bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Pairs of Mirror Aneurysms and Then Some: A Case Report
Authors: Sharma Mukesh Kumar , Sajja Kalyan Chekravarthy , Gorijala Vamsi Krishna
Published: August 2022

Multiple mirror aneurysms have been rarely reported in the literature. To the best of our knowledge, 3 pairs of mirror aneurysms in a single patient have not been reported prior. We present a case of 3 pairs of mirror aneurysms. One pair in the bifurcations of bilateral middle cerebral arteries and 2 pairs in the distal anterior cerebral arteries. The patient also had 2 unpaired aneurysms in the anterior communicating artery and left M1-anterior temporal junction, respectively. We have effectively treated these aneurysms with primary endovascular coiling.
High-throughput microarray reveals the epitranscriptome-wide landscape of m6A-modified circRNA in oral squamous cell carcinoma
Authors: Zhao Wei , Liu Jingwen , Wu Jie , Ma Xiaozhou , Wang Xi , Zhang Leyu , Han Zhe , Yang Jianming , Cui Yameng , Hu Xin , Deng Jiayin
Published: August 2022

Background

Emerging transcriptome-wide high-throughput screenings reveal the landscape and functions of RNAs, such as circular RNAs (circRNAs), in human cancer. In addition, the post-transcriptional RNA internal modifications, especially N6-methyladenosine (m6A), greatly enrich the variety of RNAs metabolism. However, the m6A modification on circRNAs has yet to be addressed.

Results

Here, we report an epitranscriptome-wide mapping of m6A-modified circRNAs (m6A-circRNA) in oral squamous cell carcinoma (OSCC). Utilizing the data of m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) and m6A-circRNAs microarray, we found that m6A-circRNAs exhibited particular modification styles in OSCC, which was independent of m6A-mRNA. Besides, m6A modification on circRNAs frequently occurred on the long exons in the front part of the coding sequence (CDS), which was distinct from m6A-mRNA that in 3’-UTR or stop codon.

Conclusion

In conclusion, our work preliminarily demonstrates the traits of m6A-circRNAs, which may bring enlighten for the roles of m6A-circRNAs in OSCC.
Patient satisfaction with computer-assisted structured initial assessment facilitating patient streaming to emergency departments and primary care practices: results from a cross-sectional observational study accompanying the DEMAND intervention in Germany
Authors: Schäfer Ingmar , Menzel Agata , Herrmann Tobias , Oltrogge Jan Hendrik , Lühmann Dagmar , Scherer Martin
Published: August 2022

Background

Patient numbers in emergency departments are on the rise. The DEMAND intervention aims to improve the efficacy of emergency services by computer-assisted structured initial assessment assigning patients to emergency departments or primary care practices. The aims of our study were to evaluate patient satisfaction with this intervention and to analyse if reduced patient satisfaction is predicted by sociodemographic data, health status or health literacy.

Methods

We conducted a cross-sectional patient survey in emergency departments and co-located primary care practices. Each intervention site was planned to participate for two observation periods, each with a duration of one full week. Study participants were recruited by the local staff. The patients filled out a written questionnaire during their waiting time. Patient satisfaction was assessed by agreement to four statements on a four point Likert scale. Predictors of patient satisfaction were identified by multilevel, multivariable logistic regression models adjusted for random effects at the intervention site level.

Results

The sample included 677 patients from 10 intervention sites. The patients had a mean age of 38.9 years and 59.0% were women. Between 67.5% and 55.0% were fully satisfied with aspects of the intervention. The most criticised aspect was that the staff showed too little interest in the patients’ personal situation. Full satisfaction (“clearly yes” to all items) was reported by 44.2%. Reduced patient satisfaction (at least one item rated as “rather yes”, “rather no”, “clearly no”) was predicted by lower age (odds ratio 0.79 for ten years difference, 95% confidence interval 0.67/0.95, p = 0.009), presenting with infections (3.08,1.18/8.05,p = 0.022) or injuries (3.46,1.01/11.82,p = 0.048), a higher natural logarithm of the symptom duration (1.23,1.07/1.30,p = 0.003) and a lower health literacy (0.71 for four points difference, 0.53/0.94,p = 0.019).

Conclusions

The patients were for the most part satisfied with the intervention. Assessment procedures should be evaluated a) regarding if all relevant patient-related aspects are included; and whether patient information can be improved b) for patients with strong opinions about cause, consequences and treatment options for their health problem; and c) for patients who have problems in the handling of information relevant to health and healthcare.

Trial registration

German Clinical Trials Register (https://www.drks.de/drks_web/setLocale_EN.do) no. DRKS00017014.
Cardio-renal benefits of sacubitril/valsartan in patients with advanced chronic kidney disease: experience in daily clinical practice
Authors: Martínez-Esteban María Dolores , Vázquez-Sánchez Teresa , Pozo-Álvarez Rafael , Moreno-Ortiz Alicia , Alonso-Titos Juana , Martín-Reyes Guillermo , Ruiz-Esteban Pedro , Gaitán-Román Daniel , Hernández Domingo
Published: August 2022

Background

The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4).

Methods

This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed.

Results

The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m2 and the left ventricular ejection fraction (LVEF) 36.4 ± 8.9%. The GFR improved after initiating the treatment (F = 3.396, p = 0.019), as did the LVEF at one year of follow-up (p = 0.018). The number of visits to the emergency department for heart failure was also reduced. No patients needed to start renal replacement therapy.

Conclusions

This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.
Family history of arterial hypertension and central adiposity: impact on blood pressure in schoolchildren
Authors: Tozo Tatiana Aparecida Affornali , Gisi Maria Lourdes , Brand Caroline , Moreira Carla Marisa Maia , Pereira Beatriz Oliveira , Leite Neiva
Published: August 2022

Background

A family history of arterial hypertension is an important risk factor for arterial hypertension. This study aimed to verify the mediating role of high central adiposity in the relationship between family history of arterial hypertension and blood pressure in schoolchildren.

Methods

Cross-sectional study with 118 schoolchildren of both sexes aged between 11 and 17 years. Weight, height, waist circumference and body mass index z score were verified. Somatic maturation was predicted by age for peak growth velocity. The family history of arterial hypertension was verified and defined as hypertensive schoolchildren with systolic blood pressure or diastolic blood pressure. Mediation analysis was used with linear regression models applied by PROCESS macro for SPSS (version 22.0), with significance p < 0.05.

Results

It was observed that 34.7% of the students have family history of arterial hypertension, 36% of the girls and 44.2% of the boys have arterial hypertension. In girls, the relationship between waist circumference and systolic blood pressure was direct (β = 0.535 p = 0.005), and those with a family history of arterial hypertension and who had a waist circumference greater than those without a family history of arterial hypertension was significant (β = -5,437 p = 0.009). Likewise, the relationship between family history of arterial hypertension and systolic blood pressure was attenuated when waist circumference was included in the model (β = -5.544; p = 0.103), indicating waist circumference as a mediator with an influence percentage of 19%. For boys, waist circumference is not a mediator of the relationship between family history of arterial hypertension and blood pressure.

Conclusions

Elevated central adiposity was a mediator of the relationship between family history of arterial hypertension and high blood pressure in girls, indicating the importance of family health strategies in the prevention and management of arterial hypertension in children and adolescents.
Where’s the “Everyday Black Woman”? An intersectional qualitative analysis of Black Women’s decision-making regarding HIV pre-exposure prophylaxis (PrEP) in Mississippi
Authors: Willie Tiara C. , Knight Deja , Baral Stefan D. , Chan Philip A. , Kershaw Trace , Mayer Kenneth H. , Stockman Jamila K. , Adimora Adaora A. , Monger Mauda , Mena Leandro A. , Philllips Karlye A. , Nunn Amy
Published: August 2022

Background

Black cisgender women in the U.S. South bear a disproportionate burden of HIV compared to cisgender women in other racial and ethnic groups and in any other part of the US. Critical to decreasing new HIV infections is the improved delivery of pre-exposure prophylaxis (PrEP) for Black cisgender women as it remains underutilized in 2021. Informed by intersectionality, the study sought to characterize the sociostructural influences on Black cisgender women’s deliberations about PrEP within the context of interlocking systems of oppression including racism, sexism, and classism.

Methods

Six focus groups were conducted with 37 Black women residing in Jackson, Mississippi. This sample was purposively recruited to include Black cisgender women who were eligible for PrEP but had never received a PrEP prescription.

Results

Six themes were identified as concerns during PrEP deliberation among Black women: 1) limited PrEP awareness, 2) low perceived HIV risk, 3) concerns about side effects, 4) concerns about costs, 5) limited marketing, and 6) distrust in the healthcare system. Three themes were identified as facilitators during PrEP deliberations: 1) women’s empowerment and advocacy, 2) need for increased PrEP-specific education, and 3) the positive influence of PrEP-engaged women’s testimonials. Black women shared a limited awareness of PrEP exacerbated by the lack of Black women-specific marketing. Opportunities to support Black women-specific social marketing could increase awareness and knowledge regarding PrEP’s benefits and costs. Black women also shared their concerns about discrimination in healthcare and distrust, but they felt that these barriers may be addressed by patient testimonials from PrEP-engaged Black women, empowerment strategies, and directly addressing provider biases.

Conclusions

An effective response to PrEP implementation among Black women in the South requires developing programs to center the needs of Black women and carry out active strategies that prioritize peer advocacy while reinforcing positive and mitigating negative influences from broader social and historical contexts.
Variation of parental feeding practices during the COVID-2019 pandemic: a systematic review
Authors: Luo Wen , Cai Qian , Zhou You , Cai Yepeng , Song Huizi , Zhang Yiran , Chen Yuying , Liao Yuexia
Published: August 2022

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and has resulted in a protracted pandemic. Infections caused by new coronavirus strains, primarily Delta and Omicron and currently highly prevalent globally. In response to the epidemic, countries, and cities implemented isolation and quarantine guidance, such as limiting social contact, which have affected the lifestyles and quality of life of the population. Parental feeding behaviors may vary as a result of factors such as prolonged home isolation of parents and children, lack of supplies during isolation, and stress. This study was designed to assess the available evidence and its implications for parental feeding practices in the context of COVID-19. We screened and reviewed research published in five electronic databases between 2020 and 2022, and eight studies met the selection criteria. Parents were observed to use a variety of feeding practices, including high levels of coercive control and reduction of rules and limits according to Vaughn’s food parenting constructs. The findings suggest that parental feeding practices are changing as a result of the pandemic and that more research is needed to further explore how to provide supportive feeding guidance to parents during emergencies in order to jointly promote child health.
Altered expression of ACOX2 in non-small cell lung cancer
Authors: Sui Jane S. Y. , Martin Petra , Keogh Anna , Murchan Pierre , Ryan Lisa , Nicholson Siobhan , Cuffe Sinead , Broin Pilib Ó , Finn Stephen P. , Fitzmaurice Gerard J. , Ryan Ronan , Young Vincent , Gray Steven G.
Published: August 2022

Peroxisomes are organelles that play essential roles in many metabolic processes, but also play roles in innate immunity, signal transduction, aging and cancer. One of the main functions of peroxisomes is the processing of very-long chain fatty acids into metabolites that can be directed to the mitochondria. One key family of enzymes in this process are the peroxisomal acyl-CoA oxidases (ACOX1, ACOX2 and ACOX3), the expression of which has been shown to be dysregulated in some cancers. Very little is however known about the expression of this family of oxidases in non-small cell lung cancer (NSCLC). ACOX2 has however been suggested to be elevated at the mRNA level in over 10% of NSCLC, and in the present study using both standard and bioinformatics approaches we show that expression of ACOX2 is significantly altered in NSCLC. ACOX2 mRNA expression is linked to a number of mutated genes, and associations between ACOX2 expression and tumour mutational burden and immune cell infiltration were explored. Links between ACOX2 expression and candidate therapies for oncogenic driver mutations such as KRAS were also identified. Furthermore, levels of acyl-CoA oxidases and other associated peroxisomal genes were explored to identify further links between the peroxisomal pathway and NSCLC. The results of this biomarker driven study suggest that ACOX2 may have potential clinical utility in the diagnosis, prognosis and stratification of patients into various therapeutically targetable options.
Vertebroplasty combined with facet joint block vs. vertebroplasty alone in relieving acute pain of osteoporotic vertebral compression fracture: a randomized controlled clinical trial
Authors: Dang Sha-Jie , Wei Wen-Bo , Wei Ling , Xu Jin
Published: August 2022

Objective

The study objective was to compare the efficacy and safety of percutaneous vertebroplasty (PVP) combined with facet joint block (FB) and vertebroplasty alone in relieving acute pain on osteoporotic vertebral compression fractures (OVCFs).

Methods

A prospective, randomized controlled study was conducted. One hundred ninety-eight patients of OVCFs undergoing surgery were randomly divided into two groups: Group P (PVP, n = 97), Group PF (PVP + FB, n = 101). The Visual analogue scale (VAS) and Oswestry disability index (ODI) were measured during pre-operation, 1 day, 1, 3, 6 and 12 months after the operation, respectively. The hospitalization time, operation time, complications, recurrence, the mean amount of cement injected and the number of patients who applied Cox-2 inhibitors within 3 days after operation were compared in the two groups.

Results

The VAS and ODI scores at each observation point of the post-operation were significantly decreased than that at the pre-operation in both groups (P < 0.05). The VAS and ODI scores in Group PF were significantly lower than that in Group P 1 day and 1 month after the operation (P < 0.05). The number of patients who applied Cox-2 inhibitors within 3 days after operation in group PF was significantly lower that in Group P (P < 0.001). There was no significant difference in hospitalization time, operation time, the mean amount of cement injected, complication rate, VAS and ODI scores at the pre-operation (P > 0.05).

Conclusion

Both PVP combined with FB and PVP alone are effective treatment methods for OVCFs. But PVP combined with FB showed better back pain relief than PVP alone in the short term after the operation for OVCFs.
The utility of intraoperative endoscopy to assist novice surgeons in the detection of gastric stenosis during laparoscopic sleeve gastrectomy
Authors: Chen I.-Sung , Tsai Ming-Shian , Chen Jian-Han , Chen Chung-Yen , Chen I.-Lin , Tai Chi-Ming
Published: August 2022

Background

Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric surgery. Gastric stenosis and leaks are 2 major complications associated with LSG and revision surgery might be needed. Herein, we report our experience of intraoperative endoscopy (IOE) to evaluate stenosis and leaks during LSG.

Methods

LSG was performed by three surgeons. Patients who underwent LSG and IOE between January 2016 and March 2020 were enrolled and assigned to two groups: group 1 (1st–30th LSG case for each surgeon) and group 2 (> 30th LSG for each surgeon). Patients’ anthropometric and biochemical data pre- and post-LSG, as well as IOE findings and follow-up esophagogastroduodenoscopy records were reviewed.

Results

In total, 352 patients were enrolled including 90 patients in group 1 and 262 patients in group 2. Three out of 352 patients (0.9%) were found to have stenosis by IOE, which was related to tightly gastropexy stitch or reinforcement stitch, all of which were in group 1. Stenosis was resolved after removal of the stitch during LSG. The incidence of gastric stenosis detected by IOE was 3.3% (3/90) and 0% (0/262) in group 1 and group 2, respectively (P = 0.003). No leakage was found in this study and no patient developed clinical or endoscopic stenosis after LSG.

Conclusions

The existing evidence showed that IOE can help detect gastric stenosis during LSG, especially for novice surgeons, and the stenosis could be resolved during operation.
Development of a human phage display-derived anti-PD-1 scFv antibody: an attractive tool for immune checkpoint therapy
Authors: Ghaderi Sepideh Safaei , Riazi-Rad Farhad , Qamsari Elmira Safaie , Bagheri Salman , Rahimi-Jamnani Fatemeh , Sharifzadeh Zahra
Published: August 2022

Background

The PD-1 checkpoint pathway plays a major role in tumor immune evasion and the development of the tumor microenvironment. Clinical studies show that therapeutic antibodies blocking the PD-1 pathway can restore anti-tumor or anti-virus immune responses by the reinvigoration of exhausted T cells. Because of the promising results of anti-PD-1 monoclonal antibodies in cancer treatment, autoimmune disorders, and infectious diseases, the PD-1 has emerged as an encouraging target for different diseases.

Results

In the present study, we employed a human semi-synthetic phage library for isolation of some scFvs against the extracellular domain of PD-1 protein by panning process. After the panning, a novel anti-PD-1 scFv (SS107) was found that exhibited specific binding to PD-1 antigen and stimulated Jurkat T cells. The selected anti-PD-1 scFv could restore the production of IL-2 and IFN-γ by Jurkat T cells that were co-cultured with PD-L1 positive tumor cells.

Conclusion

This anti-PD-1 scFv with high specificity and the ability to reactivate exhausted T cells has the potential to be developed as an anti-cancer agent or to be used in combination with other therapeutic approaches.
Standard setting Very Short Answer Questions (VSAQs) relative to Single Best Answer Questions (SBAQs): does having access to the answers make a difference?
Authors: Sam Amir H. , Millar Kate R. , Westacott Rachel , Melville Colin R. , Brown Celia A.
Published: August 2022

Background

We investigated whether question format and access to the correct answers affect the pass mark set by standard-setters on written examinations.

Methods

Trained educators used the Angoff method to standard set two 50-item tests with identical vignettes, one in a single best answer question (SBAQ) format (with five answer options) and the other in a very short answer question (VSAQ) format (requiring free text responses). Half the participants had access to the correct answers and half did not. The data for each group were analysed to determine if the question format or having access to the answers affected the pass mark set.

Results

A lower pass mark was set for the VSAQ test than the SBAQ test by the standard setters who had access to the answers (median difference of 13.85 percentage points, Z = -2.82, p = 0.002). Comparable pass marks were set for the SBAQ test by standard setters with and without access to the correct answers (60.65% and 60.90% respectively). A lower pass mark was set for the VSAQ test when participants had access to the correct answers (difference in medians -13.75 percentage points, Z = 2.46, p = 0.014).

Conclusions

When given access to the potential correct answers, standard setters appear to appreciate the increased difficulty of VSAQs compared to SBAQs.
Translating and validating a Japanese version of the instrument for patient assessment of medical professionalism (J-IPAMP): a cross-sectional survey
Authors: Fujikawa Hirohisa , Son Daisuke , Aoki Takuya , Kondo Kayo , Takemura Yousuke , Saito Minoru , Den Naoko , Eto Masato
Published: August 2022

Background

Although there are many tools to assess medical professionalism, they rarely address patients’ perspectives. The instrument for patient assessment of medical professionalism (IPAMP) comprises 11 items and has been established and validated as a valuable tool for assessing trainees’ professionalism from the patient’s perspective. However, there is no instrument to assess professionalism from the patient’s perspective in Japan. The purpose of the present study was to develop a Japanese version of the IPAMP (J-IPAMP) and test its validity and reliability.

Methods

We conducted a cross-sectional survey to examine the reliability and validity of the J-IPAMP in two hospitals (one each in an urban and rural area) in Japan. Receptionists or surveyors distributed the anonymous questionnaire to 276 inpatients; all participants were aged above 20 years and assigned to medical trainees. We evaluated its structural and criterion-related validity, as well as internal consistency reliability.

Results

Data of 235 (85.1%) patients were analyzed. Using the split-half validation technique, we performed an exploratory factor analysis (EFA) along with a confirmatory factor analysis (CFA). The EFA showed a one-factor solution. Then, to compare the model fitness between two models (the two-factor model from the original English version vs. unidimensional model suggested by the EFA), the CFA was performed. The CFA showed that almost all of the fit indices met their respective criteria and were approximately the same for the two models. Thus, we adopted a single-factor model. The Pearson correlation coefficients between the total J-IPAMP scores and the global ratings were 0.738, indicating adequate criterion-related validity. The Cronbach’s alpha of the 11 items of the instrument was 0.96 (95% confidence interval: 0.96–0.97) and the omega value was 0.96, demonstrating acceptable internal consistency reliability.

Conclusions

We developed the Japanese version of the IPAMP. Its validity and reliability were verified through analysis. This instrument can be utilized for professionalism education in the postgraduate training setting.
A comprehensive review about the utilization of immune checkpoint inhibitors and combination therapy in hepatocellular carcinoma: an updated review
Authors: Sharafi Faezeh , Hasani Sadegh Abaei , Alesaeidi Samira , Kahrizi Mohammad Saeed , Adili Ali , Ghoreishizadeh Shadi , Shomali Navid , Tamjidifar Rozita , Aslaminabad Ramin , Akbari Morteza
Published: August 2022

A pharmacological class known as immune checkpoint inhibitors (ICIs) has been developed as a potential treatment option for various malignancies, including HCC. In HCC, ICIs have demonstrated clinically significant advantages as monotherapy or combination therapy. ICIs that target programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1), as well as cytotoxic T lymphocyte antigen 4 (CTLA-4), have made significant advances in cancer treatment. In hepatocellular carcinoma (HCC), several ICIs are being tested in clinical trials, and the area is quickly developing. As immunotherapy-related adverse events (irAEs) linked with ICI therapy expands and gain worldwide access, up-to-date management guidelines become crucial to the safety profile of ICIs. This review aims to describe the evidence for ICIs in treating HCC, emphasizing the use of combination ICIs.
A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma
Authors: Wang Yang , Xiao Fan , Zhao Yi , Mao Chen-Xue , Yu Lu-Lu , Wang Lei-Yun , Xiao Qi , Liu Rong , Li Xi , McLeod Howard L. , Hu Bi-Wen , Huang Yu-Ling , Lv Qiao-Li , Xie Xiao-Xue , Huang Wei-Hua , Zhang Wei , Guo Cheng-Xian , Li Jin-Gao , Yin Ji-Ye
Published: August 2022

Background

Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown.

Methods

We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively.

Results

Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10− 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia).

Conclusions

Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy.

Trial registration

Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).
Directing ricin-based immunotoxins with targeting affibodies and KDEL signal peptide to cancer cells effectively induces apoptosis and tumor suppression
Authors: Park Seong Guk , Kim Heeyeon , Jun Heejin , Choi Sun Young , Kim Eunhee , Kang Sebyung
Published: August 2022

The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based “magic bullets” to effectively suppress tumors that are resistant to conventional anti-cancer drugs.

Graphical Abstract
Advanced biological age is associated with improved antibody responses in older high-dose influenza vaccine recipients over four consecutive seasons
Authors: Verschoor Chris P. , Belsky Daniel W. , Andrew Melissa K. , Haynes Laura , Loeb Mark , Pawelec Graham , McElhaney Janet E. , Kuchel George A.
Published: August 2022

Background

Biological aging represents a loss of integrity and functionality of physiological systems over time. While associated with an enhanced risk of adverse outcomes such as hospitalization, disability and death following infection, its role in perceived age-related declines in vaccine responses has yet to be fully elucidated. Using data and biosamples from a 4-year clinical trial comparing immune responses of standard- and high-dose influenza vaccination, we quantified biological age (BA) prior to vaccination in adults over 65 years old (n = 292) using a panel of ten serological biomarkers (albumin, alanine aminotransferase, creatinine, ferritin, free thyroxine, cholesterol, high-density lipoprotein, triglycerides, tumour necrosis factor, interleukin-6) as implemented in the BioAge R package. Hemagglutination inhibition antibody titres against influenza A/H1N1, A/H3N2 and B were quantified prior to vaccination and 4-, 10- and 20- weeks post-vaccination.

Results

Counter to our hypothesis, advanced BA was associated with improved post-vaccination antibody titres against the different viral types and subtypes. However, this was dependent on both vaccine dose and CMV serostatus, as associations were only apparent for high-dose recipients (d = 0.16–0.26), and were largely diminished for CMV positive high-dose recipients.

Conclusions

These findings emphasize two important points: first, the loss of physiological integrity related to biological aging may not be a ubiquitous driver of immune decline in older adults; and second, latent factors such as CMV infection (prevalent in up to 90% of older adults worldwide) may contribute to the heterogeneity in vaccine responses of older adults more than previously thought.
The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein
Authors: Fischer Kerstin , Topallar Selin , Kraatz Franziska , Groschup Martin H. , Diederich Sandra
Published: August 2022

Background

N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites.

Findings

To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity.

Conclusions

Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation.
Evaluation of factors associated with medication adherence in patients with bipolar disorder using a medication event monitoring system: a 6‐month follow‐up prospective study
Authors: Youn HyunChul , Lee Moon-Soo , Jeong Hyun-Ghang , Kim Seung‑Hyun
Published: August 2022

Background

Non-adherence in patients with bipolar disorder (BD) results in symptoms, such as aggravation, BD recurrence, emergency room visits, re-hospitalization, and poor psychosocial outcomes. Though non-adherence rates have been reported to range between 30–50% in patients with BD, the problem of adherence is often either overlooked by the physician or denied by the patient. An essential first step to enhancing medication adherence is to objectively estimate adherence. The Medication Event Monitoring System (MEMS), which is a pill bottle cap with a microprocessor, is an accurate device for assessing medication adherence. Using the MEMS, we aimed to measure medication adherence in patients with BD and evaluate the factors associated with and 6-month changes in medication adherence.

Methods

Participants with BD were recruited from the psychiatric outpatient clinic of the Korea University Guro Hospital. The medication adherence of each participant was assessed using the MEMS, a self-report, pill count, and clinician rating. MEMS-measured adherence was reassessed after 6 months. Patient demographics were recorded and clinical assessments were conducted. Data were analyzed using Kappa statistics and Pearson’s correlation analysis.

Results

Of the 59 participants, 50 records were included in the analysis. Patient adherence and adherence rate assessed by the MEMS were lower than those assessed by the other measures. MEMS-measured adherence was correlated more closely with pill counts than with self-reports or clinician ratings. MEMS-measured adherence was negatively associated with prescription duration and the Brief Psychiatric Rating Scale—Affect Subscale Score. Six-month changes in MEMS-measured adherence were positively associated with attitude toward drugs and negatively associated with weight gain assessed by the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale.

Conclusions

Clinicians may have to consider the limited accuracy of self-reporting and clinician rating methods and exercise caution when assessing the medication adherence of patients with BD using these methods. Our findings may assist clinicians in the assessment and improvement of medication adherence in patients with BD and, consequently, may be useful for the treatment and prevention of BD recurrence.
Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS)
Authors: Shimojima Yasuhiro , Kishida Dai , Ichikawa Takanori , Kida Takashi , Yajima Nobuyuki , Omura Satoshi , Nakagomi Daiki , Abe Yoshiyuki , Kadoya Masatoshi , Takizawa Naoho , Nomura Atsushi , Kukida Yuji , Kondo Naoya , Yamano Yasuhiko , Yanagida Takuya , Endo Koji , Hirata Shintaro , Matsui Kiyoshi , Takeuchi Tohru , Ichinose Kunihiro , Kato Masaru , Yanai Ryo , Matsuo Yusuke , Nishioka Ryo , Okazaki Ryota , Takata Tomoaki , Ito Takafumi , Moriyama Mayuko , Takatani Ayuko , Miyawaki Yoshia , Ito-Ihara Toshiko , Kawaguchi Takashi , Kawahito Yutaka , Sekijima Yoshiki
Published: August 2022

Background

This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan.

Methods

We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed.

Results

Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03–2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59–13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51–29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24–85.03, p < 0.0001).

Conclusion

GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.
Markedly increased small-sized megakaryocytes and platelets count in the circulation with pseudo-hyperkalemia following splenectomy
Authors: Li Guiying , Wang Bin , Li Dongyan , Zhu Rong , Chen Xueyan
Published: August 2022

Megakaryocytes are common in the bone marrow and appear less often in circulation. Most studies on circulatory megakaryocytes have implicated myelodysplastic syndromes and myeloproliferative disorders because of disruption of the bone marrow barrier and extramedullary hematopoiesis that is commonly seen in the spleen. As myeloproliferative disorders progress, particularly in the absence of the spleen, it is very likely that considerable numbers of megakaryocytes are present in the circulation. Myeloproliferation is associated with essential thrombocytosis or leukocytosis and is the leading cause of pseudo-hyperkalemia followed by reactive thrombocytosis due to splenectomy, rheumatoid arthritis, and renal cancer. The simultaneous measurement of plasma potassium is required when the platelet count exceeds 500 × 109/L and the level of serum potassium is  > 5.4 mmol/L.
The emerging role of furin in neurodegenerative and neuropsychiatric diseases
Authors: Zhang Yi , Gao Xiaoqin , Bai Xue , Yao Shanshan , Chang Yan-Zhong , Gao Guofen
Published: August 2022

Furin is an important mammalian proprotein convertase that catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway. In the brain, the substrates of furin include the proproteins of growth factors, receptors and enzymes. Emerging evidence, such as reduced FURIN mRNA expression in the brains of Alzheimer’s disease patients or schizophrenia patients, has implicated a crucial role of furin in the pathophysiology of neurodegenerative and neuropsychiatric diseases. Currently, compared to cancer and infectious diseases, the aberrant expression of furin and its pharmaceutical potentials in neurological diseases remain poorly understood. In this article, we provide an overview on the physiological roles of furin and its substrates in the brain, summarize the deregulation of furin expression and its effects in neurodegenerative and neuropsychiatric disorders, and discuss the implications and current approaches that target furin for therapeutic interventions. This review may expedite future studies to clarify the molecular mechanisms of furin deregulation and involvement in the pathogenesis of neurodegenerative and neuropsychiatric diseases, and to develop new diagnosis and treatment strategies for these diseases.
Assessing eating disorder symptoms in low and middle-income countries: a systematic review of psychometric studies of commonly used instruments
Authors: Ayala Camila Ospina , Scarpatto Camila , Garizábalo-Davila Claudia Milena , Valencia Paula Andrea Diaz , Irigaray Tatiana Quarti , Cañon-Montañez Wilson , Mattiello Rita
Published: August 2022

Background

Various well-validated interview and self-report instruments are available to assess eating disorder symptomatology. However, most psychometric studies have been conducted in high-income countries. The aim of the present study was to systematically review the available psychometric studies conducted in low- and middle-income countries on well-known measures for assessing eating disorder symptoms.

Methods

Psychometric studies with the following instruments were included: the Eating Disorder Examination (EDE), the Eating Disorder Examination Questionnaire (EDE-Q), the Eating Disorder Inventory (EDI), the Eating Attitudes Test (EAT), and the Children’s Eating Attitudes Test (ChEAT). Searches were conducted on August 30, 2021, in the following databases: MEDLINE, EMBASE, LILACS, Web of Science, PsycINFO, and CABI. The methodological quality of the studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The studies were considered to have conducted the minimum psychometric evaluation if they assessed at least the three types of validity (content, criteria, and construct) or diagnostic performance. The psychometric properties were also evaluated considering the cut-off points described in the literature for each of the analysis methods used to evaluate validity and reliability and two reviewers independently selected the studies and evaluated the quality criteria.

Results

A total of 28 studies were included. The studies were conducted in 13 countries (10 middle income and 3 low income). The instruments that were most used in the studies were the EAT and EDE-Q. According to the overall COSMIN assessment, in most (57%) of the studies the psychometric properties assessed were not described. Forty-three percent of the studies conducted the minimum psychometric evaluation. However, according to the described cut-off points, the results for the psychometric properties assessed showed, in general, acceptable validity and reliability.

Conclusion

The results of this review suggest a lack of studies with the recommended psychometric properties in low- and middle-income countries on these commonly used instruments. With the steady increase in the prevalence of eating disorders globally, psychometric investigations of instruments for measuring eating disorder symptoms in these countries should be encouraged to promote their early detection and treatment.
Perception of climate change in Bangladesh: local beliefs, practices and responses
Authors: Uddin Md. Borhan
Published: August 2022

There is a clear need for an understanding of the perceptions of climate change among those whose lives are most affected to inform national discourse and in particular, development and implementation of adaptation strategies. The paper is the outcome of a qualitative study among the local people of Charhajari, Anuliya and Nitpur unions of Bangladesh. The key informant technique, along with in-depth interview, had been exploited for gaining holistic perceptions on climatic scenario in the localities, while focus group discussion and case study were used for mapping out collective social consensus on the subject. The study has elucidated the threats climate change poses to established long-term beliefs, practices and perceptions by instigating erratic changes in weather patterns, shifting seasons, and questioning efficacy and authority of traditional interpretation of local weather. Local inhabitants have their own way of internalization and symbolic interpretation of climate induced debacles. Of the indicators demonstrating the impacts of climate change on local communities, seasonal diversity decline is central for affecting every aspects of socio-economic life including rituals and festivals. Apart from these, inhabitants have explored a number of independent and dependent climatic hazards they are under exposed. The paper concludes that experience of climate change impacts is for most cases ecosystem based but perception appears to be culturally specific.
The potential role of community pharmacy staff in reducing patient delay in consulting with symptoms of rheumatoid arthritis: a qualitative study
Authors: Simons Gwenda , Ismail Nour , Sandhu Karanbir , Mallen Christian D. , Stack Rebecca J. , Pontefract Sarah , Raza Karim , Falahee Marie
Published: August 2022

Background

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis which can cause joint damage and reduced quality of life. Early treatment of RA within 3 months of symptom onset is associated with improved clinical outcomes. However, this window of opportunity is often missed. One important contributing factor is patients with symptoms of RA delaying consulting their general practitioner (GP). Previous research indicates that patients with inflammatory arthritis are likely to visit pharmacies for advice before consulting their GP. Therefore, pharmacists are well positioned to identify patients with symptoms of early inflammatory arthritis and signpost them appropriately. This research examines community pharmacy staff’s knowledge, perceptions, and approaches to management of patients presenting with symptoms of RA in order to identify training needs and other opportunities for intervention to enhance the role of pharmacy staff in the pathway to care.

Methods

Semi-structured interviews were conducted with 19 community pharmacy staff in the West Midlands (UK), during a 12-month period (2017–2018). The interviews were audio-recorded, transcribed, and analyzed using thematic analysis facilitated by NVivo 12.

Results

There was considerable variation in knowledge and perceptions of RA and the need for early treatment amongst pharmacists and other pharmacy staff. The potential role of pharmacists and other pharmacy staff in reducing delay in help-seeking was also discussed. Four themes emerged from thematic analysis: (1) Variations in perceptions and knowledge about RA. (2) The role of the pharmacy in increasing public awareness about RA. (3) The role of the pharmacy staff in facilitating access to the GP. (4) Practical considerations for pharmacy-based interventions.

Conclusion

Variability in knowledge and perceptions of RA amongst pharmacists, and amongst other pharmacy staff will affect effective signposting of suspected RA cases. This study identifies opportunities for enhanced training of community pharmacists and other pharmacy staff in relation to inflammatory arthritis as well as other pharmacy-based interventions, such as public awareness campaigns about RA and other musculoskeletal conditions. Together with existing referral services and other pharmacy-based initiatives this could result in enhanced signposting to GP consultation or other appropriate NHS services for inflammatory symptoms and reduced treatment delay.