bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Central Nervous System (CNS) Involvement in Children With Non-Hodgkin’s Lymphoma (NHL) and the Diagnostic Value of CSF Flow Cytometry in CNS Positive Disease
Authors: Huang Shuang , Jin Ling , Yang Jing , Duan Yanlong , Zhang Meng , Zhou Chunju , Zhang Yong-Hong
Published: June 2021

Objective:

To investigate the characteristics of central nervous system (CNS) involvement in children with non-Hodgkin’s lymphoma (NHL) and the value of flow cytometry (FC) in the diagnosis of CNS disease in pediatric NHL.

Methods:

The data of 56 newly diagnosed pediatric NHL patients with CNS involvement (CNS+/mass, CNS+/palsy, CNS+/CSF) were analyzed. The proportions and formats of CNS disease in different pathological types were compared. In addition, FC and conventional cytology (CC) of cerebrospinal fluid (CSF) were carried out in 383 newly diagnosed NHL cases.

Results:

A total of 383 children with NHL were enrolled. Among these patients, 56 (14.6%) were diagnosed with positive CNS involvement (CNS+), 33 had bulky disease (tumor diameter >10 cm), 32 had bone marrow invasion, 32 had lactate dehydrogenase levels >1000 U/L, and 25 had invasion of more than 4 organs at the time of diagnosis. There were 14 patients with T lymphoblastic lymphoma (T-LBL), 9 with B lymphoblastic lymphoma (B-LBL), 26 with Burkitt’s lymphoma (BL), and 2 with Epstein-Barr virus-positive diffuse large B cell lymphoma (EBV + DLBCL). Among the 56 CNS+ patients, 35 were CSF-positive (CSF+); there were 2 patients who were CSF+ via CC detection and 35 who were CSF+ via FC detection. The difference between CC and FC was statistically significant ( P < 0.01). In the T-LBL group, 14 patients were CNS+/CSF, and in the B-LBL group, 8 were CNS+/mass. In the BL group, 22 patients were CNS+/mass and 15 were CNS+/CSF. In the anaplastic large-cell lymphoma group, 5 patients were CNS+/mass. Nine of the 56 CNS+ patients had events. The 2-year overall survival rate was 87% ± 0.046%, and the 2-year event-free survival rate was 76.2% ± 0.07%.

Conclusion:

CNS+ diagnoses were more common in pediatric NHL patients with bulky disease and/or bone marrow involvement and/or involvement of more than 4 organs at the time of diagnosis, and they were also common in the EBV + DLBCL and BL groups. FC of CSF showed important clinical significance in the diagnosis of CNS disease in pediatric NHL patients, and it can be used to significantly improve the CNS+ detection rate.
Investigating Dual-Energy CT Post-Contrast Phases for Liver Iron Quantification: A Preliminary Study
Authors: Basso Luca , Baldi Dario , Mannelli Lorenzo , Cavaliere Carlo , Salvatore Marco , Brancato Valentina
Published: June 2021

Background and Purpose:

Quantification of hepatic virtual iron content (VIC) by using Multidetector Dual Energy Computed Tomography (DECT) has been recently investigated since this technique could offer a good compromise between accuracy and non-invasiveness for liver iron content quantification. The aim of our study is to investigate differences in VIC at different DECT time points (namely baseline and arterial, venous and tardive phases), identifying the most reliable and also exploring the underlying temporal trend of these values.

Materials and Methods:

Eleven patients who underwent DECT examination and were characterized by low liver fat content were included in this retrospective study. By using the Syngo.via Frontier–DE IronVNC tool, regions of interest (ROI) were placed on the VIC images at 3 hepatic levels, both in left and right liver lobes, at each DECT time point. Friedman’s test followed by Bonferroni-adjusted Wilcoxon signed-rank test for post-hoc analysis was performed to assess differences between DECT timepoints. Page’s L test was performed to test the temporal trend of VIC across the 4 examined timepoints.

Results:

For both liver lobes, Friedman’s test followed by Bonferroni-adjusted Wilcoxon signed-rank test revealed that VIC values differed significantly when extracted from ROIs placed at the 4 different timepoints. The Page’s L test for multiple comparison revealed a significant growing trend for VIC, from baseline acquisition to the fourth and last time point post-contrast agent injection.

Conclusions:

The extraction of hepatic VIC in healthy subjects was found to be significantly influenced by the DECT time point chosen for the extrapolation of the VIC values.
Vaccine Strategy During the SARS-CoV-2 Pandemic: What School Nurses Need to Know
Authors: Barnby Elizabeth , Reynolds Mark , Gordon Jenny
Published: June 2021

The National Association of School Nurses supports immunization to reduce the incidence of vaccine-preventable diseases. School nurses have the obligation to discern and understand vaccine strategies to aid in the advocacy and education of their school administrators, faculty, staff, students, and caregivers. Coronavirus disease 2019 (COVID-19) has spread to all continents, and the total number of those infected or immune through effective vaccination is well below the estimated need for herd immunity. To achieve herd immunity against the global outbreak of COVID-19, the rapid development of safe and effective vaccines is essential. Using multiple strategies and vaccine platforms to speed up the vaccine development process will inherently save more lives. Equipped with this knowledge of vaccine strategy, the school nurse can more aptly advocate for the use of the COVID-19 vaccines to move toward herd immunity in their communities.
Imaging findings of trichilemmal cyst and proliferating trichilemmal tumour
Authors: Kawaguchi Masaya , Kato Hiroki , Suzui Natsuko , Miyazaki Tatsuhiko , Tomita Hiroyuki , Hara Akira , Matsuyama Kanako , Seishima Mariko , Matsuo Masayuki
Published: June 2021

Purpose

The purpose of this study was to evaluate computed tomography and magnetic resonance imaging of benign trichilemmal cysts and proliferating trichilemmal tumours.

Methods

Nineteen histologically confirmed cutaneous lesions with trichilemmal keratinisation (12 trichilemmal cysts and seven proliferating trichilemmal tumours) were enrolled. Among them, 10 lesions (six trichilemmal cysts and four proliferating trichilemmal tumours) were examined by computed tomography, while 13 lesions (eight trichilemmal cysts and five proliferating trichilemmal tumours) were examined by magnetic resonance imaging. Computed tomography and magnetic resonance imaging characteristics were retrospectively reviewed.

RESULTS

Sixteen lesions (84%, 10 trichilemmal cysts and six proliferating trichilemmal tumours) occurred on the scalp. Lobulated margins were observed in five lesions (26%, three trichilemmal cysts and two proliferating trichilemmal tumours). With respect to computed tomography attenuation, calcification (>200 Hounsfield units) was observed in seven lesions (70%, five trichilemmal cysts and two proliferating trichilemmal tumours), hyperdense areas (≥80 and ≤200 Hounsfield units) in six (60%, three trichilemmal cysts and three proliferating trichilemmal tumours), and soft tissue density areas (<80 Hounsfield units) in nine (90%, five trichilemmal cysts and four proliferating trichilemmal tumours). On T1-weighted images, intratumoral hyperintensity was only observed in eight trichilemmal cysts but no proliferating trichilemmal tumours (100% vs. 0%, P<0.01). On T2-weighted images, hypointense rim and intratumoral hypointensity was observed in all 13 lesions (100%, eight trichilemmal cysts and five proliferating trichilemmal tumours), and linear or reticular hypointensity was observed in 10 (77%, six trichilemmal cysts and four proliferating trichilemmal tumours).

Conclusion

Trichilemmal cysts and proliferating trichilemmal tumours predominantly occurred on the scalp with calcification, and usually exhibited linear or reticular T2 hypointensity. Intratumoral T1 hyperintensity may be a useful imaging feature for differentiating trichilemmal cysts from proliferating trichilemmal tumours.
The enforceability of mediation clauses: A critical analysis of English case law
Authors: Petsche Markus
Published: June 2021

This article shows that the English case law on the enforceability of mediation clauses presents a number of flaws. First, and most importantly, English courts generally fail to distinguish between the positive and the negative obligations created by such clauses. As a result, they wrongly apply the certainty requirement to the former, rather than the latter, which leads to frequent refusals to enforce mediation clauses in situations where enforcement should be granted. These decisions discourage parties from agreeing to multi-tier dispute resolution clauses providing for preliminary mediation, thus undermining the general policy favouring the use of alternative dispute resolution (ADR) mechanisms. Moreover, judicial discretion in deciding whether to give effect to a valid mediation agreement is unjustified and exercised on the basis of questionable considerations.
Hepatitis C Prevalence and Validation of a Clinical Prediction Score for Targeted Screening among People Living with HIV in Ghana
Authors: Torpey Kwasi , Ogyiri Lily , Cuylaerts Vicky , Agyeman Seth , Agyei-Nkansah Adwoa , Buyze Jozefien , Commey Joseph Oliver , Lynen Lutgarde , De Weggheleire Anja
Published: June 2021

WHO recommends hepatitis C (HCV) screening for all people living with HIV (PLHIV). Yet, HCV coinfection was shown to be rare in some Sub-Saharan HIV cohorts, and targeted testing was suggested more efficient for such settings. We studied HCV prevalence among Ghanaian PLHIV, and assessed the external validity of a score to guide targeted testing. This score was initially derived from a Cambodian HIV cohort, and uses as predictors: age, household member/partner with liver disease, diabetes, generalized pruritus, AST, platelets, and AST-to-platelet ratio index. We enrolled 4,023 PLHIV, most from Greater Accra and Central regions, 28.4% were male, median age was 47 years, and high-risk behavior was reported to be rare. HCV seroprevalence was 0.57%, and HCV-RNA was detectable in 0.5%. Sequencing revealed genotype 1(b) and 2(q/r) infections. The discriminatory performance of the score was suboptimal in the Ghanaian setting. The area under the curve was 0.69 (95% CI 0.59-0.79). HCV coinfection prevalence was very low in this Ghanaian PLHIV cohort with reported low-risk of onward transmission. To avoid the cost of screening all PLHIV in similar cohorts in resource-constrained settings, further research to develop better tools/scores to guide targeted HCV testing is needed.
Morocco and Sub-Saharan Africa: In the Shadow of the Western Sahara Dispute
Authors: Bishku Michael B.
Published: June 2021

During much of the past several decades, Moroccan actions in Western Sahara have impacted on that country’s bilateral and multilateral ties, especially with other countries in Africa, though to a lesser degree in the Arab world. In recent years, Morocco has gained the upper hand in its conflict in Western Sahara and has been increasing its political and economic footprint on the continent of Africa, an area of interest since independence. At the same time, Morocco has regarded itself as a “gateway” to Africa for the USA and Europe, while the USA, France (and the Gulf states) have provided military and financial assistance as well as diplomatic support for Morocco as that country’s policies have served Western interests. While attention is given by academics in recent years to the involvement in Africa of other middle powers from the Middle East such as Turkey, Iran and Saudi Arabia and, in the past, of Nasser’s Egypt and Qaddafi’s Libya, as well as Israel, Morocco has not stirred the same sort of interest. This article seeks to address that issue by examining all political and economic factors that have influenced Moroccan policy toward Sub-Saharan Africa, those both connected and unconnected with the issue of the Western Sahara dispute.
An elevated serum creatinine in a patient receiving palbociclib
Authors: Bonilla Marco , Bashir Khawaja Arsalan , Jhaveri Kenar D
Published: June 2021

Background:

Serum Creatinine (SCr) is the most widely used parameter in clinical practice to estimate glomerular filtration rate (GFR). Various drugs have been reported to cause a reversible and transient elevation in SCr without a true reduction in overall kidney function

Case Presentation:

We describe a case of a 66-year-old-woman with right breast poorly differentiated invasive ductal carcinoma, hormone receptor positive and HER2 negative who received treatment with fulvestrant and palbociclib. The initial dose of Palbociclib was 125 mg orally a day, then reduce to 100 mg orally a day. She presented for evaluation of elevated serum creatinine with decreased eGFR. Upon evaluation an estimated glomerular filtration rate by cystatin C showed kidney function at her baseline for the past year.

Conclusion:

Palbocicib is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Physicians should be aware that patients undergoing therapy with palbociclib require monitoring of kidney function and an increase in serum creatinine from baseline, might represent an inhibitory effect of the secretion of creatinine.
Social Solidarity Economy and Village-centric Development in North-West Cameroon
Authors: Che Charles Fonchingong , Mbah Marcellus
Published: June 2021

Amidst shrinking budgets for community development in most of sub-Saharan Africa, the social solidarity economy is touted as a model in local development. This article situates solidarity initiatives and capability-focused outcomes that deliver enhanced livelihoods, social security and community development. The conceptual framing of social theory, social capital and social economy informs this case study with focus on the Ndong Awing Cultural and Development Association, North-West region, Cameroon. The analysis of semi-structured interviews and secondary sources suggests that solidarity networks such as njangis, cooperatives, quarter development unions and diaspora networks promote village-centric development. These overlapping networks generate scarce financial and human resources–essential packages for livelihoods and welfare. Emerging state policy is yet to calibrate these mechanisms of ground-up, mutual development drives. Galvanising these solidarity assets require meaningful co-productionand revamped state−community relations. This article offers a paradigm shift in how village groups mobilise income, capital and financing of village projects, nurtured through human development and agency.
Distance Learning and Students With Extensive Support Needs: (Re)Defining Access to Education From a Distance
Authors: Hanreddy Amy
Published: June 2021

Students with Extensive Support Needs (ESN) experience multiple barriers in accessing distance learning educational programs during school closures in the context of the COVID-19 pandemic. These barriers include inaccessible formats, a lack of access to adequate support to access instruction, and a lack of available assistive technology. Access issues may result in further isolation of students and reduced access to general education peers and curriculum. Promising practices include close collaboration with families, connecting Individualized Education Program (IEP) goals to students’ daily routines, supporting access to the general education curriculum, strategic participation in online classes, meaningful engagement with typical peers, and the adaptation of progress monitoring strategies for distance learning formats.
Patient's treatment burden related to care coordination in the field of respiratory diseases
Authors: Pierucci Paola , Santomasi Carla , Ambrosino Nicolino , Portacci Andrea , Diaferia Fabrizio , Hansen Kjeld , Odemyr Mikaela , Jones Steve , Carpagnano Giovanna E.
Published: June 2021

The management of respiratory diseases requires various levels of care: multidisciplinary teams, educational and behavioural interventions, self-management and home-based technical support are vital to ensure adequate care management. However, it is often difficult to access these networks due to fragmentation of patient care and treatment burden. Care coordination aims to ensure patients have a central role and that there is continuity of care among various levels and professionals involved. Moreover, the coronavirus disease pandemic has caused strain on the global healthcare system, with care coordination becoming increasingly important in increasing the resilience of health systems, supporting healthcare professionals and ensuring the right treatment and adequate level of care for these patients.
Nasopharyngeal Microbiota in SARS-CoV-2 Positive and Negative Patients
Authors: Engen Phillip A. , Naqib Ankur , Jennings Cheryl , Green Stefan J. , Landay Alan , Keshavarzian Ali , Voigt Robin M.
Published: June 2021

We investigated nasopharyngeal microbial community structure in COVID-19-positive and -negative patients. High-throughput 16S ribosomal RNA gene amplicon sequencing revealed significant microbial community structure differences between COVID-19-positive and -negative patients. This proof-of-concept study demonstrates that: (1) nasopharyngeal microbiome communities can be assessed using collection samples already collected for SARS-CoV-2 testing (viral transport media) and (2) SARS-CoV-2 infection is associated with altered dysbiotic microbial profiles which could be a biomarker for disease progression and prognosis in SARS-CoV-2.
Cephalad misplacement of a pulmonary artery catheter in a patient with a preexisting Hickman catheter
Authors: Choi Hoon , Jeon Joon Pyo , Huh Jaewon , Kim Youme , Hwang Wonjung
Published: June 2021

Background

Pulmonary artery catheter insertion is a routine practice in high-risk patients undergoing cardiac surgery. However, pulmonary artery catheter insertion is associated with numerous complications that can be devastating to the patient. Incorrect placement is an overlooked complication with few case reports to date.

Case presentation

An 18-year-old male patient underwent elective mitral valve replacement due to severe mitral valve regurgitation. The patient had a history of synovial sarcoma, and Hickman catheter had been inserted in the right internal jugular vein for systemic chemotherapy. We made multiple attempts to position the pulmonary artery catheter in the correct position but failed. A chest radiography revealed that the pulmonary artery catheter was bent and pointed in the cephalad direction. Removal of the pulmonary artery catheter was successful, and the patient was discharged 10 days after the surgery without complications.

Conclusions

To prevent misplacement of the PAC, clinicians should be aware of multiple risk factors in difficult PAC placement, and be prepared to utilize adjunctive methods, such as TEE and fluoroscopy.
Effect of hemoglobin content on cerebral oxygen saturation during surgery for scoliosis in pediatric patients
Authors: Liu Lin , Qiang Zhipeng , Zhang Jianmin , Ren Yi , Zhao Xin , Fu Wenya , Xin Zhong , Xu Zenghua , Wang Fang , Li Lijing , Zou Nan , Zhang Xuemei , Feng Lei , Ma Shuxuan
Published: June 2021

Background

Although regional cerebral oxygen saturation (rScO2) monitoring has been widely used in clinical practice, the relationship between hemoglobin (dHB) content and rScO2 is incompletely understood. The aim of this study was to analyze the effect of hemoglobin content on rScO2 in pediatric patients undergoing general anesthesia for correction of scoliosis.

Methods

Ninety-two pediatric patients aged 3 to 14 years undergoing scoliosis correction surgery were enrolled. Continuous monitoring of bilateral regional cerebral oxygen saturation by near-infrared spectroscopy (NIRS, CASMED, USA) was performed after entering the operation room. rScO2 was recorded when the patients entered the operating room (T0, baseline), after anesthesia induced intubation (T1), and after radial artery puncture (T2). The lowest value of rScO2 during surgery was also recorded. The arterial blood pressure (ABP), heart rate (HR), pulse oxygen saturation (SpO2), end tidal carbon dioxide partial pressure (PetCO2) were continuously recorded. Patients were classified as low rScO2 or high rScO2 group according to whether the lowest intraoperative rScO2 was 15% lower than the baseline value. An analysis and comparison of differences in hemoglobin content in these two groups was carried out.

Results

The preoperative hemoglobin-postoperative hemoglobin of patients in the high rScO2 group was significantly lower than that in the low rScO2 group (t = − 7.86, p < 0.01), the amount of bleeding during the operation was also less than that in the low rScO2 group (t = − 6.05, p < 0.01), and the systolic pressure of patients was higher than that in the low rScO2 group (t = 4.27, p < 0.01).

Conclusions

The decrease in hemoglobin level which occurs during surgery leads to a decrease in cerebral oxygen saturation. In order to ensure patient safety during surgery, it is necessary to carry out volume management and appropriate transfusion and fluid replacement in a timely manner.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800016359. Registered 28 May 2018.
A method for assessing robustness of the results of a star-shaped network meta-analysis under the unidentifiable consistency assumption
Authors: Yoon Jeong-Hwa , Dias Sofia , Hahn Seokyung
Published: June 2021

Background

In a star-shaped network, pairwise comparisons link treatments with a reference treatment (often placebo or standard care), but not with each other. Thus, comparisons between non-reference treatments rely on indirect evidence, and are based on the unidentifiable consistency assumption, limiting the reliability of the results. We suggest a method of performing a sensitivity analysis through data imputation to assess the robustness of results with an unknown degree of inconsistency.

Methods

The method involves imputation of data for randomized controlled trials comparing non-reference treatments, to produce a complete network. The imputed data simulate a situation that would allow mixed treatment comparison, with a statistically acceptable extent of inconsistency. By comparing the agreement between the results obtained from the original star-shaped network meta-analysis and the results after incorporating the imputed data, the robustness of the results of the original star-shaped network meta-analysis can be quantified and assessed. To illustrate this method, we applied it to two real datasets and some simulated datasets.

Results

Applying the method to the star-shaped network formed by discarding all comparisons between non-reference treatments from a real complete network, 33% of the results from the analysis incorporating imputed data under acceptable inconsistency indicated that the treatment ranking would be different from the ranking obtained from the star-shaped network. Through a simulation study, we demonstrated the sensitivity of the results after data imputation for a star-shaped network with different levels of within- and between-study variability. An extended usability of the method was also demonstrated by another example where some head-to-head comparisons were incorporated.

Conclusions

Our method will serve as a practical technique to assess the reliability of results from a star-shaped network meta-analysis under the unverifiable consistency assumption.
Factors associated with latent tuberculosis among international migrants in Brazil: a cross-sectional study (2020)
Authors: de Jezus Sonia Vivian , do Prado Thiago Nascimento , Arcêncio Ricardo Alexandre , Mascarello Keila Cristina , Sales Carolina Maia Martins , Fauth Maysa Mabel , de Faria Marcos Terena Nahari , Amorim Raphael Florindo , Araujo Vania Maria Silva , Aragón Miguel Angel López , Maciel Ethel Leonor Noia
Published: June 2021

Background

Migrants are a high priority group for TB control measures due to their high exposure to risk factors such as poverty and social vulnerability. The study aimed to identify factors associated with latent TB among international migrants living in four Brazilian state capitals.

Methods

This was a cross-sectional study conducted in September and October 2020 in a sample of 903 international migrants living in four Brazilian state capitals: Boa Vista/RR (458), Manaus/AM (136), São Paulo/SP (257), and Curitiba/PR (52). Data were collected with a questionnaire consisting of open and closed questions on personal characteristics, information on TB, and use of preventive measures. Tuberculin skin test (TST) was performed, with reading after 72 h by trained nurses and using 5 mm induration as the positive cutoff. Chi-square test (X2) and Fisher's exact test, both two-tailed, were used to compare statistically significant levels of association between the migrants´ sociodemographic characteristics, vulnerability, and latent TB infection (LTBI). Binary logistic regression was applied to calculate odds ratios and respective 95% confidence intervals. For all the tests, type I error of 5% was defined as statistically significant (p < 0.05).

Results

Prevalence of LTBI among migrants was 46.1% in Manaus/AM, 33.3% in São Paulo/SP, 28.1% in Curitiba/PR, and 23.5% in Boa Vista/RR. Factors associated with latent infection were age, male gender, and brown or indigenous race.

Conclusions

The study showed high prevalence of latent TB among international migrants.
Discontinuation of tuberculosis treatment among children in the Kampala Capital City Authority health facilities: a mixed-methods study
Authors: Kibirige Leonard , Izudi Jonathan , Okoboi Stephen
Published: June 2021

Introduction

Discontinuation of tuberculosis treatment (DTT) among children in sub-Saharan Africa is a major obstacle to effective tuberculosis (TB) control and has the potential to worsen the emergence of multi-drug resistant TB and death. DTT in children is understudied in Uganda. We examined the level and factors associated with DTT among children at four large health facilities in Kampala Capital City Authority and documented the reasons for DTT from treatment supporters and healthcare provider perspectives.

Methods

We conducted a retrospective analysis of records for children < 15 years diagnosed and treated for TB between January 2018 and December 2019. We held focus group discussions with treatment supporters and key informant interviews with healthcare providers. We defined DTT as the stoppage of TB treatment for 30 or more consecutive days. We used a stepwise generalized linear model to assess factors independently associated with DTT and content analysis for the qualitative data reported using sub-themes.

Results

Of 312 participants enrolled, 35 (11.2%) had discontinued TB treatment. The reasons for DTT included lack of privacy at healthcare facilities for children with TB and their treatment supporters, the disappearance of TB symptoms following treatment initiation, poor implementation of the community-based directly observed therapy short-course (CB-DOTS) strategy, insufficient funding to the TB program, and frequent stock-outs of TB drugs. DTT was more likely during the continuation phase of TB treatment compared to the intensive phase (Adjusted odds ratio (aOR), 5.22; 95% Confidence Interval (CI), 1.76–17.52) and when the treatment supporter was employed compared to when the treatment supporter was unemployed (aOR, 3.60; 95% CI, 1.34–11.38).

Conclusion

Many children with TB discontinue TB treatment and this might exacerbate TB morbidity and mortality. To mitigate DTT, healthcare providers should ensure children with TB and their treatment supporters are accorded privacy during service provision and provide more information about TB symptom resolution and treatment duration versus the need to complete treatment. The district and national TB control programs should address gaps in funding to TB care, the supply of TB drugs, and the implementation of the CB-DOTS strategy.
Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer
Authors: Borrero-García Luis D. , del Mar Maldonado Maria , Medina-Velázquez Julia , Troche-Torres Angel L. , Velazquez Luis , Grafals-Ruiz Nilmary , Dharmawardhane Suranganie
Published: June 2021

Background

Even though targeted therapies are available for cancers expressing oncogenic epidermal growth receptor (EGFR) and (or) human EGFR2 (HER2), acquired or intrinsic resistance often confounds therapy success. Common mechanisms of therapy resistance involve activating receptor point mutations and (or) upregulation of signaling downstream of EGFR/HER2 to Akt and (or) mitogen activated protein kinase (MAPK) pathways. However, additional pathways of resistance may exist thus, confounding successful therapy.

Methods

To determine novel mechanisms of EGFR/HER2 therapy resistance in breast cancer, gefitinib or lapatinib resistant variants were created from SKBR3 breast cancer cells. Syngenic therapy sensitive and resistant SKBR3 variants were characterized for mechanisms of resistance by mammosphere assays, viability assays, and western blotting for total and phospho proteins.

Results

Gefitinib and lapatinib treatments reduced mammosphere formation in the sensitive cells, but not in the therapy resistant variants, indicating enhanced mesenchymal and cancer stem cell-like characteristics in therapy resistant cells. The therapy resistant variants did not show significant changes in known therapy resistant pathways of AKT and MAPK activities downstream of EGFR/HER2. However, these cells exhibited elevated expression and activation of the small GTPase Rac, which is a pivotal intermediate of GFR signaling in EMT and metastasis. Therefore, the potential of the Rac inhibitors EHop-016 and MBQ-167 to overcome therapy resistance was tested, and found to inhibit viability and induce apoptosis of therapy resistant cells.

Conclusions

Rac inhibition may represent a viable strategy for treatment of EGFR/HER2 targeted therapy resistant breast cancer.
The Great Gut Mimicker: A case report of MIS-C and appendicitis clinical presentation overlap in a teenage patient
Authors: Hwang Michelle , Wilson Kelsey , Wendt Lisa , Pohlman Joshua , Densmore Emily , Kaeppler Caitlin , Van Arendonk Kyle , Yale Sarah
Published: June 2021

Background

Abdominal pain and other gastrointestinal symptoms are common presenting features of multisystem inflammatory syndrome in children (MIS-C) and can overlap with infectious or inflammatory abdominal conditions, making accurate diagnosis challenging.

Case Presentation

We describe the case of a 16-year-old female who presented with clinical symptoms suggestive of appendicitis and an abdominal computed tomography (CT) that revealed features concerning for appendicitis. After laparoscopic appendectomy, histopathology of the appendix demonstrated only mild serosal inflammation and was not consistent with acute appendicitis. Her overall clinical presentation was felt to be consistent with MIS-C and she subsequently improved with immunomodulatory and steroid treatment.

Conclusions

We note that MIS-C can mimic acute appendicitis. This case highlights MIS-C as a cause of abdominal imaging with features concerning for appendicitis, and MIS-C should be considered in the differential for a patient with appendicitis-like symptoms and a positive COVID-19 IgG. Lab criteria, specifically low-normal white blood cell count and thrombocytopenia, appears to be of high relevance in differing MIS-C from acute appendicitis, even when appendix radiologically is dilated.
Adult ADHD and emerging models of maladaptive personality: a meta-analytic review
Authors: Jacobsson Peter , Hopwood Christopher J. , Söderpalm Bo , Nilsson Thomas
Published: June 2021

Background

ADHD is a highly consequential disorder that is estimated to affect 2.5% of the adult population. Emerging models of psychopathology posit that disorders like ADHD can be usefully situated within general models of individual differences in personality, such as those recently implemented in the DSM and ICD for the diagnosis of personality disorder. Previous research and systematic reviews have linked adult ADHD to the personality traits Conscientious Inhibition and Negative Emotionality. However, there have been some inconsistencies in the literature and research embedding ADHD-personality connections in the DSM-5 and ICD-11 personality disorder models has been limited. The goal of this paper was to systematically review associations between adult ADHD and personality traits, organized within a maladaptive five factor framework.

Method

A comprehensive literature search yielded 13 papers whose effects were meta-analyzed.

Results

Results supported associations between ADHD and low Conscientious Inhibition and high Negative Emotionality. However, interesting patterns of variability were observed, potentially related to issues such as instrumentation and facet variation.

Conclusion

Results support the clinical application of personality assessment for suggesting risk for ADHD symptoms, and point to important directions for further research.
Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan
Authors: Kawashiri Shin-ya , Endo Yushiro , Nishino Ayako , Okamoto Momoko , Tsuji Sosuke , Takatani Ayuko , Shimizu Toshimasa , Sumiyoshi Remi , Koga Tomohiro , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Aramaki Toshiyuki , Ueki Yukitaka , Yoshitama Tamami , Eiraku Nobutaka , Matsuoka Naoki , Okada Akitomo , Fujikawa Keita , Hamada Hiroaki , Nagano Shuji , Tada Yoshifumi , Kawakami Atsushi
Published: June 2021

Background

To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.

Methods

We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. ‘Power Doppler (PD) responder’ was defined as a patient whose Δtotal PD score over 6 months was greater than the median change.

Results

Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23–0.91, p = 0.043) was an independent predictor of PD responder status.

Conclusion

Serum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept.

Trial registration

Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study

Trial registration number: UMIN000012524

Date of registration: 12/9/2013

URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657
The theorisation of ‘best interests’ in bioethical accounts of decision-making
Authors: Birchley Giles
Published: June 2021

Background

Best interests is a ubiquitous principle in medical policy and practice, informing the treatment of both children and adults. Yet theory underlying the concept of best interests is unclear and rarely articulated. This paper examines bioethical literature for theoretical accounts of best interests to gain a better sense of the meanings and underlying philosophy that structure understandings.

Methods

A scoping review of was undertaken. Following a literature search, 57 sources were selected and analysed using the thematic method.

Results

Three themes emerged. The first placed best interests within the structure of wider theory, noting relationships with consequentialism, deontology, prudential value theory, rights and political philosophy. The second mapped a typology of processes of decision-making, among which best interests was ambiguously positioned. It further indicated factors that informed best interests decision-making, primarily preferences, dignity and quality of life. The final theme considered best interests from a relational perspective.

Conclusions

Characterisation of best interests as strictly paternalist and consequentialist is questionable: while accounts often suggested a consequentialist basis for best interests, arguments appeared philosophically weak. Deontological accounts, found in law and Kantianism, and theories of political liberalism influenced accounts of best interests, with accounts often associating best interests with negative patient preferences (i.e. individual refusals). There was much more emphasis on negative interests than positive interests. Besides preference, factors like dignity and quality of life were held to inform best interests decisions, but generally were weakly defined. To the extent that preferences were unable to inform decision making, decisions were either made by proxy authority or by an intersubjective process of diffuse authority. Differing approaches reflect bifurcations in liberal philosophy between new liberalism and neo-liberalism. Although neither account of authority appears dominant, bias to negative interests suggests that bioethical debate tends to reflect the widespread ascendancy of neo-liberalism. This attitude was underscored by the way relational accounts converged on private familial authority. The visible connections to theory suggest that best interests is underpinned by socio-political trends that may set up frictions with practice. How practice negotiates these frictions remains a key question.
Neuroticism, resilience, and social support: correlates of severe anxiety among hospital workers during the COVID-19 pandemic in Nigeria and Botswana
Authors: Olashore Anthony A. , Akanni Oluyemi O. , Oderinde Kehinde O.
Published: June 2021

Background

The role of healthcare workers (HCWs) during the COVID-19 pandemic may make them more susceptible to anxiety than the general population. This study aimed to determine the prevalence of anxiety and evaluate the potential effects of resilience, neuroticism, social support, and other sociodemographic factors on anxiety among HCWs from two African countries.

Methods

A cross-sectional survey of 373 HCWs was conducted in Botswana and Nigeria, using an anxiety rating scale, neuroticism subscale of Big Five Inventory, Oslo social support scale, and Resilience Scale. Data collection was done between May 1 and September 30, 2020.

Results

The participants’ mean age (SD) was 38.42 (8.10) years, and 65.1% were females. Forty-nine (13.1%) of the HCWs reported clinical anxiety. In the final model of hierarchical multiple regression, neuroticism (B = 0.51, t = 10.59, p = p < 0.01), resilience (B = 0.34, t = − 7.11, p < 0.01), and social support (B = 0.079, t = − 2.11, p = 0.035) were associated with severe anxiety, after controlling for the significant sociodemographic factors.

Conclusions

Severe anxiety exists among HCWs in Africa, although the rate was lower than reported elsewhere. Neuroticism, resilience, and social support may be vital targets for psychological intervention in a pandemic as COVID-19; thus, their roles should be further explored.
Less airway inflammation and goblet cell metaplasia in an IL-33-induced asthma model of leptin-deficient obese mice
Authors: Kurokawa Atsushi , Kondo Mitsuko , Arimura Ken , Ashino Shigeru , Tagaya Etsuko
Published: June 2021

Background

Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33.

Methods

In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay.

Results

Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro.

Conclusions

Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accelerated by mucus in ob/ob mice. These results may explain some aspects of the pathogenesis of obesity-associated asthma.
Advances in aptamer screening and aptasensors’ detection of heavy metal ions
Authors: Guo Wenfei , Zhang Chuanxiang , Ma Tingting , Liu Xueying , Chen Zhu , Li Song , Deng Yan
Published: June 2021

Heavy metal pollution has become more and more serious with industrial development and resource exploitation. Because heavy metal ions are difficult to be biodegraded, they accumulate in the human body and cause serious threat to human health. However, the conventional methods to detect heavy metal ions are more strictly to the requirements by detection equipment, sample pretreatment, experimental environment, etc. Aptasensor has the advantages of strong specificity, high sensitivity and simple preparation to detect small molecules, which provides a new direction platform in the detection of heavy metal ions. This paper reviews the selection of aptamers as target for heavy metal ions since the 21th century and aptasensors application for detection of heavy metal ions that were reported in the past five years. Firstly, the selection methods for aptamers with high specificity and high affinity are introduced. Construction methods and research progress on sensor based aptamers as recognition element are also introduced systematically. Finally, the challenges and future opportunities of aptasensors in detecting heavy metal ions are discussed.
Thrombosis and bleeding outcomes in the treatment of cerebral venous thrombosis in cancer
Authors: Abelhad Nadia I , Qiao Wei , Garg Naveen , Rojas-Hernandez Cristhiam M.
Published: June 2021

Background

There is a need for clinical outcome data of cerebral venous thrombosis (CVT) in cancer patients. We examined the recanalization, thrombosis recurrence and major bleeding during CVT treatment in a cancer exclusive adult population.

Methods

We performed a retrospective review of cancer associated CVT identified through an institutional data warehouse. The primary endpoint was radiological and comprised the evaluation of thrombus recanalization at 12 months. Secondary endpoints were clinical and included rates of bleeding complications and recurrence of CVT. Variables were compared across subgroups of study outcomes. The backward stepdown procedure was used to identify variables for the final logistic model regarding thrombosis and bleeding outcomes.

Results

The population included forty-five patients, slightly predominant of male adults (55.6%) with a median age of 54.5 years. Solid malignancies comprised 64.4% of cases. A total of 33 cases were treated with anticoagulation. CVT recanalization was documented in almost 60% of cases. The cerebral venous thrombosis recurrence or propagation rate at 12 months was 15.6%. Major bleeding complications were observed in 15 patients.

Conclusions

Our findings are suggestive of a narrow therapeutic index of anticoagulation in cancer-CVT. Careful monitoring of anticoagulation effect and bleeding complications are of utmost clinical relevance in cancer patients. Further larger and controlled studies are needed to confirm our observations.
A potential association between immunosenescence and high COVID-19 related mortality among elderly patients with cardiovascular diseases
Authors: Wang Yuanyuan , Pang Shu-Chao , Yang Ying
Published: June 2021

Elderly patients with cardiovascular diseases account for a large proportion of Corona virus Disease 2019(COVID-19)related deaths. COVID-19, as a new coronavirus, mainly targets the patient’s lung triggering a cascade of innate and adaptive immune responses in the host. The principal causes of death among COVID-19 patients, especially elderly subjects with cardiovascular diseases, are acute respiratory distress syndrome(ARDS), multiple organ dysfunction syndrome (MODS), and microvascular thrombosis. All prompted by an excessive uncontrolled systemic inflammatory response. Immunosenescence, characterized by systemic and chronic inflammation as well as innate/adaptive immune imbalance, presents both in the elderly and cardiovascular patients. COVID-19 infection further aggravates the existing inflammatory process and lymphocyte depletion leading to uncontrollable systemic inflammatory responses, which is the primary cause of death. Based on the higher mortality, this study attempts to elucidate the pathophysiological mechanisms of COVID-19 in elderly subjects with cardiovascular diseases as well as the cause of the high mortality result from COVID-19.