bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Adverse Reactions in Tattooed Skin through Histological and Chemical Analysis
Authors: Kurz Bernadett , Schreiver Ines , Siewert Katherina , Haslboeck Birgit , Weiss Katharina T. , Hannemann Julia , Berner Bianca , von Eichborn Maria Isabel , Berneburg Mark , Baeumler Wolfgang
Published: July 2023

Background: Just as the number of tattooed people has increased in recent years, so has the number of adverse reactions in tattooed skin. Tattoo colourants contain numerous, partly unidentified substances, which have the potential to provoke adverse skin reactions like allergies or granulomatous reactions. Identification of the triggering substances is often difficult or even impossible. Methods: Ten patients with typical adverse reactions in tattooed skin were enrolled in the study. Skin punch biopsies were taken and the paraffin-embedded specimens were analysed by standard haematoxylin and eosin and anti-CD3 stainings. Tattoo colourants provided by patients and punch biopsies of patients were analysed with different chromatography and mass spectrometry methods and X-ray fluorescence. Blood samples of 2 patients were screened for angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R). Results: Histology showed variable skin reactions such as eosinophilic infiltrate, granulomatous reactions, or pseudolymphoma. CD3+ T lymphocytes dominated the dermal cellular infiltrate. Most patients had adverse skin reactions in red tattoos (n = 7), followed by white tattoos (n = 2). The red tattooed skin areas predominantly contained Pigment Red (P.R.) 170, but also P.R. 266, Pigment Orange (P.O.) 13, P.O. 16, and Pigment Blue (P.B.) 15. The white colourant of 1 patient contained rutile titanium dioxide but also other metals like nickel and chromium and methyl dehydroabietate – known as the main ingredient of colophonium. None of the 2 patients showed increased levels of ACE and sIL-2R related to sarcoidosis. Seven of the study participants showed partial or complete remission after treatment with topical steroids, intralesional steroids, or topical tacrolimus. Conclusions: The combination of the methods presented might be a rational approach to identify the substances that trigger adverse reactions in tattoos. Such an approach might help make tattoo colourants safer in the future if such trigger substances could be omitted.
The Natural Evolution of Nevi with Peripheral Globules
Authors: Ilut Paula Anca , Camela Elisa , Lallas Konstantinos , Papageorgiou Chryssoula , Manoli Sofia-Magdalini , Kyrgidis Athanassios , Liopyris Konstantinos , Sgouros Dimitrios , Apalla Zoe , Lallas Aimilios
Published: July 2023

Background: Peripheral globules (PG) in melanocytic lesions represent a concerning dermoscopic feature since they might be present in growing nevi and melanomas. Their natural evolution has not been fully elucidated, and an age-based management approach has been recommended. Objectives: The aim of this study was to calculate the growth rate of lesions with PG and investigate possible association with age, sex, location, and the global dermoscopic pattern. Methods: We retrospectively selected the lesions of interest from a cohort of Caucasian patients who underwent sequential digital dermoscopy monitoring. Lesions with PG distributed at 75% or more of their circumference with available follow-up images or histopathologic report were included. The surface area was automatically calculated with the help of an incorporated tool used in the acquisition of the images. The images were also evaluated by independent investigators for the presence of pre-defined criteria. Growth-curve models were used to assess the growth rate. The outcome variable was the area of nevi in mm2, and scatterplots with Lowess curves were used to present the mean change of nevi during follow-up. Results: A total of 208 lesions from 98 patients with a median age of 36 years (range 15–75) were included. The median follow-up time was 18 months (range 4–48). The mean growth rate for all nevi was 0.16 mm2/month (95% CI, 0.14–0.18, p < 0.001), ranging from −0.29 to 0.61 mm2/month. The growth rate was higher in nevi with a homogeneous dermoscopic pattern (p < 0.001). The number of peripheral globules during follow-up varied from increasing to complete disappearance. None of the lesions developed any melanoma-specific structure at follow-up. Conclusion: Nevi with PG grew at a mean rate of 0.16 mm2/month, and the growth rate was independent of age, gender, or anatomic location. Nevi with homogeneous pattern demonstrated the highest growth rate in our cohort. None of the monitored nevi with PG developed melanoma-specific criteria at follow-up.
Comparison of Paclitaxel plus Carboplatin versus Observation in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck
Authors: Fukuda Naoki , Oki Ryosuke , Suto Hirotaka , Wang Xiaofei , Urasaki Tetsuya , Sato Yasuyoshi , Nakano Kenji , Yunokawa Mayu , Ono Makiko , Tomomatsu Junichi , Mitani Hiroki , Takahashi Shunji
Published: July 2023

Introduction: Although systemic therapy, including multi-kinase inhibitors and cytotoxic chemotherapy, is an option for recurrent or metastatic adenoid cystic carcinoma of the head and neck (HNACC), it is not proven whether these therapies can prolong overall survival (OS). The present study investigated the impact of cytotoxic chemotherapy on survival outcomes compared with observation without chemotherapy. Methods: We retrospectively reviewed the medical records of the patients diagnosed with recurrent or metastatic HNACC. We compared the survival outcomes, including survival time from recurrence/metastasis (OS) patients who received systemic chemotherapy with paclitaxel (200 mg/m2) and carboplatin (area under the curve 6) (TC) on day 1 of a 3-week cycle and observation alone. Subgroup analysis was conducted to identify patients who can get benefit from TC. Results: Seventy-five patients (32 in TC and 43 in observation) were analyzed. There was no difference in median OS between TC and observation (52.2 months vs. 44.0 months, hazard ratio 0.76, 95% confidence interval 0.32–1.30, p = 0.21). Landmark analysis to reduce immortal bias also showed no difference between TC and observation in terms of OS. Subgroup analysis showed nonsignificant trends toward longer OS in asymptomatic patients with pulmonary metastasis and without bone metastasis. Conclusions: In our non-randomized comparison, patients who underwent TC did not show prolonged survival time from recurrence and/or metastasis diagnosis compared with observation alone in patients with recurrent or metastatic HNACC. Although systemic chemotherapy is a possible option for metastatic/recurrent HNACC, initial observation might be a valid strategy for asymptomatic patients without extrapulmonary diseases. Further research is warranted to identify the optimal patients and therapeutic regimens to prolong OS in HNACC.
Safety of Cold Snare Polypectomy during Continuous Use of Antithrombotic Drugs for Delayed Post-Polypectomy Bleeding: A Pilot Study
Authors: Hayasaka Junnosuke , Yamashita Satoshi , Matsui Akira , Kawai Yusuke , Ochiai Yorinari , Okamura Takayuki , Suzuki Yugo , Mitsunaga Yutaka , Nomura Kosuke , Tanaka Masami , Fuchinoue Kazuhiro , Odagiri Hiroyuki , Kikuchi Daisuke , Takazawa Yutaka , Hoteya Shu
Published: July 2023

Background: Cold snare polypectomy is a high-risk endoscopic procedure with a low delayed post-polypectomy bleeding rate. However, it is unclear whether delayed post-polypectomy bleeding rates increase during continuous antithrombotic treatment. This study aimed to determine the safety of cold snare polypectomy during continuous antithrombotic treatment. Methods: This single-center, retrospective cohort study enrolled patients who underwent cold snare polypectomy during antithrombotic treatment between January 2015 and December 2021. Patients were divided into continuation and withdrawal groups based on whether they continued with antithrombotic drugs or not. Propensity score matching was performed using age, sex, Charlson comorbidity index, hospitalization, scheduled treatment, type of antithrombotic drugs used, multiple medications used, indication for antithrombotic drugs, and gastrointestinal endoscopist qualifications. The delayed polypectomy bleeding rates were compared between the groups. Delayed polypectomy bleeding was defined as the presence of blood in stools and requiring endoscopic treatment or a decrease in hemoglobin level by 2 g/dL or more. Results: The continuation and withdrawal groups included 134 and 294 patients, respectively. Delayed polypectomy bleeding was observed in 2 patients (1.5%) and 1 patient (0.3%) in the continuation and withdrawal groups, respectively (p = 0.23), before propensity score matching, with no significant difference. After propensity score matching, delayed polypectomy bleeding was observed in 1 patient (0.9%) in the continuation group but not in the withdrawal group, with no significant difference. Conclusion: Cold snare polypectomy during continuous antithrombotic treatment did not significantly increase delayed post-polypectomy bleeding rates. Therefore, this procedure may be safe during continuous antithrombotic treatment.
Alterations of UHRF Family Expression and UHRF1/ICBP90 Inhibits Phosphatase and Tensin Homolog Expression in Endometrial Cancer
Authors: Yoshimoto Masafumi , Tokuda Aoi , Eguchi Ayami , Nozawa Yoshihiro , Mori Tsutomu , Yaginuma Yuji
Published: July 2023

Introduction: The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (ICBP90/UHRF1) and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. To determine the role of NIRF and ICBP90 in endometrial tumorigenesis, we evaluated ICBP90 and NIRF expression levels in endometrial cancers. Also molecular alterations of phosphatase and tensin homolog (PTEN) expression are the important event for endometrial carcinogenesis; therefore, we investigated the involvement between ICBP90 and PTEN expression. Methods: We used Western blot for NIRF, ICBP90, and PTEN expression, mutation analysis of NIRF gene, and immunohistochemical staining for the expression of NIRF and ICBP90. For immunohistochemical staining, we examined atypical endometrial hyperplasia, endometrial cancers, and noncancerous samples. Results: Our data showed that the reduced expression of NIRF and overexpression of ICBP90 occurred in atypical endometrial hyperplasia and endometrial cancer compared to the normal endometrium. The decrease in NIRF expression was significantly correlated with histological grade. Expression of ICBP90 was high, especially in the peripheral margin of a cancer nest. Western blot analysis of endometrial cancer cell lines referred an opposite correlation between ICBP90 and PTEN expression. Conclusion: Our findings suggested that continually overexpressed ICBP90 may contribute to the inhibition of PTEN expression, which is a frequent and important event in endometrial carcinogenesis. We propose that the reduced NIRF expression and ICBP90 overexpression is an early event in endometrial carcinogenesis; thus ICBP90 may be useful as a therapeutic target in this disease.
Symptoms Contributing to the Diagnosis of Small Bowel Tumors
Authors: Tsuruta Kozo , Takedatsu Hidetoshi , Yoshioka Shinichiro , Yoshikai Masahiro , Tomiyasu Kensuke , Morita Masaru , Kuwaki Kotaro , Mitsuyama Keiichi , Kawaguchi Takumi
Published: July 2023

Introduction: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. Methods: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. Results: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. Conclusion: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs.
When to Consult a Geneticist Specialising in Gestational Trophoblastic Disease
Authors: McMahon Lesley , Maher Geoffrey J. , Joyce Caroline , Niemann Isa , Fisher Rosemary , Sunde Lone
Published: July 2023

Background: Gestational trophoblastic disease comprises hydatidiform moles and a rare group of malignancies that derive from trophoblasts. Although there are typical morphological features that may distinguish hydatidiform moles from non-molar products of conception, such features are not always present, especially at early stages of pregnancy. Furthermore, mosaic/chimeric pregnancies and twin pregnancies make pathological diagnosis challenging while trophoblastic tumours can also pose diagnostic problems in terms of their gestational or non-gestational origin. Objectives: The aim of this study was to show that ancillary genetic testing can be used to aid diagnosis and clinical management of GTD. Methods: Each author identified cases where genetic testing, including short tandem repeat (STR) genotyping, ploidy analysis, next-generation sequencing, and immunostaining for p57, the product of the imprinted gene CDKN1C, facilitated accurate diagnosis and improved patient management. Representative cases were chosen to illustrate the value of ancillary genetic testing in different scenarios. Outcome: Genetic analysis of placental tissue can aid in determining the risk of developing gestational trophoblastic neoplasia, facilitating discrimination between low risk triploid (partial) and high risk androgenetic (complete) moles, discriminating between a hydatidiform mole twinned with a normal conceptus and a triploid conception and identification of androgenetic/biparental diploid mosaicism/chimerism. STR genotyping of placental tissue and targeted gene sequencing of patients can identify women with an inherited predisposition to recurrent molar pregnancies. Genotyping can distinguish gestational from non-gestational trophoblastic tumours using tissue or circulating tumour DNA and can also identify the causative pregnancy which is the key prognostic factor for placental site and epithelioid trophoblastic tumours. Conclusions and Outlook: STR genotyping and p57 immunostaining have been invaluable to the management of gestational trophoblastic disease in many situations. The use of next-generation sequencing and of liquid biopsies is opening up new pathways for GTD diagnostics. Development of these techniques has the potential to identify novel biomarkers of GTD and further refine diagnosis.
Smell Outcome and Seropositivity Titre in Post-COVID-19 Patients
Authors: Harminder Singh Shalina Kaur , Husain Salina , Wan Hamizan Aneeza Khairiyah , Zahedi Farah Dayana , Othman Siti Norlia , Zainol Rashid Zetti
Published: July 2023

Introduction: The aims of the study were to perform an olfactory assessment on patients active and post-COVID-19 using the culturally adapted Malaysian version Sniffin’ Sticks identification smell test (mSS-SIT), to evaluate the patient olfactory outcome using a Malay short version of the Questionnaire of Olfactory Disorders-Negative Statements (msQOD-NS), as well as to evaluate seropositive titre (IgG) response using automated serology method. Methods: Score for mSS-SIT was performed during the hospitalization, when patients had tested positive for SARS-CoV-2 (during COVID-19), and repeated after they had tested negative (after COVID-19). Also, each patient completed msQOD-NS and serology SARS-CoV-2 antibodies blood test was evaluated. Results: During COVID-19, 2 of our patients were anosmia (6.5%), 22 (70.9%) were hyposmia, and 7 (22.6%) were normosmia. We repeated mSS-SIT on these same patients after COVID-19, and none of these subjects were hyposmia or anosmia, as they achieved a score >12. All our patients had scored 21 using msQOD-NS, meaning no impact on quality of life as they had regained their normal olfactory function. In this study also, we obtained no correlation between smell test and seropositivity titre COVID-19, and antibody levels gradually decreased over time till 6 months and remained stable up to 12 months. Conclusion: From this study, we know full recovery of the sense of smell can be expected post-COVID-19 infection and COVID-19 antibody persists in the body up to 12 months of infection.
Can We Improve Confusion, Uremia, Respiratory Rate, Blood Pressure, Age >65 with Lactate and Procalcitonin to Predict Mortality in Pneumonia?
Authors: Urfalioglu Ahmet Burak , Yapici Satuk Bugra , Uzucek Durdu Mehmet , Yildiz Dervis , Sener Kemal , Kaya Adem , Avci Akkan , Yolcu Sadiye
Published: July 2023

Introduction: Pneumonia is a common diagnosis in the emergency department (ED). Some scoring systems such as Confusion, Uremia, Respiratory Rate, Blood Pressure, Age>65 (CURB-65) are used to determine the severity of this disease. We aimed to determine the best scoring system (CURB-65, serum lactate+CURB-65, serum procalcinonin+CURB-65) to predict the severity and 30-day mortality of pneumonia patients admitted to our ED. Methods: This study was planned as a prospective study. 480 community-acquired pneumonia patients admitted to our ED between February 1, 2020, and January 31, 2021, were included. CURB-65 score, CURB-65+lactate levels, and CURB65+procalcitonin levels were evaluated to predict disease severity. Results: A total of 480 pneumonia patients, 281 (58.5%) men and 199 (41.5%) women, with a mean age of 61.7 ± 19.06 years, were included in the study. The sensitivity/specificity pair and cut-off value of CURB-65 for 30-day mortality was 71.9/74.8%. These values were 68.5% and 61.9% for CURB-65+lactate (cut-off = 17.50) and 78.1% and 90.7% for CURB-65+procalcitonin (cut-off = 2.095). Discussion: Infectious diseases such as pneumonia, urinary tract infection, and sepsis are common reasons for ED presentations and may be fatal, especially in the elderly population. In such infectious diseases, it is difficult to predict the prognosis of the patients including discharge, hospitalization service, mortality probability in the EDs those are becoming much more crowded each day and several scoring systems have been improved. In this study, the highest sensitivity and specificity were determined in CURB-65+procalcitonin. Conclusion: CURB-65 is superior to CURB-65+lactate; however, CURB-65+procalcitonin is superior to both in predicting 30-day mortality.
Chronic Kidney Disease and Obesity
Authors: Hojs Radovan , Ekart Robert , Bevc Sebastjan , Vodošek Hojs Nina
Published: July 2023

There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of CKD, and end-stage renal disease (ESRD), also after adjustment for age, sex, race, smoking status, comorbidities, and laboratory tests. In the general population, obesity increases the risk of death. In nondialysis-dependent CKD patients, the association between body mass index and weight with mortality is controversial. In ESRD patients, obesity is paradoxically associated with better survival. There are only a few studies investigating changes in weight in these patients and in most weight loss was associated with higher mortality. However, it is not clear if weight change was intentional or unintentional and this is an important limitation of these studies. Management of obesity includes life-style interventions, bariatric surgery, and pharmacotherapy. In the last 2 years, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist and GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist were shown to be effective in managing weight loss in non-CKD patients, but we are awaiting results of more definitive studies in CKD patients.
Supporting Children Who Are English Language Learners Succeed in Their Early Literacy Development
Authors: Gillon Gail
Published: July 2023

Introduction: The Better Start Literacy Approach is an example of a multi-tiered system of support (MTSS) to facilitate children’s early literacy success. It is set within a strengths-based and culturally responsive framework for literacy teaching and is being implemented in over 800 English medium schools across New Zealand. This report focuses on how children identified at school entry as English Language Learners (ELL) responded to the Better Start Literacy Approach during their first year at school. Method: Using a matched control design, the growth in phoneme awareness, phoneme-grapheme knowledge, and oral narrative skills for 1,853 ELL was compared to a cohort of 1,853 non-ELL. The cohorts were matched for ethnicity (mostly Asian, 46% and Pacific, 26%), age (M = 65 months), gender (53% male), and socioeconomic deprivation index (82% in areas of mid to high deprivation). Results: Data analyses indicated similar positive growth rates for ELL and non-ELL from baseline to the first monitoring assessment following 10 weeks of Tier 1 (universal/class level) teaching. Despite demonstrating lower phoneme awareness skills at baseline, following 10 weeks of teaching, the ELL cohort performed similarly to non-ELL in non-word reading and spelling tasks. Predictors of growth analyses indicated that ELL from areas of low socioeconomic deprivation, who used a greater number of different words in their English story retells at the baseline assessment, and females made the most growth in their phonic and phoneme awareness development. Following the 10-week monitoring assessment, 11% of the ELL and 13% of the non-ELL cohorts received supplementary Tier 2 (targeted small group) teaching. At the next monitoring assessment (20 weeks post baseline assessment) the ELL cohort showed accelerated growth in listening comprehension, phoneme-grapheme matching and phoneme blending skills, catching up to their non-ELL peers. Discussion: Despite limitations of the dataset available, it provides one of the few insights into the response of ELL to Tier 1 and Tier 2 teaching in their first year at school. The data suggest that the Better Start Literacy Approach, which includes high-quality professional learning and development for teachers, literacy specialists, and speech-language therapists, is an effective approach toward developing foundational literacy skills for ELL. The important role speech-language therapists have in collaborating with class teachers to support children’s early literacy success within a MTSS framework is discussed.
Sarcoma Research with Cancer Registry Data: Data and Peculiarities of Germany in the Light of Other Countries
Authors: Zeissig Sylke Ruth , Emrich Katharina , Reinwald Fabian , Kasper Bernd , Kleihues-van Tole Kees , Justenhoven Christina , Wardelmann Eva , Hohenberger Peter
Published: July 2023

Introduction: Sarcomas are documented in population-based and in clinic-associated databases. This study evaluated the status quo regarding the potential and obstacles of cancer registry-based research on sarcomas exemplified by Germany in comparison to similar databases in the US and Europe. Completeness and quality of data are discussed based on statistical analyses of a pooled data set established for the German Cancer Congress 2020. Methods: We analyzed data derived from 16 German institutions (federal state cancer registries and some facility-based registries). Malignant sarcomas in adults diagnosed between 2000 and 2018 with information on histology were grouped according to the WHO classification of soft tissue and bone tumors. Descriptive analyses of the study population regarding the distribution of age, sex, histology, localization of primary tumors, and metastases were performed. Survival for the ten most frequent histological groups and UICC stages was evaluated according to Kaplan-Meier and Cox regression. Time interval between surgery and subsequent radiation was calculated. Results: The initial data set contained 35,091 sarcomas. After several steps of data cleaning, 28,311 patients with known sex and unambiguous assignment to a histological subgroup remained (13,682 women and 14,629 men). Between 40 and 54 years, women were more likely to develop sarcomas, whereas in the older age groups more men were affected. Gastrointestinal stromal tumors, fibroblastic, and myofibroblastic tumors, smooth muscle tumors (mostly non-uterine leiomyosarcomas), and adipocytic tumors represented 48% of all sarcomas. Preferential sites for fibrosarcomas were the limbs, the trunk, and the head and neck region. The liposarcoma occurred most frequently on the trunk and limbs. Distant primary metastases were mostly located in the lung (43%), followed by the liver (14%), and bones (13%). Vascular and smooth muscle tumors showed the worst survival prognosis (5-year survival: approx. 15%, median survival approx. 8–16 months), whereas in low stages, the probability of survival of many sarcoma patients was beyond 5 years. Adjuvant radiotherapy was applied within 90 days in 71% of patients (n = 2,534). Conclusion: Our results correspond to the data from the literature. However, a lack of data quality and completeness hampers further meaningful analyses, especially nonspecific or missing information about morphology and stage. Compared to some other countries, a comprehensive database is presently missing in Germany. However, currently, there are important efforts and legislative initiatives to create a comprehensive database on a national level within the near future.
Interstitial Brachytherapy for Hepatocellular Carcinoma: Analysis of Prognostic Factors for Overall Survival and Progression-Free Survival and Application of a Risk Stratification Model
Authors: Thormann Maximilian , Heitmann Franziska , Wrobel Vanessa , Heinze Constanze , March Christine , Hass Peter , Damm Robert , Surov Alexey , Pech Maciej , Omari Jazan
Published: July 2023

Introduction: Interstitial brachytherapy (iBT) is an effective treatment for hepatocellular carcinoma (HCC). Identification of prognostic factors is pivotal for patient selection and treatment efficacy. This study aimed to assess the impact of low skeletal muscle mass (LSMM) on overall survival (OS) and progression-free survival (PFS) of iBT in patients with HCC. Methods: For this single-center study, we retrospectively identified 77 patients with HCC who underwent iBT between 2011 and 2018. Follow-up visits were recorded until 2020. The psoas muscle area, psoas muscle index, psoas muscle density (MD), and the skeletal muscle gauge were assessed on the L3 level on pre-treatment cross-sectional CT scans. Results: Median OS was 37 months. 42 patients (54.5%) had LSMM. An AFP level of >400 ng/ml (hazard ratio [HR] 5.705, 95% confidence interval [CI]: 2.228–14.606, p = 0.001), BCLC stage (HR 3.230, 95% CI: 0.972–10.735, p = 0.026), and LSMM (HR 3.365, 95% CI: 1.490–7.596, p = 0.002) showed a relevant association with OS. Weighted hazard ratios were used to form a predictive risk stratification model with three groups: patients with low risk (median OS 62 months), intermediate risk (median OS 31 months), and high risk (median OS 9 months). The model showed a good prediction of 1-year mortality, with an AUC of 0.71. Higher MD was associated with better PFS (HR 0.920, 95% CI: 0.881–0.962, p < 0.001). Conclusion: In patients undergoing iBT for HCC, LSMM is associated with worse OS. A risk stratification model based on LSMM, AFP >400 ng/mL, and BCLC stage successfully predicted patient mortality. The model may support and enhance patient selection.
Identifying barriers and facilitators to the inclusion of older adults living in UK care homes in research: a scoping review
Authors: Nocivelli Brittany , Shepherd Victoria , Hood Kerenza , Wallace Carolyn , Wood Fiona
Published: July 2023

Background

With an ageing population, older adults will have more complex health and social care needs and many of these older adults will be living in care homes. Despite the growth in care home populations, care home residents are often excluded from research that could potentially benefit their care. The purpose of this scoping review is to explore resident-related barriers and facilitators to including older people living in UK care homes in research and to identify potential approaches to modify such barriers.

Method

The 6-stage scoping review methodology framework proposed by Arksey and O’Malley guided this review. Five electronic databases (MedLine, PsychINFO, Scopus, Web of Science, CINAHL) and grey literature were searched. Identified articles went through two levels of screening, and those deemed relevant were collated, summarised and reported using a thematic analysis approach.

Results

90 reports were eligible for inclusion and were synthesised into 7 themes and related subthemes: (1) research design; (2) understanding and beliefs about research (resident and care home staff); (3) communication; (4) relationships; (5) eligibility criteria (resident and care home); (6) preference-based decisions; and (7) care home staff and environment. Given the complex interplay of the factors identified, both direct and indirect factors were included.

Conclusions

A number of recurring barriers and facilitators to the inclusion of care home residents in research are reported. However, isolating resident-related barriers was complex as both direct and indirect factors must be considered as influential. Understanding the barriers and facilitators to inclusion will enable these factors to be addressed and increase the evidence-base for care provided to older people living in care homes.
Predictive and prognostic markers from endoscopic ultrasound with biopsies during definitive chemoradiation therapy in esophageal squamous cell carcinoma
Authors: Du Qingwu , Wu Xiaoyue , Zhang Kunning , Cao Fuliang , Zhao Gang , Wei Xiaoying , Guo Zhoubo , Li Yang , Dong Jie , Zhang Tian , Zhang Wencheng , Wang Ping , Chen Xi , Pang Qingsong
Published: July 2023

Introduction

Endoscopic ultrasound (EUS) may play a role in evaluating treatment response after definitive chemoradiation therapy (dCRT) for esophageal squamous cell carcinoma (ESCC). This study explored the prognostic markers of EUS with biopsies and developed two nomograms for survival prediction.

Methods

A total of 821 patients newly diagnosed with ESCC between January 2015 and December 2019 were reviewed. We investigated the prognostic value of the changes in tumor imaging characteristics and histopathological markers by an interim response evaluation, including presence of stenosis, ulceration, tumor length, tumor thickness, lumen involvement, and tumor remission. Independent prognostic factors of progression-free survival (PFS) and overall survival (OS) were determined using Cox regression analysis and further selected to build two nomogram models for survival prediction. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to respectively assess its discriminatory capacity, predictive accuracy, and clinical usefulness.

Results

A total of 155 patients were enrolled in this study and divided into the training (109 cases) and testing (46 cases) cohorts. Tumor length, residual tumor thickness, reduction in tumor thickness, lumen involvement, and excellent remission (ER) of spatial luminal involvement in ESCC (ER/SLI) differed significantly between responders and non-responders. For patients undergoing dCRT, tumor stage (P = 0.001, 0.002), tumor length (P = 0.013, 0.008), > 0.36 reduction in tumor thickness (P = 0.004, 0.004) and ER/SLI (P = 0.041, 0.031) were independent prognostic markers for both PFS and OS. Time-dependent ROC curves, calibration curves, and DCA indicated that the predicted survival rates of our two established nomogram models were highly accurate.

Conclusion

Our nomogram showed high accuracy in predicting PFS and OS for ESCC after dCRT. External validation and complementation of other biomarkers are needed in further studies.
Knockdown of RBM15 inhibits tumor progression and the JAK-STAT signaling pathway in cervical cancer
Authors: Zhang Chunnian , Gu Liqin , Xiao Juan , Jin Feng
Published: July 2023

Background

RNA binding motif protein 15 (RBM15), a writer of N6-methyladenosine (m6A) methylation, contributes significantly to the development of various tumors. However, the function of RBM15 in cervical cancer (CC) has not been determined.

Methods

Based on the GSE9750, GSE63514, and m6A datasets, m6A-related differentially expressed genes (DEGs) were screened out. The hub genes were identified by generating a Protein-Protein Interaction (PPI) network. RT-qPCR was conducted to assess the mRNA expression of hub genes. CCK8, scratch wound healing, and transwell assays were utilized to examine the influence of RBM15 on HeLa and SiHa cells. Tumor xenograft models were used to assess the effects of RBM15 on tumorigenesis. A mechanistic analysis of RBM15 in CC tumors was conducted using the GeneCards and Coxpresdb databases, followed by a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the pathway-related genes were subsequently validated using Western blotting.

Results

Five DEGs were screened, including WTAP, RBM15, CBLL1, and YTHDC2. Among them, WTAP, RBM15, CBLL1, and YTHDC2 were hub genes and can be used as biomarkers for CC. RBM15 expression was considerably increased, while WTAP, CBLL1, and YTHDC2 were significantly downregulated. Knockdown of RBM15 significantly suppressed the proliferation, invasion, and migration of CC cells and tumorigenesis. Moreover, knockdown of RBM15 significantly reduced the expression levels of proteins related to the JAK-STAT pathway.

Conclusions

Knockdown of RBM15 inhibited the progression of CC cells, which probably by inhibiting the JAK-STAT pathway pathway.
Nanoparticle delivery of TFOs is a novel targeted therapy for HER2 amplified breast cancer
Authors: Yang Xiaojing , Xu Yi , Fu Jie , Shen Zan
Published: July 2023

Purpose

The human EGFR2 (HER2) signaling pathway is one of the most actively studied targets in cancer transformation research. Ttriplex-forming oligonucleotides (TFOs) activate DNA damage and induce apoptosis. We aim to encapsulate TFO-HER2 with nano-particle ZW-128 to suppress breast cell growth in vitro and in vivo.

Experimental design

We designed a set of TFO fragments targeting HER2 and verified their effectiveness. We encapsulated TFO-HER2 in ZW-128 to form nano-drug TFO@ZW-128. Cell counting kit 8, flow cytometry, and western blotting were used to evaluate the effect of TFO@ZW-128 on cell proliferation and the expressions of related proteins. The ant-itumor effect of TFO@ZW-128 was evaluated in vivo using nude mice breast cancer model.

Results

TFO@ZW-128 had efficient cellular uptake in amplified HER2 breast cancer cells. TFO@ZW-128 showed an 80-fold increase in TFO utilization compared with TFO-HER2 in the nude mouse breast cancer model. Meanwhile, TFO@ZW-128 dramatically inhibited the growth of HER2-overexpressing tumors compared with TFO-HER2 (P < 0.05). Furthermore, TFO@ZW-128-induced cell apoptosis was in a p53-independent manner.

Conclusions

In this study, we designed nano-drug TFO@ZW-128, which has proven effective and non-toxic in targeted therapy for ectopic HER2-expressing tumors.
Exploration of spatiotemporal heterogeneity and socio-demographic determinants on COVID-19 incidence rates in Sarawak, Malaysia
Authors: Phang Piau , Labadin Jane , Suhaila Jamaludin , Aslam Saira , Hazmi Helmy
Published: July 2023

Background

In Sarawak, 252 300 coronavirus disease 2019 (COVID-19) cases have been recorded with 1 619 fatalities in 2021, compared to only 1 117 cases in 2020. Since Sarawak is geographically separated from Peninsular Malaysia and half of its population resides in rural districts where medical resources are limited, the analysis of spatiotemporal heterogeneity of disease incidence rates and their relationship with socio-demographic factors are crucial in understanding the spread of the disease in Sarawak.

Methods

The spatial dependence of district-wise incidence rates is investigated using spatial autocorrelation analysis with two orders of contiguity weights for various pandemic waves. Nine determinants are chosen from 14 covariates of socio-demographic factors via elastic net regression and recursive partitioning. The relationships between incidence rates and socio-demographic factors are examined using ordinary least squares, spatial lag and spatial error models, and geographically weighted regression.

Results

In the first 8 months of 2021, COVID-19 severely affected Sarawak’s central region, which was followed by the southern region in the next 2 months. In the third wave, based on second-order spatial weights, the incidence rate in a district is most strongly influenced by its neighboring districts’ rate, although the variance of incidence rates is best explained by local regression coefficient estimates of socio-demographic factors in the first wave. It is discovered that the percentage of households with garbage collection facilities, population density and the proportion of male in the population are positively associated with the increase in COVID-19 incidence rates.

Conclusion

This research provides useful insights for the State Government and public health authorities to critically incorporate socio-demographic characteristics of local communities into evidence-based decision-making for altering disease monitoring and response plans. Policymakers can make well-informed judgments and implement targeted interventions by having an in-depth understanding of the spatial patterns and relationships between COVID-19 incidence rates and socio-demographic characteristics. This will effectively help in mitigating the spread of the disease.
Transition models of care for type 1 diabetes: a systematic review
Authors: Zurynski Yvonne , Carrigan Ann , Meulenbroeks Isabelle , Sarkies Mitchell N. , Dammery Genevieve , Halim Nicole , Lake Rebecca , Davis Elizabeth , Jones Timothy W. , Braithwaite Jeffrey
Published: July 2023

Background

Managing the care regimen for Type 1 Diabetes is challenging for emerging adults, as they take on greater responsibility for self-management. A diverse range of models of care have been implemented to improve safety and quality of care during transition between paediatric and adult services. However, evidence about acceptability and effectiveness of these is limited. Our aim was to synthesise the evidence for transition models and their components, examine the health related and psychosocial outcomes, and to identify determinants associated with the implementation of person-centred models of transition care.

Method

We searched Medline, CINAHL, EMBASE and Scopus. Peer reviewed empirical studies that focused on T1D models of care published from 2010 to 2021 in English, reporting experimental, qualitative, mixed methods, and observational studies were included.

Results

Fourteen studies reported on health and psychosocial outcomes, and engagement with healthcare. Three key models of care emerged: structured transition education programs (6 studies), multidisciplinary team transition support (5 studies) and telehealth/virtual care (3 studies). Compared with usual practice, three of the six structured transition education programs led to improvements in maintenance of glycaemic control, psychological well-being, and engagement with health services. Four MDT transition care models reported improved health outcomes, and improved engagement with health services, however, three studies reported no benefit. Reduced diabetes related stress and increased patient satisfaction were reported by two studies, but three reported no benefit. Telehealth and virtual group appointments improved adherence to self-management and reduced diabetes distress but did not change health outcomes.

Conclusions

Although some health and psychosocial benefits are reported, the results were mixed. No studies reported on T1D transition model implementation outcomes such as acceptability, adoption, and appropriateness among clinicians or managers implementing these models. This gap needs to be addressed to support future adoption of successful models.
Tumor matrix stiffness provides fertile soil for cancer stem cells
Authors: Safaei Sadegh , Sajed Roya , Shariftabrizi Ahmad , Dorafshan Shima , Saeednejad Zanjani Leili , Dehghan Manshadi Masoumeh , Madjd Zahra , Ghods Roya
Published: July 2023

Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. CSCs are thought to be responsible for metastasis, tumor recurrence, chemotherapy resistance, and consequently poor clinical outcomes. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies. In this review, we discuss how the stiffness of the ECM is sensed by the cells and how the cells respond to this environmental change as well as the effect of matrix stiffness on CSCs characteristics and also the key malignant processes such as proliferation and EMT. Then, we specifically focus on how increased matrix stiffness affects CSCs in breast, lung, liver, pancreatic, and colorectal cancers. We also discuss how the molecules responsible for increased matrix stiffness and the signaling pathways activated by the enhanced stiffness can be manipulated as a therapeutic strategy for cancer.
Printing tissue-engineered scaffolds made of polycaprolactone and nano-hydroxyapatite with mechanical properties appropriate for trabecular bone substitutes
Authors: Yazdanpanah Zahra , Sharma Nitin Kumar , Raquin Alice , Cooper David M. L. , Chen Xiongbiao , Johnston James D.
Published: July 2023

Background

Bone tissue engineering, based on three-dimensional (3D) printing technology, has emerged as a promising approach to treat bone defects using scaffolds. The objective of this study was to investigate the influence of porosity and internal structure on the mechanical properties of scaffolds.

Methods

We fabricated composite scaffolds (which aimed to replicate trabecular bone) from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp) by extrusion printing. Scaffolds with various porosities were designed and fabricated with and without an interlayer offset, termed as staggered and lattice structure, respectively. Mechanical compressive testing was performed to determine scaffold elastic modulus and yield strength. Linear regression was used to evaluate mechanical properties as a function of scaffold porosity.

Results

Different relationships between mechanical properties and porosities were noted for the staggered and lattice structures. For elastic moduli, the two relationships intersected (porosity = 55%) such that the lattice structure exhibited higher moduli with porosity values greater than the intersection point; vice versa for the staggered structure. The lattice structure exhibited higher yield strength at all porosities. Mechanical testing results also indicated elastic moduli and yield strength properties comparable to trabecular bone (elastic moduli: 14–165 MPa; yield strength: 0.9–10 MPa).

Conclusions

Taken together, this study demonstrates that scaffolds printed from PCL/30% (wt.) nHAp with lattice and staggered structure offer promise for treating trabecular bone defects. This study identified the effect of porosity and internal structure on scaffold mechanical properties and provided suggestions for developing scaffolds with mechanical properties for substituting trabecular bone.
Axonal energy metabolism, and the effects in aging and neurodegenerative diseases
Authors: Yang Sen , Park Jung Hyun , Lu Hui-Chen
Published: July 2023

Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of aging (NDAs), such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. Glucose is the major brain fuel and glucose hypometabolism has been observed in brain regions vulnerable to aging and NDAs. Many neurodegenerative susceptible regions are in the topological central hub of the brain connectome, linked by densely interconnected long-range axons. Axons, key components of the connectome, have high metabolic needs to support neurotransmission and other essential activities. Long-range axons are particularly vulnerable to injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy is often an early sign of neurodegeneration. Recent studies ascribe axonal maintenance failures to local bioenergetic dysregulation. With this review, we aim to stimulate research in exploring metabolically oriented neuroprotection strategies to enhance or normalize bioenergetics in NDA models. Here we start by summarizing evidence from human patients and animal models to reveal the correlation between glucose hypometabolism and connectomic disintegration upon aging/NDAs. To encourage mechanistic investigations on how axonal bioenergetic dysregulation occurs during aging/NDAs, we first review the current literature on axonal bioenergetics in distinct axonal subdomains: axon initial segments, myelinated axonal segments, and axonal arbors harboring pre-synaptic boutons. In each subdomain, we focus on the organization, activity-dependent regulation of the bioenergetic system, and external glial support. Second, we review the mechanisms regulating axonal nicotinamide adenine dinucleotide (NAD+) homeostasis, an essential molecule for energy metabolism processes, including NAD+biosynthetic, recycling, and consuming pathways. Third, we highlight the innate metabolic vulnerability of the brain connectome and discuss its perturbation during aging and NDAs. As axonal bioenergetic deficits are developing into NDAs, especially in asymptomatic phase, they are likely exaggerated further by impaired NAD+homeostasis, the high energetic cost of neural network hyperactivity, and glial pathology. Future research in interrogating the causal relationship between metabolic vulnerability, axonopathy, amyloid/tau pathology, and cognitive decline will provide fundamental knowledge for developing therapeutic interventions.