bluuebunny/crossref_metadata_2025 huggingface dataset:
Reset Required: The Euro-area Crisis Management and Deposit Insurance Framework
Authors: Huertas Thomas F
Published: April 2022

The crisis management and deposit insurance (CMDI) framework in the euro area requires a reset. This article explains why and proposes a new framework. This could start as early as 1 January 2024 when significant institutions in the euro area will have met requirements to have enough subordinated obligations outstanding to recapitalize the bank if it were to fail. The proposed framework has four components: a single lender of last resort (the European Central Bank); a single presumptive path for resolution (exit via the use of bail-in to facilitate orderly liquidation of the failed bank by the Single Resolution Board under a solvent wind-down strategy); an investor of last resort in a bank’s gone-concern capital (its national deposit guarantee scheme); and a Single Deposit Guarantee Scheme (the Single Resolution Fund with a backstop from the European Stability Mechanism). Together, these measures would limit forbearance, assure bail-in did not touch deposits, promote competition, limit recourse to taxpayer money, standardize resolution procedures for all banks, complete Banking Union and guarantee that a euro of covered deposits would remain a euro, all without forcing national deposit guarantee schemes to reinsure one another. Last but not least the proposed framework would promote financial stability.
ProteinsPlus: a comprehensive collection of web-based molecular modeling tools
Authors: Schöning-Stierand Katrin , Diedrich Konrad , Ehrt Christiane , Flachsenberg Florian , Graef Joel , Sieg Jochen , Penner Patrick , Poppinga Martin , Ungethüm Annett , Rarey Matthias
Published: April 2022

Upon the ever-increasing number of publicly available experimentally determined and predicted protein and nucleic acid structures, the demand for easy-to-use tools to investigate these structural models is higher than ever before. The ProteinsPlus web server (https://proteins.plus) comprises a growing collection of molecular modeling tools focusing on protein–ligand interactions. It enables quick access to structural investigations ranging from structure analytics and search methods to molecular docking. It is by now well-established in the community and constantly extended. The server gives easy access not only to experts but also to students and occasional users from the field of life sciences. Here, we describe its recently added new features and tools, beyond them a novel method for on-the-fly molecular docking and a search method for single-residue substitutions in local regions of a protein structure throughout the whole Protein Data Bank. Finally, we provide a glimpse into new avenues for the annotation of AlphaFold structures which are directly accessible via a RESTful service on the ProteinsPlus web server.
Ultrastructure and nuclear architecture of telomeric chromatin revealed by correlative light and electron microscopy
Authors: Hübner Barbara , von Otter Eric , Ahsan Bilal , Wee Mei Ling , Henriksson Sara , Ludwig Alexander , Sandin Sara
Published: April 2022

Telomeres, the ends of linear chromosomes, are composed of repetitive DNA sequences, histones and a protein complex called shelterin. How DNA is packaged at telomeres is an outstanding question in the field with significant implications for human health and disease. Here, we studied the architecture of telomeres and their spatial association with other chromatin domains in different cell types using correlative light and electron microscopy. To this end, the shelterin protein TRF1 or TRF2 was fused in tandem to eGFP and the peroxidase APEX2, which provided a selective and electron-dense label to interrogate telomere organization by transmission electron microscopy, electron tomography and scanning electron microscopy. Together, our work reveals, for the first time, ultrastructural insight into telomere architecture. We show that telomeres are composed of a dense and highly compacted mesh of chromatin fibres. In addition, we identify marked differences in telomere size, shape and chromatin compaction between cancer and non-cancer cells and show that telomeres are in direct contact with other heterochromatin regions. Our work resolves the internal architecture of telomeres with unprecedented resolution and advances our understanding of how telomeres are organized in situ.
Layer-by-layer epitaxy of multi-layer MoS2 wafers
Authors: Wang Qinqin , Tang Jian , Li Xiaomei , Tian Jinpeng , Liang Jing , Li Na , Ji Depeng , Xian Lede , Guo Yutuo , Li Lu , Zhang Qinghua , Chu Yanbang , Wei Zheng , Zhao Yanchong , Du Luojun , Yu Hua , Bai Xuedong , Gu Lin , Liu Kaihui , Yang Wei , Yang Rong , Shi Dongxia , Zhang Guangyu
Published: April 2022

The 2D semiconductor of MoS2 has great potential for advanced electronics technologies beyond silicon. So far, high-quality monolayer MoS2 wafers have been available and various demonstrations from individual transistors to integrated circuits have also been shown. In addition to the monolayer, multilayers have narrower band gaps but improved carrier mobilities and current capacities over the monolayer. However, achieving high-quality multi-layer MoS2 wafers remains a challenge. Here we report the growth of high-quality multi-layer MoS2 4-inch wafers via the layer-by-layer epitaxy process. The epitaxy leads to well-defined stacking orders between adjacent epitaxial layers and offers a delicate control of layer numbers up to six. Systematic evaluations on the atomic structures and electronic properties were carried out for achieved wafers with different layer numbers. Significant improvements in device performances were found in thicker-layer field-effect transistors (FETs), as expected. For example, the average field-effect mobility (μFE) at room temperature (RT) can increase from ∼80 cm2·V–1·s–1 for monolayers to ∼110/145 cm2·V–1·s–1 for bilayer/trilayer devices. The highest RT μFE of 234.7 cm2·V–1·s–1 and record-high on-current densities of 1.70 mA·μm–1 at Vds = 2 V were also achieved in trilayer MoS2 FETs with a high on/off ratio of >107. Our work hence moves a step closer to practical applications of 2D MoS2 in electronics.
Short-term variations of ΔT from Yángdì-eclipse on AD 616 May 21, Suiko eclipse on AD 628 April 10, and neighboring solar eclipses and occultations
Authors: Tanikawa Kiyotaka , Sôma Mitsuru , Qu Anjing
Published: April 2022

We obtain a narrower and more reliable range of the delay of Earth’s rotation, ΔT, than those obtained before. At the same time, we determine the observation sites of these eclipses in the early seventh century. The eclipses are the one on AD 616 May 21 recorded in the history book Suíshū of the Suí dynasty, and the one on AD 628 April 10 recorded in the first official Japanese history book Nihon Shoki (also called as Nihongi). Our method of analysis is to express multiple observations simultaneously on the “Sôma” diagram in which the ordinate is ΔT and the abscissa is the correction to the coefficient of the lunar tidal term. In order to increase the reliability of the present result, we analyze several solar eclipses and an occultation of Mars during the period from the fifth century to the end of the seventh century. These analyses show the short-term variations of ΔT off the smoothed spline curves of Stephenson, Morrison, and Hohenkerk (2016, Proc. R. Soc. A, 472, 20160404).
Creating a Learning Scenario for Cardiopulmonary Resuscitation Training During the COVID-19 Pandemic
Authors: Caballero Valderrama María de Regla , Allande Cussó Regina , Cervera Barajas Antonio , Pérez Ruz Rocío , Pérez López Enrique , Caballero Oliver Antonio
Published: April 2022

Introduction:

Different organizations have recommended changes in life support in the COVID-19 pandemic, just when maintaining the competence in cardiopulmonary resuscitation is compromised because on-site training must be avoided. We developed a pilot teaching-learning experience to promote cardiopulmonary resuscitation skills acquisition in this situation. The aim of this study was to describe that tool and to analyze its usefulness.

Methods:

The experience consisted of three phases: first, reviewing the scientific literature; second, defining written local recommendations and recording a short video simulating the initial attention to a cardiac arrest in this COVID-19 context; third, creating a test to be answered by hospital health professionals.

Results:

The final sample was 121 subjects; 66.1% were women; the mean age was 45.8 years (SD = 10.24). Among them, 43% were doctors, 43% nurses, 4.1% nursing assistants, and 9.9% others. 89.3% participants had received prior training in life support. In the test, questions 1, 2, 5, 6, 7, and 8 were answered correctly by more than 80%; questions 3 and 4 were answered correctly by 57.9% and 41.3%, respectively. All participants expressed that the video helped them to refresh their knowledge and skills in life support.

Discussion:

When on-site training is not possible, distance learning—as in our teaching-learning innovation because of the COVID-19 pandemic—may be a valid option to acquire/refresh cardiopulmonary resuscitation skills.
Synthetic Negative Controls: Using Simulation to Screen Large-scale Propensity Score Analyses
Authors: Wyss Richard , Schneeweiss Sebastian , Lin Kueiyu Joshua , Miller David P. , Kalilani Linda , Franklin Jessica M.
Published: April 2022

The propensity score has become a standard tool to control for large numbers of variables in healthcare database studies. However, little has been written on the challenge of comparing large-scale propensity score analyses that use different methods for confounder selection and adjustment. In these settings, balance diagnostics are useful but do not inform researchers on which variables balance should be assessed or quantify the impact of residual covariate imbalance on bias. Here, we propose a framework to supplement balance diagnostics when comparing large-scale propensity score analyses. Instead of focusing on results from any single analysis, we suggest conducting and reporting results for many analytic choices and using both balance diagnostics and synthetically generated control studies to screen analyses that show signals of bias caused by measured confounding. To generate synthetic datasets, the framework does not require simulating the outcome-generating process. In healthcare database studies, outcome events are often rare, making it difficult to identify and model all predictors of the outcome to simulate a confounding structure closely resembling the given study. Therefore, the framework uses a model for treatment assignment to divide the comparator population into pseudo-treatment groups where covariate differences resemble those in the study cohort. The partially simulated datasets have a confounding structure approximating the study population under the null (synthetic negative control studies). The framework is used to screen analyses that likely violate partial exchangeability due to lack of control for measured confounding. We illustrate the framework using simulations and an empirical example.
INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE COEXISTENT WITH RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Stappler Theodor , Montesel Andrea , Konstantinidis Lazaros , Wolfensberger Thomas J. , Eandi Chiara M.
Published: April 2022

Purpose:

To report the clinical features and treatment outcomes of patients with macular hole coexistent with rhegmatogenous retinal detachment surgically treated with pars plana vitrectomy and inverted internal limiting membrane flap technique.

Methods:

Eleven consecutive patients with rhegmatogenous retinal detachment and macular hole who underwent vitrectomy and internal limiting membrane peeling with the inverted flap technique between December 2017 and February 2021 were retrospectively evaluated. The main outcome measures were retinal reattachment rate, macular hole closure rate, and postoperative best-corrected visual acuity. A nonsystematic literature review was performed to compare the study outcomes with those previously reported.

Results:

The primary retinal reattachment rate was 90% (10/11) with one surgery and 100% with 2 surgical procedures. Macular hole closure was achieved in all patients (11/11). All patients showed an improvement in visual acuity at the final postoperative visit, and the mean postoperative best-corrected visual acuity was 0.60 ± 0.32 logarithm of the minimum angle of resolution (20/80 Snellen equivalent).

Conclusion:

Vitrectomy with the inverted internal limiting membrane flap technique achieved not only favorable anatomical retinal reattachment rates but also an encouraging recovery of central macular anatomy and visual function in patients with macular hole coexistent with rhegmatogenous retinal detachment.
“Air-Assisted” Donor Lenticule Insertion in Descemet Stripping Endothelial Keratoplasty in Aphakia With Large Iris Defect and Without Posterior Capsular Support
Authors: Basak Soham , Basak Samar K.
Published: April 2022

Purpose:

The purpose of this study was to report a novel technique of donor lenticule insertion in Descemet stripping endothelial keratoplasty (DSEK) in aphakic corneal edema with large iris defect and without any posterior capsular support.

Methods:

This was a retrospective consecutive interventional case series. Clinical records of ten 1-eyed aphakic patients with corneal edema with large iris defect and no capsular support who underwent air-assisted donor lenticule insertion in DSEK were evaluated. After making 6.0- to 6.5-mm sclerocorneal tunnel and 2 side ports, limited anterior vitrectomy was performed if required. Then, Descemetorhexis was performed under air through side ports. Manually dissected donor lenticule was inserted into the anterior chamber under full-chamber air by a 30-G needle push-in technique. Further air tamponade was given if necessary. No fluid–air exchange was performed. The patient was kept on the same operating table for at least 1 hour and then shifted. Graft attachments in early postoperative period, corrected distant visual acuity, and endothelial cell density after 3, 6, and 12 months were analyzed.

Results:

The mean postoperative follow-up period was 19.2 ± 6.7 months. There was no donor dislocation in this small group. All patients achieved a corrected distant visual acuity of 0.70 (20/100) after 3 months and maintained until 12 months. The endothelial cell density at 3 months (n = 8) was 2028 ± 151/mm2, at 6 months (n = 7) 1776 ± 198/mm2, and at 12 months (n = 7) 1721 ± 172/mm2. The corresponding endothelial cell loss was 25.8% ± 5.6%, 34.4% ± 5.1%, and 37.8% ± 7.1%, respectively. One graft failed after 15 months.

Conclusions:

“Air-assisted” donor lenticule insertion in DSEK is a safe surgical technique in aphakic patients with corneal edema with large iris defect and no capsular support.
Role of Blepharoexfoliation in Demodex Blepharitis: A Randomized Comparative Study
Authors: Mohammad-Rabei Hossein , Arabi Amir , Shahraki Toktam , Rezaee-alam Zahra , Baradaran-rafii Alireza
Published: April 2022

Purpose:

The purpose of this study was to evaluate the safety and efficacy of blepharoexfoliation in the treatment of Demodex blepharitis.

Methods:

Patients with microscopically approved Demodex blepharitis were enrolled. Patients in the treatment group were treated once with in-office blepharoexfoliation (BlephEx LLC; Franklin, TN) using tea tree oil 2% shampoo, followed by eyelid scrubs with tea tree oil 2% shampoo twice a day for 8 weeks. Patients in the control group were treated with the same protocol, except for the in-office sham blepharoexfoliation procedure. As the main outcome measurement, the changes in the severity of symptoms [Ocular Surface Disease Index (OSDI) score] were compared. The changes in Demodex count and meibomian gland dysfunction (MGD) severity were compared as the secondary outcome measurements.

Results:

Eighty-one patients (36 male and 45 female) were included. The mean age of the patients was 53.56 ± 8.13 years. The mean baseline OSDI score was 33.30 ± 11.80. The mean baseline Demodex count was 4.84 ± 1.49. The Demodex count at the baseline visit was moderately correlated with the baseline OSDI score (R = 0.526, P = 0.011) and baseline MGD severity (P = 0.02). At the 8-week visit, the OSDI score was 22.62 ± 8.23 and 27.09 ± 9.11 in the blepharoexfoliation and control groups, respectively (P = 0.016). At the 8-week visit, the Demodex count was 2.6 ± 1.08 and 3.03 ± 1.27 in the treatment and control groups, respectively (P = 0.025). MGD improved in both groups (P = 0.84). In the blepharoexfoliation group, the change in the OSDI score was moderately correlated with the baseline OSDI score (R = 0.611, P = 0.01).

Conclusions:

One session of blepharoexfoliation, followed by manual eyelid scrubs was more effective than eyelid scrubs alone in reducing patients’ symptoms and Demodex count.
Multifaceted Physical Therapy Approach in Male Adolescent With Coccydynia: A Case Report
Authors: Knepper Lauren
Published: April 2022

Background:

Coccydynia is a rare condition in the adolescent population, especially in adolescent boys. Chronic coccydynia negatively impacts quality of life, participation in school, and recreational activities. Evidence is largely lacking for physical therapy approach to treatment for chronic coccydynia.

Case Description:

This case report describes a 14-year–old adolescent boy, presenting with chronic coccydynia. This patient presented with poor posture, myofascial restrictions, coccyx hypomobility, and deficits in soft tissue length and core strength. Treatment was 45 to 60 minutes, twice per week for 12 sessions, then reduced to once per week for 2 sessions.

Outcomes:

Symptoms appeared to be as a result of prolonged poor posture, contributing to adaptive shortening of soft tissues and pelvic floor overactivity. Treatment focused on improving posture, restoring soft tissue length, addressing myofascial restrictions in the abdomen, and improving core strength to maintain proper posture. Symptoms decreased as diaphragmatic motor control improved, and myofascial restrictions lessened with instrument-assisted soft tissue mobilization and cupping. The patient was able to resume prior level of function with few activity modifications.

Discussion:

A multifaceted physical therapy treatment approach was utilized, including a combination of therapeutic exercise and manual therapies. Myofascial trigger points were difficult to address due to patient sensitivity with myofascial techniques; instrument-assisted soft tissue mobilization and cupping were effective in treatment of trigger points. Physical therapy was effective in resolving this case of coccydynia.
Distinct Worst Pain Profiles in Oncology Outpatients Undergoing Chemotherapy
Authors: Shin Joosun , Oppegaard Kate , Calvo-Schimmel Alejandra , Harris Carolyn , Cooper Bruce A. , Paul Steven M. , Conley Yvette P. , Hammer Marilyn J. , Cartwright Frances , Kober Kord M. , Levine Jon D. , Miaskowski Christine
Published: April 2022

Background

While pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics.

Objective

The aims of this study were to identify subgroups of patients with distinct worst pain severity profiles and evaluate for differences among these subgroups in demographic, clinical, and pain characteristics and stress and symptom scores.

Methods

Patients (n = 934) completed questionnaires 6 times over 2 chemotherapy cycles. Worst pain intensity was assessed using a 0- to 10-point numeric rating scale. Brief Pain Inventory was used to assess various pain characteristics. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles.

Results

Three worst pain profiles were identified (low [17.5%], moderate [39.9%], severe [42.6%]). Compared with the other 2 classes, severe class was more likely to be single and unemployed and had a lower annual household income, a higher body mass index, a higher level of comorbidity, and a poorer functional status. Severe class was more likely to have both cancer and noncancer pain, a higher number of pain locations, higher frequency and duration of pain, worse pain quality scores, and higher pain interference scores. Compared with the other 2 classes, severe class reported lower satisfaction with pain management and higher global, disease-specific, and cumulative life stress, as well as higher anxiety, depression, fatigue, sleep disturbance, and cognitive dysfunction scores.

Conclusions

Unrelieved pain is a significant problem for more than 80% of outpatients.

Implications for Practice

Clinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services.
Ethical and Moral Conflicts in the Nursing Care of Pediatric Patients With Cancer and Their Families
Authors: dos Santos Maiara R. , da Silva Lucas T. P. , de Araújo Marina M. , Ferro Taís A. , Silva Isabella N. , Szylit Regina
Published: April 2022

Background

Pediatric oncology nurses encounter ethical and moral dilemmas when providing comprehensive care to pediatric patients with cancer and their families.

Objective

The aim of this study was to explore ethical and moral conflicts arising in the field of pediatric oncology from the perspective of nursing professionals.

Method

This qualitative secondary analysis was conducted with 10 nursing professionals from a pediatric cancer hospital through semistructured interviews and analyzed using thematic data analysis.

Results

Two themes emerged: (1) living with conflicts intrinsic to the relationships, which describes multiple sources of conflict in the relationships of nursing professionals with the team, with the family, and with seriously ill children, summarizing trigger-sensitive topics to be addressed for its mediation; (2) developing moral resilience, which represents how nurses reframe the conflicts and make use of strategies to avoid being personally harmful.

Conclusions

The results highlight the challenging work environment of pediatric oncology, recognizing the multiple natures of sensitive topics to nursing professionals during clinical decision making and the incipient strategies in dealing with ethical and moral conflicts.

Implications for Practice

This study reveals self-reflection and intuitive strategies as protective factors, which could be applied as a step to support nurses encountering ethical and moral conflicts in pediatric oncology daily practice. Furthermore, because of the limited support services for nursing professionals, it is necessary to foresee institutional policies to embrace the development of moral resilience.
Fat embolism syndrome in patients with bilateral femur fractures: a systematic review and case comparison
Authors: Kalbas Yannik , Seaver Thomas , Kumabe Yohei , Halvachizadeh Sascha , Lempert Maximilian , Pfeifer Roman , Marcantonio Andrew , Pape Hans-Christoph
Published: April 2022

Objectives:

Fat embolism and fat embolism syndrome (FES) remain common complications following long bone fractures. Incidence is highest after bilateral femur fractures. We performed a systematic review of FES after bilateral femur fractures and present two cases.

Data sources:

Systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus, and, Web of Science Library databases was performed in August 2021. Terms used including plural and alternate spellings: “fat embolism,”“fat embolism syndrome,”“fat embolus,” and “bilateral femur fracture.” Articles in German and English were considered. No time frame was applied.

Study selection:

Original studies, case series and case reports on fat embolism after bilateral femur fracture were included. Insufficient documentation or patients with relevant previous heath conditions were excluded.

Data extraction:

Abstracts were organized using EndNote X9 by Carivate. Three authors independently screened the abstracts; cross check of the extracted data was performed by the senior author.

Data synthesis:

Scarcity of articles only allowed for a qualitative synthesis. Data was compared with our cases and situated within the scientific background.

Results:

Ten articles were included for qualitative synthesis (n = 144 patients). The symptoms were inhomogeneous with neurological deficits being most prominent. Degree of displacement was high, when reported. Although the modes and timing of surgery varied, this appeared unrelated with outcome.

Conclusions:

FES remains a relevant complication after bilateral femur fractures, despite damage control strategies and improved reaming techniques. Fracture displacement and reduction maneuvers might play a more substantial role in the formation than previously accredited.

Level of evidence:

4
Tips and tricks to avoid implant failure in proximal femur fractures treated with cephalomedullary nails: a review of the literature
Authors: Petfield Joseph L. , Visscher Luke E. , Gueorguiev Boyko , Stoffel Karl , Pape Hans-Christoph
Published: April 2022

Objective:

To describe the surgical aspects potentially contributing to hardware failure of cephalomedullary nails.

Data Sources:

A search of the Embase, PubMed (MEDLINE), Web of Science, and the Cochrane library for reports of hardware failures after intramedullary fixation of proximal femur fractures. Issues of cut out and cut through phenomena related to technique were excluded. Expert opinion of 3 surgeons, each trained on several fixation systems at Level | trauma centers is reported.

Data Extraction:

Three authors extracted data using a predesigned form. Implant type, reported failure mechanism, and associated factors with implant failure were recorded as well as potential bias.

Results:

Of 2182 search results screened, 64 articles were deemed relevant for our research question and were included. The authors identified factors associated with implant failure: preoperative patient and fracture characteristics, intraoperative reduction, implant handling, and postoperative nonunion. Issues were identified as independent modifiable intraoperative risk factors: inadequate fracture reduction, varus position of femoral neck, direct damage of the cephalomedullary nail aperture by eccentric drilling related to guide sleeve handling, and implant design mechanism failures.

Conclusions:

Multiple factors associated with intraoperative handling can influence the healing of proximal femur fractures. Although many of these have been well described and are taught in fracture courses, surgeons should be aware of subtle intraoperative complications reported in the literature that can weaken implants and add to the likelihood of early failure.

Level of Evidence: IV
The Confounding Ultrasound Diagnosis of Ectopic Pregnancy: Lessons From Peer Learning
Authors: Yun Jung H. , Horrow Mindy M. , Goykhman Igor , Rodgers Shuchi K.
Published: April 2022

As the treatment of ectopic pregnancy (EP) has shifted increasingly to medical therapies, the ultrasound (US) diagnosis of EP must necessarily favor specificity over sensitivity. Our review of peer learning cases of EP and early intrauterine pregnancies found several types of pitfalls and problems, which will be described in this essay. These issues include the following: differentiation of tubal EP from a corpus luteum by echogenicity relative to ovarian parenchyma, push technique, and claw sign; how to distinguish interstitial EP from eccentrically located intrauterine pregnancies (angular); use of trophoblastic flow in abnormal intrauterine locations to help identify cesarean scar or cervical implantations; recognition that hemoperitoneum without visualized EP may be due to EP or hemorrhagic cyst; and that distinguishing an abortion in progress from a pregnancy of unknown location may not always be possible and requires clinical follow-up. This essay will also illustrate the consensus terminology that our radiology department has developed in conjunction with our obstetrics and gynecology colleagues to communicate clear diagnoses and reduce the risk of misdiagnosis and adverse outcomes.
Effect of Temporal Artery Biopsy Length and Laterality on Diagnostic Yield
Authors: Shen Alice , Gruener Anna M. , Carey Andrew R. , Henderson Amanda D. , Poostchi Ali , McCulley Timothy J. , Chang Jessica R.
Published: April 2022

Background:

Giant cell arteritis (GCA) is the most common vasculitis in adults and is associated with significant morbidity and mortality. Temporal artery biopsy (TAB) remains the gold standard for diagnosis in the United States; however, practices vary in the length of artery obtained and whether bilateral simultaneous biopsies are obtained.

Methods:

Retrospective chart review of all TABs performed at the Johns Hopkins Wilmer Eye Institute between July 1, 2007, and September 30, 2017.

Results:

Five hundred eighty-six patients underwent TAB to evaluate for GCA. Of 404 unilateral biopsies, 68 (16.8%) were positive. Of 182 patients with bilateral biopsies, 25 (13.7%) had biopsies that were positive and 5 patients (2.7%) had biopsies that were discordant, meaning only 1 side was positive. There was no significant difference in the average postfixation length of positive and negative TAB specimens (positive mean length 1.38 ± 0.61 cm, negative mean length 1.39 ± 0.62 cm, P = 0.9).

Conclusions:

There is no significant association between greater length of biopsy and a positive TAB result in our data. Although the rate of positive results was not higher in the bilateral group compared with the unilateral group, 2.7% of bilateral biopsies were discordant, similar to previously published rates. Overall, this suggests that initial bilateral biopsy may increase diagnostic yield, albeit by a small amount.
Comparison of 1.5 Tesla and 3.0 Tesla Magnetic Resonance Imaging in the Evaluation of Acute Demyelinating Optic Neuritis
Authors: Hur Minjun , Madhavan Ajay A. , Hodge David O. , Eckel Laurence J. , Pittock Sean J. , Flanagan Eoin P. , Bhatti M. Tariq , Chen John J.
Published: April 2022

Background:

Optic neuritis (ON) is the most common optic neuropathy in young adults. MRI is reported to have a high sensitivity for ON. Higher signal strengths of MRI may enhance resolution and lead to better detection of ON. We sought to compare the sensitivity of 3.0 Tesla (T) MRI to that of 1.5 T MRI in detecting acute demyelinating ON.

Methods:

A retrospective chart review was performed on patients with a clinical diagnosis of optic neuritis at Mayo Clinic Health System from January 2010 to April 2020. Among 1,850 patients identified, 126 patients met the eligibility criteria. Exclusion criteria comprised questionable or alternative diagnosis, diagnosis of ON before the study period, eye examinations performed elsewhere, or absence of fat-saturated head and orbits MRIs performed locally within 30 days of symptom onset. Gadolinium contrast enhancement, T2 hyperintensity, and the radiologic diagnosis of ON were recorded by a neuro-radiologist who was masked to the clinical history and the magnet strength of the MRI.

Results:

Fifty-three patients (42.1%) had 3.0 T MRI, and 73 patients (57.9%) had 1.5 T MRI. Overall, 88.9% (112/126) of patients were determined to have a positive MRI for ON. The radiographic sensitivity for ON was higher in the 3.0 T group compared with the 1.5 T group (98.1% vs 82.2%, respectively [P = 0.004]). The frequency of gadolinium enhancement was found to be greater in the 3 T group compared with the 1.5 T group (98.1% vs 76.7%, respectively [P < 0.001]). T2 hyperintensity was also more often seen in the 3.0 T group compared with the 1.5 T group (88.7% vs 68.5%, respectively [P = 0.01]).

Conclusions:

3.0 T MRI is more sensitive than 1.5 T MRI in detecting ON. This finding suggests that 3.0 T MRI is a preferred imaging modality for the confirmation of ON.
Prevalence of Macular Microcystoid Lacunae in Autosomal Dominant Optic Atrophy Assessed With Adaptive Optics
Authors: Eckmann-Hansen Christina , Bek Toke , Sander Birgit , Grønskov Karen , Larsen Michael
Published: April 2022

Background:

To assess the prevalence of macular microcystoid lacunae in patients with autosomal dominant optic atrophy (ADOA) and its association with visual function and inner retinal morphology.

Methods:

The study included 140 participants with ADOA, with a mean age of 44 (SD ±19, range 7–82) years. Study participants with a genetically verified sequence variant in the OPA1 gene were examined with best-corrected visual acuity, contrast sensitivity, optical coherence tomography (Spectralis, Heidelberg) and adaptive optics fundus photography (rtx1, Imagine Eyes). Optically empty microcystoid spaces in the ganglion cell layer and inner plexiform layer were mapped by inspection of the 2 sets of images. Data were analyzed with a mixed model adjusted for age and sex with family and individual as random effect.

Results:

Microcystoid lacunae were present in 32 of 140 participants (23%) including 18 males and 14 females. Microcystoid lacunae were associated with younger age (P = 0.0503) and a smaller nerve fiber layer volume (P = 0.035). No association was found between presence of microcystoid lacunae and visual acuity (P = 0.2), contrast sensitivity (P = 0.8), axial length (P = 0.7), or ganglion cell layer volume (P = 0.2). The analysis showed moderately reduced visual acuity in patients with microcystoid lacunae. Normal and severely impaired visual function were seen only in participants without microcystoid lacunae.

Conclusion:

In ADOA, macular microcystoid lacunae were found in 23% of the study participants and tended to be present in younger participants with moderate visual acuity reduction and a smaller nerve fiber layer volume. Further studies are needed to investigate whether cavities left by dead ganglion cells are predictors of decrease in visual function.
Algiphilus acroporae sp. nov. and Coraliihabitans acroporae gen. nov. sp. nov., isolated from scleractinian coral Acropora digitifera
Authors: Sun Hao , Zheng Huina , Liao Baolin , Chen Bogui , Li Aihua , Xiao Baohua
Published: April 2022

Two Gram-staining-negative, aerobic, rod-shaped bacteria NNCM1T and NNCM2T were isolated from the scleractinian coral Acropora digitifera. NNCM1T grew with 0.5–12 % (w/v) NaCl (optimum, 3–6 %), at 18–37 °C (optimum, 28 °C) and at pH 6.0–10.0 (optimum, 7.0–8.0). NNCM2T grew with 0.5–10 % (w/v) NaCl (optimum, 2 %), at 18–37 °C (optimum, 28 °C) and at pH 6.5–9.0 (optimum, 7.0). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that NNCM1T formed a lineage within the genus

Algiphilus

of the family Algiphilaceae, and it was distinct from the most closely related species

Algiphilus aromaticivorans

DG1253T, with a 16S rRNA gene sequences similarity of 97.05 %. NNCM2T formed a lineage within the family Rhodobacteraceae, and it was distinct from the closely related genera

Limibaculum halophilum

CAU 1123T,

Paroceanicella profunda

D4M1T and

Pseudoruegeria aestuarii

MME-001T with 93.41, 92.78 and 91.09% identities, respectively. The major respiratory quinone was Q-8 and Q-10 for NNCM1T and NNCM2T, respectively. The predominant fatty acids (more than 10 %) were summed feature 8 (39.4 %) and C16 : 0 (19.4 %) for NNCM1T and summed feature 8 (62.8 %) and C16 : 0 (12.4 %) for NNCM2T. The DNA G+C contents of NNCM1T and NNCM2T were 63.3 and 63.4 mol% respectively. The polar lipids of NNCM1T comprised one diphosphatidylglycerol, one phosphatidylethanolamine, one phosphatidylglycerol and one unknown polar lipid, while those of NNCM2T comprised one phosphatidylethanolamine, one phosphatidylglycerol, one aminolipid and four unknown polar lipids. Phenotypic characteristics (physiological, biochemical and chemotaxonomic) also supported the taxonomic novelty of the two isolates. Thus, NNCM1T is considered to represent a novel species within genus

Algiphilus

, for which the name Algiphilus acroporae sp. nov. is proposed. The type strain is NNCM1T (=KCTC 82966T=MCCC 1K06445T). NNCM2T represents a novel genus and species within the family Rhodobacteraceae, for which the name Coraliihabitans acroporae gen. nov. sp. nov. is proposed. The type strain is NNCM2T (=KCTC 82967T=MCCC 1K06408T).
The role of hepatitis B virus surface proteins in regulating the maturation and secretion of complete and incomplete virions
Authors: Xu Mingzhu , Li Chang , Ding Jiahui , Wu Min , Tang Yijie , Yuan Zhenghong , Zhang Xiaonan
Published: April 2022

The expression of various forms of hepatitis B virus (HBV) surface proteins regulates the release of mature virion, but whether they affect the release of other incomplete viral particles, such as naked capsid, is not clear. Here, by stable overexpression of large or middle/small hepatitis B surface proteins (LHBs, M/SHBs) in HepAD38 cells, we evaluated their effects on the release of complete and incomplete viral particles. Overproduction of LHBs inhibited the release of all surface proteins, which increased the ratio of naked capsids/virions. This effect was accompanied by the elevated extracellular HBV RNA. On the other hand, overexpression of M/SHBs greatly improved the secretion of enveloped viral and subviral particles. In situ visualization of viral DNA and LHBs revealed intracellular retention of mature virions when LHBs were overexpressed. These results indicate that the molecular decision on secretion of enveloped or unenveloped viral particles is modulated by the intracellular ratio of large, middle and small surface antigens. This mechanism may be relevant in the progression and resolution of HBV-induced chronic liver disease.
Microcins reveal natural mechanisms of bacterial manipulation to inform therapeutic development
Authors: Parker Jennifer Kristen , Davies Bryan William
Published: April 2022

Microcins are an understudied and poorly characterized class of antimicrobial peptides. Despite the existence of only 15 examples, all identified from the

Enterobacteriaceae

, microcins display diversity in sequence, structure, target cell uptake, cytotoxic mechanism of action and target specificity. Collectively, these features describe some of the unique means nature has contrived for molecules to cross the ‘impermeable’ barrier of the Gram-negative bacterial outer membrane and inflict cytotoxic effects. Microcins appear to be widely dispersed among different species and in different environments, where they function in regulating microbial communities in diverse ways, including through competition. Growing evidence suggests that microcins may be adapted for therapeutic uses such as antimicrobial drugs, microbiome modulators or facilitators of peptide uptake into cells. Advancing our biological, ecological and biochemical understanding of the roles of microcins in bacterial interactions, and learning how to regulate and modify microcin activity, is essential to enable such therapeutic applications.
An optimized flow cytometry protocol for simultaneous detection of T cell activation induced markers and intracellular cytokines: application to SARS-Cov-2 vaccinated individuals
Authors: Altosole Tiziana , Rotta Gianluca , Bornheimer Scott J. , Fenoglio Daniela
Published: April 2022

Antigen (ag)-specific T cell analysis is an important step for investigation of cellular immunity in many settings, such as infectious diseases, cancer and vaccines. Multiparameter flow cytometry has advantages in studying both the rarity and heterogeneity of these cells. In the cellular immunologist’s toolbox, the expression of activation-induced markers (AIM) following antigen exposure has made possible the study and sorting of ag-specific T cells without using human leukocyte antigen (HLA)-multimers. In parallel, assessing the cytokine profile of responding T cells would support a more comprehensive description of the ongoing immune response. Here, a method and flow cytometry panel were optimized to combine the detection of activated CD4+ and CD8+ T cells in a TCR-dependent manner with the evaluation of cytokine production by intracellular staining, without affecting the positivity of activation markers. In particular, the expression of CD134 (OX40) and CD69 have been tested in conjunction with intracellular (ic) CD137 (4-1BB) to detect SARS-Cov-2 Spike protein-specific activated T cells. In our setting, assessing CD134 provided minimal contribution to detect the pool of AIM+ T cells, whereas a key role was described for ic-CD69, which was co-expressed with ic-CD137 in both CD4+ and CD8+ lymphocytes. Moreover, the analysis of TCR-triggered cytokine-producing T cells (IFNγ, TNFα and IL-2 were assessed) further confirmed the capacity of ic-CD69 to identify functionally responsive antigen-specific T cells, which were often largely negative or poorly positive for CD134 expression. In parallel, the use of CD45RA, CCR7 and CXCR5 allowed us to describe the T cell matuarion curve and detect T helper follicular CD4+ cells, including the antigen-specific activated subsets.

In conclusion, we optimized a method and flow cytometry panel combining assessment of activation induced markers and intracellular cytokines that will be useful for measuring TCR stimulation-dependent activation of CD4+ and CD8+ T cells.
Pathogen- and type-specific changes in invasive bacterial disease epidemiology during the first year of the COVID-19 pandemic in the Netherlands
Authors: Steens Anneke , Knol Mirjam J. , Graaf Wieke Freudenburg-de , de Melker Hester E. , van der Ende Arie , van Sorge Nina M.
Published: April 2022

The COVID-19 control measures have resulted in a decline in invasive bacterial disease caused byNeisseria meningitidis(IMD),Streptococcus pneumoniae(IPD), andHaemophilus influenzae(Hi-D). The species comprise different serogroups and serotypes that impact transmissibility and virulence. We evaluated type- and pathogen-specific changes in invasive bacterial disease epidemiology in the Netherlands during the first year of the SARS-CoV-2 pandemic. Cases were based on nationwide surveillance for five bacterial species with either respiratory (IMD, IPD, Hi-D) or non-respiratory (controls) transmission routes and compared between the pre-COVID period (April 2015-March 2020) and the first COVID-19 year (April 2020-March 2021). IMD, IPD, and Hi-D cases decreased by 78%, 67%, and 35%, respectively, in the first COVID-19 year compared to the pre-COVID period although effects differed per age group. Serogroup B-IMD declined by 61%, while serogroup W and Y-IMD decreased >90%. IPD caused by serotypes 7F, 15A, 12F, 33F, and 8 showed the most pronounced decline (≥76%). In contrast to an overall decrease in Hi-D cases, vaccine-preventable serotype b (Hib) increased by 51%. COVID-19 control measures had pathogen- and type-specific effects related to invasive infections. Continued surveillance is critical to monitor potential rebound effects once restriction measures are lifted and transmission is resumed.
cvlr:Finding heterogeneously methylated genomic regions using ONT reads
Authors: Raineri Emanuele , Alberola i Pla Mariona , Dabad Marc , Heath Simon
Published: April 2022

Nanopore reads encode information on the methylation status of cytosines in CpG dinucleotides. The length of the reads makes it comparatively easy to look at patterns consisting of multiple loci; here we exploit this property to look for regions where one can define subpopulations of cells based on methylation patterns. As a benchmark we run our clustering algorithm on known imprinted genes and show that the clustering based on methylation is consistent with the phasing of the genome; we then scan chromosome 15 looking for windows corresponding to heterogeneous methylation. We can also compute the covariance of methylation across these regions while keeping into account the mixture of different types of reads.

Availability

https://github.com/EmanueleRaineri/releases

Contact

emanuele.raineri@cnag.crg.eu, simon.heath@cnag.crg.eu

Supplementary information

Tables, figures, and some further explanations of the algorithms are available as online supplementary information.
How special am I? Consumer responses to promotion individualization and notification exclusivity
Authors: Lee Luri , Kim Donghoon
Published: April 2022

Purpose

Although there are at least two important characteristics of targeted promotions—promotion individualization (i.e. whether the offer is personalized for the recipient) and notification exclusivity (i.e. how small the number of recipients is)—most previous studies on targeted promotion have conceptualized them synonymously. The purpose of this study is to investigate the effect of targeted promotion on consumer purchases by conceptualizing these separately and incorporating them in a single model. Also, this study explores how the effects of these differ depending on customer loyalty. We particularly examine the promotional responses of extremely loyal customers, distinguishing them from other loyal customers.

Design/methodology/approach

Using actual customer purchase data, we develop a two-stage model of the consumer decision-making process involving decisions of whether and how much to purchase. The two characteristics of targeted promotions—promotion individualization and notification exclusivity—first influence the probability of purchase and then the purchase amount given purchase.

Findings

The results show that customers respond positively to individualization and exclusivity. The effect of individualization is reduced as customer loyalty increases from loyal customers to extremely loyal customers while that of exclusivity remains the same.

Originality/value

By clearly identifying the two characteristics of targeted promotions and developing an empirical model that captures the effects of these separately, this paper provides new academic and managerial insights that were not clearly identified in the current literature.
Higher-order accurate finite-difference simulation for tunnel propagation modeling
Authors: Rasool Hafiz Faiz , Qureshi Muhammad Ali , Aziz Abdul , Akhtar Zain Ul Abiden , Khan Usman Ali
Published: April 2022

Purpose

This paper aims to improve the computational efficiency of higher-order accurate Noye–Hayman [NH (9,9)] implicit finite difference scheme for the solution of electromagnetic scattering problems in tunnel environments.

Design/methodology/approach

The proposed method consists of two major steps: First, the higher-order NH (9,9) scheme is numerically discretized using the finite-difference method. The second step is to use an algorithm based on hierarchical interpolative factorization (HIF) to accelerate the solution of this scheme.

Findings

It is observed that the simulation results obtained from the numerical tests illustrate very high accuracy of the NH (9,9) method in typical tunnel environments. HIF algorithm makes the NH (9,9) method computationally efficient for two-dimensional (2D) or three-dimensional (3D) problems. The proposed method could help in reducing the computational cost of the NH (9,9) method very close to O(n) usual O(n3) for a full matrix.

Research limitations/implications

For simplicity, in this study, perfect electric conductor boundary conditions are considered. Future research may also include the utilization of meteorological techniques, including the effects of backward traveling waves, and make comparisons with the experimental data.

Originality/value

This study is directly applicable to typical problems in the field of tunnel propagation modeling for both national commercial and military applications.