bluuebunny/crossref_metadata_2025 huggingface dataset:
NBAT1/CASC15-003/USP36 control MYCN expression and its downstream pathway genes in neuroblastoma
Authors: Juvvuna Prasanna Kumar , Mondal Tanmoy , Di Marco Mirco , Kosalai Subazini Thankaswamy , Kanduri Meena , Kanduri Chandrasekhar
Published: April 2021

Background

MYCN has been an attractive therapeutic target in neuroblastoma considering the widespread amplification of the MYCN locus in neuroblastoma, and its established role in neuroblastoma development and progression. Thus, understanding neuroblastoma-specific control of MYCN expression at the transcriptional and post-transcriptional level would lead to identification of novel MYCN-dependent oncogenic pathways and potential therapeutic strategies.

Methods

By performing loss- and gain-of-function experiments of the neuroblastoma hotspot locus 6p22.3 derived lncRNAs CASC15-003 and NBAT1, together with coimmunoprecipitation and immunoblotting of MYCN, we have shown that both lncRNAs post-translationally control the expression of MYCN through regulating a deubiquitinase enzyme USP36. USP36 oncogenic properties were investigated using cancer cell lines and in vivo models. RNA-seq analysis of loss-of-function experiments of CASC15-003/NBAT1/MYCN/USP36 and JQ1-treated neuroblastoma cells uncovered MYCN-dependent oncogenic pathways.

Results

We show that NBAT1/CASC15-003 control the stability of MYCN protein through their common interacting protein partner USP36. USP36 harbors oncogenic properties and its higher expression in neuroblastoma patients correlates with poor prognosis, and its downregulation significantly reduces tumor growth in neuroblastoma cell lines and xenograft models. Unbiased integration of RNA-seq data from CASC15-003, NBAT1, USP36, and MYCN knockdowns and neuroblastoma cells treated with MYCN inhibitor JQ1, identified genes that are jointly regulated by the NBAT1/CASC15-003/USP36/MYCN pathway. Functional experiments on one of the target genes, COL18A1, revealed its role in the NBAT1/CASC15-003-dependent cell adhesion feature in neuroblastoma cells.

Conclusion

Our data show post-translational regulation of MYCN by NBAT1/CASC15-003/USP36, which represents a new regulatory layer in the complex multilayered gene regulatory network that controls MYCN expression.
Cystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas
Authors: Cano-Galiano Andrés , Oudin Anais , Fack Fred , Allega Maria-Francesca , Sumpton David , Martinez-Garcia Elena , Dittmar Gunnar , Hau Ann-Christin , De Falco Alfonso , Herold-Mende Christel , Bjerkvig Rolf , Meiser Johannes , Tardito Saverio , Niclou Simone P
Published: April 2021

Background

Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define glioma subtypes and are considered primary events in gliomagenesis, impacting tumor epigenetics and metabolism. IDH enzyme activity is crucial for the generation of reducing potential in normal cells, yet the impact of the mutation on the cellular antioxidant system in glioma is not understood. The aim of this study was to determine how glutathione (GSH), the main antioxidant in the brain, is maintained in IDH1-mutant gliomas, despite an altered NADPH/NADP balance.

Methods

Proteomics, metabolomics, metabolic tracer studies, genetic silencing, and drug targeting approaches in vitro and in vivo were applied. Analyses were done in clinical specimen of different glioma subtypes, in glioma patient-derived cell lines carrying the endogenous IDH1 mutation and corresponding orthotopic xenografts in mice.

Results

We find that cystathionine-γ-lyase (CSE), the enzyme responsible for cysteine production upstream of GSH biosynthesis, is specifically upregulated in IDH1-mutant astrocytomas. CSE inhibition sensitized these cells to cysteine depletion, an effect not observed in IDH1 wild-type gliomas. This correlated with an increase in reactive oxygen species and reduced GSH synthesis. Propargylglycine (PAG), a brain-penetrant drug specifically targeting CSE, led to delayed tumor growth in mice.

Conclusions

We show that IDH1-mutant astrocytic gliomas critically rely on NADPH-independent de novo GSH synthesis via CSE to maintain the antioxidant defense, which highlights a novel metabolic vulnerability that may be therapeutically exploited.
Bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1: results from a phase I expansion cohort in patients with recurrent glioblastoma
Authors: Khasraw Mustafa , Weller Michael , Lorente David , Kolibaba Kathryn , Lee Chee Khoon , Gedye Craig , I. de La Fuente Macarena , Vicente David , Reardon David A , Gan Hui K , Scott Andrew M , Dussault Isabelle , Helwig Christoph , Ojalvo Laureen S , Gourmelon Carole , Groves Morris
Published: April 2021

Background

For patients with recurrent glioblastoma (rGBM), there are few options following treatment failure with radiotherapy plus temozolomide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 antibody blocking PD-L1.

Methods

In this phase I, open-label expansion cohort (NCT02517398), patients with rGBM that progressed after radiotherapy plus temozolomide received bintrafusp alfa 1200 mg Q2W until disease progression, unacceptable toxicity, or trial withdrawal. Response was assessed per RANO criteria. The primary endpoint was disease control rate (DCR); secondary endpoints included safety.

Results

As of August 24, 2018, 35 patients received bintrafusp alfa for a median of 1.8 (range, 0.5–20.7) months. Eight patients (22.9%) experienced disease control as assessed by an independent review committee: 2 had a partial response, 4 had stable disease, and 2 had non-complete response/non-progressive disease. Median progression-free survival (PFS) was 1.4 (95% confidence interval [CI], 1.2–1.6) months; 6- and 12-month PFS rates were 15.1% and 11.3%, respectively. Median overall survival (OS) was 5.3 (95% CI, 2.6–9.4) months; 6- and 12-month OS rates were 44.5% and 30.8%, respectively. The DCR (95% CI) was 66.7% (22.3–95.7%) for patients with IDH-mutant GBM (n = 6) and 13.8% (3.9–31.7%) for patients with IDH–wild-type GBM (n = 29). Disease control was seen regardless of PD-L1 expression. Twenty-five patients (71.4%) experienced treatment-related adverse events (grade ≥3; 17.1% [n = 6]).

Conclusions

The percentage of patients achieving disease control and the manageable safety profile may warrant further investigation of bintrafusp alfa in GBM.
Cancer, cognition, and COVID: delivering direct-to-home teleneuropsychology services to neuro-oncology patients
Authors: Gardner Melissa M , Aslanzadeh Farah J , Zarrella Giuliana V , Braun Sarah E , Loughan Ashlee R , Parsons Michael W
Published: April 2021

Background

The COVID-19 pandemic induced rapid adoption of telemedicine services for neuro-oncology patients at an increased risk of infection. Neuropsychological assessment is important to neuro-oncology care yet challenging to complete outside of a structured testing environment. Teleneuropsychology (TNP) has been explored in limited populations and proven feasible and reliable. Conducting TNP visits directly to patients’ home (DTH) had minimal prior study.

Methods

We used two voluntary surveys to examine acceptance (patients) and feasibility (providers) of DTH-TNP at two regionally diverse medical institutions providing neuropsychological services to neuro-oncology patients from April to September 2020.

Results

A total of 119 patients were scheduled during the study period, 79 of whom completed neuropsychological testing via DTH-TNP. Neuropsychology providers completed surveys on 68 of these encounters (86%). In 98% of cases, neuropsychologists were able to achieve or partially achieve the individually defined goals of their assessment. Common problems reported included patient dysregulation (16%) and slow/unreliable internet (15%). Of the 52 patients who responded, 98% were satisfied with the DTH-TNP experience, and 92% would recommend the virtual visit to others. All respondents felt understood by the examiner (100%) and the majority denied technical difficulties (90%), communication challenges (94%), or privacy concerns (98%). Patients reported reduced risk of infection and saved travel time as favorable aspects of DTH-TNP.

Conclusions

These preliminary results suggest neuro-oncology patients find DTH-TNP acceptable and neuropsychologists find it a feasible practice, while also recognizing its limitations. Results suggest that further study of DTH-TNP (eg, reliability, validity) for neuro-oncology patients is warranted.
Bridging the research-implementation gap in avian conservation with translational ecology
Authors: Saunders Sarah P , Wu Joanna X , Gow Elizabeth A , Adams Evan , Bateman Brooke L , Bayard Trina , Beilke Stephanie , Dayer Ashley A , Fournier Auriel M V , Fox Kara , Heglund Patricia , Lerman Susannah B , Michel Nicole L , Paxton Eben H , Şekercioğlu Çağan H , Smith Melanie A , Thogmartin Wayne , Woodrey Mark S , van Riper Charles
Published: April 2021

The recognized gap between research and implementation in avian conservation can be overcome with translational ecology, an intentional approach in which science producers and users from multiple disciplines work collaboratively to co-develop and deliver ecological research that addresses management and conservation issues. Avian conservation naturally lends itself to translational ecology because birds are well studied, typically widespread, often exhibit migratory behaviors transcending geopolitical boundaries, and necessitate coordinated conservation efforts to accommodate resource and habitat needs across the full annual cycle. In this perspective, we highlight several case studies from bird conservation practitioners and the ornithological and conservation social sciences exemplifying the 6 core translational ecology principles introduced in previous studies: collaboration, engagement, commitment, communication, process, and decision-framing. We demonstrate that following translational approaches can lead to improved conservation decision-making and delivery of outcomes via co-development of research and products that are accessible to broader audiences and applicable to specific management decisions (e.g., policy briefs and decision-support tools). We also identify key challenges faced during scientific producer–user engagement, potential tactics for overcoming these challenges, and lessons learned for overcoming the research-implementation gap. Finally, we recommend strategies for building a stronger translational ecology culture to further improve the integration of these principles into avian conservation decisions. By embracing translational ecology, avian conservationists and ornithologists can be well positioned to ensure that future management decisions are scientifically informed and that scientific research is sufficiently relevant to managers. Ultimately, such teamwork can help close the research-implementation gap in the conservation sciences during a time when environmental issues are threatening avian communities and their habitats at exceptional rates and at broadening spatial scales worldwide.
Particle–particle particle–tree code for planetary system formation with individual cut-off method: GPLUM
Authors: Ishigaki Yota , Kominami Junko , Makino Junichiro , Fujimoto Masaki , Iwasawa Masaki
Published: April 2021

In a standard theory of the formation of the planets in our Solar System, terrestrial planets and cores of gas giants are formed through accretion of kilometer-sized objects (planetesimals) in a protoplanetary disk. Gravitational N-body simulations of a disk system made up of numerous planetesimals are the most direct way to study the accretion process. However, the use of N-body simulations has been limited to idealized models (e.g., perfect accretion) and/or narrow spatial ranges in the radial direction, due to the limited number of simulation runs and particles available. We have developed new N-body simulation code equipped with a particle–particle particle–tree (P3T) scheme for studying the planetary system formation process: GPLUM. For each particle, GPLUM uses the fourth-order Hermite scheme to calculate gravitational interactions with particles within cut-off radii and the Barnes–Hut tree scheme for particles outside the cut-off radii. In existing implementations, P3T schemes use the same cut-off radius for all particles, making a simulation become slower when the mass range of the planetesimal population becomes wider. We have solved this problem by allowing each particle to have an appropriate cut-off radius depending on its mass, its distance from the central star, and the local velocity dispersion of planetesimals. In addition to achieving a significant speed-up, we have also improved the scalability of the code to reach a good strong-scaling performance up to 1024 cores in the case of N = 106.
Variability of Comptonized X-ray spectra of a super-Eddington accretor: Approach using Boltzmann radiation transport
Authors: Ogawa Takumi , Ohsuga Ken , Makino Yoshihiro , Mineshige Shin
Published: April 2021

We investigate the radiation fields around super-Eddington accretion flow, in which multiple inverse-Compton scattering plays a principal role, by using newly developed code describing Boltzmann radiation transfer in the Schwarzschild space-time. We apply this code to post-processing spectral calculations based on general relativistic, radiation magnetohydrodynamic simulation data to obtain X-ray spectra seen from various viewing angles. The radiation fields are distinctively separated into a funnel region with an opening angle of ∼30°, which is full with hot (gas temperature of T > 108 K), tenuous, and high-velocity plasmas, and surrounding cooler (T ∼ 107 K) and optically thick outflow regions. Accordingly, there is a clear tendency that the smaller the viewing angle, the harder the spectra. In particular, hard photons with several tens of keV are observable only by observers at viewing angles less than ∼30°, consistent with past spectral studies based on simulations. Further, we investigate how the spectra are varied by a flare occurring in the innermost region, finding that the variation amplitude grows as the photon energy increases and that the harder photons emerge more quickly than softer photons. The observational implications on long-term spectral variability of ultra-luminous X-ray sources are briefly discussed.
Extracting common signal components from the X-ray and optical light curves of GX 339−4: New view for anti-correlation
Authors: Omama Tomoki , Uemura Makoto , Ikeda Shiro , Morii Mikio
Published: April 2021

Simultaneous X-ray and optical observations of black hole X-ray binaries have shown that the light curves contain multiple correlated and anti-correlated variation components when the objects are in the hard state. In the case of the black hole X-ray binary GX 339−4, the cross correlation function (CCF) of the light curves suggests a positive correlation with an optical lag of 0.15 s and anti-correlations with an optical lag of 1 s and X-ray lag of 4 s. This indicates that the two light curves have some common signal components with different delays. In this study we extracted and reconstructed those signal components from the data for GX 339−4. The results confirmed that correlation and anti-correlation with the optical lag are two common components. However, we found that the reconstructed light curve for the anti-correlated component indicates a positively correlated variation with an X-ray lag of ∼+1 s. In addition, the CCF for this signal component shows anti-correlations not only with the optical lag, but also with the X-ray lag, which is consistent with the CCF for the data. Therefore, our results suggest that the combination of the two positively correlated components, that is, the X-ray preceding signal with the 0.15 s optical lag and the optical preceding signal with the 1 s X-ray lag, can make the observed CCF without anti-correlated signals. The optical preceding signal may be caused by synchrotron emission in a magnetically dominated accretion flow or in a jet, while further study is required to understand the mechanism of the X-ray time lag.
Sexual dimorphism in hemispheric processing of faces in humans: A meta-analysis of 817 cases
Authors: Proverbio Alice M
Published: April 2021

A well-established neuroimaging literature predicts a right-sided asymmetry in the activation of face-devoted areas such as the fusiform gyrus (FG) and its resulting M/N170 response during face processing. However, the face-related response sometimes appears to be bihemispheric. A few studies have argued that bilaterality depended on the sex composition of the sample. To shed light on this matter, two meta-analyses were conducted starting from a large initial database of 250 ERP (Event-related potentials)/MEG (Magnetoencephalography) peer-reviewed scientific articles. Paper coverage was from 1985 to 2020. Thirty-four articles met the inclusion criteria of a sufficiently large and balanced sample size with strictly right-handed and healthy participants aged 18–35 years and N170 measurements in response to neutral front view faces at left and right occipito/temporal sites. The data of 817 male (n = 414) and female (n = 403) healthy adults were subjected to repeated-measures analyses of variance. The results of statistical analyses from the data of 17 independent studies (from Asia, Europe and America) seem to robustly indicate the presence of a sex difference in the way the two cerebral hemispheres process facial information in humans, with a marked right-sided asymmetry of the bioelectrical activity in males and a bilateral or left-sided activity in females.
Molecular detection and genomic characterization of diverse hepaciviruses in African rodents
Authors: Bletsa Magda , Vrancken Bram , Gryseels Sophie , Boonen Ine , Fikatas Antonios , Li Yiqiao , Laudisoit Anne , Lequime Sebastian , Bryja Josef , Makundi Rhodes , Meheretu Yonas , Akaibe Benjamin Dudu , Mbalitini Sylvestre Gambalemoke , Van de Perre Frederik , Van Houtte Natalie , Těšíková Jana , Wollants Elke , Van Ranst Marc , Pybus Oliver G , Drexler Jan Felix , Verheyen Erik , Leirs Herwig , Gouy de Bellocq Joelle , Lemey Philippe
Published: April 2021

Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about three per cent of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, eighty were found positive for the presence of hepaciviruses in twenty-nine different host species. We, here, report fifty-six novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.
MUSCLE MASS AND ESTIMATED RENAL FUNCTION IN ATHLETES
Authors: Yasuda Osamu , Yasuda Hisayo , Ohishi Mitsuru
Published: April 2021

Objective:

Serum creatinine level is the most common marker used to assess renal function. Because creatinine is a derivative of creatine phosphate, an energy source present in the skeletal muscles, serum creatinine levels are influenced by muscle mass. Elderly people with less muscle mass have low creatinine levels, which may lead to an overestimation of their true renal function. Creatinine levels also tend to be lower in females than males, as females tend to have less muscle mass. Serum cystatin C, a cysteine proteinase inhibitor, is another renal function marker that is produced by every nucleated cell in the body, and thus, unlike creatinine, is thought to be little influenced by muscle mass. Cystatin C level is a sensitive marker of reduction in glomerular filtration rate and suggested to be a better predictive factor for cardiovascular events and death.

Design and method:

Study subjects were 130 male athletes belonging to the National Institute of Fitness and Sports in Kanoya, Japan. A Smedley-type Hand Dynamometer was used to assess grip strength. Serum creatinine and cystatin C levels were measured by enzyme and latex coagulation methods, respectively.

Results:

Muscle mass was significantly correlated with both right and left grip strength, indicating that muscle mass measured in the present study represents skeletal muscle mass. Serum creatinine levels and estimated glomerular filtration rates calculated from creatinine (eGFRcre) showed significant correlations with muscle mass, suggesting that creatinine is influenced by muscle mass and that true renal function may be underestimated in athletes. Cystatin C and estimated glomerular filtration rates calculated from cystatin C (eGFRcys) were also significantly correlated with muscle mass. Serum creatinine levels were significantly correlated with serum cystatin C levels. Consistent with this, eGFRcre was significantly correlated with eGFRcys. This suggests that muscle mass influences the assessment of renal function in athletes when cystatin C is used as a marker.

Conclusions:

The findings in this study suggest that muscle mass of the subject must be considered prior to assessment of renal function using cystatin C in athletes.
Incorporating a Whole-Person Perspective in Consumer-Generated Data
Authors: Monsen Karen A. , Austin Robin R. , Jones R. Clarence , Brink Darin , Mathiason Michelle A. , Eder Milton
Published: April 2021

Given the complex health and social needs of older adults, the rapid growth of the aging population, and the increasing use of information technology in healthcare, there is a critical need for informatics solutions that advance gerontological nursing care and knowledge discovery. This article illustrates the value of standardized data for healthcare quality improvement throughout the life cycle of data capture and reuse. One such informatics solution is the MyStrengths+MyHealth app, which incorporates a whole-person perspective through the Simplified Omaha System Terms assessment, including the social and behavioral determinants of health, as well as resilience. The data describe whole-person health of older adults from MyStrengths+MyHealth for use in clinical encounters and as raw data for research. There is potential to use such standardized data to improve gerontological nursing care at the bedside and for population health management and research.
A National Survey Identifying the Factors Associated With Cardiovascular Care Nurses' Perceived Knowledge of International Practice Guidelines
Authors: McKee Gabrielle , Hayes Maria , Caples Norma , Lowry Avril , Shine Maria , Hannon Bernadette , Cronin Edel , Lodge Emer , Hill Loreena , Tuohy Margaret , Gillen Nessa , Teehan Sinead
Published: April 2021

Background

The implementation of international guidelines within everyday practice remains problematic, which can have a detrimental impact on quality of care delivered. This study aimed to ascertain the factors associated with clinical nurses' perceived knowledge of international guidelines.

Methods

In this cross-sectional survey, nurses from 45 hospitals across Ireland were recruited. A previously validated anonymous questionnaire that assessed guideline knowledge, use, and barriers to implementation was used. Data were analyzed using SPSS 23 and logistic regression.

Results

Of the 542 responses, 54% had used international guidelines relevant to their practice and 50% had consulted within the last year. Most nurses perceived that poor patient follow-up, lack of time and resources, poor clinical leadership, workload, long guidelines, and not understanding guideline detail were barriers to guideline use and implementation. Forty-five percent rated their perceived knowledge of guidelines as “low.” Logistic regression identified that “high” knowledge levels were significantly associated with having read guidelines in the last year and their use with practice. In contrast, low knowledge of the guidelines was associated with perceptions that they were lengthy and not easy to use, lack of confidence to challenge colleagues when guidelines are not implemented, or not being able to influence current practice.

Conclusions

This study identified the specific knowledge needs in this cohort of mainly basic grade registered nurses, with low perceived guideline knowledge. A whole unit or team approach led by nurse champions is needed to develop and establish practice and educational strategies that would increase the availability, application, and knowledge of guidelines within everyday practice.
Low Frequency of Acute Pancreatitis in Hospitalized COVID-19 Patients
Authors: Troncone Edoardo , Salvatori Silvia , Sena Giorgia , De Cristofaro Elena , Alfieri Norma , Marafini Irene , Paganelli Carla , Argirò Renato , Giannarelli Diana , Monteleone Giovanni , Del Vecchio Blanco Giovanna
Published: April 2021

Objective

The clinical significance of increased serum pancreatic enzymes (PEs) in coronavirus disease 2019 (COVID-19) patients has not yet been fully understood. We aimed to investigate the frequency and the impact on clinical outcome of PE elevation and acute pancreatitis in such patients.

Methods

Clinical data, laboratory tests, and cross-sectional images were analyzed from COVID-19 patients admitted to the Tor Vergata Hospital in Rome. Variables associated with PE abnormalities, intensive care unit (ICU) admission, or death were investigated through univariate and multivariate analyses and Cox proportional hazard model.

Results

Pancreatic enzymes were available in 254 of 282 COVID-19 patients. Among these, 66 patients (26%) showed mild elevation of PE, and 11 patients (4.3%) had severe elevation (>3 times of the upper limit of normal). Overall, 2 patients met the diagnostic criteria for acute pancreatitis. Hepatic and renal involvements were associated with PE elevation. Multivariate analysis showed that mild and severe PE elevations were significantly associated with ICU admission (odds ratios, 5.51 [95% confidence interval, 2.36–12.89; P < 0.0001] and 26.2 [95% confidence interval, 4.82–142.39; P < 0.0001]).

Conclusions

Increase in serum PE, but not acute pancreatitis, is frequent in hospitalized COVID-19 patients and associates with ICU admission.
Pancreatic Cancer Stem-Like Cells With High Calreticulin Expression Associated With Immune Surveillance
Authors: Fujiwara Yasuhiro , Tsunedomi Ryouichi , Yoshimura Kiyoshi , Matsukuma Satoshi , Fujiwara Nobuyuki , Nishiyama Mitsuo , Kanekiyo Shinsuke , Matsui Hiroto , Shindo Yoshitaro , Tokumitsu Yukio , Yoshida Shin , Iida Michihisa , Suzuki Nobuaki , Takeda Shigeru , Ioka Tatsuya , Hazama Shoichi , Nagano Hiroaki
Published: April 2021

Objective

Pancreatic cancer stem-like cells (P-CSLCs) are thought to be associated with poor prognosis. Previously, we used proteomic analysis to identify a chaperone pro-phagocytic protein calreticulin (CALR) as a P-CSLC–specific protein. This study aimed to investigate the association between CALR and P-CSLC.

Methods

PANC-1-Lm cells were obtained as P-CSLCs from a human pancreatic cancer cell line, PANC-1, using a sphere induction medium followed by long-term cultivation on laminin. To examine the cancer stem cell properties, subcutaneous injection of the cells into immune-deficient mice and sphere formation assay were performed. Cell surface expression analysis was performed using flow cytometry.

Results

PANC-1-Lm showed an increased proportion of cell surface CALR-positive and side-population fractions compared with parental cells. PANC-1-Lm cells also had higher frequency of xenograft tumor growth and sphere formation than PANC-1 cells. Moreover, sorted CALRhigh cells from PANC-1-Lm had the highest sphere formation frequency among tested cells. Interestingly, the number of programmed death-ligand 1–positive cells among CALRhigh cells was increased as well, whereas that of human leukocyte antigen class I–positive cells decreased.

Conclusion

In addition to the cancer stem cell properties, the P-CSLC, which showed elevated CALR expression on the cell surface, might be associated with evasion of immune surveillance.
Cultural Identity Conflict and Psychological Well-Being in Bicultural Young Adults
Authors: Rahim Haza F. , Mooren Trudy T.M. , van den Brink Femke , Knipscheer Jeroen W. , Boelen Paul A.
Published: April 2021

The present study examined the relationship between cultural identity conflict and psychological well-being, as well as the role of self-concept clarity and self-esteem in mediating this linkage. Elevated cultural identity conflict was hypothesized to be associated with lower psychological well-being via both (lower) self-concept clarity and (lower) self-esteem, with self-concept clarity preceding self-esteem. In a cross-sectional design, 473 bicultural young adults (age range, 18–35) completed an online questionnaire assessing cultural identity conflict, self-concept clarity, self-esteem, emotional distress, psychopathological symptoms, and satisfaction with life. Correlation analyses revealed that elevated cultural identity conflict was positively associated with emotional distress and psychopathological symptoms, and negatively associated with satisfaction with life. Mediation analyses indicated that these associations were mediated by lower self-concept clarity and lower self-esteem. The results support the importance of interventions that foster the development of skills in bicultural young adults to obtain more self-concept clarity and promote self-esteem and psychological well-being.
Initial Failure of Pristinamycin Treatment in a Case of Multidrug-Resistant Mycoplasma genitalium Urethritis Eventually Treated by Sequential Therapy
Authors: Palich Romain , Gardette Marie , Bébéar Cécile , Caumes Éric , Pereyre Sabine , Monsel Gentiane
Published: April 2021

We present a case of persistent Mycoplasma genitalium urethritis with documented macrolide and fluoroquinolone resistance, and we describe the A2062T mutation in the 23S rRNA gene, possibly associated with pristinamycin resistance. After several treatment failures and loss of the A2062T mutation, M. genitalium urethritis was finally cured by a sequential antibiotic treatment including minocycline.
Predictors of Human Papillomavirus Seropositivity in Appalachian Women Aged 18 to 26 Years
Authors: Ruffin Mack T. , Hade Erinn M. , Fahey Patrick , Christian Lisa M. , Paskett Electra D. , Harper Diane M.
Published: April 2021

Background

Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women.

Method

Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed.

Results

Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti–HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity.

Conclusions

Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.
Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility
Authors: Anyalechi Gloria E. , Hong Jaeyoung , Kirkcaldy Robert D. , Wiesenfeld Harold C. , Horner Paddy , Wills Gillian S. , McClure Myra O. , Hammond Karen R. , Haggerty Catherine L. , Kissin Dmitry M. , Hook Edward W. , Steinkampf Michael P. , Bernstein Kyle , Geisler William M.
Published: April 2021

Background

Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay.

Methods

In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI.

Results

All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%–33.8%) for non-Black cases, 15.2% (95% CI, 12.3%–18.7%) for non-Black controls, 66.0% (95% CI, 51.7%–77.8%) for Black cases, and 71.7% (95% CI, 59.2%–81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5–4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%–32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis).

Conclusions

Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women.
Expedited Partner Therapy in Female Adolescents: A Study of Acceptance and the Impact on Reinfection Rates
Authors: Gannon-Loew Kathryn E. , Holland-Hall Cynthia , Ebersole Ashley M. , Alexy Emily , Jackson Kenneth , Bonny Andrea E.
Published: April 2021

Background

Given the high risk of sexually transmitted infections (STIs) in adolescents and young adults (AYAs), this study evaluated expedited partner therapy (EPT) acceptance and STI reinfection rates in female AYA before and after availability of EPT.

Methods

The pre-EPT cohort was a 3-year (November 2012 to November 2015) retrospective chart review of female AYA positive for Chlamydia trachomatis (CT) and/or Trichomonas vaginalis (TV) before introduction of EPT. An EPT protocol for CT and TV infections was implemented after legalization in Ohio in 2016. The post-EPT cohort was a prospective review of patients positive for CT and TV for 2 years (5/2016–5/2018) after EPT introduction. We evaluated EPT acceptance and compared reinfection rates (positive test 1–6 months after initial infection) in the pre-EPT versus post-EPT cohorts and by EPT acceptance.

Results

Among patients offered EPT, 28% (67/237) with CT and 25% (24/97) with TV accepted EPT. There were no significant differences in the reinfection rates for CT or TV in the pre-EPT versus post-EPT cohorts (CT: 24% (57/240) vs 20% (38/192), P = 0.42; TV: 23% (22/97) versus 14% (12/87), P = 0.11). Although lower, reinfections rates were not significantly different among patients who accepted versus did not accept EPT (CT, 13% (6/48) vs 21% (23/110), P = 0.50 and TV, 6% (1/18) vs 18% (9/49), P = 0.69).

Conclusions

Despite the implementation of an EPT protocol, STI reinfection rates among female AYA remained high, and many declined EPT. Further research is needed to identify barriers to the provision and acceptance of EPT and ways to address these factors.
Wall Falls
Authors: Jackson Nicole R. , Lathrop Sarah , Dvorscak Lauren
Published: April 2021

The border wall between the United States and Mexico consists of stretches of metal fencing of varying heights alternating and overlapping with areas of electronic surveillance. Despite national conversations centered around the social, environmental, economic, and political implications of this wall, there is a paucity of studies on deaths occurring in this region. Herein are described 2 cases of fatal injuries sustained from scaling the fence and accidentally falling onto the United States’ side in New Mexico. These injuries are compared with those typically incurred in falls from lower and higher heights, and implications of both lateral and vertical expansion of the wall are discussed.
Fatal Sea Snake Envenomation
Authors: Tiemensma Marianne , Byard Roger W.
Published: April 2021

A 23-year-old man working on a prawn trawler off the Northern Australian coast was bitten on the right hand by a black-banded sea snake (Laticauda colubrina), resulting in the rapid onset of ptosis, blurred vision, and respiratory difficulties with convulsions, loss of consciousness, and death. Resuscitation was unsuccessful. No antivenom was available because of the remote location. At autopsy, a small puncture wound was identified on the middle interphalangeal joint of the right little finger. No other significant abnormalities were detected. Elevations in creatine kinase (1558 μ/L) and myoglobin (24,800 μg/L) levels were found. Death was caused by respiratory failure after sea snake envenomation. This case demonstrates potential difficulties in establishing the diagnosis of lethal sea snake envenomation, including the inconspicuous nature of the bite marks with no local reaction and the underlying neurotoxic nature of the lethal mechanisms, which leaves very nonspecific pathological findings. Myonecrosis may occur but is variable. Unless reliably witnessed, sea snake envenomation may not be suspected. Failing vision or unexplained paresis in fishermen or individuals who have been in the sea may point to the diagnosis.
Utility of CDC Screening Guidelines and Autopsy Findings in Identifying Decedents Who Die of SARS-CoV-2 Infection
Authors: Konopka Kristine E. , Nguyen Teresa , Hlavaty Leigh , Rayes Omar , Schmidt Carl J. , Dahl Julia , Myers Jeffrey L.
Published: April 2021

We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.

SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all “checklist-positive” decedents. Additional “checklist-negative” decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19–associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19–related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.
Diagnostic Errors in Pediatric Critical Care: A Systematic Review*
Authors: Cifra Christina L. , Custer Jason W. , Singh Hardeep , Fackler James C.
Published: April 2021

OBJECTIVES:

To summarize the literature on prevalence, impact, and contributing factors related to diagnostic error in the PICU.

DATA SOURCES:

Search of PubMed, EMBASE, and the Cochrane Library up to December 2019.

STUDY SELECTION:

Studies on diagnostic error and the diagnostic process in pediatric critical care were included. Non-English studies with no translation, case reports/series, studies providing no information on diagnostic error, studies focused on non-PICU populations, and studies focused on a single condition/disease or a single diagnostic test/tool were excluded.

DATA EXTRACTION:

Data on research design, objectives, study sample, and results pertaining to the prevalence, impact, and factors associated with diagnostic error were abstracted from each study.

DATA SYNTHESIS:

Using independent tiered review, 396 abstracts were screened, and 17 studies (14 full-text, 3 abstracts) were ultimately included. Fifteen of 17 studies (88%) had an observational research design. Autopsy studies (autopsy rates were 20–47%) showed a 10–23% rate of missed major diagnoses; 5–16% of autopsy-discovered diagnostic errors had a potential adverse impact on survival and would have changed management. Retrospective record reviews reported varying rates of diagnostic error from 8% in a general PICU population to 12% among unexpected critical admissions and 21–25% of patients discussed at PICU morbidity and mortality conferences. Cardiovascular, infectious, congenital, and neurologic conditions were most commonly misdiagnosed. Systems factors (40–67%), cognitive factors (20–3%), and both systems and cognitive factors (40%) were associated with diagnostic error. Limited information was available on the impact of misdiagnosis.

CONCLUSIONS:

Knowledge of diagnostic errors in the PICU is limited. Future work to understand diagnostic errors should involve a balanced focus between studying the diagnosis of individual diseases and uncovering common system- and process-related determinants of diagnostic error.
Trends of Medicare Reimbursement Rates for Common Plastic Surgery Procedures
Authors: Siotos Charalampos , Cheah Michael A. , Damoulakis George , Kelly Jonathan , Siotou Kalliopi , Schechter Loren S. , Shenaq Deana S. , Derman Gordon H. , Dorafshar Amir H.
Published: April 2021

Background:

Knowledge of Medicare reimbursement is essential for plastic surgeons providing care to Medicare beneficiaries. The authors sought to evaluate changes in Medicare reimbursement for common plastic surgery procedures from 2010 to 2020.

Methods:

The authors assessed the Physician Fee Schedule of the Centers for Medicare and Medicaid Services website. Rates of work-, facility-, or malpractice-related relative value units and total monetary units for 26 common plastic surgery procedures between 2010 and 2020 were evaluated. Descriptive statistics were used to calculate relative differences and to compare observed changes over time with the rate of inflation.

Results:

For the selected procedures, the authors found an average relative difference in terms of monetary units of an increase by 2.02 percent. However, after adjusting for inflation, the average relative difference was a decrease by 14.31 percent. The authors’ analysis indicates that, on average, there was a 1.55 percent decrease in physician relative value units between 2010 and 2020.

Conclusions:

Medicare reimbursement rates have changed significantly over the past decade. However, these changes did not keep pace with the rate of inflation. Plastic surgeons should be aware of these trends and advocate for more fair reimbursement rates.
Revision Rates in Prepectoral Versus Subpectoral Delayed-Immediate Autologous Breast Reconstruction
Authors: Patel Ashraf A. , Cemaj Sophie L. , Martin Shanique A. , Cheesborough Jennifer E. , Lee Gordon K. , Nazerali Rahim S.
Published: April 2021

Introduction

Breast reconstruction in the prepectoral plane has recently fallen into favor. Minimizing the number of revisionary procedures after reconstruction is an important factor in improving patient care, but long-term studies on the effects of prepectoral reconstruction are limited. In this study, we compare the revision rates after delayed-immediate, autologous reconstruction between prepectoral and subpectoral reconstructions.

Methods

Postoperative charts for all patients undergoing subpectoral or prepectoral delayed-immediate autologous breast reconstruction were retrospectively reviewed at our single tertiary-care institution between 2009 and 2018. Patient demographics, comorbidities, and oncologic history were recorded. Charts after second stage reconstruction were reviewed for up to eighteen months to determine if revisions were necessary. Data collected included the total number of surgeries performed, the average number of procedures performed during each surgery, and the type of revision that was performed. Statistical tests included the chi squared test, unpaired t-test, and logistic regressions.

Results

Data from 89 patients with 125 breast reconstructions were collected. There was a 41.6% of these that were prepectoral reconstructions (P), and 58.4% were subpectoral reconstructions (S). For both groups, nipple sparing, followed by skin sparing mastectomies were most common. Mastectomy rates were not statistically different. Fewer breasts in the prepectoral cohort required any revisions (P, 21.2% vs S, 47.9%; P = 0.002). The subpectoral cohort had higher rates of soft tissue rearrangement (P, 7.7% vs S, 21.9%, P = 0.032), fat grafting (P, 9.6% vs S, 27.4%; P = 0.014), and nipple reconstruction (P: 5.8% vs 20.5%, P = 0.020). Mean follow-up time was not significantly different between patient groups (P, 290.5 days vs S, 375.0 days, P = 0.142). Subpectoral expander placement was found to be the only variable independently predictive of requiring 1 or more revision (P = 0.034).

Conclusions

Breast reconstruction performed in the prepectoral plane is associated with lower overall rates of revisionary surgery. Rates of soft tissue rearrangement, fat grafting, and nipple reconstruction after autologous reconstruction trended higher in subpectoral reconstructions.