolar lavage (BAL) fluid, and blood were collected. Lung tissue was analyzed for histopathology, irisin myokine levels, and S1P receptor levels. BAL fluid and blood were analyzed for cellularity and myokine/S1P levels, respectively. One-hour postinjury, TBI damaged lung alveoli and increased neutrophil infiltration; RIC preserved alveoli. BAL from TBI mice had more neutrophils and higher neutrophil/monocyte ratios compared with sham, where TBI RIC mice showed no injury-induced change. Further, S1P receptor 3 and irisin-associated protein levels were significantly increased in the lungs of TBI mice compared with sham, which was prevented by RIC. However, there was no RIC-associated change in plasma irisin or S1P. At 7 DPI, ALI in TBI mice was largely resolved, with evidence for residual lung pathology. Thus, RIC may be a viable intervention for TBI-induced ALI to preserve lung function and facilitate clinical management.
Aluminum Adjuvant Improves Survival Via NLRP3 Inflammasome and Myeloid Non-Granulocytic Cells in a Murine Model of Neonatal Sepsis
Authors: Rincon Jaimar C. , Hawkins Russell B. , Hollen Mckenzie , Nacionales Dina C. , Ungaro Ricardo , Efron Philip A. , Moldawer Lyle L. , Larson Shawn D.
Published: August 2020

Neonatal sepsis leads to significant morbidity and mortality with the highest risk of death occurring in preterm (<37 weeks) and low birth weight (<2,500 g) infants. The neonatal immune system is developmentally immature with well-described defects in innate and adaptive immune responses. Immune adjuvants used to enhance the vaccine response have emerged as potential therapeutic options, stimulating non-specific immunity and preventing sepsis mortality. Aluminum salts (“alum”) have been used as immune adjuvants for over a century, but their mechanism of action remains poorly understood. This study aims to identify potential mechanisms by which pretreatment with alum induces host protective immunity to polymicrobial sepsis in neonatal mice. Utilizing genetic and cell-depletion studies, we demonstrate here that the prophylactic administration of aluminum adjuvants in neonatal mice improves sepsis survival via activation of the nucleotide oligomerization domain-like receptor family, pyrin-domain-containing 3 inflammasome and dendritic cell activation. Furthermore, this beneficial effect is dependent on myeloid, non-granulocytic Gr1-positive cells, and MyD88-signaling pathway activation. These findings suggest a promising therapeutic role for aluminum-based vaccine adjuvants to prevent development of neonatal sepsis and improve mortality in this highly vulnerable population.
The Risk of Incarceration During Nonoperative Management of Incisional Hernias
Authors: Dadashzadeh Esmaeel R. , Huckaby Lauren V. , Handzel Robert , Hossain M. Shanaz , Sanin Gloria D. , Anto Vincent P. , Bou-Samra Patrick , Moses J. B. , Cai Stephen , Phelos Heather M. , Simmons Richard L. , Rosengart Matthew R. , van der Windt Dirk J.
Published: August 2020

Objective:

The aim of the study was to quantify the risk of incarceration of incisional hernias.

Background:

Operative repair is the definitive treatment for incisional ventral hernias but is often deferred if the perceived risk of elective operation is elevated secondary to comorbid conditions. The risk of incarceration during nonoperative management (NOM) factors into shared decision making by patient and surgeon; however, the incidence of acute incarceration remains largely unknown.

Methods:

A retrospective analysis of adult patients with an International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis of incisional hernia was conducted from 2010 to 2017 in 15 hospitals of a single healthcare system. The primary outcome was incarceration necessitating emergent operation. The secondary outcome was 30-, 90-, and 365-day mortality. Univariate and multivariate analyses were used to determine independent predictors of incarceration.

Results:

Among 30,998 patients with an incisional hernia (mean age 58.1 ± 15.9 years; 52.7% female), 23,022 (78.1%) underwent NOM of whom 540 (2.3%) experienced incarceration, yielding a 1- and 5-year cumulative incidence of 1.24% and 2.59%, respectively. Independent variables associated with incarceration included: age older than 40 years, female sex, current smoker, body mass index 30 or greater, and a hernia-related inpatient admission. All-cause mortality rates at 30, 90, and 365 days were significantly higher in the incarceration group at 7.2%, 10%, and 14% versus 1.1%, 2.3%, and 5.3% in patients undergoing successful NOM, respectively.

Conclusions:

Incarceration is an uncommon complication of NOM but is associated with a significant risk of death. Tailored decision making for elective repair and considering the aforementioned risk factors for incarceration provides an initial step toward mitigating the excess morbidity and mortality of an incarceration event.
Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands
Authors: Daamen Lois A. , Groot Vincent P. , Besselink Marc G. , Bosscha Koop , Busch Olivier R. , Cirkel Geert A. , van Dam Ronald M. , Festen Sebastiaan , Groot Koerkamp Bas , Haj Mohammad Nadia , van der Harst Erwin , de Hingh Ignace H. J. T. , Intven Martijn P. W. , Kazemier Geert , Los Maartje , Meijer Gert J. , de Meijer Vincent E. , Nieuwenhuijs Vincent B. , Pranger Bobby K. , Raicu Mihaela G. , Schreinemakers Jennifer M. J. , Stommel Martijn W. J. , Verdonk Robert C. , Verkooijen Helena M. , Molenaar Izaak Quintus , van Santvoort Hjalmar C. ,   for the Dutch Pancreatic Cancer Group
Published: August 2020

Objective:

To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival.

Summary of Background data:

International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.

Methods:

A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014–2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence.

Results:

Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5–17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42–0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29–0.70); P < 0.001].

Conclusions:

Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.
Enhanced Stress Resilience Training in Surgeons
Authors: Lebares Carter C. , Coaston Troy N. , Delucchi Kevin L. , Guvva Ekaterina V. , Shen Wen T. , Staffaroni Adam M. , Kramer Joel H. , Epel Elissa S. , Hecht Frederick M. , Ascher Nancy L. , Harris Hobart W. , Cole Steven W.
Published: August 2020

Objective:

To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers.

Summary of Background and Data:

Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown.

Methods:

In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile “conserved transcriptional response to adversity”).

Results:

Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls.

Conclusions:

This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.
Changes in error patterns in unanticipated trauma deaths during 20 years: In pursuit of zero preventable deaths
Authors: LaGrone Lacey N. , McIntyre Lisa , Riggle Andrew , Robinson Bryce R.H. , Maier Ronald V. , Bulger Eileen , Cuschieri Joseph
Published: August 2020

BACKGROUND

A fundamental goal of continuous process improvement programs is to evaluate and improve the ratio of actual to expected mortality. To study this, we examined contributors to error-associated deaths during two consecutive periods from 1996 to 2004 (period 1) and 2005 to 2014 (period 2).

METHODS

All deaths at a level I trauma center with an anticipated probability of death less than 50% and/or identified through process improvement committees were examined. Demographics were assessed for trend only because period 1 data were only available in median and interquartile range. Each death was critically appraised to identify potential error, with subsequent classification of error type, phase, cause, and contributing cognitive processes, with comparison of outcomes made using χ2 test of independence.

RESULTS

During period 1, there were a total of 44,401 admissions with 2,594 deaths and 64 deaths (2.5%) associated with an error, compared with 60,881 admissions during period 2 with 2,659 deaths and 77 (2.9%) associated with an error. Deaths associated with an error occurred in younger and less severely injured patients in period 1 and were likely to occur during the early phase of care, primarily from failed resuscitation and hemorrhage control. In period 2, deaths occurred in older more severely injured patients and were likely to occur in the later phase of care primarily because of respiratory failure from aspiration.

CONCLUSION

Despite injured patients being older and more severely injured, error-associated deaths during the early phase of care that was associated with hemorrhage improved over time. Successful implementation of system improvements resolved issues in the early phase of care but shifted deaths to later events during the recovery phase including respiratory failure from aspiration. This study demonstrates that ongoing evaluation is essential for continuous process improvement and realignment of efforts, even in a mature trauma system.

LEVEL OF EVIDENCE

Therapeutic/Care Management, level IV.
In situarchitecture of neuronal α-Synuclein inclusions
Authors: Trinkaus Victoria A. , Riera-Tur Irene , Martínez-Sánchez Antonio , Bäuerlein Felix J.B. , Guo Qiang , Arzberger Thomas , Baumeister Wolfgang , Dudanova Irina , Hipp Mark S. , Hartl F. Ulrich , Fernández-Busnadiego Rubén
Published: August 2020

α-Synuclein (α-Syn) aggregation is a hallmark of devastating neurodegenerative disorders including Parkinson’s disease (PD) and multiple systems atrophy (MSA)1,2. α-Syn aggregates spread throughout the brain during disease progression2, suggesting mechanisms of intercellular seeding. Formation of α-Syn amyloid fibrils is observedin vitro3,4and fibrillar α-Syn has been purified from patient brains5,6, but recent reports questioned whether disease-relevant α-Syn aggregates are fibrillar in structure7-9. Here we use cryo-electron tomography (cryo-ET) to image neuronal Lewy body-like α-Syn inclusionsin situat molecular resolution. We show that the inclusions consist of α-Syn fibrils crisscrossing a variety of cellular organelles such as the endoplasmic reticulum (ER), mitochondria and autophagic structures, without interacting with membranes directly. Neuronal inclusions seeded by recombinant or MSA patient-derived α-Syn aggregates have overall similar architecture, although MSA-seeded fibrils show higher structural flexibility. Using gold-labeled seeds we find that aggregate nucleation is predominantly mediated by α-Syn oligomers, with fibrils growing unidirectionally from the seed. Our results conclusively demonstrate that neuronal α-Syn inclusions contain α-Syn fibrils intermixed with cellular membranes, and illuminate the mechanism of aggregate nucleation.
An Epitope-based Malaria Vaccine Targeting the Junctional Domain of Circumsporozoite Protein
Authors: Jelínková Lucie , Jhun Hugo , Eaton Allison , Petrovsky Nikolai , Zavala Fidel , Chackerian Bryce
Published: August 2020

A malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen onPlasmodium falciparumsporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat domains of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high titer and long-lived anti-CSP antibody responses in mice and non-human primates. Immunization with CIS43 VLPs confers partial protection from malaria infection in a mouse model, and both immunogenicity and protection were enhanced when mice were immunized with CIS43 VLPs in combination with adjuvants including delta inulin polysaccharide particles and TLR9 agonists. Passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qß VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.
Rhizobium leguminosarumsymbiovarviciaestrains are natural wheat endophytes and can stimulate root development and colonization by arbuscular mycorrhizal fungi
Authors: Bartoli Claudia , Boivin Stéphane , Marchetti Marta , Gris Carine , Gasciolli Virginie , Gaston Mégane , Auriac Marie-Christine , Cottret Ludovic , Carlier Aurélien , Masson-Boivin Catherine , Lepetit Marc , Lefebvre Benoit
Published: August 2020

Although rhizobia establishing a nitrogen-fixing symbiosis with legumes are also known to promote growth in non-legumes, studies on rhizobia association with wheat roots are scarce.

We searched forRhizobium leguminosarumsymbiovarviciae(Rlv) strains naturally competent for wheat roots colonization. We isolated 20 strains and tested the ability of a subset for wheat roots colonization when co-inoculated with otherRlv. We also measured the effect of these strains on wheat root architecture and Arbuscular Mycorrhizal Fungal (AMF) colonization.

We found a low diversity ofRlvin wheat roots compared to that observed in theRlvspecies complex. Only a few strains, including those isolated from wheat roots, and one strain isolated from pea nodules, were efficient to colonize wheat roots in co-inoculation conditions. These strains had a high ability for endophytic colonization of wheat root and were able to stimulate root development and AMF colonization in single strain inoculation conditions.

These results suggest that wheat is an alternative host for someRlv; nevertheless, there is a strong competition betweenRlvstrains for wheat root colonization. Furthermore, our study suggests that the level of endophytic colonization is critical forRlvability to promote wheat growth.
Robust Estimation of Noise for Electromagnetic Brain Imaging with the Champagne Algorithm
Authors: Cai Chang , Diwakar Mithun , Hashemi Ali , Haufe Stefan , Sekihara Kensuke , Nagarajan Srikantan S
Published: August 2020

Robust estimation of the number, location, and activity of multiple correlated brain sources has long been a challenging task in electromagnetic brain imaging from M/EEG data, one that is significantly impacted by interference from spontaneous brain activity, sensor noise, and other sources of artifacts. Recently, we introduced the Champagne algorithm, a novel Bayesian inference algorithm that has shown tremendous success in M/EEG source reconstruction. Inherent to Champagne and most other related Bayesian reconstruction algorithms is the assumption that the noise covariance in sensor data can be estimated from “baseline” or “control” measurements. However, in many scenarios, such baseline data is not available, or is unreliable, and it is unclear how best to estimate the noise covariance. In this technical note, we propose several robust methods to estimate the contributions to sensors from noise arising from outside the brain without the need for additional baseline measurements. The incorporation of these methods for noise covariance estimation improves the robust reconstruction of complex brain source activity under high levels of noise and interference, while maintaining the performance features of Champagne. Specifically, we show that the resulting algorithm, Champagne with noise learning, is quite robust to initialization and is computationally efficient. In simulations, performance of the proposed noise learning algorithm is consistently superior to Champagne without noise learning. We also demonstrate that, even without the use of any baseline data, Champagne with noise learning is able to reconstruct complex brain activity with just a few trials or even a single trial, demonstrating significant improvements in source reconstruction for electromagnetic brain imaging.
Examining the accounts of oil spills crises in Nigeria through sensegiving and defensive behaviours
Authors: Egbon Osamuyimen , Mgbame Chijoke Oscar
Published: August 2020

Purpose

The paper examines how oil multinational companies (MNCs) in Nigeria framed accounts to dissociate themselves from causing oil spills.

Design/methodology/approach

The authors utilised data from relevant corporate reports, external accounts and interviews, and used sensegiving with defensive behaviours theoretical framing to explore corporate narratives aimed at altering stakeholders' perceptions.

Findings

The corporations gave sense to their audience by invoking scapegoating blame avoidance narrative in attributing the cause of most oil spills in Nigeria to outsiders (sabotage), despite potentially misclassifying the sabotage-corrosion dichotomy. Corporate stance was reinforced through justifying narrative, which suggested that multi-stakeholders jointly determined the causes of oil spills, thus portraying corporate accounts as transparent, credible and objective.

Research limitations/implications

The socio-political dynamics in an empirical setting affect corporate accounts and how those accounts appear persuasive, implying that such contextual factors merit consideration when evaluating corporate accounts. For example, despite contradictions in corporate accounts, corporate attribution of oil spills to external factors appeared persuasive due to the inherently complicated socio-political dynamics.

Practical implications

With compensation to oil spills' victims only legally permitted for non-sabotage-induced spills alongside the burden of proof on the victims, the MNCs are incentivised to attribute most oil spills to sabotage. On policy implication, accountability would be best served when the MNCs are tasked both with the burden of proof and a responsibility to demonstrate their transparency in preventing oil spills, including those caused by sabotage.

Originality/value

Crisis situations generate multiple and competing perspectives, but sensegiving and defensive behaviours lenses enrich our understanding of how crisis-ridden companies frame narratives to alter stakeholders' perceptions. Accounts-giving therefore partly satisfies accountability demands, and acts as sensegiving signals aimed at reframing/redefining existing perceptions.
Online Pricing Mistakes
Authors: Pathak Akhileshwar
Published: August 2020

Online stores sell thousands of products and services. Despite all care, mistakes can occur. These mistakes can have severe implications for the seller. A contract once formed is normally binding on the parties. The seller gets bound to sell at the mistaken price. Can an online seller get out of the contract on the ground that the price was a mistake? The only court judgement on the theme is Chwee Kin Keong v. Digilandmall.com Pte Ltd, a judgement of the Singapore High Court. With reference to the judgement, the case explores pricing mistakes by online stores.
Zee Films and the BCCI: The Award of Broadcasting Rights
Authors: Pathak Akhileshwar
Published: August 2020

The case discusses the issues related to Zee Tele Films Limited's claims that the Board of Cricket Control of India was “state” and could act arbitrarily in the award of telecasting rights. The “state” as defined in Article 12 includes “other authorities”, and these are subject to the constitutional limitations. The right to equality requires them to not act arbitrarily. A body which is an instrumentality or agency of the government is “other authority”. The term has been subject to judicial interpretation. The Supreme Court, by a majority judgement, in the Zee Tele Films Case ruled that the Board is not “other authorities” within Article 12 of the Constitution.
Ousting Conditions and Warranties (Buyer's Rights): The Mercini Lady Case
Authors: Pathak Akhileshwar
Published: August 2020

The Mercini Lady Case is a modern statement of the law on the rights of the buyer in a sale contract. The seller has to supply goods in conformity with description, of merchantable quality and fit for the stated use. These rights, the ‘implied conditions’, however, can be ousted by express terms in the contract. The Court of Appeal judgement of the UK keenly considered that the exclusion clause should be interpreted in its business sense. However, it sided with precedence established over hundred years that the exclusion clauses take away valuable rights of the buyer and must be strictly and technically constructed.
Contractual Damages: Kailash Nath Associates v Delhi Development Authority
Authors: Pathak Akhileshwar
Published: August 2020

The Supreme Court judgement, Kailash Nath Associates v. Delhi Development Authority consolidates the law on award of liquidated damages and stipulations on penalties. Contractual damages are to cover losses and not to profit from or penalise the party in breach. Stipulated amounts in damages or penalties are appraised by the courts and only a reasonable compensation is given. Earnest money, and its forfeiture, stood distinct. It could be forfeited without appraisal. The case integrates the different categories and re-states the principles for award of damages.
Indore City Bus Transport Service (B)
Authors: Raghuram G , Sundaram Satyam Shivam , Patni Himanshu
Published: August 2020

Towards the end of 90s, mounting losses forced Madhya Pradesh State Road Transport Corporation (MPSRTC), the sole provider of public transport in Madhya Pradesh, to suspend their urban services. As a consequence, organized public transport services ceased to exist in Indore, the largest metropolitan city of the state of Madhya Pradesh. This void was filled by Intermediate Public Transport (IPT) consisting of minibuses, tempos and auto rickshaws. As of January 2004, 300 private minibuses, 150 tempos, and 10,000 auto rickshaws were plying as IPT, but with poor service levels. Lack of public transport was a catalyst for rapid increase in personalized vehicles, and high level of pollution and accidents. Worried over the rapid growth of personalized vehicles, and high levels of pollution and accidents in Indore, policy makers and administrators had made several attempts of reviving the public transport system in the city. In 2005, the Collector and District Magistrate of Indore decided to make another attempt of reviving the public transport. The two cases, Indore City Bus Transport Service (A) and Indore City Bus Transport Service (B) discuss the complexity involved in the planning, rolling out, and running of public transport services in Indore on a sustainable basis. Case (A) details the prevalent socio-economic condition, travel characteristics, and positions taken by various stakeholders on provisioning of public transport service in Indore as of November 2005. Case (B) discusses the challenges during the growth and operation of the services as of June 2008. Unprecedented rise in crude oil prices along with (i) increase in maintenance cost of buses, price of new buses, and bank interest and (ii) decrease/marginal increase in the fare box revenue (more people were shifting to passes) and advertisement revenue depleted the margin of the operators. The fares had not been increased since the launch of services in February 2006. It was clear that Indore City Transport Service Limited (ICTSL), the SPV created to run the transport system, would survive only if operators were able to survive. The readers have to take the position of the board of ICTSL and consider various options available to them for running the services on a sustainable basis.
Drivers for adoption of sustainability initiatives in supply chains of large Russian firms under environmental uncertainty
Authors: Aray Yulia , Veselova Anna , Knatko Dmitri , Levchenko Anna
Published: August 2020

Purpose

In reaction to the environmental challenge, many firms are looking for the ways how to integrate sustainability into their operations, business models and strategies. Very often sustainable initiatives go beyond the boundaries of a focal firm engaging a wide variety of partners within the supply chain. In conditions of countries with institutional deficiencies and voids such as emerging economies, the task of sustainability integration is challenging as many critical conditions needed for sustainability development are missing. To understand how firms can integrate sustainability initiatives in their supply chains under the conditions of environmental uncertainty, this paper aims to investigate firm-level and supply chain drivers that stimulate sustainability implementation in Russian firms.

Design/methodology/approach

Using the sample of 273 large Russian firms the paper explores how firm-level drivers such as innovativeness, risk-taking and internationalization, as well as collaboration and integration in the supply chain are related to sustainability performance and sustainability transformation in supply chain. The hypotheses are tested using regression analysis and the bootstrapping technique.

Findings

The study indicates the positive association between sustainability performance and sustainability transformation of the firm and such strategic drivers as a firm’s innovativeness and internationalization. The positive moderating effect of environmental uncertainty was found for innovativeness indicating that innovative firms show better sustainable performance in the supply chain under uncertain conditions. Also, the findings indicate that environmental uncertainty positively moderates the relationships between a firm’s transformation for sustainability, its internationalization and supply chain integration and coordination.

Originality/value

The obtained results contribute to a better understanding of mechanisms that drive firms’ sustainability performance and transformation in conditions of emerging markets. The paper provides an adaptation and empirical testing of Silvestre’s (2015) theoretical model for sustainable supply chain management in emerging economies.
A critical review of digital capability frameworks: a consumer perspective
Authors: Malchenko Yulia , Gogua Megi , Golovacheva Ksenia , Smirnova Maria , Alkanova Olga
Published: August 2020

Purpose

This study aims to systematize and critically analyse existing indices and frameworks on digital capabilities with the focus on consumers’ digital capabilities, identify opportunities for their further development and suggest agenda for future research.

Design/methodology/approach

A sample of 18 frameworks and indices of consumers’ digital capabilities were compared based on their purposes, stakeholders, scope and application areas.

Findings

The study concludes with propositions that generalise current views on conceptualisation, measurement and management of consumers’ digital capabilities. Each proposition is further investigated in terms of possible implications for research and practice.

Practical implications

The study indicates opportunities for businesses not only to consider consumers as recipients and adopters of digital technologies but also to aim to understand how to proactively involve consumers in value co-creation, help them be better educated and have a comprehensive understanding of potential outcomes of their participation in the digital economy.

Social implications

Highlighting individual consumer perspective in existing indices and frameworks will help consider the interests of society and provide win-win opportunities for everyone involved in the digital marketplace through bottom-up engagement in addition to top-down regulation and monitoring.

Originality/value

This study contributes to the extant literature threefold: firstly, existing digital capability frameworks and indices are systematized and critically investigated using criteria of stakeholders, purpose and aims; secondly, consumers are identified as principal stakeholder group whose interests are insufficiently presented in existing indices; thirdly, an integrative approach is suggested for a crucial comparison of existing indices, frameworks and their methodology with the focus on consumers’ interests.
Cylinders to pipelines: Abu Dhabi’s city gas project
Authors: Al Marzooqi Mashael , Ahmad Syed Zamberi
Published: August 2020

Learning outcomes

This case study focuses on the problems that a company have in segmenting a local market of a gas distribution company and some strategies that they can use for developing a viable market segmentation to target the right segment that will provide a good economics, revenue base customers who also have the mindset to change to a new product. At the end of this exercise, students should have a clear understanding of the following: the essentials concepts of market segmentation, targeting and positioning and how they can be leveraged so that businesses increase their returns; the main elements/steps that drive market segmentation and business positioning; the appropriate methods for market segmentation when targeting local markets for a city gas project; and the challenges companies might face when changing a product.

Case overview/synopsis

In 2018, commercial customers began asking Abu Dhabi National Oil Company (ADNOC) Distribution to provide a sustainable solution to ensure a continuous supply of safe gas and avoid the interruptions and hazards associated with the supply of liquefied petroleum gas (LPG) to their premises. The request was discussed with the ADNOC marketing, supply and trading (MST) Division to investigate the possibility of growing the natural gas business in the Emirate of Abu Dhabi, thus contributing to the Emirate’s security, economy, environment and community, and ultimately to ADNOC Strategy 2030. Khaled Salmeen, Director of the ADNOC MST Division, believed that industrial customers accounted for higher business volume and profitability. Nevertheless, he advised Shuhab Al Shehhi, the City Gas Project Manager, to study the potential benefits in targeting both residential and commercial customers as part of ADNOC’s responsibility towards community engagement and investments. Al Shehhi had to address several questions: How could the City Gas Project be strategized and positioned so as to target all market segments? What were the potential outcomes? Would targeting all market segments strengthen ADNOC’s brand position?

Complexity academic level

This case study was written for Marketing and Strategic Management courses in Bachelor of Business Administration programs.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS: 8 Marketing