bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical application of personalized medicine: heart failure with preserved left ventricular ejection fraction
Authors: Gori Mauro , D’Elia Emilia , Iorio Anita , Iacovoni Attilio , Senni Michele
Published: November 2020

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest ‘unmet medical need’, because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ∼50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve ‘surrogate’ outcomes, such as quality of life.
Focus on arrhythmogenic right ventricular cardiomyopathy
Authors: Sinagra Gianfranco , Cappelletto Chiara , DE Luca Antonio , Romani Simona , Paldino Alessia , Korcova Renata , Ferro Matteo Dal , Vitrella Giancarlo , Pagnan Lorenzo , Pinamonti Bruno
Published: November 2020

Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease generally caused by desmosomal mutations and characterized by progressive replacement of cardiomyocites with fibro-adipose tissue. In the classic form of the disease right ventricle is predominantly affected. However, biventricular and left-dominant variants have been recently recognized, leading to the new nosological definition of arrhythmogenic cardiomyopathy. The condition affects mostly young adults and athletes and is clinically characterized by ventricular arrhythmias, heart failure and sudden cardiac death. The diagnosis is based on clinical-instrumental criteria, including family history, morpho-functional and electrocardiographic abnormalities, ventricular arrhythmias and genetic defects (Task Force Criteria, 2010). The main goal in the management of patients is the prevention of sudden cardiac death, where implantable cardioverter-defibrillator is the only effective therapeutic strategy. Many arrhythmic risk factors have been described. Recently, an on-line calculator has been proposed, but it needs further validation.
Time is brain: timing of revascularization of brain arteries in stroke
Authors: Risitano Angela , Toni Danilo
Published: November 2020

Ischaemic stroke is the second leading cause of mortality and disability in the western world. Revascularization interventions are the cornerstone of the acute treatment of this pathology and must be administered as soon as possible after the patient’s arrival. They consist of intravenous thrombolysis (IVT) with alteplase, recommended by the guidelines within 4.5 h of the onset of symptoms, and endovascular treatment, recommended within 6 h of the onset of symptoms. The individualized patient selection based on the extent of the mismatch between the penumbra and the ischaemic core allowed to overcome the limits imposed by the rigid time windows, defining a benefit of mechanical revascularization therapies up to 24 h from the theoretical onset of symptoms (last time the patient was known to be well) and up to 9 h for IVT since the theoretical onset of symptoms (last time the patient was known to be well). Advanced neuroimaging methods with perfusion studies are a fundamental tool in patient selection. Their spread in the territory, together with a greater availability of neurovascular treatment units are desirable to ensure a fair delivery of treatment to all patients with ischaemic stroke.
Advancing health literacy measurement in old age
Authors: Konopik Nadine , Kaspar Roman , Penger Susanne , Oswald Frank , Himmelsbach Ines
Published: November 2020

Health literacy is described as a domain of competence across the life-span, gaining particular prominence in light of age-associated health restrictions. However, no specific measurement approach has been proposed for old age. The aim of this study is to augment the existing HLS-EU-Q16 scale (16 items) by items sensitive to age-specific aspects of health literacy to ensure validity and reliability for use in old age. In a first step, the HLS-EU-Q16 was administered in a sample of 463 individuals aged 72 − 92 years. Psychometric properties were evaluated using confirmatory factor analysis and item-response-theory item fit statistics. Scale reliability was found to be poor in this population segment. In a second step, age-specific items were developed based on qualitative in-depth interviews with older persons. In a third step, we tested if the additional set of age-specific items was able to enhance a valid and reliable measurement of health literacy in a second sample of older adults (N = 107, 49 − 91 years). With the inclusion of an eight-item add-on, it was possible to measure health literacy in old and very old age with both high validity and satisfying precision (reliability = 0.80). The study contributes to a population-specific measurement of health literacy.
Catch-up and the entry strategies of latecomers: Chinese firms in the mobile phone sector
Authors: Capone Gianluca , Li Daitian , Malerba Franco
Published: November 2020

As interfaces between human beings and the digital world, mobile phones have evolved from relatively simple devices (e.g., feature phones) to complex products (e.g., smartphones). Many firms in emerging countries such as China have successfully entered the mobile phone sector. A research question that emerges from the evidence on China is whether the entry strategies of these catching up firms have been affected by the introduction of smartphones. In order to investigate this question, the article follows the methodology of evolutionary theory and history-friendly models. It first examines historically the various strategies of the Chinese entrants in the mobile phone sector. On the basis of this empirical analysis, it then develops appreciative theorizing on the factors that have affected the catch-up entry strategies. Our results show that the successful catch-up entry strategies differ depending on the sectoral environment. A technology-driven strategy is more appropriate when there is a market sheltered from competition, so that technological capabilities can be accumulated; on the contrary a marketing-driven strategy is more appropriate when standardized technological solutions become widely available. The article contributes to the catch-up literature by identifying a new entry strategy and by pointing at the role of the sectoral environment, and to the sectoral innovation system literature by addressing the catch-up strategies of latecomer firms under different technological, industrial structure, and market conditions.
Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: an observational study in a tertiary hospital in Northern Taiwan, 2017–19
Authors: Kao Shu-Wei , Liu Zhuo-Hao , Wu Ting-Shu , Ku Stephane Wen-Wei , Tsai Chia-Lung , Shie Shian-Sen , Huang Po-Yen , Wu Yen-Mu , Hsiao Yu-Hsiang , Chen Nan-Yu
Published: November 2020

Background

Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics.

Objectives

To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV.

Methods

A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV.

Results

Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV.

Conclusions

HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.
The Future of Analytical and Interpretative Toxicology: Where are We Going and How Do We Get There?
Authors: Wille Sarah M R , Elliott Simon
Published: November 2020

(Forensic) toxicology has faced many challenges, both analytically and interpretatively, especially in relation to an increase in potential drugs of interest. Analytical toxicology and its application to medicine and forensic science have progressed rapidly within the past centuries. Technological innovations have enabled detection of more substances with increasing sensitivity in a variety of matrices. Our understanding of the effects (both intended and unintended) have also increased along with determination and degree of toxicity. However, it is clear there is even more to understand and consider. The analytical focus has been on typical matrices such as blood and urine but other matrices could further increase our understanding, especially in postmortem (PM) situations. Within this context, the role of PM changes and potential redistribution of drugs requires further research and identification of markers of its occurrence and extent. Whilst instrumentation has improved, in the future, nanotechnology may play a role in selective and sensitive analysis as well as bioassays. Toxicologists often only have an advisory impact on pre-analytical and pre-interpretative considerations. The collection of appropriate samples at the right time in an appropriate way as well as obtaining sufficient circumstance background is paramount in ensuring an effective analytical strategy to provide useful results that can be interpreted within context. Nevertheless, key interpretative considerations such as pharmacogenomics and drug–drug interactions as well as determination of tolerance remain and in the future, analytical confirmation of an individual’s metabolic profile may support a personalized medicine and judicial approach. This should be supported by the compilation and appropriate application of drug data pursuant to the situation. Specifically, in PM circumstances, data pertaining to where a drug was not/may have been/was contributory will be beneficial with associated pathological considerations. This article describes the challenges faced within toxicology and discusses progress to a future where they are being addressed.
Review and Commentary on the Importance of Bile Acids in the Life Cycle ofClostridioides difficilein Children and Adults
Authors: Faden Howard
Published: November 2020

Clostridioides difficile, a spore-forming anaerobe, resides in the intestine. The life cycle of C. difficile illustrates an interdependent relationship between bile acids, commensal microbiota, and C. difficile. Primary bile acids are critical for the germination of C. difficile spores in the small intestine, while secondary bile acids serve as a counterbalance to inhibit the growth of the organism in the colon. Many commensal bacteria especially Clostridium spp. are responsible for transforming primary bile acids into secondary bile acids. Antibiotics eliminate bacteria that convert primary bile acids into secondary bile acids and, thus, allow C. difficile to flourish and cause diarrhea. In children younger than 2 years of age, who normally only produce primary bile acids, colonization with toxin-producing C. difficile is exceedingly common. The reason for the absence of C. difficile diarrhea in the children remains unexplained.
Impact of lifetime attributable risk of radiation-induced secondary cancer in proton craniospinal irradiation with vertebral-body-sparing for young pediatric patients with medulloblastoma
Authors: Suzuki Shunsuke , Kato Takahiro , Murakami Masao
Published: November 2020

We used the method proposed by Schneider et al. Theor Biol Med Model 2011;8:27, to clarify how the radiation-induced secondary cancer incidence rate changes in patients after proton craniospinal irradiation (CSI) without and with vertebral-body-sparing (VBS). Eight patients aged 3–15 years who underwent proton CSI were enrolled in the study. For each case, two types of plan without and with VBS in the target were compared. The prescribed doses were assumed to be 23.4 Gy relative biological effectiveness (RBE) and 36 Gy (RBE). Using the dose–volume histograms of the two plans, the lifetime attributable risk (LAR) was calculated by both methods for each patient based on the dose data calculated using an XiO-M treatment planning system. Eight organs were analyzed as follows: lung, colon, stomach, small intestine, liver, bladder, thyroid and bone. When the prescribed dose used was 23.4 Gy (RBE), the average LAR differences and the average number needed to treat (NNT) between proton CSI without and with VBS were 4.04 and 24.8, respectively, whereas the average LAR difference and the average NNT were larger at 8.65 and 11.6, respectively, when the prescribed dose of 36 Gy (RBE) was used. The LAR for radiation-induced secondary cancer was significantly lower in proton CSI with VBS than without VBS in pediatric patients, especially for the colon, lung, stomach and thyroid. The results of this study could serve as reference data when considering how much of vertebral bodies should be included when performing proton CSI according to age in clinical settings.
COVID-19 genome surveillance at international airport quarantine stations in Japan
Authors: Sekizuka Tsuyoshi , Itokawa Kentaro , Yatsu Koji , Tanaka Rina , Hashino Masanori , Kawano-Sugaya Tetsuro , Ohnishi Makoto , Wakita Takaji , Kuroda Makoto ,   COVID-19 Genomic Surveillance Network in Japanese Airport Quarantine
Published: November 2020

A coronavirus disease (COVID-19) genome surveillance has been conducted at four international airports in Japan, revealing a potential imported COVID-19 risk from multiple countries. The quarantine surveillance based on genome sequencing can enhance sequencing efforts worldwide, as returning travelers may serve as excellent sentinels for the global pandemic.
Brucellosis, a forgotten cause of hepatitis in travellers
Authors: Ljubas Dominik , Lalovac Milos , Vince Adriana , Papic Neven
Published: November 2020

A 43-year-old male patient developed fever after a trip to Balkans, which resolved on doxycycline treatment. However, abnormal liver function tests persisted, and 6 months later, he was diagnosed with non-viral chronic hepatitis. Clues to the diagnosis came from a thorough medical history. Blood cultures and molecular testing identified Brucella melitensis.
Heart Rate Variability as a Possible Predictive Marker for Acute Inflammatory Response in COVID-19 Patients
Authors: Hasty Frederick , García Guillermo , Dávila Héctor , Wittels S Howard , Hendricks Stephanie , Chong Stephanie
Published: November 2020

Introduction

Increases in C-reactive protein (CRP) are used to track the inflammatory process of COVID-19 and are associated with disease state progression. Decreases in heart rate variability (HRV) correlate with worsening of disease states. This observational study tracks changes in HRV relative to changes in CRP in COVID-19 patients.

Materials and Methods

In accordance with an Institutional Review Board-approved study, 17 patients were followed using the wearable, noninvasive Tiger Tech Warfighter Monitor (WFM) that records HRV from a single limb electrocardiogram. Intermittent, daily short-segment data sets of 5 to 7 minutes over a minimum of 7 days were analyzed. Changes in HRV were compared to changes in CRP.

Results

Decreases in HRV of greater than 40% preceded a 50% increase in CRP during the ensuing 72 hours in 10 of the 12 patients who experienced a dramatic rise in CRP. The effectiveness of HRV as a leading indicator of a rise in CRP was evaluated; the sensitivity, specificity, positive predictive value, and negative predictive value for 40% decreases in HRV preceding 50% increases in CRP were 83.3%, 75%, 90.9%, and 60%, respectively.

Conclusion

Substantial decreases in HRV preceded elevations in CRP in the ensuing 72 hours with a 90.9% positive predictive value. Early detection of increasing inflammation may prove vital in mitigating the deleterious effects of an abnormal inflammatory response, particularly in COVID-19 patients. This capability could have a major impact in triage and care of moderate to severe COVID-19 patients in major medical centers as well as field hospitals. This study demonstrates the potential value of short-segment, intermittent HRV analysis in COVID-19 patients.
Einstein@Home discovery of the gamma-ray millisecond pulsar PSR J2039–5617 confirms its predicted redback nature
Authors: Clark C J , Nieder L , Voisin G , Allen B , Aulbert C , Behnke O , Breton R P , Choquet C , Corongiu A , Dhillon V S , Eggenstein H B , Fehrmann H , Guillemot L , Harding A K , Kennedy M R , Machenschalk B , Marsh T R , Mata Sánchez D , Mignani R P , Stringer J , Wadiasingh Z , Wu J
Published: November 2020

The Fermi Large Area Telescope gamma-ray source 3FGL J2039.6–5618 contains a periodic optical and X-ray source that was predicted to be a ‘redback’ millisecond pulsar (MSP) binary system. However, the conclusive identification required the detection of pulsations from the putative MSP. To better constrain the orbital parameters for a directed search for gamma-ray pulsations, we obtained new optical light curves in 2017 and 2018, which revealed long-term variability from the companion star. The resulting orbital parameter constraints were used to perform a targeted gamma-ray pulsation search using the Einstein@Home-distributed volunteer computing system. This search discovered pulsations with a period of 2.65 ms, confirming the source as a binary MSP now known as PSR J2039–5617. Optical light-curve modelling is complicated, and likely biased, by asymmetric heating on the companion star and long-term variability, but we find an inclination i ≳ 60°, for a low pulsar mass between $1.1\, \mathrm{M}_{\odot } \lt M_{\rm psr} \lt $ 1.6 M⊙, and a companion mass of 0.15–$0.22\, \mathrm{M}_{\odot }$, confirming the redback classification. Timing the gamma-ray pulsations also revealed significant variability in the orbital period, which we find to be consistent with quadrupole moment variations in the companion star, suggestive of convective activity. We also find that the pulsed flux is modulated at the orbital period, potentially due to inverse Compton scattering between high-energy leptons in the pulsar wind and the companion star’s optical photon field.
Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity
Authors: Ruiz-Dueñas Francisco J , Barrasa José M , Sánchez-García Marisol , Camarero Susana , Miyauchi Shingo , Serrano Ana , Linde Dolores , Babiker Rashid , Drula Elodie , Ayuso-Fernández Iván , Pacheco Remedios , Padilla Guillermo , Ferreira Patricia , Barriuso Jorge , Kellner Harald , Castanera Raúl , Alfaro Manuel , Ramírez Lucía , Pisabarro Antonio G , Riley Robert , Kuo Alan , Andreopoulos William , LaButti Kurt , Pangilinan Jasmyn , Tritt Andrew , Lipzen Anna , He Guifen , Yan Mi , Ng Vivian , Grigoriev Igor V , Cullen Daniel , Martin Francis , Rosso Marie-Noëlle , Henrissat Bernard , Hibbett David , Martínez Angel T
Published: November 2020

As actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates—namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose–methanol–choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases—we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.
G-Quadruplex loops regulate PARP-1 enzymatic activation
Authors: Edwards Andrea D , Marecki John C , Byrd Alicia K , Gao Jun , Raney Kevin D
Published: November 2020

G-Quadruplexes are non-B form DNA structures present at regulatory regions in the genome, such as promoters of proto-oncogenes and telomeres. The prominence in such sites suggests G-quadruplexes serve an important regulatory role in the cell. Indeed, oxidized G-quadruplexes found at regulatory sites are regarded as epigenetic elements and are associated with an interlinking of DNA repair and transcription. PARP-1 binds damaged DNA and non-B form DNA, where it covalently modifies repair enzymes or chromatin-associated proteins respectively with poly(ADP-ribose) (PAR). PAR serves as a signal in regulation of transcription, chromatin remodeling, and DNA repair. PARP-1 is known to bind G-quadruplexes with stimulation of enzymatic activity. We show that PARP-1 binds several G-quadruplex structures with nanomolar affinities, but only a subset promote PARP-1 activity. The G-quadruplex forming sequence found in the proto-oncogene c-KIT promoter stimulates enzymatic activity of PARP-1. The loop-forming characteristics of the c-KIT G-quadruplex sequence regulate PARP-1 catalytic activity, whereas eliminating these loop features reduces PARP-1 activity. Oxidized G-quadruplexes that have been suggested to form unique, looped structures stimulate PARP-1 activity. Our results support a functional interaction between PARP-1 and G-quadruplexes. PARP-1 enzymatic activation by G-quadruplexes is dependent on the loop features and the presence of oxidative damage.
Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation
Authors: Faramand Andrew , Kano Hideyuki , Niranjan Ajay , Atik Ahmet F , Lee Cheng-chia , Yang Huai-che , Mohammed Nasser , Liscak Roman , Hanuska Jaromir , Tripathi Manjul , Kondziolka Douglas , Sheehan Jason , Mathieu David , Flickinger John C , Lunsford L Dade
Published: November 2020

BACKGROUND

Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible.

OBJECTIVE

To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project.

METHODS

A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively.

RESULTS

Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure.

CONCLUSION

GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
Laparoscopic-Assisted Versus Mini-Open Laparotomy for Ventriculoperitoneal Shunt Placement in the Medicare Population
Authors: Khalid Syed I , Nunna Ravi S , Maasarani Samantha , Shanker Rachyl M , Behbahani Mandana , Edmondson Corbin P , Mehta Ankit I , Gupta Samir K , Chan Edie Y , Torquati Alfonso , Byrne Richard W , Adogwa Owoicho
Published: November 2020

BACKGROUND

Placement of the distal shunt catheter into the peritoneum during ventriculoperitoneal shunt (VPS) surgery can be done with either laparoscopic assistance or laparotomy.

OBJECTIVE

To compare outcomes in laparoscopic-assisted vs laparotomy for placement of VPS in the Medicare population.

METHODS

Patients undergoing VPS placement, between 2004 and 2014, were identified by International Classification of Disease, Ninth Revision and Current Procedural Terminology codes in the Medicare database. Demographic data including age, sex, comorbidities, and indications were collected. Six- and twelve-month complication rates were analyzed.

RESULTS

A total of 1966 (3.2%) patients underwent laparoscopic-assisted VPS and 60 030 (96.8%) patients underwent nonlaparoscopic-assisted VPS placement. Compared with traditional open VPS placement, the laparoscopic approach was associated with decreased odds of distal revision at 6- and 12-mo postoperatively (6 mo: odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.21-0.74; 12 mo: OR = 0.60, 95% CI: 0.39-0.94). At 6- and 12-mo postoperatively, multivariable regression analysis demonstrated increased odds of distal revision in patients with a body mass index (BMI) > 30 Kg/M2, history of open abdominal surgery, and history of laparoscopic abdominal surgery. Additionally, history of prior abdominal surgery and BMI > 30 Kg/M2 were significantly associated with increase odds of shunt infection at 6 and 12-mo, respectively.

CONCLUSION

In the largest retrospective analysis to date, patients with a history of abdominal surgery and obesity were found to be at increased risk of infection and distal revision after VPS placement. However, the laparoscopic approach for abdominal placement of the distal catheter was associated with reduced rates of distal revision in this population, suggesting an avenue for reducing complications in well-selected patients.
Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study
Authors: Kunisaki Ken M , De Francesco Davide , Sabin Caroline A , Winston Alan , Mallon Patrick W G , Anderson Jane , Bagkeris Emmanouil , Boffito Marta , Doyle Nicki , Haddow Lewis , Post Frank A , Sachikonye Memory , Vera Jaime , Khalil Wajahat , Redline Susan
Published: November 2020

Background

Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA).

Methods

Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires.

Results

We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2–12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia.

Conclusions

Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.
Clinical Effectiveness of Intravenous Peramivir Compared With Oseltamivir in Patients With Severe Influenza A With Primary Viral Pneumonia: A Randomized Controlled Study
Authors: Chen Hong-Dou , Wang Xu , Yu Shu-Le , Ding Yue-Hui , Wang Meng-Lei , Wang Jin-Na
Published: November 2020

Background

High-quality evidence confirms that the clinical efficacy of peramivir in severe influenza patients with primary viral pneumonia is lacking. To optimize clinical medication, we evaluate the different efficacy between peramivir and oseltamivir in the treatment of severe influenza A with primary viral pneumonia.

Methods

A single-center, randomized, controlled trial was conducted during the Chinese influenza season from December 2018 to April 2019 in patients with severe influenza A with primary viral pneumonia. A total of 40 inpatients were enrolled and treated with either intravenous peramivir (300 mg, once daily for 5 days) or oral oseltamivir (75 mg, twice daily for 5 days).

Results

The duration of influenza virus nucleic acid positivity in the oseltamivir group and the peramivir group was 2.95 days and 2.80 days, respectively. The remission times of clinical symptoms in the oseltamivir group and the peramivir group were 3.90 days and 3.25 days, respectively. In addition, the remission time of cough symptoms in the peramivir group (63.89 hours) was shorter than that in the oseltamivir group (75.53 hours). There was no significant difference between these values (P > .05). The remission time of fever symptoms in the oseltamivir group was 23.67 hours, which was significantly longer than that in the peramivir group (12.32 hours) (P = .034).

Conclusions

Peramivir is no less effective than oseltamivir in the treatment of severe influenza A with primary viral pneumonia, and patients treated with peramivir had significantly shorter remission times of fever symptoms than those treated with oseltamivir.
Low Back Pain–Related Disability Is Associated with Pain-Related Beliefs Across Divergent Non–English-Speaking Populations: Systematic Review and Meta-Analysis
Authors: Alamam Dalyah M , Leaver Andrew , Alsobayel Hana I , Moloney Niamh , Lin Jianhua , Mackey Martin G
Published: November 2020

Objectives

This systematic review and meta-analysis examined relationships between low back pain (LBP)–related disability and pain beliefs, including pain catastrophizing, pain-related fear, self-efficacy, and back pain beliefs, in non–English-speaking populations. Additionally, the effects of selected cultural factors (i.e., language/geographic area) on the strength of relationships were examined.

Study design

Systematic review and meta-analysis.

Methods

Nine databases were searched. Studies included observational or randomized control clinical trials. Eligible studies had to report estimates of the association between pain beliefs and disability. Pooled estimates of correlation coefficients were obtained through random-effects meta-analysis methods.

Results

Fifty-nine studies, (n = 15,383) were included. Moderate correlations were identified between disability and pain self-efficacy (chronic LBP r = −0.51, P ≤ 0.001), between disability and pain catastrophizing (acute LBP r = 0.47, P ≤ 0.001; chronic LBP r = 0.44, P ≤ 0.001), and also between disability and pain-related fear (chronic LBP r = 0.41, P ≤ 0.001). Otherwise, weak correlations were identified between disability and most pain beliefs (range r = −0.23 to 0.35, P ≤ 0.001). Pooled correlation coefficients between disability and all pain beliefs (except the Fear Avoidance Belief Questionnaire–Work subscale) represent medium effects and suggest that lower disability was associated with greater pain self-efficacy, less pain-related fear, less catastrophic thinking, and less negative back pain beliefs about the nature and cause of back pain. Results were consistent across most language groups and geographic regions; few studies reported ethnicity or religion.

Discussion

LBP-related disability was associated with pain-related beliefs, with consistency demonstrated for each pain belief construct across divergent non–English-speaking populations. Further research examining cultural factors, such as ethnicity or religion, and with a more diverse population is warranted.
COVID-19 vaccine hesitancy among medical students
Authors: Lucia Victoria C , Kelekar Arati , Afonso Nelia M
Published: November 2020

Background

Medical students are among the group of frontline healthcare providers likely to be exposed to COVID-19 patients. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as a vaccine is available. As future healthcare providers, they will be entrusted with providing vaccine recommendations and counseling vaccine-hesitant patients.

Methods

This project used self-report to assess vaccine hesitancy and acceptance among medical students towards the novel COVID-19 vaccine.

Results

Nearly all participants had positive attitudes towards vaccines and agreed they would likely be exposed to COVID-19; however, only 53% indicated they would participate in a COVID-19 vaccine trial and 23% were unwilling to take a COVID-19 vaccine immediately upon FDA approval. Students willing to immediately take the vaccine were more likely to trust public health experts, have fewer concerns about side effects and agree with vaccine mandates (P < 0.05). Concern for serious side effects was independently predictive of lower odds of intent to participate in a COVID-19 vaccine trial (AOR = 0.41, P = 0.01).

Conclusion

This is the first study to evaluate COVID-19 vaccine hesitancy among US medical students and highlights the need for an educational curriculum about the safety and effectiveness to promote uptake of the COVID-19 vaccine.
Crisis Poison Pills*
Authors: Eldar Ofer , Wittry Michael D.
Published: November 2020

We show that a large number of firms adopt poison pills during periods of market turmoil. Specifically, during the coronavirus pandemic, many firms adopted poison pills following declines in valuations, and stock prices increased upon the announcement of firms’ poison pill adoption. Stock price increases are driven by (1) firms in which activist shareholders acquire ownership stakes and (2) firms in industries that had high exposure to the crisis. Likewise, we find a positive reaction to pills with provisions directed at stalling activists’ interventions. Our results suggest that crisis pills that target potentially disruptive ownership changes may benefit current shareholders. (JEL G30, G32, G34, G38, E32)

Received August 14, 2020; editorial decision October 23, 2020 by Editor Andrew Ellul. Authors have furnished an Internet Appendix,which is available on the Oxford University Press Web site next to the link to the final published paper online.
Implications of Stochastic Transmission Rates for Managing Pandemic Risks
Authors: Hong Harrison , Wang Neng , Yang Jinqiang
Published: November 2020

We introduce aggregate transmission shocks to an epidemic model and link firm valuations to infections via an asset pricing framework with vaccines. Infections lower earnings growth but firms can mitigate damages. We estimate a large reproduction number ${\mathcal R}_0$ and transmission volatility for COVID-19. Using these estimates, we quantify the bias of deterministic approximations based on ${\mathcal R}_0$. Our model generates predictions consistent with the data: unexpected infection resurgence, nonmonotonic mitigation policies, and higher price-to-earnings ratios during a pandemic. Valuations would be significantly lower absent mitigation and a high vaccine arrival rate.
Nuclear Restart Politics: How the ‘Nuclear Village’ Lost Policy Implementation Power
Authors: KOPPENBORG Florentine
Published: November 2020

The March 2011 nuclear accident (3.11) shook Japan’s nuclear energy policy to its core. In 2012, the Liberal Democratic Party (LDP) returned to government with a pro-nuclear policy and the intention to swiftly restart nuclear power plants. In 2020, however, only six nuclear reactors were in operation. Why has the progress of nuclear restarts been so slow despite apparent political support? This article investigates the process of restarting nuclear power plants. The key finding is that the ‘nuclear village’, centered on the LDP, Ministry of Economy Trade and Industry, and the nuclear industry, which previously controlled both nuclear policy goal-setting and implementation, remained in charge of policy decision making, i.e. goal-setting, but lost policy implementation power to an extended conflict over nuclear reactor restarts. The main factors that changed the politics of nuclear reactor restarts are Japan’s new nuclear safety agency, the Nuclear Regulation Authority (NRA), and a substantial increase in the number of citizens’ class-action lawsuits against nuclear reactors. These findings highlight the importance of assessing both decision making and implementation in assessments of policy change.
The relationship between endoplasmic reticulum stress and autophagy in apoptosis of BEAS-2B cells induced by cigarette smoke condensate
Authors: Yu Qi , Yang Sa , Li Zhongqiu , Zhu Yonghang , Li Zhenkai , Zhang Jiatong , Li Chunyang , Feng Feifei , Wang Wei , Zhang Qiao
Published: November 2020

Cigarette smoke (CS) is one of the severe risk factors for the development of the pulmonary disease. However, the underlying mechanisms, especially the CS-induced the human bronchial epithelial cells (BEAS-2B) apoptosis related to endoplasmic reticulum stress (ERS) and autophagy, remains to be studied. This study aims to investigate the relationship between ERS and autophagy in apoptosis induced by CS condensate (CSC). BEAS-2B cells were stimulated with 0.02, 0.04 and 0.08 mg/ml CSC for 24 h to detect the ERS, autophagy and apoptosis. Then, ERS and autophagy of BEAS-2B cells were inhibited, respectively, by using 4-PBA and 3-MA, and followed by CSC treatment. The results showed that CSC decreased cell viability, increased cell apoptosis, elevated cleaved-caspase 3/pro-caspase 3 ratio and Bax expressions, but decreased Bcl-2 expressions. The GRP78 and CHOP expressions and LC3-II/LC3-I ratio were dose-dependently increased. The structure of the endoplasmic reticulum was abnormal and the number of autolysosomes was increased in BEAS-2B cells after CSC stimulation. The LC3-II/LC3-I ratio was decreased after ERS inhibition with 4-PBA, but GRP78 and CHOP expressions were enhanced after autophagy inhibition with 3-MA. CSC-induced apoptosis was further increased, Bax expressions and cleaved-caspase 3/pro-caspase 3 ratio were improved, but Bcl-2 expressions were decreased after 3-MA or 4-PBA treatment. In conclusion, the study indicates that ERS may repress apoptosis of BEAS-2B cells induced by CSC via activating autophagy, but autophagy relieves ERS in a negative feedback. This study provides better understanding and experimental support on the underlying mechanisms of pulmonary disease stimulated by CS.
Use of Chitosan and Other Natural Compounds Alone or in Different Strategies with Copper Hydroxide for Control of Grapevine Downy Mildew
Authors: Romanazzi Gianfranco , Mancini Valeria , Foglia Renzo , Marcolini Diego , Kavari Mojtaba , Piancatelli Simone
Published: November 2020

Grapevine downy mildew (GDM) is one of the most serious diseases of grapevines. Limitations to the use of copper-based products in organic agriculture according to the European Union (EU) regulation EU/2002/473 and the later EU Commission implementing regulation 2018/1981 have promoted a search for alternatives. This 5-year field trial evaluated the effectiveness of several strategies against GDM using different chitosan-based formulations and application rates in comparison with other natural compounds applied individually or with copper hydroxide. Trials were performed in commercial vineyards with different environmental conditions and grapevine cultivars. For the natural compounds applied as individual treatments, a 0.5%/0.8% chitosan formulation provided the best protection against GDM; the other compounds and formulations were less effective. When copper hydroxide use was halved by combining it with the natural compounds according to three different strategies, the GDM incidence, severity, and McKinney index were reduced, particularly for copper hydroxide applied in combination with the 0.5%/0.8% chitosan formulation. The 0.5%/0.8% chitosan formulation alone and with copper hydroxide provided good protection against GDM during both high-pressure and low-pressure disease seasons. Therefore, chitosan represents a good alternative to copper formulations for the control of GDM and both organic and integrated disease management.
Status and Influential Factors of Intelligent Healthcare in Nursing Homes in China
Authors: Meng Fanli , Song Fengbin , Guo Mengna , Wang Fujie , Feng Xiaoli , Wang Dahui , Xu Liangwen
Published: November 2020

With the support of the Chinese government, nursing homes have increasingly adopted Internet and intelligent information technology to provide daily healthcare services to residents. However, no research has reported the status of intelligent healthcare in nursing homes. From September 2017 to May 2018, we conducted a survey of 197 nursing homes and collected information on their general characteristics, the intelligent healthcare services provided, the effectiveness of the application products used, and the attitudes of the staff and residents toward intelligent healthcare. Overall, 79.69% of the surveyed nursing homes have provided intelligent healthcare services, including medical care services (eg, chronic disease management and intelligent nursing) and daily life services (eg, fall monitoring and wireless positioning). Portable health monitoring devices and data management and service platforms are the most used healthcare products. The attitudes of staff probably affected the development of intelligent healthcare. Financial investment and the attitudes of staff and residents are factors that influence the effectiveness of the application of intelligent healthcare products in nursing homes. With the support of national policies, nursing homes have implemented primary intelligent healthcare. Stakeholders play pivotal roles in the provision of intelligent healthcare services.
Defining the Histopathological Term Atypical Intraepidermal Melanocytic Proliferation: A Retrospective Cross-Sectional Study
Authors: Bou-Prieto Alfredo , Sarriera-Lázaro Carlos J. , Valentín-Nogueras Sheila M. , Sánchez Julio E. , Sánchez Jorge L.
Published: November 2020

Background:

Atypical intraepidermal melanocytic proliferation (AIMP) is a general term assigned to melanocytic proliferations of uncertain biological potential when a definitive histopathological diagnosis cannot be achieved. There are few data available describing the possibility of malignancy of AIMP, or ways to further define diagnosis.

Objective:

To determine the rate of diagnostic change of AIMP to melanoma or melanoma in situ (MIS) after conventional excision. In addition, to determine the role of immunohistochemistry (IHC) in defining AIMP biopsies.

Methods:

Retrospective cross-sectional, single-center review of biopsies with a diagnosis of AIMP with a follow-up conventional excision from 2012–2016 was performed. In a separate analysis, a search was performed for AIMP biopsied lesions in which IHC was subsequently performed.

Results:

The rate of diagnostic change of AIMP to MIS was 4.8% (8/167) after excision. Punch biopsy was a risk factor for diagnostic change to MIS (odds ratio 12.94, confidence interval 2.56–65.38, P = 0.008). The rate of diagnostic change of AIMP biopsies after examining with IHC was 21.3% (34/160) to MIS and 4.4% (7/160) to melanoma.

Conclusion:

The possibility of malignancy of AIMP lesions must be taken into consideration when counseling patients and when planning treatment options. IHC is a useful tool and should be used in the evaluation of AIMP specimens.
Systemic treatment of a metastatic carotid body tumor
Authors: Xing Jiazhang , Cheng Yuejuan , Ying Hongyan , Guan Mei , Jia Ning , Bai Chunmei
Published: November 2020

Rationale:

Carotid body tumors (CBTs) are head and neck paragangliomas (PGLs) with a low incidence of distant metastasis. To date, only a few metastatic cases treated with detailed systemic therapy are reported and effective management is still inconclusive. Herein, we reported a metastatic CBT case with systemic therapy and reviewed the reported systemic treatment.

Patient concerns:

A 56-year-old man noticed multiple painless nodules on the right side of the neck and developed debilitating chest and back pain 7 years after the CBT resection.

Diagnoses:

Widespread bone and lymph nodes CBT metastases.

Interventions:

Biopsies of the enlarged lymph nodes confirmed the diagnosis of metastatic CBT and 18F-FDG PET-CT detected multiple right cervical lymph nodes and bone metastases. 24 cycles of cyclophosphamide, vincristine and dacarbazine (CVD) chemotherapy were given since May 2016 to Jul 2018 and dacarbazine maintenance therapy was given in the next 15 months follow-up period.

Outcomes:

Partial remission was achieved according to the Response Evaluation in Criteria in Solid Tumors 1.1 criteria. A prominent control in the metastatic lesions were also observed in 18F-FDG PET-CT scan.

Lessons:

Evidence for systemic management of metastatic CBTs is mainly based on studies of PGLs and pheochromocytoma. According to our review on metastatic CBT cases treated with systemic therapy from 1981 to 2018, chemotherapy, especially the CVD regimen, was a common reported management. In SDHB mutated patients, sunitinib and temozolomide could also be considered.