bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Antimicrobial Resistance Among Blood and Respiratory Specimens in the United States Using Genotypic Analysis From a Cloud-Based Population Surveillance Network
Authors: Timbrook Tristan T , Olin Katherine E , Spaulding Usha , Galvin Ben W , Cox Charles B
Published: June 2022

Background

Antimicrobial resistance (AMR) surveillance is critical in informing strategies for infection control in slowing the spread of resistant organisms and for antimicrobial stewardship in the care of patients. However, significant challenges exist in timely and comprehensive AMR surveillance.

Methods

Using BioFire Pneumonia and Blood Culture 2 Panels data from BioFire Syndromic Trends (Trend), a cloud-based population surveillance network, we described the detection rate of AMR among a US cohort. Data were included from 2019 to 2021 for Gram-positive and -negative organisms and their related AMR genomic-resistant determinants as well as for detections of Candida auris. Regional and between panel AMR detection rate differences were compared. In addition, AMR codetections and detection rate per organism were evaluated for Gram-negative organisms.

Results

A total of 26 912 tests were performed, primarily in the Midwest. Overall, AMR detection rate was highest in the South and more common for respiratory specimens than blood. methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus detection rates were 34.9% and 15.9%, respectively, whereas AMR for Gram-negative organisms was lower with 7.0% CTX-M and 2.9% carbapenemases. In addition, 10 mcr-1 and 4 C auris detections were observed. For Gram-negative organisms, Klebsiella pneumoniae and Escherichia coli were most likely to be detected with an AMR gene, and of Gram-negative organisms, K pneumoniae was most often associated with 2 or more AMR genes.

Conclusions

Our study provides important in-depth evaluation of the epidemiology of AMR among respiratory and blood specimens for Gram-positive and -negative organism in the United States. The Trend surveillance network allows for near real-time surveillance of AMR.
Anatomic Site–Specific Gonorrhea and Chlamydia Testing and Incidence Among People With HIV Engaged in Care at 4 US Clinical Centers, 2014–2018
Authors: Menza Timothy W , Berry Stephen A , Dombrowski Julie , Cachay Edward , Crane Heidi M , Kitahata Mari M , Mayer Kenneth H
Published: June 2022

Background

The incidence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is increasing in the United States; however, there are limited data on anatomic site–specific GC/CT among people with HIV (PWH).

Methods

We reviewed records of all PWH in care between January 1, 2014, and November 16, 2018, at 4 sites in the CFAR Network of Integrated Clinical Systems Cohort (CNICS; n = 8455). We calculated anatomic site–specific GC/CT testing and incidence rates and used Cox proportional hazards models modified for recurrent events to examine sociodemographic and clinical predictors of GC/CT testing and incidence at urogenital, rectal, and pharyngeal sites. We also calculated site-specific number needed to test (NNT) to detect a positive GC/CT test.

Results

Of 8455 PWH, 2460 (29.1%) had at least yearly GC/CT testing at any anatomic site. The rates of urogenital, rectal, and pharyngeal GC were 1.7 (95% CI, 1.6–1.9), 3.2 (95% CI, 3.0–3.5), and 2.7 (95% CI, 2.5–2.9) infections per 100 person-years, respectively. The rates of urogenital, rectal, and pharyngeal CT were 1.9 (95% CI, 1.7–2.1), 4.3 (95% CI, 4.0–4.5), and 0.9 (95% CI, 0.8–1.0) infections per 100 person-years, respectively. PWH 16–39 years old experienced greater GC/CT rates at all anatomic sites, while men who have sex with men experienced greater rates of extragenital infections. NNTs for urogenital, rectal, and pharyngeal GC/CT were 20 (95% CI, 19–21), 5 (95% CI, 5–5), and 9 (95% CI, 8–9), respectively.

Conclusions

Many PWH are not tested annually for GC/CT, and rates of GC/CT infection, particularly rates of extragenital infections, are high. We identified groups of PWH who may benefit from increased site-specific GC/CT testing.
Mass gain and stopover dynamics among migrating songbirds are linked to seasonal, environmental, and life-history effects
Authors: de Zwaan Devin R , Huang Andrew , McCallum Quinn , Owen Kiirsti , Lamont Myles , Easton Wendy
Published: June 2022

During migration, birds must stopover at refueling sites to replenish energy stores, with the rate of refueling linked to stopover length, migration speed, and the timing of critical life stages, such as breeding. Under optimal migration theory, birds are expected to maximize fuel intake and minimize stopover length (the time minimization hypothesis). Within a multi-species framework, we demonstrate that time minimization behavior is context-dependent, as refueling rate, stopover length, and departure decisions vary between seasons, among species with different ecological traits (e.g., diet and migration distance), and in response to density-dependent factors and prevailing environmental conditions. Using long-term banding data (10 years) from southwestern British Columbia, Canada, we investigated the ecological processes shaping stopover dynamics among 5 warbler (Parulidae) and 5 sparrow species (Passerellidae). Specifically, we assessed variation in fuel deposition rates (FDRs) as well as the associations between mass gain, stopover length, and departure probability. FDR was greater in insectivorous warblers during spring migration and in species migrating long distances. FDR responded positively to temperature and habitat productivity, but negatively to precipitation events, particularly for insectivorous, long-distance migrants during spring migration. Similarly, density-dependent refueling rate was only observed in insectivores and long-distance migrants during spring migration, where higher densities of foliage-gleaning insectivores were associated with a lower FDR. Stopover duration was more closely associated with body condition upon arrival and subsequent mass gain than direct environmental effects, especially during northward spring migration, providing support for time minimization and a mass threshold influencing departure decisions. These results highlight that refueling rates and stopover quality vary among species depending on their life-history strategies, with particular implications for long-distance, migratory insectivores, which may be most susceptible to climate shifts.
Steady-like topology of the dynamical hydrogen bond network in supercooled water
Authors: Martelli Fausto
Published: June 2022

We investigate the link between topology of the hydrogen bond network (HBN) and large-scale density fluctuations in water from ambient conditions to the glassy state. We observe a transition from a temperature-dependent topology at high temperatures, to a steady-like topology below the Widom temperature TW ∼ 220 K signaling the fragile-to-strong crossover and the maximum in structural fluctuations. As a consequence of the steady topology, the network suppresses large-scale density fluctuations much more efficiently than at higher temperatures. Below TW, the contribution of coordination defects of the kind A2D1 (two acceptors and one donor) to the kinetics of the HBN becomes progressively more pronounced, suggesting that A2D1 configurations may represent the main source of dynamical heterogeneities. Below the vitrification temperature, the freezing of rotational and translational degrees of freedom allow for an enhanced suppression of large-scale density fluctuations and the sample reaches the edges of nearly hyperuniformity. The formed network still hosts coordination defects, hence implying that nearly hyperuniformity goes beyond the classical continuous random network paradigm of tetrahedral networks and can emerge in scenarios much more complex than previously assumed. Our results unveil a hitherto undisclosed link between network topology and properties of water essential for better understanding water’s rich and complex nature. Beyond implications for water, our findings pave the way to a better understanding of the physics of supercooled liquids and disordered hyperuniform networks at large.
The role of YAP1 target gene CTGF in the anoikis resistance of rheumatoid arthritis synovial fibroblasts
Authors: Janczi Tomasz , Fehrl Yuliya , Kinne Raimund W , Böhm Beate , Burkhardt Harald
Published: June 2022

Objective

To analyse pro-survival mechanisms elicited in RA synovial fibroblasts (RASFs) upon detachment from their extracellular matrix dependent on the disintegrin metalloproteinase ADAM15 and Yes-associated protein kinase 1 (YAP1).

Methods

Detachment-induced apoptosis was determined by caspase 3/7 assays. Immunofluorescent stainings, cell surface biotinylation and immunoblotting were applied to analyse phosphorylated kinases and subcellular localization of YAP1 and connective tissue growth factor (CTGF). Caspase and transwell transmigration assays served to study CTGF function.

Results

Silencing of ADAM15 or YAP1 in RASFs leads to significantly increased levels of detachment-induced caspase activity. In non-silenced RASFs detachment causes simultaneous ADAM15-enhanced phosphorylation of YAP1 at S127, known for promoting its cytoplasmic localization, and Src-dependent phosphorylation at tyrosine Y357. The majority of nuclear YAP1 leaves the nucleus shortly after cell detachment, but prolonged detachment causes a marked nuclear re-entry of YAP1, resulting in significantly increased synthesis of CTGF. The newly synthesized CTGF, however, is not detectable in the supernatant, but is bound to the outside of the plasma membrane. In vitro studies demonstrated autocrine binding of CTGF to the EGF receptor and β1 integrin, with concomitant triggering of survival kinases, AKT1, ERK1/2, Src and focal adhesion kinase. Functional studies revealed anti-apoptotic effects of CTGF on detached RASFs and an enhancement of their potential for endothelial transmigration using HUVEC-coated transwells.

Conclusion

The elucidation of a new molecular mechanism that protects RASFs in the highly pro-apoptotic environment of inflamed RA joints by promoting anoikis-resistance and transendothelial migration via ADAM15/YAP1-mediated CTGF upregulation uncovers potentially new targets for future therapeutic intervention.
Controversies in rheumatology: maintenance therapy with low-dose glucocorticoids in rheumatoid arthritis
Authors: Buttgereit Frank , Kvien Tore K
Published: June 2022

Since the beginning of the use of glucocorticoids in clinical medicine, the risk–benefit ratio of these still very important drugs has been debated. There is no doubt that they produce many desirable therapeutic effects quickly and reliably. However, their potential to cause adverse effects, especially with prolonged use in high doses, limits their applicability. We discuss the arguments against and in favour of maintenance therapy with low-dose glucocorticoids in patients with RA, and present recent studies, assessments and conclusions on this question.
Clinico–pathological phenotypes of systemic sclerosis–associated myopathy: analysis of a large multicentre cohort
Authors: Matas-García Ana , Guillén-Del-Castillo Alfredo , Kisluk Boris , Selva-O'Callaghan Albert , Espinosa Gerard , Prieto-González Sergio , Moreno Lozano Pedro , Garrabou Glòria , Grau-Junyent Josep María , Simeon-Aznar Carmen Pilar , Milisenda José C
Published: June 2022

Objective

The objective of this study was to analyse the clinico–serological and histological phenotypes of patients with SSc with associated myopathy.

Methods

From November 2002 to September 2020, 52 patients with SSc underwent a muscle biopsy for suspected myopathy. We established two subgroups according to the histological findings based on the presence of isolated fibrosis or fibrosis together with significant inflammation. These patterns were designated as fibrosing and inflammatory, respectively. Clinical data, antibody profile, electrophysiologic studies, muscle biopsy findings and data regarding treatment, mortality and survival were compared between the two groups.

Results

Fourteen biopsies had a fibrosing pattern, whereas 26 showed an inflammatory pattern that could be classified (according to the predominant pattern) into DM (n = 7), necrotizing myopathy (n = 4) and non-specific myositis (n = 15). Additionally, 12 muscle biopsies were reported as neurogenic atrophy (n = 2), or normal muscle or minimal changes (n = 10). Compared with the inflammatory group, SSc patients with the fibrosing pattern presented a higher prevalence of ischaemic heart disease (38.5% vs 3.8%, P = 0.011), conduction abnormalities or arrhythmias (61.5% vs 26.9%, P = 0.036), anti-topo I antibodies (42.9% vs 11.5%, P = 0.044), greater median ESR (53.5 mm/h vs 32.5 mm/h, P = 0.013), with poor response to treatment and a higher mortality (42.9% vs 3.8%, P = 0.004) and lower cumulative survival (P = 0.035).

Conclusions

Patients with SSc-associated myopathy require a comprehensive approach that encompasses clinical, serological and histopathological aspects, given their outcome predictive capacity. At least two different phenotypes can be drawn, considering clinico–pathological features. Significant differences are delineated between both a fibrotic and an inflammatory phenotype.
Recoding Amino Acids to a Reduced Alphabet may Increase or Decrease Phylogenetic Accuracy
Authors: Foster Peter G , Schrempf Dominik , Szöllősi Gergely J , Williams Tom A , Cox Cymon J , Embley T Martin
Published: June 2022

Common molecular phylogenetic characteristics such as long branches and compositional heterogeneity can be problematic for phylogenetic reconstruction when using amino acid data. Recoding alignments to reduced alphabets before phylogenetic analysis has often been used both to explore and potentially decrease the effect of such problems. We tested the effectiveness of this strategy on topological accuracy using simulated data on four-taxon trees. We simulated alignments in phylogenetically challenging ways to test the phylogenetic accuracy of analyses using various recoding strategies together with commonly used homogeneous models. We tested three recoding methods based on amino acid exchangeability, and another recoding method based on lowering the compositional heterogeneity among alignment sequences as measured by the Chi-squared statistic. Our simulation results show that on trees with long branches where sequences approach saturation, accuracy was not greatly affected by exchangeability-based recodings, but Chi-squared-based recoding decreased accuracy. We then simulated sequences with different kinds of compositional heterogeneity over the tree. Recoding often increased accuracy on such alignments. Exchangeability-based recoding was rarely worse than not recoding, and often considerably better. Recoding based on lowering the Chi-squared value improved accuracy in some cases but not in others, suggesting that low compositional heterogeneity by itself is not sufficient to increase accuracy in the analysis of these alignments. We also simulated alignments using site-specific amino acid profiles, making sequences that had compositional heterogeneity over alignment sites. Exchangeability-based recoding coupled with site-homogeneous models had poor accuracy for these data sets but Chi-squared-based recoding on these alignments increased accuracy. We then simulated data sets that were compositionally both site- and tree-heterogeneous, like many real data sets. The effect on the accuracy of recoding such doubly problematic data sets varied widely, depending on the type of compositional tree heterogeneity and on the recoding scheme. Interestingly, analysis of unrecoded compositionally heterogeneous alignments with the NDCH or CAT models was generally more accurate than homogeneous analysis, whether recoded or not. Overall, our results suggest that making trees for recoded amino acid data sets can be useful, but they need to be interpreted cautiously as part of a more comprehensive analysis. The use of better-fitting models like NDCH and CAT, which directly account for the patterns in the data, may offer a more promising long-term solution for analyzing empirical data. [Compositional heterogeneity; models of evolution; phylogenetic methods; recoding amino acid data sets.]
Detection of schistosome infection in the invasive snail Melanoides tuberculata (Gastropoda: Thiaridae) by polymerase chain reaction from Plateau State, Nigeria: a novel turning point in disease epidemiology and control?
Authors: Adubi Taiwo Oluwakemi , Otubanjo Olubunmi Adetoro , Atalabi Tolulope Ebenezer
Published: June 2022

Background

Melanoides tuberculata is a freshwater snail that serves as an intermediate host for 11 parasitic flukes. This study was conducted with the aim of identifying and screening the snail intermediate hosts in the study site for schistosomiasis using the molecular technique.

Methods

DNA was extracted from the snails by the hexadecyl trimethyl ammonium bromide method and the Dra1 primer was used to amplify the Dra1 repeated sequence of Schistosoma haematobium.

Results

The presence of schistosome DNA in M. tuberculata by polymerase chain reaction was confirmed.

Conclusions

Our findings show that M. tuberculata is a potential intermediate host of schistosomes.
High phosphate‐induced progressive proximal tubular injury is associated with the activation of Stat3/Kim‐1 signaling pathway and macrophage recruitment
Authors: Richter Beatrice , Kapanadze Tamar , Weingärtner Nina , Walter Stefanie , Vogt Isabel , Grund Andrea , Schmitz Jessica , Bräsen Jan Hinrich , Limbourg Florian P. , Haffner Dieter , Leifheit‐Nestler Maren
Published: June 2022

Dietary phosphate intake in the Western population greatly exceeds the recommended dietary allowance and is linked to enhanced cardiovascular and all‐cause mortality. It is unclear whether a chronic high phosphate diet (HPD) causes kidney injury in healthy individuals. Here, we show that feeding a 2% HPD in C57BL/6N mice for one up to six months resulted in hyperphosphatemia, hyperphosphaturia, increased plasma levels of fibroblast growth factor (FGF) 23, and parathyroid hormone (PTH) compared to mice on a 0.8% phosphate diet. Kidney injury was already noted after two months of HPD characterized by loss of proximal tubular (PT) cell polarity, flattened epithelia, disruption of brush border membranes, vacuolization, increased PT cell proliferation, marked interstitial mononuclear infiltration, and progressive accumulation of collagen fibers. HPD increased Stat3 activation and Kim‐1 expression in PT epithelial cells and enhanced renal synthesis of chemokines recruiting monocytes and macrophages as well as macrophage related factors. Enhanced recruitment of F4/80+ macrophages around injured PT lesions was timely associated with increased Kim‐1 synthesis, tubular MCP‐1 expression, and degree of PT injury score. Likewise, tubulointerstitial fibrosis was associated with activation of Stat3/Kim‐1 signaling pathway. The stimulation of human proximal tubular cells with high phosphate activated Stat3 signaling and induced HAVCR1 and CCL2 expression. We conclude that high phosphate results in progressive proximal tubular injury, indicating that high dietary phosphate intake may affect kidney health and therefore represents an underestimated health problem for the general population.
A framework of the institutional policies and practice environments of nurse practitioner primary care models
Authors: Hogan Tory H. , Maurer Nicholas R. , Stevens Lena , Hefner Jennifer L.
Published: June 2022

Purpose

The purpose of this article was to compare the implementation of distinct models of nurse practitioner (NP) integration into primary care offices.

Design/Methodology

A multiple case study design of three NP primary care practice models allowed for in-depth exploration of the management processes supporting the utilization of NPs. At each site, semistructured qualitative interviews, document review, and site tours/observations were conducted and subject to cross-case analysis guided by the NP Primary Care Organizational Framework (NP-PCOF)—developed for this study based on existing theory.

Results

Our case study sites represent three distinct NP primary care models. In the restricted practice model, NPs care for same-day/walk-in acute patients. NPs in the independent practice model have an independent panel of patients and interact collegially as independent coworkers. NPs in the comanagement model function on a team (a physician and two NPs), have a team office space, collectively care for a shared panel of patients, and can earn financial bonuses contingent upon meeting team quality metrics. Our cross-case analysis confirmed differences in physical space design, the relational structure of a workplace, and the capacity for innovation via NP compensation and performance metrics across different NP primary care models.

Conclusion

Our findings suggest that NP primary care models are supported by complex management systems and the NP-PCOF is a tool to help understand this complexity.

Implications

The NP-PCOF is a framework to understand the management systems that facilitate the utilization of NPs within primary care organizations.
Making do by getting real
Authors: Mitra Mahima , Dopson Sue , Hoff Timothy
Published: June 2022

Background

Health care professionals face greater uncertainty in their careers as traditional jobs wither and new, organizationally controlled jobs proliferate, reducing economic security and professional autonomy.

Purpose

We apply psychological contract and self-efficacy theory to examine the career agency of early-career physicians. We ask the following: (a) What are the unfulfilled expectations and emotions experienced by young physicians at the training and early career stages? (b) What are the forms of career agency exhibited by young physicians in response to unfulfillment?

Methodology

We conducted a study on 48 U.K. early-career primary care physicians, known as general practitioners. The sample comprised both trainees as well as newly qualified physicians. Data were collected through in-depth interviews and focus group discussions.

Results

Physicians interpreted their early-career experiences based on predominantly ideological expectations around what it means to be a successful professional. However, the realities of practice resulted in highly emotional experiences of violation that were associated with a “reactive” agency and job behaviors that were more transactional and less relational.

Conclusion

This study identifies the expectations of early career professionals, which helps understand how and why psychological contract violations occur. It also expands the conceptualization of career agency from a positively framed aspect of professional behavior to one that includes haphazard and self-serving elements.

Practice Implications

Our study highlights several implications of the shifts in physician career agency for primary care practice. It discusses the potential effects of the purposeful self-interest among doctors on professional identity and power, as well as patient care.
The buffering effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants working in aged care facilities
Authors: Pariona-Cabrera Patricia , Meacham Hannah , Tham Tse Leng , Cavanagh Jillian , Halvorsen Beni , Holland Peter , Bartram Timothy
Published: June 2022

Purpose

The purpose of this study was to examine the effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants (PCAs) working in aged care using the job demands–resources theory.

Methodology

Data were collected from 254 nurses and PCAs of the Australian Nursing Midwifery Federation located in Victoria, Australia. The study takes a quantitative approach and tests the hypotheses through regression analyses.

Findings

The results indicate that experiencing physical violence increases levels of stress, depression, and anxiety. This, in turn, increases nurses’ and PCAs’ intention to leave. However, increased psychological capital can assist nurses and PCAs in dealing with physical violence.

Research Implications

The study acknowledges that physical violence is a factor in nurses’ intention to leave. The significant finding is that psychological capital plays a protective role in ameliorating the negative impact of physical violence on individual well-being and intentions to leave. We note, however, that this is a cross-section study, and more longitudinal research needs to be undertaken.

Practical Implications

There are clear implications for managers to create a supportive organization that cultivates hope, self-efficacy, and resilience, thereby increasing psychological capital. Leadership development programs could build a supportive foundation for nurses to seek support and build resilience. Job construction should be focused on protecting nurses from risk by utilizing manageable workloads to limit stress, depression, and anxiety.

Originality

Our study extends research on retention of these skilled and important health care workers in a demanding environment that has largely been absent from the literature. Specifically, physical violence is often considered part of nursing work, but its impact on mental health, well-being, and intention to leave are underexplored in this sector, as well as the effectiveness of specific measures that bolster the negative impact of physical violence on nurses.
Knowledge of COVID-19 among Brazilian health care professionals and associated factors
Authors: Bernardes João Marcos , Magalhães Daniela Mendes dos Santos , Alonso Melissa Spröesser , Gómez-Salgado Juan , Ruiz-Frutos Carlos , Romero Adolfo , Días Adriano
Published: June 2022

Health care professional's knowledge is essential to contain epidemics. This research aimed to evaluate the knowledge of Brazilian health care professionals regarding COVID-19 to analyze whether there is a difference in knowledge between professionals in Primary Health Care and those in other levels of care or not; and to identify factors associated with knowledge. This is a cross-sectional study, including 716 participants who answered an online questionnaire between April and May 2020. Descriptive statistics, difference tests between groups, and logistic regression models were used to analyze the data. The average knowledge score was 12.42 points (out of a possible total of 15). There was no significant difference between professionals in Primary Health Care and those in other levels of care. Knowledge was associated with age, profession, perception regarding media's information quality, and hours exposed to information on COVID-19. Participants showed adequate knowledge, despite some specific gaps. Continuing education actions should prioritize younger nonmedical professionals.
Dolutegravir plus rilpivirine: benefits beyond viral suppression
Authors: Troya Jesús , Dueñas Carlos , Irazola Idoia , de los Santos Ignacio , de la Fuente Sara , Gil Desiré , Hernández Cristina , Galindo María José , Gómez Julia , Delgado Elisabeth , Moreno-García Estela , Pousada Guillermo , Aldámiz Teresa , Iribarren Jose Antonio , Guerra José Manuel , Morán Miguel Ángel , Galera Carlos , De La Fuente Javier , Peláez Ana , Cervero Miguel , Garcinuño María , Montero Marta , Ceballos Francisco , Buzón Luis
Published: June 2022

Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.

A multicentric retrospective cohort study.

Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.

The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR –40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = –23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.

In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.
KIF23 is a potential biomarker of diffuse large B cell lymphoma
Authors: Gong Yuqi , Zhou Lingna , Ding Liya , Zhao Jing , Wang Zhe , Ren Guoping , Zhang Jing , Mao Zhengrong , Zhou Ren
Published: June 2022

Diffuse Large B Cell Lymphoma (DLBCL), the most common form of blood cancer. The genetic and clinical heterogeneity of DLBCL poses a major barrier to diagnosis and treatment. Hence, we aim to identify potential biomarkers for DLBCL.

Differentially expressed genes were screened between DLBCL and the corresponding normal tissues. Kyoto Encyclopedia of Genes and Genomes and Gene oncology analyses were performed to obtain an insight into these differentially expressed genes. PPI network was constructed to identify hub genes. survival analysis was applied to evaluate the prognostic value of those hub genes. DNA methylation analysis was implemented to explore the epigenetic dysregulation of genes in DLBCL.

In this study, Kinesin family member 23 (KIF23) showed higher expression in DLBCL and was identified as a risk factor in DLBCL. The immunohistochemistry experiment further confirmed this finding. Subsequently, the univariate and multivariate analysis indicated that KIF23 might be an independent adverse factor in DLBCL. Upregulation of KIF23 might be a risk factor for the overall survival of patients who received an R-CHOP regimen, in late-stage, whatever with or without extranodal sites. Higher expression of KIF23 also significantly reduced 3, 5, 10-year overall survival. Furthermore, functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes, Gene oncology, and Gene Set Enrichment Analysis) showed that KIF23 was mainly involved in cell cycle, nuclear division, PI3K/AKT/mTOR, TGF-beta, and Wnt/beta-catenin pathway in DLBCL. Finally, results of DNA methylation analysis indicated that hypomethylation in KIF23's promoter region might be the result of its higher expression in DLBCL.

The findings of this study suggested that KIF23 is a potential biomarker for the diagnosis and prognosis of DLBCL. However, further studies were needed to validate these findings.
Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene
Authors: Yue Fagui , Zhang Hongguo , Luo Lili , Liu Ruizhi , Jing Jili
Published: June 2022

Trisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211–0.242 Mb duplications of 6q14.1 (chr6: 80109532–80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.
Trajectories of perceived susceptibility to COVID-19 over a year
Authors: Opsasnick Lauren A. , Curtis Laura M. , Kwasny Mary J. , O’Conor Rachel , Wismer Guisselle A. , Benavente Julia Yoshino , Lovett Rebecca M. , Eifler Morgan R. , Zuleta Andrea M. , Bailey Stacy Cooper , Wolf Michael S.
Published: June 2022

The U.S. public health response to coronavirus disease 2019 (COVID-19) has been widely criticized as having downplayed the potential implications COVID-19 could have on one's personal health. Despite the unprecedented threat of COVID-19, many individuals still believed that it was not at all likely that they would become infected. We sought to investigate trends in adults’ perceived susceptibility to COVID-19 over the first year of the pandemic, whether distinct trajectories emerged, and if these trajectories differed by participant socio-demographic characteristics.

This was a longitudinal cohort study with 5 time points of data collection (March 13, 2020–March 3, 2021). Subjects included 627 adults living with ≥1 chronic conditions, who completed a baseline interview and at least one follow-up interview. In addition to collecting relevant socio-demographic characteristics, participants’ perceived susceptibility to COVID-19 across time was assessed and classified into distinct trajectories.

Nearly two-thirds (62.2%) of participants perceived themselves to be highly susceptible to COVID-19 from the onset of the pandemic (“early responders”) and sustained this over a year, a third (29.0%) eventually perceived themselves to be highly susceptible (“late responders”), and 8.8% maintained a low likelihood of susceptibility throughout the pandemic (“non-responders”). In multivariable analyses, compared to White participants, Latinx participants were significantly more likely to be non-responders and report low likelihood of perceived susceptibility (Risk Ratio [RR]: 3.46; 95% confidence interval: 1.19, 10.1), as were Black participants (RR: 5.49; 95% confidence interval: 2.19, 13.8).

A year into the COVID-19 pandemic, 1 out of 11 participants persistently did not think they might be susceptible and potentially infected. Future studies are needed to understand reasons why certain individuals, particularly those of racial/ethnic minorities, did not perceive themselves at risk for infection.
Effects of self-quarantine during the COVID-19 pandemic on patients with lumbar spinal stenosis
Authors: Hayashi Kazunori , Tanaka Toru , Sakawa Akira , Ebara Tsuneyuki , Tanaka Hidekazu , Nakamura Hiroaki
Published: June 2022

Prospective case-control study

This study aimed to investigate the effect of self-quarantine on the changes in low back symptoms and activities of daily living (ADL) due to low physical activity because of the COVID-19 pandemic in patients with lumbar spinal stenosis (LSS).

The frequency and intensity of low back and leg pain have reportedly increased in healthy subjects because of self-quarantine.

Patients with LSS who self-quarantined from baseline (SQ group) were matched to controls who did not self-quarantine (non-SQ group), based on age, sex, medication, ADL, and the numeric rating scale score for low back symptoms. The change in low back symptoms, ADL, and health-related quality of life between baseline and follow-up were compared between the groups.

The SQ and non-SQ group included 80 and 60 patients, respectively. Compared with the baseline, the numeric rating scale score for low back pain at follow-up in the SQ group significantly improved (P = .004, median; 1 point), but not in the non-SQ group. No significant difference was found regarding changes in leg pain or numbness. Low back pain improvement did not lead to ADL improvement. The short form 12 evaluation revealed the role/social component score in the SQ group to be significantly lower than that in the non-SQ group; no difference was found for the physical or mental components at follow-up.

Self-quarantine with conservative treatment effected short-term low back pain improvement in patients with LSS. However, no improvement in ADL was found. Self-quarantine had an unfavorable impact for health-related quality of life. The effect of self-quarantine can influence the treatment results of LSS.
Imaging findings of vertebral osteomyelitis caused by nontuberculous mycobacterial organisms
Authors: Yu Xiao Jing , Lin Yu Dong , Hu Peng , Zee Chi Shing , Ji Shu Juan , Zhou Fei
Published: June 2022

Rationale:

Prompt diagnosis of nontuberculous Mycobacterial (NTM) vertebral osteomyelitis is challenging, yet necessary to prevent serious morbidity and mortality. Here, we report 3 cases of vertebral osteomyelitis caused by NTM with imaging findings.

Patient concerns:

Case 1, a 58-year-old male patient, was admitted to our hospital because of the presence of a pulmonary mass for 6 months with cough and chest pain.

Case 2, a 50-year-old male patient, had fever and cough for 3 years and was diagnosed with tuberculosis. Antituberculosis treatment was ineffective, accompanied by lymph node enlargement and osteosclerotic changes involving vertebral bodies.

Case 3, a 66-year-old female patient, was admitted to our hospital with a mass on the top of her head for 1 month, which ruptured in the last 2 weeks.

Diagnoses:

Case 1: Sputum culture revealed Mycobacterium (M.) avium.

Case 2: The final culture results of the lymph node biopsy samples were M. intracellulare.

Case 3: Culture results of the sputum and pus from the abscess were M. gordon.

We found sclerosing lesions in the spine in all 3 NTM patients, which were easily misdiagnosed as metastatic tumors. In 2 cases, there was bone destruction in the ilium with limbic sclerosis, and there were abscesses near the ilium and in front of the sacrum in 1 case.

Interventions:

Case 1 was transferred to other specialist hospital.

Case 3 received surgical treatment for cranial lesions and abscess drainage.

Case 2 and case 3 received targeted treatment for nontuberculous mycobacteria in our hospital.

Outcome:

The condition of case 1 was unknown.

Recovery of case 2 was uneventful because of prolonged illness; however, inflammation gradually improved overall.

Case 3 had no recurrence following surgical treatment.

Lessons:

In our 3 cases of NTM vertebral osteomyelitis, bone lesions were often misdiagnosed as bony metastases because of the presence of multiple sclerotic lesions. Diagnoses were challenging and delayed. It is important to consider osteomyelitis by NTM when disseminated osteosclerosis with or without osteolytic bone lesions is present in conjunction with continuous inflammatory symptoms and signs. Moreover, an open biopsy of the lesion should be performed for a definitive diagnosis.
Diffuse midline glioma with H3-K27M mutation
Authors: Wang Yi-Hua , Gu Jian , Yu Juan-Han , Fu Lin , Li Qing-Chang , Qiu Xue-Shan , Wang En-Hua
Published: June 2022

Introduction:

Diffuse midline glioma with H3-K27M mutation is an infiltrative high-grade glioma, with predominantly astrocytic differentiation.

Patient concerns:

A 54-year-old Chinese woman presented with memory loss for a month and walking instability for 15 days.

Diagnosis:

Magnetic resonance imaging showed a mass shadow of isometric T1 and slightly longer T2 with mild mixed signals in the third ventricle of the suprasellar region. Histologically, the tumor was primarily sheet-like, with many “anucleate areas” composed of long and thin fibrillary processes of the bipolar cells, which formed “whorls.” The neoplastic nuclei were ovoid and moderate in size. The tumor showed brisk mitotic activity and vascular proliferation, with no necrosis. In addition to histone H3K27M mutation, immunohistochemical staining showed that the tumor cells were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, alpha-thalassemia/mental retardation syndrome X, S-100 and Vimentin. The “anucleate areas” were positive for glial fibrillary acidic protein and negative for synaptophysin. The Ki-67 proliferation index was about 10%. Molecular genetic analyses detected H3F3A K27M mutation, but no mutations in IDH1 or IDH2, TERT promoter mutations, MGMT promoter methylation, KIAA1549-BRAF fusion or deletion of 1p/19q were found. Based on these findings, the patient was diagnosed as diffuse midline glioma with H3-K27M mutation in the third ventricle, corresponding to WHO grade 4.

Interventions:

A craniotomy with total excision of the tumor was performed.

Outcomes:

After surgery, she was routinely treated with temozolomide for chemotherapy and synchronous radiotherapy. It has been 11 months now, and the patient is living well.

Conclusion:

This case report provides information on the microscopic morphological features of diffuse midline glioma with H3K27M mutation, which can help pathologists to make a definitive diagnosis of this tumor.
All in the Family
Authors: Fletcher Paula C. , Pollock Stephanie , Luymes Nicole , Bryden Pamela J.
Published: June 2022

Purpose

The overarching purpose of this research was to examine the experiences of 1 family living with a child with Helsmoortel-Van Der Aa syndrome or activity-dependent neuroprotective protein (ADNP) syndrome.

Design

A retrospective qualitative design was used for this study.

Methods

Two primary caregivers for a 5-year-old child with ADNP syndrome completed background questionnaires to provide context for semistructured interviews. Each caregiver completed 2 interviews, approximately 2 months apart. Field notes, member checks, and triangulation were used to enhance the credibility of the study.

Results

This article summarizes the theme “All in the Family.” Having a child with ADNP syndrome affected all aspects of family life. Participants revealed that family dynamics were shaped by experiences stemming from their living arrangements and caregiving responsibilities.

Conclusions

Findings from this research highlighted the need for increased support for families faced with ADNP syndrome, as well as the role clinical nurse specialists can play in the lives of caregivers faced with such a rare diagnosis. Furthermore, given the paucity of ADNP syndrome information, the need for more research is warranted.
Data-driven nonlinear model reduction to spectral submanifolds in mechanical systems
Authors: Cenedese M. , Axås J. , Yang H. , Eriten M. , Haller G.
Published: June 2022

While data-driven model reduction techniques are well-established for linearizable mechanical systems, general approaches to reducing nonlinearizable systems with multiple coexisting steady states have been unavailable. In this paper, we review such a data-driven nonlinear model reduction methodology based on spectral submanifolds. As input, this approach takes observations of unforced nonlinear oscillations to construct normal forms of the dynamics reduced to very low-dimensional invariant manifolds. These normal forms capture amplitude-dependent properties and are accurate enough to provide predictions for nonlinearizable system response under the additions of external forcing. We illustrate these results on examples from structural vibrations, featuring both synthetic and experimental data.

This article is part of the theme issue ‘Data-driven prediction in dynamical systems’.
GFINNs: GENERIC formalism informed neural networks for deterministic and stochastic dynamical systems
Authors: Zhang Zhen , Shin Yeonjong , Em Karniadakis George
Published: June 2022

We propose the GENERIC formalism informed neural networks (GFINNs) that obey the symmetric degeneracy conditions of the GENERIC formalism. GFINNs comprise two modules, each of which contains two components. We model each component using a neural network whose architecture is designed to satisfy the required conditions. The component-wise architecture design provides flexible ways of leveraging available physics information into neural networks. We prove theoretically that GFINNs are sufficiently expressive to learn the underlying equations, hence establishing the universal approximation theorem. We demonstrate the performance of GFINNs in three simulation problems: gas containers exchanging heat and volume, thermoelastic double pendulum and the Langevin dynamics. In all the examples, GFINNs outperform existing methods, hence demonstrating good accuracy in predictions for both deterministic and stochastic systems.

This article is part of the theme issue ‘Data-driven prediction in dynamical systems’.
Temporal dynamics of cholinergic activity in the septo-hippocampal system
Authors: Kopsick Jeffrey D. , Hartzell Kyle , Lazaro Hallie , Nambiar Pranav , Hasselmo Michael E. , Dannenberg Holger
Published: June 2022

Cholinergic projection neurons in the medial septum and diagonal band of Broca are the major source of cholinergic modulation of hippocampal circuit functions that support neural coding of location and running speed. Changes in cholinergic modulation are known to correlate with changes in brain states, cognitive functions, and behavior. However, whether cholinergic modulation can change fast enough to serve as a potential speed signal in hippocampal and parahippocampal cortices and whether the temporal dynamics in such a signal depend on the presence of visual cues remain unknown. In this study, we use a fiber-photometric approach to quantify the temporal dynamics of cholinergic activity in freely moving mice as a function of the animal’s running speed and visual cues. We show that the population activity of cholinergic neurons in the medial septum and diagonal band of Broca changes fast enough to be aligned well with changes in the animal’s running speed and is strongly and linearly correlated to the logarithm of the animal’s running speed. Intriguingly, the cholinergic modulation remains strongly and linearly correlated to the speed of the animal’s neck movements during periods of stationary activity. Furthermore, we show that cholinergic modulation is unaltered during darkness. Lastly, we identify rearing, a discrete behavior where the mouse stands on its hindlimbs to scan the environment from an elevated perspective, is associated with higher cholinergic activity than expected from neck movements on the horizontal plane alone. Taken together, these data show that temporal dynamics in the cholinergic modulation of hippocampal circuits are fast enough to provide a potential running speed signal in real-time. Moreover, the data show that cholinergic modulation is primarily a function of the logarithm of the animal’s movement speed, both during locomotion and during stationary activity, with no significant interaction with visual inputs. These data advance our understanding of temporal dynamics in cholinergic modulation of hippocampal circuits and their functions in the context of neural coding of location and running speed.