Future Oncol. 2022 Jun;18(20):2545-2558. doi: 10.2217/fon-2021-1228. Epub 2022 Jun 1.

ABSTRACT

Non-muscle invasive bladder cancer accounts for the majority of new bladder cancer diagnoses, and endoscopic transurethral resection of bladder tumor (TURBT) represents the standard-of-care. Although a relatively safe and common procedure, TURBT is often hampered by the questionable quality of resection. The evolution of surgical techniques has brought en bloc resection of bladder tumor (ERBT) to the forefront. ERBT has emerged as an alternative to conventional TURBT, incorporating a more delicate en bloc sculpting and tumor excision, in contrast to 'piecemeal' resection by conventional TURBT. ERBT appears safe, feasible and effective with demonstrably higher rates of detrusor muscle in the pathologic specimen, all while providing better staging and obviating the need for a re-TURBT in selected patients. However, the method's adoption in the field is still limited. This review summarizes the recent evidence relevant to ERBT while further highlighting the technique's limitations and unmet needs.

PMID:35642479 | DOI:10.2217/fon-2021-1228

J Food Drug Anal. 2021 Dec 15;29(4):717-725. doi: 10.38212/2224-6614.3383.

ABSTRACT

The Rare Disease and Orphan Drug Act (the Act) was enacted in 2000 in Taiwan for the facilitation of the research, development, and accessibility of orphan drugs and special nutritional foods; for the prevention and early diagnosis of rare diseases; and for providing intensive care for patients with rare diseases. The aim was to investigate the impact of the Act on the availability and use of orphan drugs in Taiwan in the hope of identifying the remaining challenges and possible solutions to assist future policy making, which may be applicable in other countries as well. The information and statistics for rare diseases and orphan drugs retrieved from the official annual reports and documents were analyzed. There were 225 diseases recognized as rare diseases, and one-third (75/225) of them were congenital metabolic disorders. Among the 110 designated orphan drugs that could apply for listing in the National Health Insurance (NHI) Pharmaceutical Benefits and Reimbursement Scheme, approximately half (62/110) of them were granted marketing authorization. While the NHI program compulsory for all citizens increased patient accessibility to orphan drugs, the rapidly increasing economic burden became an urgent issue for the government. Emerging gene therapies may be the solution to unmet medical needs and also a financial obstacle to tackle. The Act increased the availability of orphan drugs while the NHI system facilitated patient access, which benefited many patients with rare diseases in Taiwan. However, the soaring economic burden was noticed and was anticipated to aggravate. More communication and cooperation between stakeholders is critical in finding solutions for the long-term sustainability of the NHI system.

PMID:35649145 | DOI:10.38212/2224-6614.3383

Orphanet J Rare Dis. 2022 May 31;17(1):212. doi: 10.1186/s13023-022-02357-y.

ABSTRACT

BACKGROUND: Patients' involvement (PI) in research is recognized as a valuable strategy for increasing the quality, developing more targeted research and to speed up more innovative research dissemination. Nevertheless, patient involvement in rare diseases research (PI-RDR) is scarce. The aims were: To study the Norwegian researchers` experiences and perceptions of PI-RDR and review the literature on PI-RDR.

METHODS: 1. A systematic scoping review of the literature on PI-RDR. 2. A cross-sectional questionnaire study with close-ended and open-ended questions to investigate the researchers` experiences.

RESULTS: In the scoping review 608 articles read in full-text and 13 articles (one review and twelve primary studies) were included. The heterogeneity of the design, methodology and results was large. Most studies described several benefits of PI, but few described methods for measuring impacts and effectiveness of PI-RDR. In the cross sectional part of this study, 145 of 251 employees working in the nine Norwegian Centers on Rare Diseases participated, of these 69 were researchers. Most (95%) of the researchers claimed that rare diseases research is more challenging than for the more common diseases. The majority (95%) argued that PI-RDR may increase the quality of the studies and the relevance, and most (89%) agreed that PI-RDR in dissemination may increase the awareness and public interest for rare diseases. In the open-ended questions several researchers also claimed challenges related to PI-RDR, and many had proposal for improving PI and promotion of rare disease research.

CONCLUSION: Both the literature and researchers emphasized that PI-RDR is important for improving research quality and increase the public attention on rare diseases, but what constitutes effective PI-RDR still remain unclear. More research on the design, methodology and assessment for measuring the impact of PI-RDR is warranted.

PMID:35642001 | DOI:10.1186/s13023-022-02357-y

JNMA J Nepal Med Assoc. 2022 Mar 11;60(247):314-317. doi: 10.31729/jnma.7029.

ABSTRACT

Diaphragmatic eventration is a rare condition, and its association with dextrocardia is even a rarer clinical entity. Patients are usually asymptomatic, but the typical features include rapid breathing and recurrent respiratory infections. Here we present a rare case of a seven months old infant, who presented with cough, noisy breathing and chest retraction. The patient was diagnosed to have dextrocardia with diaphragmatic eventration with pneumonia by chest imaging and was treated in coordination with the medical team for underlying pneumonia. Afterwards, plication of the diaphragm was done through the trans-abdominal approach and the symptoms gradually improved postoperatively. For dextrocardia, since there were no structural abnormalities, the patient was kept in regular follow-up in the pediatric cardiology unit. Though most patients are asymptomatic, diaphragmatic eventration increases the risk of recurrent chest infection and hampers the quality of life of the patient, so timely diagnosis and intervention will greatly improve their quality of life.

KEYWORDS: dextrocardia; diaphragm; diaphragmatic eventration.

PMID:35633268 | DOI:10.31729/jnma.7029

Int J Environ Res Public Health. 2022 May 16;19(10):6057. doi: 10.3390/ijerph19106057.

ABSTRACT

BACKGROUND: Education plays a fundamental role in everyone's wellbeing. That means it is essential to provide quality inclusive activities to ensure equity and equality of opportunity in order to shape a cohesive, democratic, healthy society.

METHODS: In this study we focus on how inclusive educational practice addresses students with rare diseases, looking at teachers' knowledge and opinions in this regard. A questionnaire was administered to 574 teachers who taught in various stages of non-university education to determine their knowledge and opinions about different dimensions: conceptualization, legislation, intervention, and diagnosis.

RESULTS: The results suggested various ideas for improvement in pursuit of positive, real inclusion, such as the need to improve teachers' knowledge and understanding of these students' characteristics and potential, with widespread specific training being urgently needed.

CONCLUSIONS: in summary, students' rights to education without discrimination is a basic premise of an educational system, leading to the need for a complete educational response that allows each student to develop as a person.

PMID:35627593 | PMC:PMC9140519 | DOI:10.3390/ijerph19106057

Genes (Basel). 2022 Apr 22;13(5):741. doi: 10.3390/genes13050741.

ABSTRACT

Chimeric RNAs are transcripts that are generated by gene fusion and intergenic splicing events, thus comprising nucleotide sequences from different parental genes. In the past, Northern blot analysis and RT-PCR were used to detect chimeric RNAs. However, they are low-throughput and can be time-consuming, labor-intensive, and cost-prohibitive. With the development of RNA-seq and transcriptome analyses over the past decade, the number of chimeric RNAs in cancer as well as in rare inherited diseases has dramatically increased. Chimeric RNAs may be potential diagnostic biomarkers when they are specifically expressed in cancerous cells and/or tissues. Some chimeric RNAs can also play a role in cell proliferation and cancer development, acting as tools for cancer prognosis, and revealing new insights into the cell origin of tumors. Due to their abilities to characterize a whole transcriptome with a high sequencing depth and intergenically identify spliced chimeric RNAs produced with the absence of chromosomal rearrangement, RNA sequencing has not only enhanced our ability to diagnose genetic diseases, but also provided us with a deeper understanding of these diseases. Here, we reviewed the mechanisms of chimeric RNA formation and the utility of RNA sequencing for discovering chimeric RNAs in several types of cancer and rare inherited diseases. We also discussed the diagnostic, prognostic, and therapeutic values of chimeric RNAs.

PMID:35627126 | PMC:PMC9140685 | DOI:10.3390/genes13050741

BMC Pediatr. 2022 May 27;22(1):312. doi: 10.1186/s12887-022-03376-1.

ABSTRACT

BACKGROUND: Myelodysplastic syndrome (MDS) is a rare disease in children and the treatment option before the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely reported. Our main objective was to report our single-center experience with the DNA-hypomethylating agent, decitabine-combined minimally myelosuppressive regimen (DAC + MMR) bridged allo-HSCT in children with MDS.

METHODS: Twenty-eight children with de novo MDS who underwent allo-HSCT between 2011 and 2020 were enrolled. Patients were divided into subgroups (refractory cytopenia of childhood [RCC] and advanced MDS [aMDS]) and treated by HSCT alone or pre-transplant combination treatment based on risk stratification. The patients' clinical characteristics, treatment strategies and outcomes were retrospectively evaluated.

RESULTS: Twenty patients with aMDS had received pre-transplant treatment (three were treated with decitabine alone, thirteen with DAC + MMR, and four with acute myeloid leukemia type [AML-type] induction therapy). DAC + MMR was well tolerated and the most common adverse events were myelosuppression and gastrointestinal reaction. DAC + MMR had shown an improved marrow complete remission (mCR) compared with AML-type chemotherapy (13/13, 100% versus 2/4, 50%, P = 0.044). The median follow-up for total cohort was 53.0 months (range, 2.3-127.0 months) and the 4-year overall survival (OS) was 71.4 ± 8.5%. In the subgroup of aMDS, pretreatment of DAC + MMR resulted in a much better survival rate than AML-type chemotherapy (84.6 ± 10.0% versus 0.0 ± 0.0%, P < 0.001).

CONCLUSIONS: The DAC + MMR bridged allo-HSCT may be recommended as a novel and effective approach.

PMID:35624441 | PMC:PMC9137053 | DOI:10.1186/s12887-022-03376-1

Orphanet J Rare Dis. 2022 May 26;17(1):211. doi: 10.1186/s13023-022-02354-1.

ABSTRACT

BACKGROUND: Rare diseases are serious and chronic diseases that affect no more than 1 person in 2000 (in European Union criteria). Patients suffering from RDs may come to the emergency department for life-threatening symptoms, such as acute aortic dissection, intracranial haemorrhage, and severe respiratory distress. Diagnostic delay of rare disease patients is common and often caused by low rare disease awareness among physicians. The main aim of this study was to investigate Chinese emergency physicians' basic knowledge, information access and educational needs regarding rare diseases. An online questionnaire was completed by Chinese emergency physicians during January and March 2021.

METHODS AND RESULTS: A total of 539 emergency physicians, including 200 females and 339 males, responded to the questionnaire-based study. More than half of the respondents were from Tertiary A hospitals and had engaged in medical clinical work for more than 10 years. Only 4.27% of respondents correctly estimated the prevalence of rare diseases. A few respondents knew the exact number of RDs in the first official list of rare diseases in 2018. A total of 98.5% of respondents rated their knowledge about rare diseases as minimal or insufficient. Most emergency physicians preferred to obtain information through search engines instead of specialized websites on rare diseases. A lack of practice guidelines or consensus was considered the most important reason for the diagnostic delay of RD. Practice guidelines or consensus and professional websites on rare diseases are urgently needed for emergency physicians.

CONCLUSION: The investigation shows poor knowledge of rare diseases among emergency physicians. Practice guidelines and professional websites on rare diseases were the primary urgent needs for emergency physicians. Specialized RD courses should also be added to medical education.

PMID:35619153 | PMC:PMC9137093 | DOI:10.1186/s13023-022-02354-1

Stud Health Technol Inform. 2022 May 25;294:844-848. doi: 10.3233/SHTI220604.

ABSTRACT

The wide adoption of Electronic Health Records (EHR) in hospitals provides unique opportunities for high throughput phenotyping of patients. The phenotype extraction from narrative reports can be performed by using either dictionary-based or data-driven methods. We developed a hybrid pipeline using deep learning to enrich the UMLS Metathesaurus for automatic detection of phenotypes from EHRs. The pipeline was evaluated on a French database of patients with a rare disease characterized by skeletal abnormalities, Jeune syndrome. The results showed a 2.5-fold improvement regarding the number of detected skeletal abnormalities compared to the baseline extraction using the standard release of UMLS. Our method can help enrich the coverage of the UMLS and improve phenotyping, especially for languages other than English.

PMID:35612223 | DOI:10.3233/SHTI220604

Korean J Gastroenterol. 2022 May 25;79(5):222-227. doi: 10.4166/kjg.2022.031.

ABSTRACT

Primary esophageal melanoma is a rare disease with a poor prognosis. To date, 18 cases have been reported in Korea. Four patients visited the Chonnam National University Hwasun Hospital with dysphagia, followed by epigastric pain and discomfort, odynophagia, and weight loss. Esophagogastroduodenoscopy revealed a black pigmented polypoid mass, protruding mass, or black-pigmented flat lesions. Two patients had distant metastases and lymphadenopathies in imaging studies. Two patients underwent esophagectomy and intrathoracic esophagogastrostomy. One patient was treated with chemotherapy and interferon-alpha. The other patient declined further treatment. The routine histology using H&E revealed brown-colored atypical melanocytes. Immunohistochemical staining exhibited strong reactivity for Melan-A, S-100, and HMB-45 proteins. The biopsy specimens were interpreted to be malignant melanoma. One patient had multiple distant metastases 13 months after surgery. The other patient had no recurrence for 33 months after surgery. The patient treated with chemotherapy and interferon-alpha showed disease progression in the follow-up examination. Primary esophageal melanoma in Korea is a rare disease characterized by aggressive behavior, early metastasis, and poor prognosis.

PMID:35610553 | DOI:10.4166/kjg.2022.031

CMAJ Open. 2022 May 24;10(2):E460-E465. doi: 10.9778/cmajo.20210272. Print 2022 Apr-Jun.

ABSTRACT

BACKGROUND: Genome-wide sequencing has emerged as a promising strategy for the timely diagnosis of rare diseases, but it is not yet available as a clinical test performed in Canadian diagnostic laboratories. We describe the protocol for evaluating a 2-year pilot project, Genome-wide Sequencing Ontario, to offer high-quality clinical genome-wide sequencing in Ontario, Canada.

METHODS: The Genome-wide Sequencing Ontario protocol was codesigned by the Ontario Ministry of Health, the Hospital for Sick Children in Toronto and the Children's Hospital of Eastern Ontario in Ottawa. Enrolment of a prospective cohort of patients began on Apr. 1, 2021. Eligible cases with blood samples available for the index case and both parents (i.e., trios) are randomized to receive exome sequencing or genome sequencing. We will collect patient-level data and ascertain costs associated with the laboratory workflow for exome sequencing and genome sequencing. We will compare point estimates for the diagnostic utility and timeliness of exome sequencing and genome sequencing, and we will determine an incremental cost-effectiveness ratio (expressed as the incremental cost of genome sequencing versus exome sequencing per additional patient with a causal variant detected).

INTERPRETATION: Findings from this work will provide robust evidence for the diagnostic utility, cost-effectiveness and timeliness of exome sequencing and genome sequencing, and will be disseminated via academic publications and policy briefs. Findings will inform provincial and cross-provincial policy related to the long-term organization, delivery and reimbursement of clinical-grade genome diagnostics for rare disease.

PMID:35609929 | DOI:10.9778/cmajo.20210272

Minerva Urol Nephrol. 2022 Jun;74(3):376-378. doi: 10.23736/S2724-6051.22.04954-0.

NO ABSTRACT

PMID:35607787 | DOI:10.23736/S2724-6051.22.04954-0

Orphanet J Rare Dis. 2022 May 23;17(1):210. doi: 10.1186/s13023-022-02365-y.

ABSTRACT

BACKGROUND: In order to facilitate the diagnostic process for adult patients suffering from a rare disease, the Undiagnosed Disease Program (UD-PrOZA) was founded in 2015 at the Ghent University Hospital in Belgium. In this study we report the five-year results of our multidisciplinary approach in rare disease diagnostics.

METHODS: Patients referred by a healthcare provider, in which an underlying rare disease is likely, qualify for a UD-PrOZA evaluation. UD-PrOZA uses a multidisciplinary clinical approach combined with state-of-the-art genomic technologies in close collaboration with research facilities to diagnose patients.

RESULTS: Between 2015 and 2020, 692 patients (94% adults) were referred of which 329 (48%) were accepted for evaluation. In 18% (60 of 329) of the cases a definite diagnosis was made. 88% (53 of 60) of the established diagnoses had a genetic origin. 65% (39 of 60) of the genetic diagnoses were made through whole exome sequencing (WES). The mean time interval between symptom-onset and diagnosis was 19 years. Key observations included novel genotype-phenotype correlations, new variants in known disease genes and the identification of three new disease genes. In 13% (7 of 53), identifying the molecular cause was associated with therapeutic recommendations and in 88% (53 of 60), gene specific genetic counseling was made possible. Actionable secondary findings were reported in 7% (12 of 177) of the patients in which WES was performed.

CONCLUSION: UD-PrOZA offers an innovative interdisciplinary platform to diagnose rare diseases in adults with previously unexplained medical problems and to facilitate translational research.

PMID:35606766 | DOI:10.1186/s13023-022-02365-y

J Assoc Physicians India. 2022 May;70(5):11-12.

NO ABSTRACT

PMID:35598138

Int Braz J Urol. 2022 Jul-Aug;48(4):607-608. doi: 10.1590/S1677-5538.IBJU.2022.04.01.

NO ABSTRACT

PMID:35594321 | DOI:10.1590/S1677-5538.IBJU.2022.04.01

Stud Health Technol Inform. 2022 May 16;293:187-188. doi: 10.3233/SHTI220367.

ABSTRACT

BACKGROUND: The Open Source Registry System for Rare Diseases (OSSE), a web-based tool to create rare disease patient registries, currently offers no possibility to view aggregated registry data within the system. Here, we present the development and implementation of a dashboard for the registry of the German NEOCYST (Network for early onset cystic kidney diseases) consortium.

METHODS: Based on user requirements from NEOCYST, we developed a general dashboard for all OSSE registries, which was extended with NEOCYST-specific statistics.

RESULTS: The dashboard now allows users to gain a quick overview of key data, such as patient counts or the availability of biospecimens.

CONCLUSION: This work represents a first prototypical approach for an OSSE dashboard, demonstrated in an existing rare disease registry, to be further evaluated and enhanced in the future.

PMID:35592980 | DOI:10.3233/SHTI220367

Stud Health Technol Inform. 2022 May 16;293:11-18. doi: 10.3233/SHTI220341.

ABSTRACT

The diagnosis of rare diseases is often challenging for physicians, but can be supported by Clinical Decision Support Systems. The MIRACUM consortia, which includes ten university hospitals in Germany, develops a Clinical Decision Support System to support the diagnosis of patients with rare diseases. The users are involved in different phases using a user-centred design process. This publication has the objective to summarize the results of all studies performed in context of the requirements elicitation and to derive concrete requirements for the development of the system. Several studies were performed for requirements elicitation: a cross-sectional survey, expert interviews and a focus group. Participants were experts in rare diseases of the MIRACUM locations. 32 requirements were derived and implemented in a prototype. The prototype allows similarity analyses as a decision support functionality by comparing patients without a diagnosis to patients with a rare disease. In the final evaluation, the prototype was rated with a good usability. Since the system is limited in its functionality, further work and improvements are necessary to make it ready for clinical usage.

PMID:35592954 | DOI:10.3233/SHTI220341

BMC Musculoskelet Disord. 2022 May 17;23(1):464. doi: 10.1186/s12891-022-05238-4.

ABSTRACT

BACKGROUND: Neuromuscular choristomas (NMCs), are extremely rare developmental lesions that, have been previously established associated with recurrent fibromatosis after surgery, leading to several operations or even amputation. However, reports on the ultrasound imaging features and clinical conditions of NMCs are rare. The purpose of this study is to describe the ultrasound features and clinical analysis of NMCs to provide suggestions to identify the optimal management strategy.

METHODS: From September 2020 to September 2021, 7 patients with a confirmed diagnosis of NMC who underwent ultrasound examination in our department were enrolled in our study. Physical examinations were performed to detect motor deficits, sensory deficits, neuropathic pain, limb undergrowth, muscular atrophy, cavus foot and bone dysplasia. Ultrasound imaging was performed and investigated both in affected nerves and neuromuscular choristomas associated desmoid-type fibromatosis (NMC-DTF). All patients had a definite history and regular follow-up. The clinical course, physical examinations, ultrasound features and pathologic results of NMC patients were analyzed.

RESULTS: Seven patients with an average age of 7.0 ± 7.2 years (range: 2-22 years) were enrolled in our study. The affected nerves included the sciatic nerve (6 cases) and the brachial plexus (1 case). Six patients (85.7%) presented with limb undergrowth, 6 (85.7%) with muscular atrophy, and 5 (71.4%) with cavus foot deformity. Based on ultrasound findings, all the visibly affected nerve segments presented with hypoechoic and fusiform enlargement with intraneural skeletal muscle elements. Five patients (71.4%) had NMC-DTFs at the site of the affected nerve. All NMC-DTFs were shown as hypoechoic solid lesions adjacent to the nerve and were well circumscribed. In the subset of the surgery group, all 5 patients presented with progression to NMC-DTFs at the site of the NMCs. No fibromatosis was detected in the other two nonsurgical patients.

CONCLUSIONS: Understanding the typical ultrasound features and clinically associated conditions would support the early diagnosis of this rare disease. When a potential diagnosis is determined, an invasive procedure such as biopsy or resection might not be a good choice given the frequent occurrence of complications such as aggressive recurrence.

PMID:35581638 | DOI:10.1186/s12891-022-05238-4

Orphanet J Rare Dis. 2022 May 16;17(1):203. doi: 10.1186/s13023-022-02362-1.

ABSTRACT

BACKGROUND: Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China.

METHODS: After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021.

RESULTS: There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far.

CONCLUSIONS: Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.

PMID:35578266 | PMC:PMC9112470 | DOI:10.1186/s13023-022-02362-1

Front Endocrinol (Lausanne). 2022 Apr 28;13:886552. doi: 10.3389/fendo.2022.886552. eCollection 2022.

ABSTRACT

Congenital hyperinsulinism (HI) is a rare disease affecting newborns. HI causes severe hypoglycemia due to the overproduction of insulin. The signs and symptoms of hypoglycemia in HI babies is often not discovered until brain damage has already occurred. Prolonged hypoglycemia from HI can even lead to death. Disease management is often complex with a high burden on caregivers. Treatment options are extremely limited and often require long hospital stays to devise. Cascading from suboptimal treatments and diagnostic practices are a host of other problems and challenges that many with HI and their families experience including continued fear of hypoglycemia and feeding problems. The aim of this paper is (1) to describe the current challenges of living with HI including diagnosis and disease management told from the perspective of people who live with the condition (2), to provide family stories of life with HI, and (3) to share how a rare disease patient organization, Congenital Hyperinsulinism International (CHI) is working to improve the lives of HI patients and their families. CHI is a United States based nonprofit organization with a global focus. The paper communicates the programs the patient advocacy organization has put into place to support HI families through its virtual and in-person gatherings. The organization also helps individuals access diagnostics, medical experts, and treatments. CHI also raises awareness of HI to improve patient outcomes with information about HI and prolonged hypoglycemia in twenty-three languages. CHI drives innovation for new and better treatments by funding research pilot grants, conducting research through the HI Global Registry, and providing patient experience expertise to researchers developing new treatments. The organization is also the sponsor of the CHI Collaborative Research Network which brings medical and scientific experts together for the development of a patient-focused prioritized research agenda.

PMID:35573986 | PMC:PMC9097272 | DOI:10.3389/fendo.2022.886552