bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective Well-Being and Prosociality Around the Globe: Happy People Give More of Their Time and Money to Others
Authors: Kushlev Kostadin , Radosic Nina , Diener Ed
Published: September 2021

Subjective well-being (SWB) is positively related to prosocial giving and helping others, but so far, research has not explored the association of individual aspects of well-being with prosocial behavior across the world. We used a representative sample from the Gallup World Poll across 163 countries from 2006 to 2017 to explore the relationship between each aspect of well-being and prosocial behavior ( N = 1,797,630). We found that different aspects of SWB are not equally associated with prosocial behavior: While life satisfaction and positive affect consistently predicted being more prosocial across the globe, negative affect did not consistently predict being more or less prosocial. We further explore economic and cultural moderators of these relationships. Our findings underline the importance of studying the effects of the different components of SWB separately, indicating that life satisfaction and positive emotions—more so than negative emotions—consistently predict being more prosocial across the globe.
Assessment of the anti-norovirus activity in cell culture using the mouse norovirus: Early mechanistic studies
Authors: Dycke Jana Van , Rymenants Jasper , Neyts Johan , Rocha-Pereira Joana
Published: September 2021

Human norovirus is the main cause of viral gastroenteritis, resulting annually in ∼ 700 million infections and 200,000 deaths, of whom most are children <5 years. Mouse norovirus-infected macrophages are the most widely used in vitro system to screen and characterize the antiviral effect of norovirus-targeting small molecules. We have previously established antiviral assays using this system, identified novel inhibitors and performed additional studies in order to have a first insight into their mechanism of action. After the identification of novel small molecules with anti-norovirus activity (part 1 of this protocol), we here describe the logical next step which entails the generation of early information of their mode of action. This information together with a continuous improvement of the potency of compounds will contribute to the optimization of a compound class towards in vivo efficacy and a successful preclinical development.
Bullous choroidal detachment requiring drainage following endoscopic cyclophotocoagulation
Authors: Al Owaifeer Adi Mohammed , AlDarrab Abdulrahman , Owaidhah Ohoud
Published: September 2021

Endoscopic cyclophotocoagulation is a relatively safe cyclodestructive procedure with a lower complication rate compared to trans-scleral cyclophotocoagulation. Serous choroidal detachment is a complication that has been reported following endoscopic cyclophotocoagulation; however, it is usually mild and transient. A case of bullous choroidal detachment with a flat anterior chamber requiring drainage after endoscopic cyclophotocoagulation is presented, along with a discussion on the risk factors precipitating such complication.
Dislocations of the second and third metatarsophalangeal joints after local steroid injection in patients with refractory metatarsalgia: A case report
Authors: Ito Eichi , Shima Hiroaki , Togei Kosho , Hirai Yoshihiro , Tsujinaka Seiya , Yasuda Toshito , Neo Masashi
Published: September 2021

Local steroid injections are frequently administered to patients with refractory metatarsalgia. No reports have described dislocation of the second and third metatarsophalangeal joints after local steroid injections. A 46-year-old woman had suffered from metatarsalgia and received multiple local steroid injections for over 2 years. The second and third metatarsophalangeal joints revealed dorsal dislocations on the lateral radiograph. Therefore, collateral ligament reconstruction of the metatarsophalangeal joints was performed. Intraoperative findings suggested that the rupture of the plantar plate may have caused dorsal dislocation of both joints. Thus, unnecessary multiple steroid injections around the lesser metatarsophalangeal joint should be avoided.
Time in Therapeutic Range Using a Nomogram for Dose Adjustment of Warfarin in Patients on Hemodialysis With Atrial Fibrillation
Authors: Defoe Kimberly , Wichart Jenny , Leung Kelvin
Published: September 2021

Background:

Patients treated with hemodialysis and prescribed warfarin typically have lower time in therapeutic range (TTR) compared to the general population. This may result in less benefit or increased risk of over anticoagulation in these patients.

Objective:

To assess effectiveness of use of an electronic nomogram for the management of warfarin therapy in patients treated with hemodialysis.

Design:

Retrospective chart review.

Setting:

Adult patients treated with hemodialysis.

Patients:

Patients on hemodialysis receiving warfarin for the management of atrial fibrillation (AF) with therapy managed by nursing led electronic nomogram.

Measurements:

Time in therapeutic range (as fraction and Rosendaal).

Methods:

Retrospective chart review over 1 year of international normalized ratio (INR) results was completed, and TTR was calculated. Comparison of patients with TTR greater than 60% to those less than 60% was completed using chi-square analysis.

Results:

Of 43 patients with warfarin therapy managed by the nomogram, the mean TTR was 55.2% (calculated by fraction method) or 61.2% (calculated by Rosendaal method). More than half of the patients (63.5%) had moderate to good control, defined as TTR greater than 60%. Female sex, liver disease, or history of substance use and more medication holds were associated with lower TTR.

Limitations:

Small sample size and retrospective nature of review.

Conclusions:

The results of this review supports the use of an electronic, nursing-led nomogram for the maintenance management of warfarin therapy in stable patients treated with hemodialysis, as use results in TTR greater than 60% for more than half of patients.
Pediatric Tibial Spine Fractures: Exploring Case Burden by Age and Sex
Authors: DeFrancesco Christopher J. , Wilson Lauren , Lebrun Drake G. , Memtsoudis Stavros G. , Fabricant Peter D.
Published: September 2021

Background:

Pediatric tibial spine fractures (TSFs) are a well-known clinical entity, but the epidemiology of these injuries is not fully understood. Further, there are limited data on outcomes after TSF treatment, specifically the proportion of patients requiring subsequent anterior cruciate ligament (ACL) reconstruction.

Purpose:

To describe the distribution of TSF case burden by age and sex and to determine the proportion of patients undergoing subsequent ACL reconstruction or developing ACL insufficiency.

Study Design:

Descriptive epidemiology study.

Methods:

The Truven Health MarketScan database was queried to identify patients aged 7 to 18 years with TSFs between 2016 and 2018. Diagnosis and initial treatment (surgical vs nonoperative) were recorded based on database coding. Case burden by age and sex was calculated. The database, which includes longitudinal data, was then queried for subsequent diagnoses of ACL insufficiency as well as subsequent ACL reconstruction procedures performed among the patients.

Results:

We found 876 cases of TSF, 71.3% of which were treated nonoperatively. The male to female ratio for case burden was 2.2:1. Cases peaked at age 13 to 14 years for boys and age 11 to 12 years for girls. Of all cases identified, 3.7% also had either a diagnosis code for ACL laxity entered in a delayed fashion into the database or a later procedure code for ACL reconstruction (considered together to represent “subsequent ACL insufficiency”). Only 15 subsequent ACL reconstructions (1.7% of cases) were found, all of which were among boys and 9 of which were among boys aged 13 to 14 years.

Conclusion:

This longitudinal study is the largest epidemiological analysis of pediatric TSFs to date. We found low rates of subsequent ACL insufficiency and ACL reconstruction, with boys aged 13 to 14 years accounting for most of those cases. Rates of subsequent ACL reconstruction were lower than previously reported. Boys accounted for more than two times as many TSF cases as girls.
Narrating the Territorial Foundations of Privilege: Racial Discourse and Indigenous Peoples
Authors: Everson David W.
Published: September 2021

This article focuses on the cultural narratives underlying U.S. society’s racialized inequalities. Informed by settler colonial theory and Charles Tilly’s work on “durable inequality,” I outline a privilege narratives framework that centers the dual mechanisms of racial dispossession that construct white supremacy’s material foundations: (1) the exploitation of non-Indigenous bodies and (2) the opportunity hoarding of Indigenous resources. I argue that these complementary, yet divergent, mechanisms shape distinctive patterns in contemporary racial discourse. In contrast to color-blind racism’s ahistoric and spatially disembedded storylines, the hoarding of Indigenous resources requires narrations that historically legitimate the dominant culture’s territoriality. Thus, in comparison with other racialized groups, racial discourse surrounding Indigenous peoples remains rooted in the defense of the territorial foundations of white property. Empirical support for the theoretical framework is provided through a sample of purposive follow-up interviews of non-Indigenous bystanders with historical connections to the American Indian Movement’s (AIM) “Red Power” activism in the 1970s.
An Analytical Cross-Sectional Study to Assess the Effects of Smoking on Common Carotid Intima-Media Thickness and Resistivity Index Among Current Smokers
Authors: Kaur Harmeet , Tiwari Punit , Sharma Sanjeev , Verma Madhur
Published: September 2021

Objective:

The aim was to assess the structural and hemodynamic effects of smoking on the common carotid arteries (CCAs) in current smokers from Himachal Pradesh. In addition, it was important to determine any association between smoking duration, frequency, pack-years, and the occurrence of common carotid atherosclerosis.

Materials and Methods:

The study evaluated 50 current smokers for common carotid intima-media thickness (CIMT), plaque presence, and resistive index (RI) with sonography. The findings were compared with 50 healthy control patients, who had never smoked.

Results:

A positive association was observed between smoking and an increase in CIMT ( P = .001) and occurrence of plaques ( P = .007), with substantially higher mean CIMT values in smokers above 45 years ( P < .05) in both genders ( P < .05). No difference in overall RI was seen in both groups taken as a whole, while higher RI values ( P < .05) were noticed in smokers exclusively above 60 years. A positive association was noted between smoking frequency, pack-years, and an increase in CIMT, RI, and occurrence of plaques. For every unit increase in the number of pack-years and smoking duration, there was a 0.01 unit increase in CIMT among the current smokers.

Conclusion:

This research provides evidence that smoking has a structural impact on CIMT while its hemodynamic effect is still unclear.
How I treat chronic-phase chronic myelogenous leukemia
Authors: Berman Ellin
Published: September 2021

When imatinib, the first tyrosine kinase inhibitor (TKI) developed for use in chronic myelogenous leukemia (CML), was approved in 2001, the treatment of this disease was forever changed. Significant reductions in the molecular burden of disease were seen with the first-generation TKI imatinib and, with the addition of dasatinib (2006), nilotinib (2007), bosutinib (2012), and ponatinib (2013), deeper and more rapid reductions were noted. Physicians could begin to tailor TKI therapy to individual patients, and patients who did not respond to or could not tolerate first-line therapy now had options. Importantly, the number of patients who developed accelerated or blast phase disease decreased dramatically. Research in CML continues to evolve; by presenting illustrative cases, this article reviews some of the newer aspects of clinical care in this disease. Updated information regarding bosutinib and asciminib, the latter currently in clinical trials, will be presented; bosutinib is of particular interest as the drug’s transit through the United States Food and Drug Administration highlights the question of what is considered optimal response to TKI therapy. The challenge of understanding the cardiac safety data of ponatinib and the unique dosing schedule based on individual response will be discussed. Lastly, two cases will focus on features of TKI treatment that, remarkably, have become part of the treatment algorithm: family planning for women with CML and stopping therapy after meeting a specific treatment milestone.
PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke
Authors: Dhanesha Nirav , Patel Rakesh B. , Doddapattar Prakash , Ghatge Madankumar , Flora Gagan D. , Jain Manish , Thedens Daniel , Olalde Heena , Kumskova Mariia , Leira Enrique C. , Chauhan Anil K.
Published: September 2021

There is a critical need for cerebro-protective interventions to improve the suboptimal outcomes of patients with ischemic stroke who have been treated with reperfusion strategies. We found that nuclear pyruvate kinase muscle 2 (PKM2), a modulator of systemic inflammation, was upregulated in neutrophils after the onset of ischemic stroke in both humans and mice. Therefore, we determined the role of PKM2 in stroke pathogenesis by using murine models with preexisting comorbidities. We generated novel myeloid cell–specific PKM2−/− mice on wild-type (PKM2fl/flLysMCre+) and hyperlipidemic background (PKM2fl/flLysMCre+Apoe−/−). Controls were littermate PKM2fl/flLysMCre– or PKM2fl/flLysMCre–Apoe−/− mice. Genetic deletion of PKM2 in myeloid cells limited inflammatory response in peripheral neutrophils and reduced neutrophil extracellular traps after cerebral ischemia and reperfusion, suggesting that PKM2 promotes neutrophil hyperactivation in the setting of stroke. In the filament and autologous clot and recombinant tissue plasminogen activator stroke models, irrespective of sex, deletion of PKM2 in myeloid cells in either wild-type or hyperlipidemic mice reduced infarcts and enhanced long-term sensorimotor recovery. Laser speckle imaging revealed improved regional cerebral blood flow in myeloid cell–specific PKM2-deficient mice that was concomitant with reduced post-ischemic cerebral thrombo-inflammation (intracerebral fibrinogen, platelet [CD41+] deposition, neutrophil infiltration, and inflammatory cytokines). Mechanistically, PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. To enhance the translational significance, we inhibited PKM2 nuclear translocation using a small molecule and found significantly reduced neutrophil hyperactivation and improved short-term and long-term functional outcomes after stroke. Collectively, these findings identify PKM2 as a novel therapeutic target to improve brain salvage and recovery after reperfusion.
Assessment of HLA-B Genetic Variation with an HLA-B Leader Tool and Implications in Clinical Transplantation
Authors: Sajulga Ray , Bolon Yung-Tsi , Maiers Martin , Petersdorf Effie W
Published: September 2021

Sequence variation in the HLA-B gene is critically linked to differential immune responses. A dimorphism at -21 of HLA-B exon 1 gives rise to leader peptides that are markers for risk of acute graft-versus-host disease (GVHD), relapse, and mortality after unrelated donor and cord blood transplantation. To optimize the selection of stem cell transplant sources based on the HLA-B leader, an HLA-B Leader Assessment Tool ("BLEAT") was developed to automate the assignment of leader genotypes, define HLA-B leader match statuses, and rank order candidate stem cell sources according to clinical risk. The base cohort consisted of 9,417,614 registered donors from the Be The Match Registry® with HLA-B typing. Among these donors, the performance of BLEAT was assessed in 1,098,358 donors with sequence data for HLA-B exon 1 (2,196,716 haplotypes). The accuracy of leader assignment was then assessed in a second cohort of 1,259 patients and their unrelated transplant donors. We furthermore established the frequencies of HLA-B leader genotype (MM, MT, TT) representations in broad racial categories in the 9.42 million donors. BLEAT has direct applications for the selection of optimal stem cell sources for transplantation and broad utility in basic and clinical research in pharmacogenomics, vaccine development, and cancer and infectious disease studies of human populations.
PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome
Authors: Kontandreopoulou Christina-Nefeli , Diamantopoulos Panagiotis T. , Tiblalexi Despina , Giannakopoulou Nefeli , Viniou Nora-Athina
Published: September 2021

Poly(ADP-ribose) polymerase 1 (PARP1) is a key mediator of various forms of DNA damage repair and plays an important role in the progression of several cancer types. The enzyme is activated by binding to DNA single-strand and double-strand breaks. Its contribution to chromatin remodeling makes PARP1 crucial for gene expression regulation. Inhibition of its activity with small molecules leads to the synthetic lethal effect by impeding DNA repair in the treatment of cancer cells. At first, PARP1 inhibitors (PARPis) were developed to target breast cancer mutated cancer cells. Currently, PARPis are being studied to be used in a broader variety of patients either as single agents or in combination with chemotherapy, antiangiogenic agents, ionizing radiation, and immune checkpoint inhibitors. Ongoing clinical trials on olaparib, rucaparib, niraparib, veliparib, and the recent talazoparib show the advantage of these agents in overcoming PARPi resistance and underline their efficacy in targeted treatment of several hematologic malignancies. In this review, focusing on the crucial role of PARP1 in physiological and pathological effects in myelodysplastic syndrome and acute myeloid leukemia, we give an outline of the enzyme’s mechanisms of action and its role in the pathophysiology and prognosis of myelodysplastic syndrome/acute myeloid leukemia and we analyze the available data on the use of PARPis, highlighting their promising advances in clinical application.
Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?
Authors: Imber Brandon S. , Chau Karen W. , Lee Jasme , Lee Jisun , Casey Dana L. , Yang Joanna C. , Wijentunga N. Ari , Shepherd Annemarie , Hajj Carla , Qi Shunan , Chelius Monica R. , Hamlin Paul A. , Palomba M. Lia , Joffe Erel , Zhang Zhigang , Zelenetz Andrew D. , Salles Gilles A. , Yahalom Joachim
Published: September 2021

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size >6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.
Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy
Authors: Dhar Arushi , Leung Tung Ming , Appiah-Kubi Abena , Gruber Dorota , Aygun Banu , Serigano Olivia , Mitchell Elizabeth
Published: September 2021

Cardiac abnormalities such as left ventricular hypertrophy, left ventricular dilation, and pulmonary hypertension in sickle cell anemia have been previously described. Hydroxyurea, a disease-modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia receiving hydroxyurea therapy is lacking. The goal of this retrospective study was to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children’s Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were being treated with hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for <1 year; these patients had a significantly greater prevalence of left ventricular dilation compared with those who had been on treatment for >1 year. Serial echocardiograms of patients receiving hydroxyurea were then analyzed. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. In addition, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow up this patient cohort for a longer duration.
Poor neutralizing antibody responses in 106 patients with WM after vaccination against SARS-CoV-2: a prospective study
Authors: Gavriatopoulou Maria , Terpos Evangelos , Ntanasis-Stathopoulos Ioannis , Briasoulis Alexandros , Gumeni Sentiljana , Malandrakis Panagiotis , Fotiou Despina , Migkou Magdalini , Theodorakakou Foteini , Eleutherakis-Papaiakovou Evangelos , Kanellias Nikolaos , Kastritis Efstathios , Trougakos Ioannis P. , Dimopoulos Meletios A.
Published: September 2021

Immunocompromised patients with hematologic malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with the general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenström macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. A US Food and Drug Administration–approved enzyme-linked immunosorbent assay–based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on days 22 and 50 afterward. A total of 106 patients with WM (43% men; median age, 73 years) and 212 healthy controls (46% men; median age, 66 years) who were vaccinated during the same period at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as #NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls on days 22 and 50 (P < .001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either rituximab or Bruton’s tyrosine kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response after vaccination. In conclusion, patients with WM have low humoral response after COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.
Health service utilisation associated with chronic breathlessness: random population sample
Authors: Currow David C. , Chang Sungwon , Ekström Magnus , Hutchinson Ann , Luckett Tim , Kochovska Slavica , Hay Phillipa , Touyz Stephen , Dal Grande Eleonora , Johnson Miriam J.
Published: September 2021

Background

Most health service utilisation studies are of people with specific diagnoses or demographic characteristics, and rarely of specific chronic symptoms. The aim of this study was to establish whether population-level health service utilisation increases in people with chronic breathlessness.

Methods

A cross-sectional analysis was carried out of the South Australian Health Omnibus Survey 2017, a multi-stage, clustered area, systematic sampling survey of adults where questions are administered face-to-face in respondents’ homes. Self-report of health service utilisation in the previous 3 months (medical consultations, emergency department, hospital admission), chronic breathlessness (severity, duration, modified Medical Research Council (mMRC) breathlessness scale) and demographic data were used to predict self-reported health service utilisation.

Results

A total of 2898 people were included (49.0% male; median age 48.0 years (IQR 32.0–63.0); 64.1% educated beyond school; 55.4% in work; 73.5% had outpatient contact; 6.3% had a hospital admission in the previous 3 months). Chronic breathlessness (mMRC ≥1) was reported by 8.8% of respondents. In bivariable analyses, people with greater contact with health services were older, and a higher proportion were overweight/obese and had more severe chronic breathlessness. In multivariable analyses, chronic breathlessness and older age were positively associated with outpatient care and inpatient care, and people with chronic breathlessness were hospitalised for longer (incidence rate ratio 2.5; 95% CI 1.4–4.5).

Conclusion

There is a significant association between worse chronic breathlessness and increased health service utilisation. There is a need for greater understanding of factors that initiate contact with health services.
Multicolor Emission from Ultraviolet GaN-Based Photonic Quasicrystal Nanopyramid Structure with Semipolar InxGa1−xN/GaN Multiple Quantum Wells
Authors: Chen Cheng-Chang , Lin Hsiang-Ting , Chang Shih-Pang , Kuo Hao-Chung , Hung Hsiao-Wen , Chien Kuo-Hsiang , Chang Yu-Choung , Shih M. H.
Published: September 2021

In this study, we demonstrated large-area high-quality multi-color emission from the 12-fold symmetric GaN photonic quasicrystal nanorod device which was fabricated using the nanoimprint lithography technology and multiple quantum wells regrowth procedure. High-efficiency blue and green color emission wavelengths of 460 and 520 nm from the regrown InxGa1−xN/GaN multiple quantum wells were observed under optical pumping conditions. To confirm the strong coupling between the quantum well emissions and the photonic crystal band-edge resonant modes, the finite-element method was applied to perform a simulation of the 12-fold symmetry photonic quasicrystal lattices.
Gold Nanobiosensor Based on the Localized Surface Plasmon Resonance is Able to Diagnose Human Brucellosis, Introducing a Rapid and Affordable Method
Authors: Vakili Sina , Samare-Najaf Mohammad , Dehghanian Amirreza , Tajbakhsh Amir , Askari Hassan , Tabrizi Reza , Iravani Saadi Mahdiyar , Movahedpour Ahmad , Alizadeh Marzieh , Samareh Ali , Taghizadeh Saeed , Noroozi Saam
Published: September 2021

Brucellosis is considered as the most common bacterial zoonosis in the world. Although the laboratory findings are the most reliable diagnosis today, the current laboratory methods have many limitations. This research aimed to design and evaluate the performance of a novel technique based on the localized surface plasmon resonance (LSPR) to eliminate or reduce existing shortcomings. For this purpose, smooth lipopolysaccharides were extracted from Brucella melitensis and Brucella abortus and fixed on the surface of the gold nanoparticles through covalent interactions. After some optimizing processes, dynamic light scattering was used to characterize the probe. The detection of captured anti-Brucella antibody was performed by measuring the redshift on LSPR peak followed by the determination of cutoff value, which indicated a significant difference between controls and true positive patients (P value < 0.01). Furthermore, 40 sera from true negative samples and positive patients were used to evaluate the performance of this method by comparing its outcomes with the gold standard (culture), standard tube agglutination test, and anti-brucellosis IgM and IgG levels (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value showed an appropriate performance of the LSPR-based method (85%, 100%, 100%, and 86%, respectively). The current research results provide a promising fast, convenient, and inexpensive method for detecting the anti-Brucella antibodies in human sera, which can be widely used in medical laboratories to diagnose brucellosis quickly and effectively.
Multimodal imaging supporting the pathophysiology of white dot syndromes
Authors: Testi Ilaria , Modugno Rocco Luigi , Pavesio Carlos
Published: September 2021

White dot syndromes (WDS) represent a heterogeneous group of inflammatory diseases, primarily affecting the outer retina, choriocapillaris and choroid. Recent advances in the field of ocular imaging and development of new technologies, including optical coherence tomography angiography (OCT-A), have allowed a better characterization of the morphology of these conditions. This review will analyse the WDS from an imaging-based perspective, providing a better understanding of the pathophysiology underlying these disorders.
Randomized boosting with multivariable base-learners for high-dimensional variable selection and prediction
Authors: Staerk Christian , Mayr Andreas
Published: September 2021

Background

Statistical boosting is a computational approach to select and estimate interpretable prediction models for high-dimensional biomedical data, leading to implicit regularization and variable selection when combined with early stopping. Traditionally, the set of base-learners is fixed for all iterations and consists of simple regression learners including only one predictor variable at a time. Furthermore, the number of iterations is typically tuned by optimizing the predictive performance, leading to models which often include unnecessarily large numbers of noise variables.

Results

We propose three consecutive extensions of classical component-wise gradient boosting. In the first extension, called Subspace Boosting (SubBoost), base-learners can consist of several variables, allowing for multivariable updates in a single iteration. To compensate for the larger flexibility, the ultimate selection of base-learners is based on information criteria leading to an automatic stopping of the algorithm. As the second extension, Random Subspace Boosting (RSubBoost) additionally includes a random preselection of base-learners in each iteration, enabling the scalability to high-dimensional data. In a third extension, called Adaptive Subspace Boosting (AdaSubBoost), an adaptive random preselection of base-learners is considered, focusing on base-learners which have proven to be predictive in previous iterations. Simulation results show that the multivariable updates in the three subspace algorithms are particularly beneficial in cases of high correlations among signal covariates. In several biomedical applications the proposed algorithms tend to yield sparser models than classical statistical boosting, while showing a very competitive predictive performance also compared to penalized regression approaches like the (relaxed) lasso and the elastic net.

Conclusions

The proposed randomized boosting approaches with multivariable base-learners are promising extensions of statistical boosting, particularly suited for highly-correlated and sparse high-dimensional settings. The incorporated selection of base-learners via information criteria induces automatic stopping of the algorithms, promoting sparser and more interpretable prediction models.
Transcriptomic analysis of salt tolerance-associated genes and diversity analysis using indel markers in yardlong bean (Vigna unguiculata ssp. sesquipedialis)
Authors: Zhang Hongmei , Xu Wenjing , Chen Huatao , Chen Jingbin , Liu Xiaoqing , Chen Xin , Yang Shouping
Published: September 2021

Background

High salinity is a devastating abiotic stresses for crops. To understand the molecular basis of salinity stress in yardlong bean (Vigna unguiculata ssp. sesquipedalis), and to develop robust markers for improving this trait in germplasm, whole transcriptome RNA sequencing (RNA-seq) was conducted to compare the salt-tolerant variety Suzi 41 and salt-sensitive variety Sujiang 1419 under normal and salt stress conditions.

Results

Compared with controls, 417 differentially expressed genes (DEGs) were identified under exposure to high salinity, including 42 up- and 11 down-regulated DEGs in salt-tolerant Suzi 41 and 186 up- and 197 down-regulated genes in salt-sensitive Sujiang 1419, validated by qRT-PCR. DEGs were enriched in “Glycolysis/Gluconeogenesis” (ko00010), “Cutin, suberine and wax biosynthesis” (ko00073), and “phenylpropanoid biosynthesis” (ko00940) in Sujiang 1419, although “cysteine/methionine metabolism” (ko00270) was the only pathway significantly enriched in salt-tolerant Suzi 41. Notably, AP2/ERF, LR48, WRKY, and bHLH family transcription factors (TFs) were up-regulated under high salt conditions. Genetic diversity analysis of 84 yardlong bean accessions using 26 InDel markers developed here could distinguish salt-tolerant and salt-sensitive varieties.

Conclusions

These findings show a limited set of DEGs, primarily TFs, respond to salinity stress in V. unguiculata, and that these InDels associated with salt-inducible loci are reliable for diversity analysis.
The role of brain natriuretic peptide in atrial fibrillation: a substudy of the Substrate Modification with Aggressive Blood Pressure Control for Atrial Fibrillation (SMAC-AF) trial
Authors: Weng Willy , Choudhury Rajin , Sapp John , Tang Anthony , Healey Jeff S. , Nault Isabelle , Rivard Lena , Greiss Isabelle , Bernick Jordan , Parkash Ratika
Published: September 2021

Background

Catheter ablation is an established therapy for atrial fibrillation but is limited by recurrence; efforts have been made to identify biomarkers that predict recurrence. We investigated the effect of baseline NT-proBNP on AF recurrence following catheter ablation in patients randomized to aggressive (< 120/80 mmHg) or standard blood pressure management (< 140/90 mmHg) in the Substrate Modification with Aggressive Blood Pressure Control trial (SMAC-AF).

Methods

The SMAC-AF study included 173 patients resistant or intolerant to at least one class I or III antiarrhythmic drug. We studied the effect of baseline NT-proBNP on the primary outcome of AF recurrence > 3 months post-ablation.

Results

Of the 173 patients, 88 were randomized to the aggressive cohort, and 85 into the standard group. The primary outcome occurred in 61.4% of those in the aggressive arm, versus 61.2% in the standard arm. In the aggressive group, logNT-proBNP predicted recurrence (HR 1.28, p = 0.04, adjusted HR 1.43, p = 0.03), while in the standard cohort, it did not (HR 0.94, p = 0.62, adjusted HR 0.83, p = 0.22). NT-proBNP ≥ 280 pg/mL also predicted occurrence in the aggressive (HR 1.98, p = 0.02) but not the standard cohort (HR 1.00, p = 1.00).

Conclusion

We conclude that pre-ablation NT-proBNP may be useful in predicting recurrence in hypertensive patients and identifying patients who benefit from aggressive blood control and upstream therapies.

Trial registration: NCT00438113, registered February 21, 2007.
Combined association of multiple chronic diseases and social isolation with the functional disability after stroke in elderly patients: a multicenter cross-sectional study in China
Authors: Liu Xiangxiang , Yu Hong-jie , Gao Yan , Zhou Jing , Zhou Mingchao , Wan Li , Xiong Feng , Zhao Jingpu , He Qi-qiang , Wang Yulong
Published: September 2021

Background

Multiple chronic diseases (MCDs) and social isolation are independent risk factors related to stroke and disability, but it is unknown whether the combination of these two conditions resulted from aging-related to functional disability in stroke patients. This study aimed to probe the relationship between the combination of MCDs, social isolation, and functional disability after stroke in elderly patients.

Methods

A multicenter and cross-sectional study was conducted in the Departments of Rehabilitation of 103 hospitals located in 23 cities across China. Stroke patients aged 60–90 years were selected for analysis. Demographic characteristics, lifestyles, and clinical information were investigated by questionnaires and medical records. MCDs (hypertension/ diabetes/ hyperlipidemia/heart disease/kidney disease) were categorized into three levels: 0, 1, and ≥ 2. Functional disability was assessed by the Barthel Index and categorized into four groups: no, mild, moderate, and severe disability. The multi-nominal logistic regression model was used to explore the independent and combined association of MCDs and social isolation with functional disability.

Results

A total of 4046 elderly stroke patients (55 % males) were included in the final analysis. The prevalence of social isolation, MCDs ≥ 2, and severe disability increased with aging. In the fully adjusted model, patients with social isolation or MCDs had a higher risk of functional disability significantly than those without. Patients with social isolation combined MCDs ≥ 2 were 35 times (95 % CI: 18.89–64.69) more likely to suffer severe disability after stroke, and 8 times (95 % CI: 18.89–64.69) for moderate disability than those without social isolation and MCDs.

Conclusions

MCDs, social isolation, and their combination were associated with a higher risk of functional disability after stroke in Chinese elderly patients. The elderly population should be encouraged to participate in more social activities, particularly in those with MCDs. Future secondary prevention and rehabilitation treatments to the functional ability of elderly stroke patients should underscore both social activity and the combined treatments of MCDs.

Trial registration

NO: ChiCTR2000034067.
A case of paraplegia due to asymptomatic varicella-zoster virus infection in AIDS patient unexpectedly diagnosed by CSF metagenomic next-generation sequencing
Authors: Xie Zhiman , Lai Jingzhen , Ning Chuanyi , Ruan Guangjing , Liang Hao
Published: September 2021

Background

Varicella-zoster virus (VZV) infection may induce central nervous system complications in HIV/AIDS patients. However, it is rare to have paraplegia caused by VZV infection but no herpes zoster clinically. Asymptomatic VZV infection in HIV/AIDS patient increased the difficulty of diagnosis.

Case presentation

We reported a 41-year-old male AIDS patient with rare asymptomatic VZV infection-induced paraplegia after his anti-retroviral therapy initiation. MRI of the spinal cord showed the morphology of the thoracic spinal cord was irregular and locally inflated. The patient was confirmed as VZV induced thoracic myelomyelitis by using the cerebrospinal fluid for metagenomic next-generation sequencing (mNGS).

Conclusions

mNGS may contribute to disease diagnosis for asymptomatic VZV infection-induced myelitis.
Rare incidence of non-secretory myeloma with talaromycosis: a case report
Authors: Qin Haiting , Qiu Ye , Huang Yanmei , Pan Mianluan , Lan Dong , Zeng Wen , Zhang Jianquan
Published: September 2021

Background

Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM.

Case presentation

We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years.

Conclusion

TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis.
Case report: change of dominant strain during dual SARS-CoV-2 infection
Authors: Samoilov Andrei E. , Kaptelova Valeriia V. , Bukharina Anna Y. , Shipulina Olga Y. , Korneenko Elena V. , Saenko Stepan S. , Lukyanov Alexander V. , Grishaeva Antonina A. , Ploskireva Antonina A. , Speranskaya Anna S. , Akimkin Vasiliy G.
Published: September 2021

Background

The dual infection with SARS-CoV-2 is poorly described and is currently under discussion. We present a study of two strains of SARS-CoV-2 detected in the same patient during the same disease presentation.

Case presentation

A patient in their 90 s was hospitalised with fever. Oropharyngeal swab obtained on the next day (sample 1) tested positive for SARS-CoV-2. Five days later, the patient was transferred to the ICU (intensive care unit) of the hospital specialising in the treatment of COVID-19 patients, where the patient's condition progressively worsened and continuous oxygen insufflation was required. Repeated oropharyngeal swab (sample 2), which was taken eight days after the first one, also tested positive for SARS-CoV-2. After 5 days of ICU treatment, the patient died. The cause of death was a coronavirus infection, which progressed unfavourably due to premorbid status. We have performed sequencing of full SARS-CoV-2 genomes from oropharyngeal swabs obtained eight days apart. Genomic analysis revealed the presence of two genetically distant SARS-CoV-2 strains in both swabs. Detected strains belong to different phylogenetic clades (GH and GR) and differ in seven nucleotide positions. The relative abundance of strains was 70% (GH) and 30% (GR) in the first swab, and 3% (GH) and 97% (GR) in the second swab.

Conclusions

Our findings suggest that the patient was infected by two genetically distinct SARS-CoV-2 strains at the same time. One of the possible explanations is that the second infection was hospital-acquired. Change of the dominant strain ratio during disease manifestation could be explained by the advantage or higher virulence of the GR clade strain.
Transmission of SARS-CoV-2 considering shared chairs in outpatient dialysis: a real-world case-control study
Authors: Thadhani Ravi , Willetts Joanna , Wang Catherine , Larkin John , Zhang Hanjie , Fuentes Lemuel Rivera , Usvyat Len , Belmonte Kathleen , Wang Yuedong , Kossmann Robert , Hymes Jeffrey , Kotanko Peter , Maddux Franklin
Published: September 2021

Background

SARS-CoV-2 can remain transiently viable on surfaces. We examined if use of shared chairs in outpatient hemodialysis associates with a risk for indirect patient-to-patient transmission of SARS-CoV-2.

Methods

We used data from adults treated at 2,600 hemodialysis facilities in United States between February 1st and June 8th, 2020. We performed a retrospective case-control study matching each SARS-CoV-2 positive patient (case) to a non-SARS-CoV-2 patient (control) treated in the same dialysis shift. Cases and controls were matched on age, sex, race, facility, shift date, and treatment count. For each case-control pair, we traced backward 14 days to assess possible prior exposure from a ‘shedding’ SARS-CoV-2 positive patient who sat in the same chair immediately before the case or control. Conditional logistic regression models tested whether chair exposure after a shedding SARS-CoV-2 positive patient conferred a higher risk of SARS-CoV-2 infection to the immediate subsequent patient.

Results

Among 170,234 hemodialysis patients, 4,782 (2.8 %) tested positive for SARS-CoV-2 (mean age 64 years, 44 % female). Most facilities (68.5 %) had 0 to 1 positive SARS-CoV-2 patient. We matched 2,379 SARS-CoV-2 positive cases to 2,379 non-SARS-CoV-2 controls; 1.30 % (95 %CI 0.90 %, 1.87 %) of cases and 1.39 % (95 %CI 0.97 %, 1.97 %) of controls were exposed to a chair previously sat in by a shedding SARS-CoV-2 patient. Transmission risk among cases was not significantly different from controls (OR = 0.94; 95 %CI 0.57 to 1.54; p = 0.80). Results remained consistent in adjusted and sensitivity analyses.

Conclusions

The risk of indirect patient-to-patient transmission of SARS-CoV-2 infection from dialysis chairs appears to be low.
Association of uric acid and uric acid to creatinine ratio with chronic kidney disease in hypertensive patients
Authors: Silva Nathalia Rabello , Gonçalves Camila Evangelista Torres , Gonçalves Danilo Lemes Naves , Cotta Rosângela Minardi Mitre , da Silva Luciana Saraiva
Published: September 2021

Background

Recent studies have shown that the serum uric acid/creatinine ratio (SUA/SCr) is a better predictor of chronic kidney disease (CKD) than serum uric acid (SUA) isolated. The aim of the present study was to evaluate the association of isolated SUA and the SUA/SCr with CKD in hypertensive patients.

Methods

Cross-sectional study conducted with hypertensive patients followed-up by the Primary Health Care Service (PHC). Sociodemographic, economic, lifestyle, clinical, anthropometric, and biochemical variables were evaluated. The association between SUA parameters (quartiles of SUA and quartiles of SUA/SCr) and CKD was evaluated by bivariate and multivariate logistic regression. The association between SUA parameters (SUA and SUA/SCr) and estimated glomerular filtration rate (eGFR) was evaluated by linear regression. The analyses were performed considering four adjustment models. SUA and SUA/SCr were compared by receiver operating characteristic (ROC) curve.

Results

In the fully adjusted model, SUA was positively associated with the presence of CKD (OR = 6.72 [95 % CI 1.96–22.96]) and inversely associated with eGFR (β Coef. = -2.41 [95 % CI -3.44; -1.39]). SUA/SCr was positively associated with eGFR (β Coef. = 2.39 [1.42; 3.36]). According to the ROC curve, the SUA is a better predictor of CKD than the SUA/SCr.

Conclusions

Elevated levels of isolated SUA were associated with CKD and eGFR. However, the SUA/SCr was not associated with CKD. We do not recommend using the SUA/SCr to predict CKD in hypertensive patients.