bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe hypercalcemia caused by parathyroid hormone in a rectal cancer metastasis: a case report
Authors: Brun Vegard Heimly , Knutsen Erik , Stenvold Helge , Halvorsen Hanne 
Published: January 2021

Abstract
Background
Hypercalcemia of malignancy is relatively common in several cancers. However, in colorectal cancer, paraneoplastic phenomena that cause hypercalcemia is uncommon. In the few cases that are reported, secretion of parathyroid hormone-related peptide mediates the effect. We describe the first case of severe hypercalcemia mediated by intact parathyroid hormone secretion from a bone metastasis of colorectal origin. This was a diagnostic and therapeutic challenge.

Case presentation
A 68-year-old male treated for rectal adenocarcinoma 10 years earlier developed a bone metastasis. After initial treatment of the metastasis with surgery and irradiation, he developed a relapse with severe hypercalcemia and corresponding elevated parathyroid hormone levels. The workup showed no signs of parathyroid adenomas, but the metastasis produced intact parathyroid hormone. The hypercalcemia was successfully treated by irradiation and osteoclast inhibitor, and the patient received chemotherapy. Survival was 24 months from the onset of hypercalcemia.

Conclusions
Proper diagnosis of the uncommon endocrine disturbance allowed targeted therapy and avoidance of neck exploration for wrongly suspecting primary hyperparathyroidism. Intact parathyroid hormone should be measured in cases of malignant hypercalcemia.
Upfront F18-choline PET/CT versus Tc99m-sestaMIBI SPECT/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2
Authors: Quak Elske , Lasne Cardon Audrey , Ciappuccini Renaud , Lasnon Charline , Bastit Vianney , Le Henaff Véronique , Lireux Barbara , Foucras Gauthier , Jaudet Cyril , Berchi Celia , Grellard Jean-Michel , Lequesne Justine , Clarisse Bénédicte , Bardet Stéphane 
Published: January 2021

Abstract
Background
The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society.

Methods
We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1.

Discussion
FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications.
In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs.

Trial registration
NCT04040946, registered August 1, 2019.
Protocol version
Version 2.1 dated from 2020/04/23.
Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report
Authors: Gezer Emre , Çetinarslan Berrin , Karakaya Dilek , Cantürk Zeynep , Selek Alev , Sözen Mehmet , İşgören Serkan 
Published: January 2021

Abstract
Background
Neuroendocrine tumors (NETs) are rare tumors harboring overexpression of somatostatin receptors (SSTRs) on their cell membrane. Because some organs, such as the spleen, adrenal glands and liver, physiologically express SSTR, it might be challenging to distinguish some pancreatic NETs located in the pancreatic tail from the accessory spleen next to the splenic hilum. In this manuscript, we report a case with hypoglycemia attack and 2 different masses displayed by Gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT).

Case presentation
A 63-year-old woman presented to the hospital with confusion and profuse sweating. Biochemical diagnosis of insulinoma was established. 68Ga-DOTATATE PET/CT revealed two masses with increased tracer uptake located adjacent to the splenic hilum and inferior pole of the spleen which were initially reported as two separate accessory spleens. Then, 99mTc-labelled heat-denaturated red blood cell (99mTc-HDRBC) scintigraphy-single-photon emission computed tomography (SPECT)/CT was performed to distinguish a NET in the pancreatic tail from accessory spleen at the splenic hilum. Enhanced tracer uptake remained in the inferior pole of spleen, but not in the splenic hilum. The lesions were suggestive of insulinoma in the pancreatic tail and an accessory spleen adjacent to the inferior pole of the spleen.

Conclusion
Approximately 10% of the population have an accessory spleen which can show similar imaging characteristics with pancreatic NETs, especially if located in the pancreatic tail. In our presented case, 99mTc-HDRBC scintigraphy-SPECT/CT is a useful nuclear medicine method to differentiate a NET in the pancreatic tail from accessory spleen at the splenic hilum which may avoid unnecessary surgeries in the presence of enhanced tracer uptake or vice versa.
Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial
Authors: Chae Min Suk , Lee Mihyun , Choi Min Ho , Park Je Uk , Park Misun , Kim Young Hoon , Choi Hoon , Joo Jin , Moon Young Eun 
Published: January 2021

Abstract
Background
Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.

Methods
This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL.

Results
Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.

Conclusion
As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.
Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2&ltype=my&rtype=my.
Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway
Authors: Lu Xinhua , Xu Chenyang , Xu Zhexuan , Lu Chunya , Yang Rui , Zhang Furui , Zhang Guojun 
Published: January 2021

Abstract
Background
Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear.

Methods
We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines.

Results
PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells.

Conclusions
PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.
Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma
Authors: Li Hui , Bi Qianyu , Cui Hongxia , Lv Chuanfeng , Wang Meng 
Published: January 2021

AbstractBackgroundAsthma is a chronic inflammatory disease characterized by airway remodeling and inflammation. Rhynchophylline is a kind of indole alkaloid isolated fromUncaria rhynchophylla. Here we investigated the effect of rhynchophylline on autophagy in asthma.MethodsA mice model of asthma was established by ovalbumin challenge. Histopathological changes were assessed by hematoxylin-eosin staining, periodic acid-schiff staining and Masson staining. The levels of IgE in serum, interleukin-6 and interleukin-13 in bronchoalveolar lavage fluid, as well as the activities of superoxide dismutase and catalase in lung tissues were detected. The expression of autophagy-related genes and Janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 signal was detected by western blot and immunofluorescence. Airway smooth muscle cells (ASMCs) were isolated, and the effect rhynchophylline on autophagy in ASMCs was explored.ResultsOur data showed that rhynchophylline treatment alleviated inflammation, airway remodeling, and oxidative stress in asthma. In addition, autophagy, which was implicated in asthma, was suppressed by rhynchophylline with decreased level of autophagy-related proteins. Furthermore, rhynchophylline suppressed the JAK2/STAT3 signaling pathway, which was activated in asthma. In vitro study showed that rhynchophylline suppressed ASMC autophagy through suppressing the activation of JAK2/STAT3 signal.ConclusionsOur study demonstrated that rhynchophylline can alleviate asthma through suppressing autophagy in asthma, and that JAK2/STAT3 signal was involved in this effect of rhynchophylline. This study indicates that rhynchophylline may become a promising drug for the treatment of asthma.
Norwogonin attenuates hypoxia-induced oxidative stress and apoptosis in PC12 cells
Authors: Jing Linlin , Gao Rongmin , Zhang Jie , Zhang Dongmei , Shao Jin , Jia Zhengping , Ma Huiping 
Published: January 2021

Abstract
Background
Norwogonin is a natural flavone with three phenolic hydroxyl groups in skeletal structure and has excellent antioxidant activity. However, the neuroprotective effect of norwogonin remains unclear. Here, we investigated the protective capacity of norwogonin against oxidative damage elicited by hypoxia in PC12 cells.

Methods
The cell viability and apoptosis were examined by MTT assay and Annexin V-FITC/PI staining, respectively. Reactive oxygen species (ROS) content was measured using DCFH-DA assay. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and antioxidant enzyme levels were determined using commercial kits. The expression of related genes and proteins was measured by real-time quantitative PCR and Western blotting, respectively.

Results
We found that norwogonin alleviated hypoxia-induced injury in PC12 cells by increasing the cell viability, reducing LDH release, and ameliorating the changes of cell morphology. Norwogonin also acted as an antioxidant by scavenging ROS, reducing MDA production, maintaining the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and decreasing the expression levels of HIF-1α and VEGF. In addition, norwogonin prevented cell apoptosis via inhibiting the expression levels of caspase-3, cytochrome c and Bax, while increasing the expression levels of Bcl-2 and the ratio of Bcl-2/Bax.

Conclusions
Norwogonin attenuates hypoxia-induced injury in PC12 cells by quenching ROS, maintaining the activities of antioxidant enzymes, and inhibiting mitochondrial apoptosis pathway.
The effectiveness and safety of Tai Chi for patients with essential hypertension: study protocol for an open-label single-center randomized controlled trial
Authors: Li Yuxi , Zhong Dongling , Dong Chao , Shi Lihong , Zheng Yaling , Liu Yongguo , Li Qiaoqin , Zheng Hui , Li Juan , Liu Tianyu , Jin Rongjiang 
Published: January 2021

Abstract
Background
Evidence showed that Tai Chi may have beneficial effects among hypertensive individuals, although the results are not convincing. We aim to conduct a high-quality clinical trial with 24-h BP measurement to provide robust evidence of Tai Chi for essential hypertension.

Methods
This is an open-label single-center randomized controlled trial with 3 parallel arms. We will compare Tai Chi with walking and waiting-list control. We will recruit 234 hypertensive patients with mild to moderate essential hypertension and randomly assign them to 3 different groups. Participants in Tai Chi group will receive a group-format Yang style 24-form Tai Chi exercise program, 3 sessions per week for 12 weeks. The walking group will be asked to walk, 3 sessions per week for 12 weeks. The waiting-list group will not receive any interventions and/or exercise training. The primary outcome is the change in average 24-h systolic blood pressure (SBP) between baseline and 12 weeks after randomization. The secondary outcomes include 24-h Diastolic Blood Pressure (DBP), average SBP and average DBP during the daytime and night-time, blood pressure (BP) variability, SBP load and DBP load, circadian rhythm of BP, and morning BP surge, endothelial functional indicators, home measured BP, quality of life, adverse events and so on.

Discussion
We expect findings of this trial will provide important insight into application of Tai Chi as an effective and acceptable method for hypertensive patients. Successful completion of this proposed study will also contribute to promotion of Tai Chi in the community in the future.

Trial registration
Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT04267471, date: February 12, 2020.
Simulation-based curriculum development: lessons learnt in Global Health education
Authors: Sawaya Rasha D. , Mrad Sandra , Rajha Eva , Saleh Rana , Rice Julie 
Published: January 2021

AbstractBackgroundSimulation based medical education (SBME) allows learners to acquire clinical skills without exposing patients to unnecessary risk. This is especially applicable to Emergency Medicine training programs where residents are expected to demonstrate proficiency in the management of time critical, low frequency, and highly-morbidity conditions. This study aims to describe the process through which a SBME curriculum was created, in a limited simulation resource setting at a 4-year Emergency Medicine (EM) residency program at the American University of Beirut Medical Center.MethodsA case-based pilot simulation curriculum was developed following Kern’s 6 step approach to curriculum design. The curricular objectives were identified through an anonymous survey of the program’s residents and faculty. Curriculum outcomes were assessed, and the curriculum was revised to address curricular barriers. Evaluations of the revised curriculum were collected during the simulation sessions and through a whole revised curriculum evaluation at the end of the first year of its implementation.Results14/20 residents (70%) and 8/8 faculty (100%) completed the needs assessment from which objectives for the pilot curriculum were developed and implemented through 6 2-h sessions over a 1-year period. Objectives were not met and identified barriers included cost, scheduling, resources, and limited faculty time. The revised curriculum addressed these barriers and 24 40-min sessions were successfully conducted during the following year. The sessions took place 3 at a time, in 2-h slots, using the same scenario to meet the objectives of the different learners’ levels. 91/91 evaluations were collected from participants with overall positive results. The main differences between the pilot and the revised curricula included: a better understanding of the simulation center resources and faculty’s capabilities.ConclusionSimulation-based education is feasible even with limited-resources. However, understanding the resources available, and advocating for protected educator time are essential to implementing a successful EM simulation curriculum.
Closing the knowledge gap in pelvic neuroanatomy: assessment of a cadaveric training program
Authors: Marcu Ioana , Balica Adrian , Gavard Jeffrey A. , Campian Eugen C. , Fernandes Gustavo Leme , Solnik M. Jonathon , Morozov Vadim , Lemos Nucelio 
Published: January 2021

Abstract
Background
The objective of this study is to characterize participants in a laparoscopic cadaveric neuroanatomy course and assess knowledge of pelvic neuroanatomy before and after this course.

Methods
This is a survey-based cohort study with a setting in a university educational facility. The participants are surgeons in a multiday laparoscopic cadaveric pelvic neuroanatomy course. Participants completed a precourse survey, including demographics and comfort with laparoscopic surgery. They then completed an identical precourse and postcourse anatomic knowledge test. Main outcomes are scores on the anatomic knowledge test precourse and postcourse.

Results
44 respondents were included: 25 completed fellowship, 15 completed residency, 2 were residents, and 2 were fellows. Participants were on average 11.09 years post training, with an average of 8.67 years from training if they completed fellowship and 18.62 years if they completed residency only. 22 of 42 respondents strongly agreed or agreed they are comfortable performing complex laparoscopic hysterectomies. The average precourse score was 32.18/50 points and the mean difference score (MDS, defined as mean of Postcourse scores minus Precourse scores) was 9.80, showing significant improvement (p <  0.001). Precourse and MDS scores were not significantly different when comparing country of practice, level of training, or time since training.

Conclusion
Baseline knowledge of pelvic neuroanatomy was similar among groups when comparing fellowship status, place of training, or time since training. There was significant improvement in knowledge after training in this dissection method. This course garnered interest from surgeons with broad training backgrounds.
Leadership curricula and assessment in Australian and New Zealand medical schools
Authors: Ross Simone Jacquelyn , Sen Gupta Tarun , Johnson Peter 
Published: January 2021

Abstract
Background
The Australian Medical Council, which accredits Australian medical schools, recommends medical leadership graduate outcomes be taught, assessed and accredited. In Australia and New Zealand (Australasia) there is a significant research gap and no national consensus on how to educate, assess, and evaluate leadership skills in medical professional entry degree/programs. This study aims to investigate the current curricula, assessment and evaluation of medical leadership in Australasian medical degrees, with particular focus on the roles and responsibilities of medical leadership teachers, frameworks used and competencies taught, methods of delivery, and barriers to teaching leadership.

Methods
A self-administered cross-sectional survey was distributed to senior academics and/or heads or Deans of Australasian medical schools. Data for closed questions and ordinal data of each Likert scale response were described via frequency analysis. Content analysis was undertaken on free text responses and coded manually.

Results
Sixteen of the 22 eligible (73%) medical degrees completed the full survey and 100% of those indicate that leadership is taught in their degree. In most degrees (11, 69%) leadership is taught as a common theme integrated throughout the curricula across several subjects. There is a variety of leadership competencies taught, with strengths being communication (100%), evidence based practice (100%), critical reflective practice (94%), self-management (81%), ethical decision making (81%), critical thinking and decision making (81%). Major gaps in teaching were financial management (20%), strategic planning (31%) and workforce planning (31%). The teaching methods used to deliver medical leadership within the curricula are diverse, with many degrees providing opportunities for leadership teaching for students outside the curricula. Most degrees (10, 59%) assess the leadership education, with one-third (6, 35%) evaluating it.

Conclusions
Medical leadership competencies are taught in most degrees, but key leadership competencies are not being taught and there appears to be no continuous quality improvement process for leadership education. There is much more we can do as medical educators, academics and leaders to shape professional development of academics to teach medical leadership, and to agree on required leadership skills set for our students so they can proactively shape the future of the health care system.