bluuebunny/crossref_metadata_2025 huggingface dataset:
The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson’s disease
Authors: Biondetti Emma , Santin Mathieu D , Valabrègue Romain , Mangone Graziella , Gaurav Rahul , Pyatigorskaya Nadya , Hutchison Matthew , Yahia-Cherif Lydia , Villain Nicolas , Habert Marie-Odile , Arnulf Isabelle , Leu-Semenescu Smaranda , Dodet Pauline , Vila Miquel , Corvol Jean-Christophe , Vidailhet Marie , Lehéricy Stéphane
Published: May 2021

In Parkinson’s disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson’s disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system.

Patients with Parkinson’s disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson’s disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson’s disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta.

The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time.

In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content.
Development of a stability-indicating assay method by HPLC–DAD and MS characterization of forced degradation products of ravuconazole
Authors: Gazzinelli Bernardo Pontes , Brêtas Camila Machado , César Isabela Costa
Published: May 2021

Ravuconazole (RAV) is a triazole antifungal with broad spectrum and a novel alternative in the treatment of systemic fungal infections. A stability-indicating method by high-performance liquid chromatography–diode array detection was developed and fully validated to assay ravuconazole in the presence of its degradation products. Separation was achieved with a Sunfire C18 column (250 mm × 4.6 mm id, 5 μm), mobile phase composed of acetonitrile and water (80:20), at 1 mL/min. The volume of injection was 5 μL and DAD detection was performed at 287 nm. RAV was well resolved from its degradation products and the method proved to be linear, selective, accurate, precise and robust. A forced degradation study was conducted on the pure drug under oxidative conditions in presence of H2O2 and metallic ions and under acid, alkaline and neutral hydrolysis. RAV was degraded mainly under alkaline hydrolysis, forming two main degradation products. The chemical structures were proposed according to the data obtained by liquid chromatography coupled to mass spectrometry (LC-MS) analysis. This study provided a new and selective stability-indicating method to evaluate the intrinsic stability of ravuconazole in active pharmaceutical ingredients. The developed method was found to be suitable for quality control routine analysis and to stability studies of ravuconazole.
Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults
Authors: Isturiz Raul , Grant Lindsay , Gray Sharon , Alexander-Parrish Ronika , Jiang Qin , Jodar Luis , Peyrani Paula , Ford Kimbal D , Pride Michael W , Self Wesley H , Counselman Francis , Volturo Gregory , Ostrosky-Zeichner Luis , Wunderink Richard G , Sherwin Robert , Overcash J Scott , File Thomas , Ramirez Julio
Published: May 2021

Background

Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine.

Methods

This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20).

Results

Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes.

Conclusions

The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.
Development of the Three Antimicrobial Stewardship E’s (TASE) Framework and Association Between Stewardship Interventions and Intended Results Analysis to Identify Key Facility-Specific Interventions and Strategies for Successful Antimicrobial Stewardship
Authors: Kimball Joanna M , Deri Connor R , Nesbitt Whitney J , Nelson George E , Staub Milner B
Published: May 2021

Background

Successful antimicrobial stewardship (AS) interventions have been described previously. Currently, a uniform operational approach to planning and implementing successful AS interventions does not exist. From 2015 to 2019, concomitant vancomycin and piperacillin-tazobactam use (CVPTU) for >48 hours at Vanderbilt University Medical Center (VUMC) significantly decreased through AS efforts. We analyzed the interventions that led to this change and created a model to inform future intervention planning and development.

Methods

Adult admissions at VUMC from January 2015 to August 2019 were evaluated for CVPTU. The percentage of admissions receiving CVPTU for >48 hours, the primary outcome, was evaluated using statistical process control charts. We created the Three Antimicrobial Stewardship E’s (TASE) framework and Association between Stewardship Interventions and Intended Results (ASIR) analysis to assess potential intensity and impact of interventions associated with successful change during this time period and to identify guiding principles for development of future initiatives.

Results

The mean percentage of admissions receiving CVPTU per month declined from 4.2% to 0.7%. Over 8 time periods, we identified 4 periods with high, 3 with moderate, and 1 with low intervention intensity. Continuous provider-level AS education was present throughout. Creation and dissemination of division and department algorithms and reinforcement via computerized provider order entry sets preceded the largest reduction in CVPTU and sustained prescribing practice changes.

Conclusions

The TASE framework and ASIR analysis successfully identified pivotal interventions and strategies needed to effect and sustain change at VUMC. Further research is needed to validate the effectiveness of this framework as a stewardship intervention planning tool at our institution and others.
Evaluating the Presence of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Nursing Home Residents With Persistently Positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) Results
Authors: Lutgring Joseph D , Tobolowsky Farrell A , Hatfield Kelly M , Lehnertz Nicholas B , Sullivan Maureen M , Martin Karen G , Keaton Amelia , Sexton D Joseph , Tamin Azaibi , Harcourt Jennifer L , Thornburg Natalie J , Reddy Sujan C , Jernigan John A
Published: May 2021

Replication-competent virus has not been detected in individuals with mild to moderate coronavirus disease 2019 (COVID-19) more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.
Learning curve for robot-assisted Ivor Lewis esophagectomy
Authors: Han Yu , Zhang Yajie , Zhang Wentian , Xiang Jie , Chen Kai , Huang Maosheng , Li Hecheng
Published: May 2021

This study aimed to demonstrate the learning curve of robot-assisted minimally invasive esophagectomy (RAMIE). A retrospective analysis of the first 124 consecutive patients who underwent RAMIE with intrathoracic anastomosis (Ivor Lewis) by a single surgeon between May 2015 and August 2020 was performed. An risk-adjusted cumulative sum (RA-CUSUM) analysis was applied to generate a learning curve of RAMIE considering the major complication rate, which reflected the technical proficiency. The overall 30-day morbidity rate was 38.7%, while the major complication rate was 25.8%. The learning curve was divided into two phases based on the RA-CUSUM analysis: phase I, the initial learning phase (cases 1–51) and phase II, the proficiency phase (cases 52–124). As we compared the proficiency phase with the initial learning phase, significantly decreased trends were observed in relation to the major complication rate (37.3% vs. 18.7%, P = 0.017), total operation time (330.9 ± 55.6 vs. 267.3 ± 39.1 minutes, P < 0.001), and length of hospitalization (10 [IQR, 9–14] days vs. 9 [IQR, 8–11] days, P = 0.034). In conclusion, the learning curve of RAMIE consisted of two phases, and at least 51 cases were required to gain technical proficiency.
Effects of preoperative nutrition on postoperative outcomes in esophageal cancer: a systematic review and meta-analysis
Authors: Cao Yuqin , Han Dingpei , Zhou Xiang , Han Yu , Zhang Yajie , Li Hecheng
Published: May 2021

Postoperative enteral nutrition has been widely implemented in esophageal cancer, but the efficacy and safety of preoperative nutrition, particularly immune-enhancing nutrition (IEN), remain controversial. This meta-analysis aims to provide a quantitative synthesis of whether preoperative nutrition improves postoperative morbidity and mortality in patients with resectable esophageal cancer. A systematic search was conducted in Medline, Embase, Cochrane, and databases of clinical trials dated up to December 2019. Randomized controlled trials and observational studies comparing postoperative outcomes between esophageal cancer patients with and without preoperative nutritional support were included. Random-effects model was applied in the meta-analysis of primary outcomes (overall complication rate, in-hospital mortality) and secondary outcomes (infectious complication rate, anastomotic leak rate, length of postoperative hospital stay). Complications of feeding tube access and perioperative weight loss were evaluated by qualitative synthesis. Subgroup analyses were performed by stratifying immunonutrition and standard nutrition before surgery. Subgroup analysis of randomized controlled trials alone was also done. A total of 15 studies enrolling 1864 participants were included. The overall meta-analysis found that preoperative nutrition could reduce infectious complications (odds ratio [OR] = 0.51, 95% confidence interval [CI] [0.26, 0.98]; I2 = 48%) and length of hospital stay (mean difference = −2.10 day, 95% CI [−3.72, −0.47]; I2 = 78%) after esophagectomy, whereas no significant difference was revealed in the incidence of overall complications (OR = 0.76, 95% CI [0.52, 1.11]; I2 = 32%), in-hospital mortality (OR = 1.03, 95% CI [0.41, 2.61]; I2 = 12%), and anastomotic leak (OR = 1.05, 95% CI [0.69, 1.58]; I2 = 0%). Subgroup of preoperative immunonutrition showed more prominent benefits. The complication rate of feeding tube access was low (1.6–16%). In conclusion, preoperative nutrition is safe in esophageal cancer, but benefits are observed in infectious complication rate and length of stay on a limited scale. IEN holds more advantages over standard nutrition. Randomized trials in the context of nutritional support during neoadjuvant therapy are in demand.
Twiddler’s syndrome after implantation of baroreflex activation therapy: a case report
Authors: Dalos Daniel , Khazen Cesar , Schukro Christoph , Gwechenberger Marianne
Published: May 2021

Background

Twiddler’s syndrome is a rare complication after implantation of cardiac pacemakers or cardioverter-defibrillators that usually occurs within the first year after the procedure. However, it has not yet been described following implantation of baroreflex activation therapy (BAT).

Case summary

A 61-year-old female patient was referred to the cardiology outpatient clinic due to uncontrolled arterial hypertension despite maximal doses of several established drugs. Therefore, right-sided BAT implantation was successfully performed in February 2017 with good clinical response. Because of sustained neck pain at the site of stimulator, surgical revision was performed in November 2019 including a switch of the lead to the contralateral position. Approximately 1 month later, Twiddler’s syndrome was identified on the basis of recurrent pain at the generator site necessitating pocket-revision, however, the lead was only untwisted but not replaced. A few weeks afterwards, unfortunately, lead revision was indispensable due to lead fracture.

Discussion

This case presents the uncommon phenomenon of Twiddler’s syndrome after BAT implantation. In addition, the commonly twisted lead should always be replaced as well during surgical pocket-revision in order to ensure proper long-term function.
Case series of iatrogenic coronary stent avulsion: a rare complication with varied management strategies
Authors: Protty Majd B , O’Neill Elinor H M , Kinnaird Tim , Gallagher Sean
Published: May 2021

Background

Coronary stent avulsion is a rare, infrequently reported complication of percutaneous coronary intervention (PCI) with no consensus on management options.

Case summary

This case series presents three descriptions of iatrogenic coronary stent avulsions, and three different bailout management strategies. All patients presented with acute coronary syndrome and required PCI. In the first case, a freshly implanted stent was entrapped in a coronary guidewire and avulsed upon withdrawal of the wire into the aortic sinus. In the second case, a staged procedure to implant a new stent was complicated by stent dislodgement and entanglement with a recently implanted stent leading to avulsion of both stents into the aortic sinus and resultant dissection to the coronary arteries. In the third case, following a successful stent implantation, the tip of the coronary guidewire was bound to the proximal edge of the stent resulting in avulsion of the newly implanted stent into the ascending aorta upon retraction of the wire at the end of the procedure. The first two patients were managed percutaneously, and the third surgically. All patients have had acceptable technical and clinical outcomes.

Discussion

In the absence of a consensus on best bailout management strategy, we discuss the mechanisms of and the potential management options for this rare, but serious, complication.
A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis
Authors: Abbott Claire B , Lawrence Marcus M , Kobak Kamil A , Lopes Erika Barboza Prado , Peelor Frederick F , Donald Elizabeth J , Van Remmen Holly , Griffin Timothy M , Miller Benjamin F
Published: May 2021

Age-related deterioration in turnover of collagen proteins accelerates extracellular matrix fibrosis and hinders adaptation to external stimuli. This project sought to understand factors that increase skeletal muscle fibrosis with age by studying what we term the dynamic protein pool. We hypothesized that the dynamic protein pool size of muscle collagen decreases with age, thus indicating a decrease in proteostatic maintenance (ie, ability to maintain proteostasis), and that failure to account for these changes impacts the interpretation of tracer-measured synthesis rates. We used deuterium oxide (D2O) labeling for up to 60 days in adult (6 months) and old (23 months) mice. The dynamic protein pool in adult skeletal muscle was 65% in tibialis anterior (TA), but only 28% in gastrocnemius (Gastroc). In aged muscle, the dynamic protein pool was further decreased to only 35% and 14% for TA and Gastroc, respectively. We showed that this loss in dynamic pool size was associated with increases in markers of fibrosis and decreased proteostatic maintenance. We demonstrate that aged muscle has higher rates of collagen protein synthesis and lower rates of collagen protein breakdown, which causes collagen accumulation. We further demonstrated that the normal assumption of complete protein renewal and the standard practice of taking a single sample with isotope labeling have profound impacts on interpretation of the genesis of fibrosis. Strategies to maintain muscle function with aging should focus on the dynamic protein pool with attention to methodological strategies to assess those changes.
Aging Delays Epimorphic Regeneration in Mice
Authors: Brunauer Regina , Xia Ian G , Asrar Shabistan N , Dawson Lindsay A , Dolan Connor P , Muneoka Ken
Published: May 2021

Epimorphic regeneration is a multitissue regeneration process where amputation does not lead to scarring, but blastema formation and patterned morphogenesis for which cell plasticity and concerted cell–cell interactions are pivotal. Tissue regeneration declines with aging, yet if and how aging impairs epimorphic regeneration is unknown. Here, we show for the first time that aging derails the spatiotemporal regulation of epimorphic regeneration in mammals, first, by exacerbating tissue histolysis and delaying wound closure, and second, by impairing blastema differentiation and skeletal regrowth. Surprisingly, aging did not limit stem cell availability in the blastema but reduced osteoblast-dependent bone formation. Our data suggest that aging delays regeneration not by stem cell exhaustion, but functional defects of differentiated cells that may be driven by an aged wound environment and alterations in the spatiotemporal regulation of regeneration events. Our findings emphasize the importance of accurate timing of signaling events for regeneration and highlight the need for carefully timed interventions in regenerative medicine.
3-D parallel inversion of multichannel transient electromagnetic data using a moving footprint
Authors: Wang Xianxiang , You Nongren , Di Qingyun , Deng Juzhi , Chang Yongbang
Published: May 2021

The multichannel transient electromagnetic method (MTEM), sensitive to both near-surface and deeply buried geoelectric structures, is a useful geophysical tool to map resistive targets. A typical MTEM survey consists of a large number of receiver and transmitter positions. The produced data volume is much larger than a traditional transient electromagnetic method survey, posing computational difficulties for its data inversion and interpretation. We proposed a 3-D parallel inversion algorithm for MTEM data based on nonlinear conjugate gradient method and the moving footprint technique. The electromagnetic response and Fréchet derivative are first calculated in the frequency domain with integral equation method and then cosine transformed into time domain. We not only fully parallelize the forward modelling and Fréchet derivative calculation but also use a moving footprint to speed up the inversion. The footprints for different offsets are carefully evaluated through synthetic models. The effectiveness of the developed algorithm has been demonstrated through synthetic and case studies.
Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities
Authors: Yaden David B , Johnson Matthew W , Griffiths Roland R , Doss Manoj K , Garcia-Romeu Albert , Nayak Sandeep , Gukasyan Natalie , Mathur Brian N , Barrett Frederick S
Published: May 2021

Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called “hard problem of consciousness,” which involves explaining how first-person experience can emerge. However, psychedelics bear on multiple “easy problems of consciousness,” which involve relations between subjectivity, brain function, and behavior. In this review, we discuss common meanings of the term “consciousness” when used with regard to psychedelics and consider some models of the effects of psychedelics on the brain that have also been associated with explanatory claims about consciousness. We conclude by calling for epistemic humility regarding the potential for psychedelic research to aid in explaining the hard problem of consciousness while pointing to ways in which psychedelics may advance the study of many specific aspects of consciousness.
Homotopy Exact Sequence for the Pro-Étale Fundamental Group
Authors: Lara Marcin
Published: May 2021

The pro-étale fundamental group of a scheme, introduced by Bhatt and Scholze, generalizes the usual étale fundamental group $\pi _1^{\acute{\mathrm{e}}{\mathrm{t}}}$ defined in SGA1 and leads to an interesting class of “geometric coverings” of schemes, generalizing finite étale covers. We prove exactness of the general homotopy sequence for the pro-étale fundamental group, i.e., that for a geometric point $\bar{s}$ on $S$ and a flat proper morphism $X \rightarrow S$ of finite presentation whose geometric fibres are connected and reduced, the sequence $ \pi _1^{{\mathrm{pro}}\acute{\mathrm{e}}{\mathrm{t}}}(X_{\bar{s}}) \rightarrow \pi _1^{{\mathrm{pro}}\acute{\mathrm{e}}{\mathrm{t}}}(X) \rightarrow \pi _1^{{\mathrm{pro}}\acute{\mathrm{e}}{\mathrm{t}}}(S) \rightarrow 1 $ is “nearly exact.” This generalizes a theorem of Grothendieck from finite étale covers to geometric coverings. We achieve the proof by constructing an infinite (i.e., non-quasi-compact) analogue of the Stein factorization in this setting.
Implementing a new antibiotic allergy protocol in clinical practice: well-trusted but not used
Authors: Hanssen P , Nieuwhof C , van Mens S , van de Plas A , Horstman K
Published: May 2021

Background

Suboptimal antibiotic prescriptions in patients with an antibiotic allergy label lead to increased incidence of adverse events and antimicrobial resistance (AMR). An antibiotic allergy protocol was developed in a Dutch academic hospital guiding optimal and safe antibiotic use in potentially penicillin-allergic patients. Informed by previous studies of implementation processes in clinical care, we studied the implementation of this protocol.

Methods

Medical professionals in the Departments of Surgery, Internal Medicine, and Pulmonary Care were interviewed. Additionally, focus groups were conducted in Internal Medicine and Pulmonary Care to validate the outcomes of the interviews.

Results

Dissemination of the protocol via the regular online hospital-wide guidance system did not have a significant impact on the knowledge about or use of the protocol. If healthcare professionals found the protocol, they thought it was valuable and expressed trust in the expertise embodied in it. However, its use in practice was rather minimal. Interviewees doubted the accuracy of the patient’s histories about their previous adverse drug reactions, and/or the information in their medical records and concluded that adherence to the expert guideline was needlessly risky. They felt the acute allergic reaction risk for a patient outweighed the risk of suboptimal therapy or future AMR.

Conclusions

For successful implementation and dissemination of the protocol, the accessibility of the protocol, the information about the actual risks of following the protocol and the registration of allergic history should be improved. However, whether this actually results in improvement also depends on changes in the hospital culture and organization.
Addressing the Situation of Women Deprived of Liberty: Recent Practice of the UN Working Group on Arbitrary Detention
Authors: Toomey Leigh
Published: May 2021

The arbitrary deprivation of liberty of women is a global problem. Women continue to be deprived of their liberty on discriminatory grounds in proceedings that do not meet basic standards of due process, both in the criminal justice and administrative detention contexts. Despite the development of standards to address this phenomenon and greater recognition by international human rights mechanisms of the challenges faced by female detainees, governments and private actors repeatedly exercise control over women by depriving them of their liberty, often for prolonged periods. This not only violates the right to liberty, but may in some circumstances prevent women from enjoying other fundamental human rights to equality, dignity, fair trial, privacy and family life, health, housing, education, work, as well as freedom from torture and ill-treatment, freedom of movement, religion or belief, expression, peaceful assembly and association. In this practice note, I consider five recent cases encountered by the UN Working Group on Arbitrary Detention involving women deprived of their liberty in different detention settings and countries. I argue that the increasing focus on gendered detention practices by the Working Group, which has a worldwide mandate from the Human Rights Council to investigate cases of arbitrary deprivation of liberty, may offer opportunities for change.
Cryo-EM performance testing of hardware and data acquisition strategies
Authors: Danev Radostin , Yanagisawa Haruaki , Kikkawa Masahide
Published: May 2021

The increasing popularity and adoption rate of cryo-electron microscopy (cryo-EM) is evidenced by a growing number of new microscope installations around the world. The quality and reliability of the instruments improved dramatically in recent years, but site-specific issues or unnoticed problems during installation could undermine productivity. Newcomers to the field may also have limited experience and/or low confidence in the capabilities of the equipment or their own skills. Therefore, it is recommended to perform an initial test of the complete cryo-EM workflow with an ‘easy’ test sample, such as apoferritin, before starting work with real and challenging samples. Analogous test experiments are also recommended for the quantification of new data acquisition approaches or imaging hardware. Here, we present the results from our initial tests of a recently installed Krios G4 electron microscope equipped with two latest generation direct electron detector cameras—Gatan K3 and Falcon 4. Three beam-image shift–based data acquisition strategies were also tested. We detail the methodology and discuss the critical parameters and steps for performance testing. The two cameras performed equally, and the single- and multi-shot per-hole acquisition schemes produced comparable results. We also evaluated the effects of environmental factors and optical flaws on data quality. Our results reaffirmed the exceptional performance of the software aberration correction in Relion in dealing with severe coma aberration. We hope that this work will help cryo-EM teams in their testing and troubleshooting of hardware and data collection approaches.
Hypoxia-Related Radiomics and Immunotherapy Response: A Multicohort Study of Non-Small Cell Lung Cancer
Authors: Tunali Ilke , Tan Yan , Gray Jhanelle E , Katsoulakis Evangelia , Eschrich Steven A , Saller James , Aerts Hugo J W L , Boyle Theresa , Qi Jin , Guvenis Albert , Gillies Robert J , Schabath Matthew B
Published: May 2021

Background

Immunotherapy yields survival benefit for some advanced stage non-small cell lung cancer (NSCLC) patients. Because highly predictive biomarkers of immunotherapy response are an unmet clinical need, we used pretreatment radiomics and clinical data to train and validate a parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy.

Methods

Three cohorts of NSCLC patients treated with immunotherapy were analyzed: training (n = 180), validation 1 (n = 90), and validation 2 (n = 62). The most informative clinical and radiomic features were subjected to decision tree analysis, which stratified patients into risk groups of low, moderate, high, and very high risk of death after initiation of immunotherapy. All statistical tests were 2-sided.

Results

The very high-risk group was associated with extremely poor overall survival (OS) in validation cohorts 1 (hazard ratio [HR] = 5.35, 95% confidence interval [CI] = 2.14 to 13.36; 1-year OS = 11.1%, 95% CI = 1.9% to 29.8%; 3-year OS = 0%) and 2 (HR = 13.81, 95% CI = 2.58 to 73.93; 1-year OS = 47.6%, 95% CI = 18.2% to 72.4%; 3-year OS = 0%) when compared with the low-risk group (HR = 1.00) in validation cohorts 1 (1-year OS = 85.0%, 95% CI = 60.4% to 94.9%; 3-year OS = 38.9%, 95% CI = 17.1% to 60.3%) and 2 (1-year OS = 80.2%, 95% CI = 40.3% to 94.8%; 3-year OS = 40.1%, 95% CI = 1.3% to 83.5%). The most informative radiomic feature, gray-level co-occurrence matrix (GLCM) inverse difference, was positively associated with hypoxia-related carbonic anhydrase 9 using gene-expression profiling and immunohistochemistry.

Conclusion

Utilizing standard-of-care imaging and clinical data, we identified and validated a novel parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Based on this model, clinicians can identify patients who are unlikely to respond to immunotherapy.
Successful management of cervical ectopic pregnancy with embryo reduction: report of three cases
Authors: Ortiz Ginna , Kameyama Nicolas , Sulaiman Jean Paul , Lopez-Bayghen Esther
Published: May 2021

If methotrexate (MTX) fails to resolve cervical ectopic pregnancies (CEP), the remaining surgical options result in the potential loss of the patient’s fertility. Therefore, we examined if the embryo reduction technique can resolve the CEP without any complications while conserving the patient’s fertility. We report three cases in which CEP didn’t respond to MTX but was successfully solved by embryo reduction. Each patient underwent a standard in vitro fertilization (IVF) protocol. Once CEP was confirmed, the pregnancy’s location, the fetus’s size and gestational sac and heartbeat were determined. Afterward, embryo reduction was performed under general anesthesia (operative time: ~30 min). All patients had successful procedures without any postoperative complications. Since the procedure, one woman was pregnant and delivered, the second has registered a positive β-human chorionic gonadotropin test and the last is waiting for IVF preparation. In summary, embryo reduction is a feasible approach in the management of CEP with favorable fertility outcomes.
Searching for dark energy in the matter-dominated era
Authors: Bull Philip , White Martin , Slosar Anže
Published: May 2021

Most efforts to detect signatures of dynamical dark energy (DE) are focused on late times, z ≲ 2, where the DE component begins to dominate the cosmic energy density. Many theoretical models involving dynamical DE exhibit a ‘freezing’ equation of state however, where w → −1 at late times, with a transition to a ‘tracking’ behaviour at earlier times (with w ≫ −1 at sufficiently high redshift). In this paper, we study whether constraints on background distance indicators from large-scale structure (LSS) surveys in the post-reionization matter-dominated regime, 2 ≲ z ≲ 6, are sensitive to this behaviour, on the basis that the DE component should remain detectable (despite being strongly subdominant) in this redshift range given sufficiently precise observations. Using phenomenological models inspired by parameter space studies of Horndeski (generalized scalar-tensor) theories, we show how existing CMB and LSS measurements constrain the DE equation of state in the matter-dominated era, and examine how forthcoming galaxy surveys and 21 cm intensity mapping instruments can improve constraints in this regime at the background level. We also find that the combination of existing CMB and LSS constraints with DESI will already come close to offering the best possible constraints on H0 using BAO/galaxy power spectrum measurements, and that either a spectroscopic follow-up of the LSST galaxy sample (e.g. MegaMapper or SpecTel) or a Stage 2/PUMA-like intensity mapping survey, both at z ≳ 2, would offer better constraints on the class of models considered here than a comparable cosmic variance-limited galaxy survey at z ≲ 1.5.
The NIRVANDELS Survey: a robust detection of α-enhancement in star-forming galaxies at z ≃ 3.4
Authors: Cullen F , Shapley A E , McLure R J , Dunlop J S , Sanders R L , Topping M W , Reddy N A , Amorín R , Begley R , Bolzonella M , Calabrò A , Carnall A C , Castellano M , Cimatti A , Cirasuolo M , Cresci G , Fontana A , Fontanot F , Garilli B , Guaita L , Hamadouche M , Hathi N P , Mannucci F , McLeod D J , Pentericci L , Saxena A , Talia M , Zamorani G
Published: May 2021

We present results from the NIRVANDELS survey on the gas-phase metallicity (Zg, tracing O/H) and stellar metallicity (Z⋆, tracing Fe/H) of 33 star-forming galaxies at redshifts 2.95 < z < 3.80. Based on a combined analysis of deep optical and near-IR spectra, tracing the rest-frame far-ultraviolet (FUV; 1200–2000 Å) and rest-frame optical (3400–5500 Å), respectively, we present the first simultaneous determination of the stellar and gas-phase mass–metallicity relationships (MZRs) at z ≃ 3.4. In both cases, we find that metallicity increases with increasing stellar mass (M⋆) and that the power-law slope at M⋆ ≲ 1010M⊙ of both MZRs scales as $Z \propto M_{\star }^{0.3}$. Comparing the stellar and gas-phase MZRs, we present direct evidence for super-solar O/Fe ratios (i.e. α-enhancement) at z > 3, finding (O/Fe) = 2.54 ± 0.38 × (O/Fe)⊙, with no clear dependence on M⋆.
Spectral and timing evolution of MAXI J1631–479 during the 2018–19 outburst with NICER
Authors: Rout Sandeep K , Méndez Mariano , Belloni Tomaso M , Vadawale Santosh
Published: May 2021

The X-ray transient MAXI J1631–479 went into outburst on 2018 December 21 and remained active for about seven months. Owing to various constraints it was monitored by NICER only during the decay phase of the outburst for about four months. The NICER observations were primarily in the soft state with a brief excursion to the hard intermediate state. While the soft state spectrum was dominated by thermal disc emission, the hard intermediate state spectrum had maximum contribution from the thermal Comptonization. Almost all intermediate-state power spectra had a Type-C low frequency quasi-periodic oscillation (within 4–10 Hz), often accompanied by a harmonic component. The frequency of these oscillations increased and the fractional rms decreased with inner-disc temperature suggesting a geometric origin. The rms spectra during the intermediate state had a hard shape from above 1 keV. Below 1 keV the shape could not be constrained in most cases, while only a few observations showed a rise in amplitude.
Symmetric wave modes in coronal flux tubes with magnetically twisted layer
Authors: Lopin Igor P
Published: May 2021

The properties of axisymmetric magnetohydrodynamic wave modes are studied for the model of coronal magnetic tube, consisting of a central cord with homogeneous axial magnetic field, surrounded by an annulus with twisted magnetic field. This model mimics the coronal loops with radially localized magnetic twist. The derived dispersion relation is solved numerically. A number of limiting cases are examined analytically. The two families of axisymmetric modes are found to exist in the model. The first one includes an infinite number of fast-sausage modes (FSMs), modified by the twist and the second one is a set of modes with frequencies, lying in a narrow band, closed to Alfvén frequency of a twisted layer ωA0. The fundamental FSM (the mode of the lowest radial order) exists as a trapped mode for the entire range of axial wavenumbers. Its phase speed is always below the Alfvén speed of a magnetically twisted layer. This mode has a weak dispersion in the range of long and intermediate wavelengths. The higher radial order FSMs were found to be less sensitive to the presence of the magnetic twist. Both the fundamental FSM in the case of a weak magnetic twist and a set of symmetric modes for arbitrary twist have very similar frequencies, which are nearly equal to ωA0. This property implies that aforementioned wave modes behave like Alfvén torsional modes in the twisted annulus and like the radial modes in the untwisted core and environment, moreover they are strongly coupled. The main results of the study are discussed in the framework of their applications to coronal seismology.
Evaluation of a Smoking Cessation Patient Decision Aid That Integrates Information About E-Cigarettes
Authors: Kollath-Cattano Christy , Thrasher James F , Salloum Ramzi G , Albano Andrew W , Jindal Meenu , Durkin Martin , Strayer Scott M
Published: May 2021

Introduction

Smokers increasingly use e-cigarettes to try to quit smoking, even more than recommended cessation methods. However, few smokers discuss the range of cessation options with their physicians. Decision aids can inform smokers about smoking cessation options, including evidence about e-cigarettes, and encourage smokers to engage in shared decision making with their physician.

Aims and Methods

This study aimed to evaluate a smoking cessation decision aid that included e-cigarette risks and benefits. Adult smokers were recruited from primary care clinics for two research phases: (1) usability and acceptability testing of the decision aid (n = 37); and (2) pre-post study that compared usual care (n = 90) with implementation of the decision aid in clinics (n = 90). For the latter, outcome measures included frequency of clinical discussions of readiness to quit, methods to quit in general, and of specific cessation methods, in addition to decisional conflict, communication satisfaction, and overall patient satisfaction.

Results

Smokers indicated high usability and acceptability of the decision aid. In the pre-post evaluation, decision aid implementation was associated with higher rates of smokers: being asked if they were ready to quit smoking (89% vs. 67%, respectively; p < .001); discussing methods for smoking cessation in general (81% vs. 48%; p < .001); and discussing specific cessation methods (NRT 55% vs. 26%, p < .001; prescription medications 26% vs. 12%, p = .022). Decision aid use was also associated with higher overall patient satisfaction with the physician visit.

Conclusions

Smoking cessation decision aids that incorporate information about e-cigarettes are acceptable among smokers and can lead to evidence-based clinical discussions about smoking cessation.

Implications

Smokers use e-cigarettes more than recommended cessation methods when they are trying to quit smoking, yet few physicians discuss the risks and benefits of e-cigarettes with their patients who smoke. This study presents preliminary findings about the feasibility and usability of a clinically based iPad-delivered smoking cessation decision aid that integrates information about e-cigarettes. Although promising, further research with randomized designs, larger samples, and longer-term follow-up is needed to determine whether this type of intervention can effectively promote cessation of all tobacco products and, for those not ready to quit smoking, the use of e-cigarettes for harm reduction.
Evaluation of 6 Commercial SARS-CoV-2 Serology Assays Detecting Different Antibodies for Clinical Testing and Serosurveillance
Authors: Nicholson Suellen , Karapanagiotidis Theo , Khvorov Arseniy , Douros Celia , Mordant Francesca , Bond Katherine , Druce Julian , Williamson Deborah A , Purcell Damian , Lewin Sharon R , Sullivan Sheena , Subbarao Kanta , Catton Mike
Published: May 2021

Background

Serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complements nucleic acid tests for patient diagnosis and enables monitoring of population susceptibility to inform the coronavirus disease 2019 (COVID-19) pandemic response. It is important to understand the reliability of assays with different antigen or antibody targets to detect humoral immunity after SARS-CoV-2 infection and to understand how antibody (Ab) binding assays compare to those detecting neutralizing antibody (nAb), particularly as we move into the era of vaccines.

Methods

We evaluated the performance of 6 commercially available enzyme-linked immunosorbent assays (ELISAs), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total or nAb. A result subset was compared with a cell culture–based microneutralization (MN) assay. We tested sera from patients with prior reverse transcription polymerase chain reaction–confirmed SARS-CoV-2 infection, prepandemic sera, and potential cross-reactive sera from patients with other non-COVID-19 acute infections.

Results

For sera collected >14 days post–symptom onset, the assay achieving the highest sensitivity was the Wantai total Ab at 100% (95% CI, 94.6%–100%), followed by 93.1% for Euroimmun NCP-IgG, 93.1% for GenScript sVNT, 90.3% for Euroimmun S1-IgG, 88.9% for Euroimmun S1-IgA, and 83.3% for Wantai IgM. Specificity for the best-performing assay was 99.5% for the Wantai total Ab, and for the lowest-performing assay it was 97.1% for sVNT (as per the Instructions for Use [IFU]). The Wantai Total Ab had the best agreement with MN at 98% followed by Euroimmun S1-IgA, Euro NCP-IgG, and sVNT (as per IFU) with 97%, 97% and 95%, respectively; Wantai IgM had the poorest agreement at 93%.

Conclusions

Performance characteristics of the SARS-CoV-2 serology assays detecting different antibody types are consistent with those found in previously published reports. Evaluation of the surrogate virus neutralization test in comparison to the Ab binding assays and a cell culture–based neutralization assay showed good result correlation between all assays. However, correlation between the cell-based neutralization test and some assays detecting Ab’s not specifically involved in neutralization was higher than with the sVNT. This study demonstrates the reliability of different assays to detect the humoral immune response following SARS-CoV-2 infection, which can be used to optimize serological test algorithms for assessing antibody responses post–SARS-CoV-2 infection or vaccination.
Danger-associated molecular pattern molecules and the receptor for advanced glycation end products enhance ANCA-induced responses
Authors: Page Theresa H , Chiappo Derick , Brunini Francesca , Garnica Josep , Blackburn Jack , Dudhiya Fayaz , Prendecki Maria , McAdoo Stephen P , Pusey Charles D
Published: May 2021

Objectives

The pro-inflammatory activities of the calgranulins and HMGB1 can be counteracted by sRAGE, the soluble form of their shared receptor. To understand the role of these molecules in AAV and their potential as therapeutic targets we have studied (i) the relationship between these DAMPS and disease activity; (ii) the expression of RAGE and sRAGE in biopsy tissue and peripheral blood; and (iii) the effect of these molecules on ANCA-mediated cytokine production.

Methods

We examined circulating levels of calgranulins (S100A8/A9 and S100A12), HMGB1 and sRAGE by ELISA. RAGE was examined in AAV kidney and lung biopsies by immunohistochemistry and RAGE expression was monitored in peripheral blood by qPCR. In vitro, the effect of co-stimulating PBMC with ANCA and S100A8/A9 on cytokine production was studied by ELISA.

Results

We found significantly raised levels of calgranulins and HMGB1 in active AAV regardless of clinical phenotype (PR3+/MPO+ AAV). Levels of calgranulins showed significant correlations with each other. RAGE protein and message was raised in peripheral blood and in cells infiltrating kidney and lung biopsy tissue, while sRAGE was lowered. Furthermore, ANCA-mediated production of IL-8 from PBMC was significantly enhanced by the presence of S100A8/A9 in a RAGE/TLR4-dependent manner.

Conclusions

Raised circulating calgranulins provide a good marker of disease activity in AAV and are unlikely to be counteracted by sRAGE. Increased RAGE expression in AAV indicates receptor stimulation in active disease that may exacerbate ANCA-induced cytokine production. Targeting the RAGE pathway may provide a useful therapeutic approach in AAV.
Sleep profile predicts the cognitive decline of mild-moderate Alzheimer’s disease patients
Authors: Targa Adriano D S , Benítez Iván D , Dakterzada Faridé , Carnes Anna , Pujol Montse , Jorge Carmen , Minguez Olga , Dalmases Mireia , Sánchez-de-la-Torre Manuel , Barbé Ferran , Piñol-Ripoll Gerard
Published: May 2021

Study Objectives

To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer’s disease.

Methods

Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer’s disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers).

Results

The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of −1.51 (95% CI: −2.43 to −0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose–response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023).

Conclusions

Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer’s disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline.

Clinical Trial Information

Role of Hypoxia Ans Sleep Fragmentation in Alzheimer’s Disease. and Sleep Fragmentation. Completed. NCT02814045