bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundGenetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown.MethodsWe 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.ResultsFive 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).ConclusionsRs6711678, 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 registrationChinese 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

AbstractThe 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractMegakaryocytes 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

AbstractFurin 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

Abstract
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

AbstractThere 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

AbstractBackgroundRheumatoid 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.MethodsSemi-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.ResultsThere 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.ConclusionVariability 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.
Pediatric push pin aspiration: clinical, radiologic, and pathologic correlation — case report
Authors: Hickey Tyler Bruce Malcolm , Mathews Rohit Zachariah , Pickup Michael James 
Published: August 2022

Abstract

Background
Aspiration of foreign bodies is not uncommon in the pediatric setting, and the consideration and recognition of an aspiration event are vital to prompt management. Pointed and sharp-edged foreign bodies have the potential to lodge in the airway and increase the difficulty of identification and removal. Here, we describe a fatal aspiration of a push pin that was unrecognized prior to death.

Methods
Review of police and medical records was completed prior to postmortem CT imaging and full pediatric autopsy with high resolution photography.

Case presentation
A 15-month-old boy was playing at home when he acutely vomited and then became unresponsive. Paramedic and hospital physicians performed pediatric CPR protocols, including intubation, without success. Postmortem radiographic imaging revealed a metallic foreign body at the level of the larynx. Autopsy demonstrated a push pin fully occluding the trachea at the level of the vocal cords.

Conclusions
The diagnosis of aspirated FBs may be elusive, and clinicians and autopsy pathologists ought to be mindful that children with FBs may have atypical presentations. Use of postmortem radiologic imaging can assist in the diagnosis and allow for a targeted autopsy approach to best visualize the offending foreign body.