bluuebunny/crossref_metadata_2025 huggingface dataset:
Amantadine therapy for Parkinson’s Disease: In Vivo Confocal Microscopy corneal findings, case report and revision of literature
Authors: Cennamo Michela , Dragotto Francesco , Favuzza Eleonora , Morelli Alberto , Mencucci Rita
Published: May 2022

Background

To report a case of a patient showing bilateral corneal opacities after amantadine chronic treatment for Parkinson’s Disease (PD) and corneal edema associated with intra-epithelial and -endothelial depositions. After amantadine discontinuation a complete clinical remission with only a partial ultrastructural corneal recovery was reported.

Case presentation

We describe a 78-year-old man with non-medical-responding bilateral corneal edema in treatment with systemic Amantadine for PD. In vivo confocal Microscopy (IVCM) analysis revealed hyperreflective particles at the epithelial level and expanded hyperreflective keratocyte and a disarrangement of stromal lamellae; endothelial cells showed hyperreflective intracellular inclusions in central and in peripheral areas with central polymegatism and pleomorphism. After 1 and 6 months the amantadine discontinuation, the absence of bilateral corneal edema and opacities were noted at the slit lamp examination, associated with the disappearance of epithelial and stromal abnormalities, but the persistence of endothelial hyperreflective deposits with a pleomorphism and polymegatism worsening at the IVCM exam.

Conclusion

The evaluation of a patient’s cornea 6 months after the discontinuation of systemic amantadine therapy showed a clinical complete remission, with a complete resolution of the bilateral corneal oedema. On the other hand, ultrastructurally, amantadine toxicity is a completely reversible phenomenon at the epithelial level; conversely IVCM showed persistent endothelial degradation.
Survival and predictors of asphyxia among neonates admitted in neonatal intensive care units of public hospitals of Addis Ababa, Ethiopia, 2021: a retrospective follow-up study
Authors: Getaneh Fekadeselassie Belege , sebsbie Girum , Adimasu Mekonen , Misganaw Natnael Moges , Jember Desalegn Abebaw , Mihretie Dires Birhanu , Abeway Shiferaw , Bitew Zebenay Workneh
Published: May 2022

Background

Globally, perinatal asphyxia (PNA) is a significant cause of most neonatal deaths. Similarly, the burden of birth asphyxia in Ethiopia remains high (22.52%) and has been noted the second leading cause of neonatal mortality. Thus, researches on survival status and predictors of perinatal asphyxia are critical to tackle it. Therefore, the current study intended to determine the survival status and predictors of asphyxia among neonates admitted in Neonatal Intensive Care Units of public hospitals, Addis Ababa, Ethiopia.

Methods

Hospital-based retrospective follow-up study was conducted in four selected public hospitals of Addis Ababa from January 2016 to December 2020. Data were collected using a pretested structured questionnaire. Epi-data 4.6 and STATA Version 16 was used for data entry and analysis, respectively. Kaplan–Meier survival curve, log-rank test and Median time were computed. To find the predictors of time to recovery, a multivariable Cox proportional hazards regression model was fitted, and variables with a P-value less than 0.05 were considered statistically significant. Finally, the Schoenfeld residual test was used to check overall model fitness.

Result

Four hundred eleven admitted asphyxiated babies were followed a total of 3062 neonate-days with a minimum of 1 h to a maximum of 28 days. The Overall incidence density rate of survival was 10 (95% CI: 0.08–0.11) per 100 neonate-days of observation with a median recovery time of 8 days (95% CI: 7.527–8.473). Low birth weight (Adjusted hazard ratio [AHR]: 0.67, 95% CI: 0.47–0.96), stage II hypoxic ischemic encephalopathy (HIE) (AHR: 0.70, 95% CI: 0.51–0.97), stage III HIE (AHR: 0.44, 95% CI: 0.27–0.71), seizure (AHR: 0.61, 95% CI: 0.38—0.97), thrombocytopenia (AHR: 0.44, 95% CI: 0.24–0.80) and calcium gluconate (AHR: 0.75, 95% CI: 0.58–0.99) were found to be independent predictors of time to recovery of asphyxiated neonates.

Conclusion

In the current findings, the recovery time was prolonged compared to others finding. This implies early prevention, strict monitoring and taking appropriate measures timely is mandatory before babies transferred into highest stage of HIE and managing complications are recommended to hasten recovery time and increase survival of neonates.
Sex-specific ranges and ratios for anogenital distance among Thai full-term newborns
Authors: Numsriskulrat Nattakarn , Srilanchakon Khomsak , Pronprechatham Chaiyat , Pornkunwilai Sopon , Supornsilchai Vichit
Published: May 2022

Introduction

Anogenital distance (AGD) is a marker of prenatal androgen exposure and a tool for assessment of differences of sex development. Data for AGD in newborns have been published, but these findings may not be applicable to Thai newborns.

Aim

To provide the sex-specific ranges for AGD in Thai full-term newborns.

Methods

A cross-sectional study was conducted in term newborns in Thailand, during 2016–2018. AGD was measured from anus to anterior base of penis (AGDAP) and to perineoscrotal junction (AGDAS) in males and from anus to clitoris (AGDAC) and to posterior fourchette (AGDAF) in females. AGD ratio is defined as AGDAS divided by AGDAP in males and AGDAF divided by AGDAC in females.

Results

A total of 364 newborns were studied (male 51.4%). The mean AGDAS, AGDAP and AGD ratio in males were 25.20 ± 4.80, 52.60 ± 6.90 and 0.48 ± 0.08 mm, respectively. The mean AGDAF, AGDAC, and AGD ratio in females were 16.50 ± 3.90, 42.60 ± 6.20 and 0.39 ± 0.08 mm, respectively. There were significant differences between AGDAS and AGDAF, AGDAP and AGDAC, and AGD ratio between males and females (p < 0.001). The AGDAS, AGDAP, AGDAF, AGDAC were correlated with birth weight and length, but AGD ratio showed no correlation.

Conclusion

The sex-specific ranges for AGD in Thai full-term newborns were determined. AGD ratio is a useful marker of prenatal androgen exposure since it differs between sexes, but constant between races and did not vary by body size.
Changes in the rankings of leading causes of death in Japan, Korea, and Taiwan from 1998 to 2018: a comparison of three ranking lists
Authors: Tai Shu-Yu , Cheon Soyeon , Yamaoka Yui , Chien Yu-Wen , Lu Tsung-Hsueh
Published: May 2022

Background

The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018.

Methods

We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard.

Results

The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of “garbage codes” into relevant specific COD in IHME list.

Conclusions

Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making.
Surgical treatment of recurrent intussusception induced by intestinal lymphoid hyperplasia in a child: is bowel resection always necessary? A case report
Authors: Wang Hui , Li Hongyan , Xin Wang , Xu Liandi , Zhang Guoqing , Yan Qingtao
Published: May 2022

Background

Intussusception recurrence (IR) induced by intestinal lymphoid hyperplasia (ILH) in children is rare, and surgical treatment is the final resort if IR is refractory to medications and non-surgical interventions. To date, only a few case reports have described surgical management of ILH-induced IR in children, all involving bowel resection regardless of whether there are bowel necrosis and perforation.

Case presentation

A 2-year-old boy was transferred to our department due to IR. His main complaint was abdominal pain. Color Doppler ultrasound confirmed ileocecal intussusception while no other abnormalities were found. A final diagnosis of IR with unknown causes was made. Repeated saline enema reductions and dexamethasone failed to cure the IR. Laparotomy was eventually performed after almost 10 episodes of IR. Intraoperatively, distal ileum thickening with palpable masses without bowel necrosis and perforation was noted. ILH was suspected and a biopsy of the affected intestine was performed. Histopathological analysis confirmed ILH. The intussusception was manually reduced, the terminal ileum and the ileocecal junction were fixed to the paralleled ascending colon and the posterior peritoneum respectively, and no bowel resection was performed. The postoperative recovery was uneventful and no IR was observed during over 5 years of follow-up.

Conclusions

As far as we are aware, this is the first report of successful surgical treatment of ILH-induced pediatric IR without bowel resection in a child. Our experience suggests bowel resection may be unnecessary if bowel necrosis and perforation are absent.
Clinicopathological study of gastric schwannoma and review of related literature
Authors: Zhong Zhihan , Xu Yuhao , Liu Junwei , Zhang Chengwu , Xiao Zunqiang , Xia Yan , Wang Yu , Wang Jianfeng , Xu Qiuran , Lu Yi
Published: May 2022

Background

This study aimed to investigate the clinical features, diagnostic criteria, treatment options, and prognosis of patients with gastric schwannoma (GS).

Methods

We collected the clinical data of all patients pathologically diagnosed with GS in Zhejiang Provincial People's Hospital from May 2012 to October 2021.

Results

A total of 26 cases of GS were analyzed clinicopathologically, where the sizes of the tumor were found to be in the range of 1–6 cm (mean: 3.16 cm, median: 3.05 cm). A computed tomography (CT) scan analysis revealed that most masses were either moderately progressive or uniformly enhanced. According to ultrasound gastroscopy results, most of them were hypoechoic masses. There were 23 cases of surgery and three cases of endoscopic submucosal tumor dissection. Immunohistochemistry demonstrated that S100 was positive in 26 patients, immunomarker SOX10 was positive in five, whereas CD34, CD117, and SMA were negative in most patients. CK (Pan), Dog-1, and Desmin were also found negative. All 26 cases were followed up after the conclusion of the study where no evidence of recurrence or metastasis was observed.

Conclusions

GS is a unique form of peripheral schwannoma. The diagnosis of this type of tumor depends on the pathology and immunohistochemistry of the individual. The key to treating this type of tumor is endoscopy and surgery. Follow up and related literature review showed that GS was a benign tumor with little possibility of malignant transformation.
Available prediction scores of conversion for laparoscopic rectal cancer surgery seem to be unsuitable for nowadays rectal cancer management
Authors: Sekkat Hamza , Souadka Amine , Courtot Lise , Rafik Ali , Amrani Laila , Benkabbou Amine , Peyrafort Pierre , Giger-Pabst Urs , Karam Elias , Mohsine Raouf , Majbar Anass M. , Ouaissi Mehdi
Published: May 2022

Introduction

This study aimed to externally evaluate the accuracy of four predictive scores for conversion to open surgery after rectal laparoscopic resection. None of the four scores achieved external validation previously.

Methods

This was a retrospective analysis of two prospectively maintained databases from two academic centers in France and Morocco. All consecutive patients who underwent laparoscopic resection for rectal adenocarcinoma between 2005 and 2020 were included. Logistic regression was used to assess the association between the factors present in the four scores and conversion. The accuracy of each score was assessed using the area under the curve (AUC). Observed and predicted conversion rates were compared for each score using the Chi-square goodness-of-fit test.

Results

Four hundred patients were included. There were 264 men (66%) with a mean age of 65.95 years (standard deviation 12.2). The median tumor height was 7 cm (quartiles 4–11) and 29% of patients had low rectal tumors. Conversion rate was 21.75%. The accuracy to predict conversion was low with an AUC lower than 0,62 for the four models. The observed conversion rates were significantly different from the predicted rates, except for one score.

Conclusions

The four models had low accuracy in predicting the conversion to open surgery for laparoscopic rectal resection. There is a need for new well-designed studies, analyzing more specific variables, in a multicentric design to ensure generalizability of the results for daily surgical practice.
A multilevel analysis of prevalence and factors associated with female child marriage in Nigeria using the 2018 Nigeria Demographic and Health Survey data
Authors: Bolarinwa Obasanjo Afolabi , Ahinkorah Bright Opoku , Okyere Joshua , Seidu Abdul-Aziz , Olagunju Olalekan Seun
Published: May 2022

Background

Globally, there has been a decline in female child marriage (FCM) from 1 in 4 girls married a decade ago to approximately 1 in 5 currently. However, this decline is not homogenous because some regions are still experiencing a high prevalence of FCM. As such, the United Nations reiterated the need for concentrated efforts towards ending FCM to avoid more than 120 million girls getting married before their eighteenth birthday by 2030. Following this, we examined the prevalence and factors associated with FCM in Nigeria using multi-level analysis.

Methods

We used cross-sectional data from the women’s file of the Nigeria Demographic and Health Survey (NDHS) conducted in 2018. A sample of 4143 young women aged 20–24 was included in the study. Our analysis involved descriptive, chi-square (χ2) and multi-level analyses. Results were presented in percentages, frequencies, and adjusted odds ratios (aOR) with their respective confidence intervals (CIs).

Results

The prevalence of FCM in 2018 was 65.30%. Young Muslim women aged 20–24 [aOR = 1.40; 95% CI (4.73–7.52)], those with parity between one and two [aOR = 5.96, 95% CI 4.73–7.52], those residing in North East [aOR = 1.55; 95% CI (1.19–2.10)] and North West [aOR = 1.59; 95% CI (1.18–2.16)] had a higher odd of practicing FCM respondents with secondary education and above [aOR = 0.36; 95% CI (0.29–0.46)], those within the richer wealth index [aOR = 0.35; 95% CI (0.23–0.54)] and young women living in communities with high literacy level [aOR = 0.74; 95% CI (0.59–0.92)] were less likely to get married before age 18 years.

Conclusion

Our findings indicate that FCM is high in Nigeria. Formal education, being rich and living in communities with high literacy levels were some protective factors that can be strengthened to ensure that FCM is reduced or eliminated in Nigeria. On the other hand, residing in North-East or North-West and having children between one and two were some prevailing factors that exacerbated the odds of experiencing FCM in Nigeria. Therefore, attention should be channelled towards mitigating these prevailing negative factors.
On the job training in the dissection room: from physical therapy graduates to junior anatomy instructors
Authors: Peleg Smadar , Yona Tomer , Almog Yuval , Barash Alon , Pelleg-Kallevag Ruth
Published: May 2022

Background

 The training of near-peer (NP) teachers and junior faculty instructors received major attention as a possible solution for the shortage of experienced anatomy instructors in faculties of medicine and health professions. Several studies described the training of NP teachers and junior instructors (≤ 2 years of teaching experience) using various methods. However, few publications include On the Job Training (OJT), which enables reflection and performance evaluation and encourages professionals to cope with their blind spots. Previous publications describing OJT did not include formal observation of the NP teacher or junior instructor. Therefore, this study aimed to present a novel approach to OJT inclusion during prosection laboratories based on the Lewinian experiential model.

Methods

 Eight physical therapy (PT) graduates were recruited as junior anatomy instructors into the prosection laboratories. All participated in a unique training program during two consecutive academic years (2017, 2018) and received OJT during the teaching sessions. Two questionnaires were filled out to evaluate the educational impact of the training program. Eighty-three first-year PT students participated in prosection laboratories in anatomy taught by junior instructors, and filled out a questionnaire evaluating the performance of both junior and senior instructors. In addition, we compared the final grades in anatomy obtained by students taught by senior instructors to the grades of those taught by junior instructors.

Results

 Each junior anatomy instructor participated in four OJT sessions. Based on self-reported measures, all professional and didactic aspects of the training program received a median score of 4.5 or higher on a five-point Likert scale. Students obtained similar grades in anatomy when taught by junior instructors compared with senior ones, and were similarly satisfied from the teaching performance of both senior and junior anatomy instructors.

Conclusions

 OJT is applicable in a small-sized PT program facing a shortage of anatomy instructors. Including junior anatomy instructors in prosection laboratories for PT students is a viable solution to the shortage of experienced anatomy instructors. Further study, involving a larger cohort with a longer follow up will strengthen the preliminary results presented here.
Developing a best practice framework for clinical competency education in the traditional East-Asian medicine curriculum
Authors: Han Sang Yun , Lee Seung-Hee , Chae Han
Published: May 2022

Background

While clinical competency is crucial for traditional East-Asian medical education, available studies on the educational system for fostering clinical performance are scarce. This study aimed to review the educational system, curriculum, facilities, and management of current traditional East-Asian medicine in a well-established university of Korea and develop a Best Practice Framework (BPF) of clinical competency education.

Methods

The clinical competency education system in Pusan National University School of Korean Medicine was systematically described through 5 steps of governance of the educational system, competency of the graduates, educational resources, assessment strategies and tools, and gaps in the curriculum. We also reviewed the experiences in education and the points to be improved.

Results

The Office of Traditional Korean Medicine Education governs the development, implementation, and evaluation of the educational curriculum for cultivating students’ clinical competency. Medical students have undertaken 39 modules of clinical biomedicine and 21 of traditional medicine during the clinical clerkship courses in an affiliated hospital, Clinical Skill Practice Center, clinical research center, practice lab for medical herb, and other locations. After training, 15 modules of simulated clinical training using standardized patients, students’ clinical competency are evaluated by a Clinical Performance Test using a Clinical Performance Examination (CPX) and an Objective Structured Clinical Examination (OSCE) for biomedical and traditional medical skills.

Conclusions

A clinical competency framework is required for a qualified physician of traditional East-Asian medicine. This study reviewed the current well-organized educational system of Korean traditional medicine in detail, which can be used for the BPF of competency-based clinical education. We expect the current study to be a representative reference for establishing an educational system of traditional medicine such as acupuncture and medical herbs in other countries.
Nursing students’ development of using physical assessment in clinical rotation—a stimulated recall study
Authors: Byermoen Kirsten Røland , Eide Tom , Egilsdottir H. Ösp , Eide Hilde , Heyn Lena Günterberg , Moen Anne , Brembo Espen Andreas
Published: May 2022

Background

The overall aim of this study was to explore third-year bachelor nursing students’ stimulated recall reflections on their physical assessment competence development. The choice of learning strategies in nursing education seems to have great impact on nursing students’ use of physical assessment skills while in clinical rotation. There is a need to explore nursing students’ learning processes related to the use of physical assessments.

Methods

Explorative qualitative design using a triangulation of data collection methods. Nine final-year nursing students’ physical assessment performances during patient encounters were audio-taped and observed. Shortly after, an individual stimulated recall interview based on the audio-recorded patient encounter and observation notes was conducted. A two-fold analysis was conducted: 1) analysis of students’ performed assessments, and 2) phenomenological hermeneutical analysis of the stimulated recall interviews.

Results

Nursing students assessments shifted from a checklist approach to a symptom-based, more holistic and person-centred approach, emphasizing conversation as part of their assessments. The nursing students also reported that a safe and stimulating learning environment was a prominent feature for their continuing development. Learning from skilled role models with expectations to them using physical assessment skills facilitated their continuing skills appliance, interprofessional communication and reflective practice.

Conclusions

This study contribute with a novel, comprehensive and in-depth description of what influenced nursing students’ learning processes experiences of using physical assessment skills during clinical rotation. The results reveal the need for targeted course designs by implementing scaffolded learning activities in practical and theoretical courses aimed at strengthening students’ learning of physical assessment skills—building upon and emphasizing their prior knowledge and competence, which may lead to more confident registered nurses and promote patient safety in different health care contexts. We propose using stimulated recall systematically as a novel reflective learning activity in nursing education to foster clinical reasoning and metacognition skills and achieve deep learning.
Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review
Authors: Shafi Ovais , Siddiqui Ghazia
Published: May 2022

Background

Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.

Methods

Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes.

Results

The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression.

Conclusion

Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.
Unusual site of pseudomyxoma peritonei recurrence after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a case report of intraluminal disease manifestation in the small bowel
Authors: Rauwerdink Paulien , Brosens Lodewijk A. A. , van Diepen Karin K. , Ghedri Okan N. , Kranenburg Onno , Boerma Djamila , Witkamp Arjen J. , van Grevenstein Helma M. U.
Published: May 2022

Background

Pseudomyxoma peritonei (PMP) is an uncommon clinical condition characterized by the presence of mucinous ascites, mainly induced by perforated appendiceal mucinous neoplasms (AMN). The peritoneal surface of the small bowel is usually spared from disease manifestation due to peristaltic movements. Mucinous tumours can disseminate as PMP on the entire peritoneum, but are rarely intraluminal. For the first time in literature, we report a case of intraluminal PMP involving the ileum.

Case presentation

A 75-year-old male was treated for perforated AMN and disseminated PMP with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. During follow-up, the patient developed intraperitoneal recurrence together with intraluminal depositions in the ileum, both disease manifestations with identical KRAS and SMAD4 mutations. Hereafter, the patient was treated with palliative care.

Conclusion

This case illustrates the variation in the biological and clinical behaviour of this rare disease. Clinicians should be aware of unusual tumour distribution patterns of PMP, including the presence of mucinous tumour within the small bowel.
Multiple endocrine neoplasia type 1 involving both the liver and lung: a case report
Authors: Lai Jianlin , Huang Yangyang , Wu Junyi , Cheng Hui , Qiu Funan
Published: May 2022

Background

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant tumor syndrome with a high degree of heterogeneity in clinical phenotypes, generally involving the parathyroid, anterior pituitary, and enteropancreas. In recent years, several new insights into the clinical features of MEN1 have been reported in the literature. However, it is not clear whether MEN1-associated primary tumors can occur in the liver.

Case presentation

We report the case of a 52-year-old man with multiple endocrine neoplasia type 1 diagnosed by genetic sequencing. After uniportal thoracoscopic right middle lobectomy, laparoscopic radical resection of the liver tumors, and radiofrequency ablation of the parathyroid space, the parathyroid hormone level decreased from 177 pg/ml to a normal level (20 pg/ml). No local tumor recurrence was observed during a follow-up of 5 months.

Conclusion

We report the first case of MEN1 with simultaneous liver and lung involvement in which the patient underwent radical resection of the tumors, and we propose the possibility that the liver and other nonendocrine organs may also develop diseases associated with MEN1; although, this view needs further verification. Gene detection has crucial clinical significance for guiding diagnosis and treatment.
Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites
Authors: Luo Ning , Sulaiman Zubaidan , Wang Chunyan , Ding Jinye , Chen Yingying , Liu Biting , Cheng Zhongping , Liu Shupeng
Published: May 2022

Purpose

As a common complication of epithelial ovarian cancer (EOC), malignant ascites contributes to the peritoneal metastasis of EOC. CircRNAs play essential roles in tumor metastasis. However, no circRNAs have been reported to be involved in EOC peritoneal metastasis via ascites.

Methods

Total of 22 samples from 9 EOC patients containing primary lesions (T), tumor cells from ascites (ASC), and metastatic lesions (M) were included for RNA sequencing to identify differentially expressed circRNAs and mRNAs among different tumors. Bioinformatic analyses, including single-sample Gene Set Enrichment Analysis and soft cluster analysis, were performed to find circRNAs potentially correlated with ascitic metastasis. Wound healing and transwell analysis were performed to evaluate tumor cells metastasis in vitro. Quantitative real-time PCR and western-blot were used for gene expression evaluation.

Results

According to transcriptomic analysis, ASC showed mesenchymal phenotype while T and M showed epithelial phenotype. 10 circRNAs were differentially expressed among ASC, T, and M. Among them, hsa_circ_0000497 and hsa_circ_0000918 were significantly up-regulated in ASC. Functional analysis showed that both hsa_circ_0000497 and hsa_circ_0000918 promoted metastasis of EOC via epithelial-mesenchymal transition (EMT) in vitro. The regulatory network construction identified 8 miRNAs and 19 mRNAs, and 7 miRNAs and 17 mRNAs as potential downstream target genes of hsa_circ_0000497 and hsa_circ_0000918, respectively, which may play pivotal roles in EOC ascitic metastasis.

Conclusions

circRNAs (hsa_circ_0000497 and hsa_circ_0000918) contribute to metastasis of EOC via ascites by regulating EMT. These circRNAs may serve as novel potential therapeutic targets or prognostic biomarkers for EOC peritoneal metastasis.
Patient-derived xenograft (PDX) models, applications and challenges in cancer research
Authors: Abdolahi Shahrokh , Ghazvinian Zeinab , Muhammadnejad Samad , Saleh Mahshid , Asadzadeh Aghdaei Hamid , Baghaei Kaveh
Published: May 2022

The establishing of the first cancer models created a new perspective on the identification and evaluation of new anti-cancer therapies in preclinical studies. Patient-derived xenograft models are created by tumor tissue engraftment. These models accurately represent the biology and heterogeneity of different cancers and recapitulate tumor microenvironment. These features have made it a reliable model along with the development of humanized models. Therefore, they are used in many studies, such as the development of anti-cancer drugs, co-clinical trials, personalized medicine, immunotherapy, and PDX biobanks. This review summarizes patient-derived xenograft models development procedures, drug development applications in various cancers, challenges and limitations.
An optimized method for the isolation of urinary extracellular vesicles for molecular phenotyping: detection of biomarkers for radiation exposure
Authors: Hinzman Charles P. , Jayatilake Meth , Bansal Sunil , Fish Brian L. , Li Yaoxiang , Zhang Yubo , Bansal Shivani , Girgis Michael , Iliuk Anton , Xu Xiao , Fernandez Jose A. , Griffin John H. , Ballew Elizabeth A. , Unger Keith , Boerma Marjan , Medhora Meetha , Cheema Amrita K.
Published: May 2022

Background

Urinary extracellular vesicles (EVs) are a source of biomarkers with broad potential applications across clinical research, including monitoring radiation exposure. A key limitation to their implementation is minimal standardization in EV isolation and analytical methods. Further, most urinary EV isolation protocols necessitate large volumes of sample. This study aimed to compare and optimize isolation and analytical methods for EVs from small volumes of urine.

Methods

3 EV isolation methods were compared: ultracentrifugation, magnetic bead-based, and size-exclusion chromatography from 0.5 mL or 1 mL of rat and human urine. EV yield and mass spectrometry signals (Q-ToF and Triple Quad) were evaluated from each method. Metabolomic profiling was performed on EVs isolated from the urine of rats exposed to ionizing radiation 1-, 14-, 30- or 90-days post-exposure, and human urine from patients receiving thoracic radiotherapy for the treatment of lung cancer pre- and post-treatment.

Results

Size-exclusion chromatography is the preferred method for EV isolation from 0.5 mL of urine. Mass spectrometry-based metabolomic analyses of EV cargo identified biochemical changes induced by radiation, including altered nucleotide, folate, and lipid metabolism. We have provided standard operating procedures for implementation of these methods in other laboratories.

Conclusions

We demonstrate that EVs can be isolated from small volumes of urine and analytically investigated for their biochemical contents to detect radiation induced metabolomic changes. These findings lay a groundwork for future development of methods to monitor response to radiotherapy and can be extended to an array of molecular phenotyping studies aimed at characterizing EV cargo.
Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma
Authors: Keyhanian Kianoosh , Phillips William J. , Yeung Benjamin S. , Gomes Marcio , Lo Bryan , Sekhon Harmanjatinder S.
Published: May 2022

Background

Neuroendocrine (NE) differentiation is widely studied in non-small cell lung carcinomas (NSCLC) however, its significance remains unclear in basaloid squamous cell carcinomas (B-SqCC). This study aims to assess the extent of NE differentiation in B-SqCC and characterize the underlying molecular process.

Methods

This study evaluated resected B-SqCC, small cell lung cancer (SCLC) and poorly differentiated SqCC (PD-SqCC) from 2005 to 2020 at the Ottawa Hospital. Samples were subject to pathological review, immunohistochemistry (IHC) and survival analysis. Gene expression analysis was performed on B-SqCC samples exhibiting NE+ and NE- regions (paired samples) to identify differentially expressed genes (DEGs). These DEGs were subsequently validated in unpaired B-SqCC and TCGA samples.

Results

B-SqCC cases were more likely to exhibit nuclear molding, resetting and peripheral palisading than PD-SqCC. B-SqCC were also more likely to demonstrate NE differentiation compared to PD-SqCC (p = 0.006). Pure basaloid squamous cell carcinoma (PB-SqCC) experienced poorer disease-free survival (HR = 3.12, p = 0.043) adjusted for stage.

Molecular characterization of paired B-SqCC samples demonstrated DEGs implicated in NOTCH signaling, SCLC and pulmonary neuroendocrine differentiation. Hierarchical clustering using discovered DEGs in unpaired B-SqCC samples distinguished tumors based on NE status (p = 0.048). Likewise, clustering The Cancer Genome Atlas (TCGA) samples with DEGs distinguished B-SqCC from SqCC samples (p = 0.0094).

Conclusion

This study provides IHC and molecular evidence of significant NE-differentiation in B-SqCC and demonstrates their aggressive clinical behavior. These findings suggest that B-SqCC are biologically distinct from SqCC and share characteristics with SCLC.
Co-occurrence of relapsing polychondritis and autoimmune thyroid diseases
Authors: Nakajima Toshiki , Yoshifuji Hajime , Yamano Yoshihisa , Yurugi Kimiko , Miura Yasuo , Maekawa Taira , Yoshida Tsuneyasu , Handa Hiroshi , Ohmura Koichiro , Mimori Tsuneyo , Terao Chikashi
Published: May 2022

Background

Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed the clinical and genetic profiles of patients in whom these diseases co-occur.

Methods

We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1, and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD.

Results

The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p = 2.44 × 10–7, binomial test). RP patients with GD tended to have nasal involvement (p = 0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p = 0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP.

Conclusions

Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 characterize the subset of RP patients with GD, which may guide attempts to characterize a distinct subtype of RP for precision medicine.
Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries
Authors: Magner Martin , Almássy Zsuzsanna , Gucev Zoran , Kieć-Wilk Beata , Plaiasu Vasilica , Tylki-Szymańska Anna , Zafeiriou Dimitrios , Zaganas Ioannis , Lampe Christina
Published: May 2022

Background

Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries. Aim of this statement is to provide evidence-based guidance for the enzyme replacement treatment of Morquio A patients, harmonizing recommendations from published guidelines with the real-life clinical practice in the Central and South-Eastern European region.

Participants

The Consensus Group, convened by 8 Steering Committee (SC) members from 7 Central and South-Eastern European countries, consisted of a multidisciplinary group of 17 experts in the management of MPS in Central and South-Eastern Europe.

Consensus process

The SC met in a first virtual meeting with an external scientific coordinator, to discuss on clinical issues to be analyzed in guidance statements. Statements were developed by the scientific coordinator, evaluated by the SC members in a first modified-Delphi voting and adapted accordingly, to be submitted to the widest audience in the Consensus Conference. Following discussion and further modifications, all participants contributed to a second round of modified-Delphi voting.

Results

Nine of ten statements, concerning general guidelines for management of MPS IVA patients and specific recommendations for treatment, received final consensus.

Conclusions

European guidelines and evidence-based recommendations for Morquio A patients should be considered in the real life of Central and South-Eastern European countries and adapted to unique clinical practice approaches and criteria for patients’ access to treatment and reimbursement in the region.
Fisetin-induced cell death in human ovarian cancer cell lines via zbp1-mediated necroptosis
Authors: Liu Yaxian , Cao Hongwen , Zhao Yanhui , Shan Lijuan , Lan Shuhai
Published: May 2022

Background

Among reproductive cancers, ovarian cancer leads to the highest female mortality rate. Fisetin, a natural flavonoid, exerts pharmacological effects, inhibiting cancer growth with various origins. Although multiple mechanisms are involved in regulating cell death, it is still unclear whether and how fisetin exhibits anticancer effects on ovarian cancer. The present study aimed to evaluate cell apoptotic and necroptotic processes occurring in ovarian carcinoma (OC) cell lines induced by fisetin.

Methods

Cell growth was evaluated by MTT assay in OC cell lines treated with or without fisetin. Annexin V/propidium iodide staining followed by flow cytometry was used to characterize fisetin-induced cell death. The apoptotic process was suppressed by z-VAD intervention, and cell necroptosis was assessed by introducing ZBP1-knockdown OC cell lines coupled with fisetin intervention. The expression of necroptosis-related mediators and the migration capability of the respective cells were evaluated by Western blotting and in vitro cell invasion assay.

Result

Fisetin successfully reduced cell growth in both OC cell lines in a dose-dependent manner. Both apoptosis and necroptosis were induced by fisetin. Suppression of the cell apoptotic process failed to enhance the proliferation of fisetin-treated cells. The induced cell death and robust expression of the necroptotic markers RIP3 and MLKL were alleviated by knocking down the expression of the ZBP1 protein in both OC cell lines.

Conclusion

The present study provided in vitro evidence supporting the involvement of both apoptosis and necroptosis in fisetin-induced OC cell death, while ZBP1 regulates the necroptotic process via the RIP3/MLKL pathway.
Wip1 suppresses angiogenesis through the STAT3-VEGF signalling pathway in serous ovarian cancer
Authors: Yin Sheng , Yang Lina , Zheng Yiyan , Zang Rongyu
Published: May 2022

Multifaceted functions of the so-called “oncogene” Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo. Mechanistic studies indicated that overexpression of Wip1 decreased the expression of VEGF at both the protein and mRNA levels and that the inhibitory effect was mediated by dephosphorylation of STAT3 at Ser727. Our study uncovered the role of Wip1 in SOC and provides a novel therapeutic strategy for suppressing angiogenesis.
Refining colorectal cancer classification and clinical stratification through a single-cell atlas
Authors: Khaliq Ateeq M. , Erdogan Cihat , Kurt Zeyneb , Turgut Sultan Sevgi , Grunvald Miles W. , Rand Tim , Khare Sonal , Borgia Jeffrey A. , Hayden Dana M. , Pappas Sam G. , Govekar Henry R. , Kam Audrey E. , Reiser Jochen , Turaga Kiran , Radovich Milan , Zang Yong , Qiu Yingjie , Liu Yunlong , Fishel Melissa L. , Turk Anita , Gupta Vineet , Al-Sabti Ram , Subramanian Janakiraman , Kuzel Timothy M. , Sadanandam Anguraj , Waldron Levi , Hussain Arif , Saleem Mohammad , El-Rayes Bassel , Salahudeen Ameen A. , Masood Ashiq
Published: May 2022

Background

Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells.

Results

Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance.

Conclusions

Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.
Apolipoprotein C-III in patients with systemic lupus erythematosus
Authors: Martín-González Candelaria , Ferrer-Moure Carmen , Carlos Quevedo-Abeledo Juan , de Vera-González Antonia , González-Delgado Alejandra , Sánchez-Martín Julio , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: May 2022

Background

Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease.

Methods

This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features.

Results

Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 [95% CI 0.02–0.19] mg/dl, 0.020) and Katz severity (beta coef. 0.11 [95% CI 0.03–0.19] mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 [95% CI 0.05–0.08] mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3.

Conclusion

Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.