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In this paper, we report the development, evaluation, and application of ultra-small low-power wireless sensor nodes for advancing animal husbandry, as well as for innovation of medical technologies. A radio frequency identification (RFID) chip with hybrid interface and neglectable power consumption was introduced to enable switching of ON/OFF and measurement mode after implantation. A wireless power transmission system with a maximum efficiency of 70% and an access distance of up to 5 cm was developed to allow the sensor node to survive for a duration of several weeks from a few minutes’ remote charge. The results of field tests using laboratory mice and a cow indicated the high accuracy of the collected biological data and bio-compatibility of the package. As a result of extensive application of the above technologies, a fully solid wireless pH sensor and a surgical navigation system using artificial magnetic field and a 3D MEMS magnetic sensor are introduced in this paper, and the preliminary experimental results are presented and discussed.

Diagnosing rare diseases is challenging due to their low prevalence, diverse presentations, and limited recognition, often leading to diagnostic delays and errors. This study evaluates the effectiveness of multiple large language models (LLMs) in identifying rare diseases, comparing their performance with that of human physicians using real clinical cases. We analyzed 152 rare disease cases from the Chinese Medical Case Repository using four LLMs: ChatGPT-4o, Claude 3.5 Sonnet, Gemini Advanced, and Llama 3.1 405B. Overall, the LLMs performed better than human physicians, and Claude 3.5 Sonnet achieved the highest accuracy at 78.9%, significantly surpassing the accuracy of human physicians, which was 26.3%. These findings suggest that LLMs can improve rare disease diagnosis and serve as valuable tools in clinical settings, particularly in regions with limited resources. However, further validation and careful consideration of ethical and privacy issues are necessary for their effective integration into medical practice.

Objective To conduct a comprehensive bibliometric analysis of the application of artificial intelligence (AI) in Rare diseases (RDs), with a focus on analyzing publication output, identifying leading contributors by country, assessing the extent of international collaboration, tracking the emergence of research hotspots, and detecting trends through keyword bursts. Methods In this bibliometric study, we identified and retrieved publications on AI applications in RDs spanning 2003 to 2023 from the Web of Science (WoS). We conducted a global research landscape analysis and utilized CiteSpace to perform keyword clustering and burst detection in this field. Results A total of 1501 publications were included in this study. The evolution of AI applications in RDs progressed through three stages: the start-up period (2003–2010), the steady development period (2011–2018), and the accelerated growth period (2019–2023), reflecting this field’s increasing importance and impact at the time of the study. These studies originated from 85 countries, with the United States as the leading contributor. “Mutation”, “Diagnosis”, and “Management” were the top three keywords with high frequency. Keyword clustering analysis identified gene identification, effective management, and personalized treatment as three primary research areas of AI applications in RDs. Furthermore, the keyword burst detection indicated a growing interest in the areas of “biomarker”, “predictive model”, and “data mining”, highlighting their potential to shape future research directions. Conclusions Over two decades, research on the AI applications in RDs has made remarkable progress and shown promising results in the development. Advancing international transboundary cooperation is essential moving forward. Utilizing AI will play a more crucial role across the spectrum of RDs management, encompassing rapid diagnosis, personalized treatment, drug development, data integration and sharing, and continuous monitoring and care.

Background In many countries worldwide orphan drug regulations are installed but only the United States of America and Japan have an orphan device regulation. For many years surgeons have used off-label or self-assembled medical devices for the prevention, diagnosis or treatment of rare disorders. Four examples are given: an external cardiac pacemaker, a metal brace for clubfoot in newborns, a transcutaneous nerve stimulator and a cystic fibrosis mist tent. Conclusion In this article we argue that we need authorized medical devices as well as medicinal products to prevent, diagnose and treat patients with life-threatening or chronically debilitating disorders with a low prevalence/incidence. Several arguments are given to support this statement.

Aim To determine the level of evidence for innovative high-risk medical devices at market entry. Methods We reviewed all Belgian healthcare payer (RIZIV-INAMI) assessor reports on novel implants or invasive medical devices (n = 18, Class IIb-III) available between 2018 to mid-2019 on applications submitted for inclusion on their reimbursement list. We also conducted a review of the literature on evidence gaps and an analysis of relevant legal and ethical frameworks within the European context. Findings Conformity assessment of medical devices is based on performance, safety, and an acceptable risk-benefit balance. Information submitted for obtaining CE marking is confidential and legally protected, limiting access to clinical evidence. Seven out of the 18 RIZIV-INAMI assessor reports (39%) included a randomized controlled trial (RCT) using the novel device, whilst 2 applications (11%) referred to an RCT that used a different device. The population included was inappropriate or unclear for 3 devices (17%). Only half of the applications presented evidence on quality of life or functioning and 2 (11%) presented overall survival data. Four applications (22%) included no data beyond twelve months. The findings from the literature demonstrated similar problems with the study design and the clinical evidence. Discussion and conclusions CE marking does not indicate that a device is effective, only that it complies with the law. The lack of transparency hampers evidence-based decision making. Despite greater emphasis on clinical benefit for the patient, the provisions of the European Medical Device Regulation (MDR) are not yet fully aligned with international ethical standards for clinical research. The MDR fails to address key issues, such as the lack of access to data submitted for CE marking and a failure to require evidence of clinical effectiveness. Indeed, a first report shows no improvement in the clinical evidence for implantable devices generated under the MDR. Thus, patients may continue to be exposed to ineffective or unsafe novel devices. The Health Technology Assessment Regulation plans for Joint Scientific Consultations for specific high-risk devices before companies begin their pivotal clinical investigations. The demanded comparative evidence should facilitate payer decisions. Nevertheless, there is also a need for legislation requiring comparative RCTs assessing patient-relevant outcomes for high-risk devices to ensure implementation, including development and implementation of common specifications for study designs.

Background Bardet–Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in 26 BBS genes. It affects multiple organs, including the kidney and liver, with varying degrees regarding extent and time of first manifestation. Structural renal anomalies are an early feature and end-stage kidney disease (ESKD) cumulates to 25% in adulthood. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Materials and methods Patients with genetically proven BBS were recruited from the University Children’s Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients’ digital records or medical letters. High-resolution ultrasound (US) imaging was utilized, including attenuation imaging (ATI), shear wave elastography (SWE) and dispersion (SWD) of liver tissue. Results 49 BBS patients (24/49 male; 1.1–51.0 years, mean 17.8 years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48), and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) of whom 3 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49), suggesting hepatic fibrosis, and it correlated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI, reduced GFR, and higher BMI SDS. Conclusions We detected kidney and liver abnormalities in a higher percentage of BBS patients than previously reported, indicating a high sensitivity and diagnostic yield of the evaluated high-end US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.

Background Peripheral odontogenic keratocyst (POKC) is a rare extraosseous manifestation of odontogenic keratocyst (OKC). Because of their anatomical locations, OKCs and POKCs necessitate slightly different treatment approaches. However, the reported literature has not yet reached a definitive conclusion on this matter. Methods This study included 2 patients who experienced postoperative recurrence of POKCs in the right buccal mucosa from 2018 to 2020. Additionally, we reviewed the reported cases and summarized the clinical features, treatment and prognosis of the POKCs. Results The two patients with POKCs in this report experienced recurrence after the first surgery, and the second operation involved microscopic excision of the lesion with its adherent tissue. No recurrence was observed. Conclusions Because POKCs are located in the soft tissue, they are difficult to remove and therefore prone to recur. In the treatment of POKCs, the surrounding adhesions can also be removed. Microscopic excision should be performed as well. Highlights This is the first report on the primary and recurrence of POKCs in the buccal mucosa, with a long follow-up period. Complete excision is effective for POKCs, especially when the cyst wall is hard to separate from the surrounding tissue. Using a surgical microscope can improve separation accuracy and reduce damage to adjacent tissue.

Objective Poor fetal and perinatal outcomes in fetuses associated with umbilical artery thrombosis (UAT), such as severe intrauterine growth restriction (IUGR) and intrauterine asphyxia have been reported by some case series. Its hemodynamic impact remains unclear. The aim of this study was to evaluate the hemodynamic changes and perinatal outcome in UAT fetuses with a relatively large sample. Methods We included singleton fetuses diagnosed with UAT and with at least one available Doppler evaluation before the end of pregnancy in our center from 2016 to 2023. Fetuses with structural abnormalities and with no follow-up results were excluded. Doppler waveforms from the Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine artery (UtA) were routinely evaluated according to ISUOG Practice Guidelines from diagnosis. The same sample of GA-matched normal fetuses with Doppler measurements during the same period were randomly selected as control group. Results Eighty-nine singleton fetuses with UAT with at least one Doppler evaluation before the end of pregnancy were identified, 13 fetuses with no follow-up results were excluded. After comprehensive prenatal counseling, 14 cases received urgent cesarean section, the remaining 55 cases received expectant management, the median day between GA at diagnosis and end of pregnancy was 13 (5–53) days (range, 2-159). 7 (7/76, 9.2%) cases occurred stillbirth, and the incidence of IUGR and Neonatal Intensive Care Unit (NICU) admission were 18.4% (14/76) and 13.2% (10/76) respectively. 49 fetuses (49/76, 64.5%) combined with Doppler abnormalities. UA abnormalities (35/76, 46.1%) and MCA abnormalities (34/76, 44.7%) were the most changes at presentation. Compared to control group, UA-EDV was significantly increased in UAT fetuses [21.84 (15.59–26.64) vs. 16.40 (12.43–20.70) cm/s, p  < 0.001], UA-PI and UA-RI significantly decreased [0.68 (0.57–0.84) vs. 0.92 (0.79–1.11), p <0.001; 0.51 (0.44–0.59) vs. 0.62 (0.55–0.68), p  < 0.001, respectively]. Both the MCA-PSV and MCA-EDV were significantly higher in UAT fetuses [54.60 (48.00-61.34) vs. 44.47 (29.66–57.60) cm/s, p  < 0.001; 11.19 (7.84–17.60) vs. 8.22 (5.21-12.00) cm/s, p  < 0.001, respectively], this led to a lower MCA-PI and MCA-RI. Meanwhile, DV-PIV was significantly higher in UAT fetuses [0.6 (0.47–0.87) vs. 0.45 (0.37–0.55), p <  0.001], CPR and UtA-PI were no significant difference between these two groups. Multivariate logistic regression analysis showed that DV-PIV was an independent risk factor for adverse pregnancy outcomes (OR 161.922, p <0.001), the area under the ROC curve (AUC) was 0.792 (95% CI 0.668–0.917; p  < 0.001). Conclusion Our data showed serious adverse pregnancy consequences are combined with UAT fetuses. Hemodynamic changes in UAT fetuses showed the remaining artery for compensation and brain perfusion derangement. With a comprehensive and standardized Doppler evaluation, progression of fetal deterioration may be detailed presented.

Background In patients without a family history, Duchenne muscular dystrophy (DMD) is typically diagnosed at around 4–5 years of age. It is important to diagnose DMD during infancy or toddler stage in order to have timely access to treatment, opportunities for reproductive options, prevention of potential fatal reactions to inhaled anesthetics, awareness of a child’s abilities needed for good parenting, and opportunities for enrolment in clinical trials. Method We aimed to develop a short risk assessment tool based on developmental milestones that may contribute to the early detection of boys with DMD in primary care. As part of the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with DMD), data on developmental milestones, symptoms and therapies for 76 boys with DMD and 12,414 boys from a control group were extracted from the health records of youth health care services and questionnaires. Multiple imputation, diagnostic validity and pooled backward logistic regression analyses with DMD (yes/no) as the dependent variable and attainment of 26 milestones until 36 months of age (yes/no) as the independent variable were performed. Descriptive statistics on symptoms and therapies were provided. Results A tool with seven milestones assessed at specific ages between 12 and 36 months resulted in a sensitivity of 79% (95CI:67–88%), a specificity of 95.8% (95%CI:95.3–96.2), and a positive predictive value of 1:268 boys. Boys with DMD often had symptoms (e.g. 43% had calf muscle pseudohypertrophy) and were referred to therapy (e.g. 59% for physical therapy) before diagnosis. Discussion This tool followed by the examination of other DMD-related symptoms could be used by youth health care professionals during day-to-day health assessments in the general population to flag children who require further action. Conclusions The majority of boys (79%) with DMD can be identified between 12 and 36 months of age with this tool. It increases the initial a priori risk of DMD from 1 in 5,000 to approximately 1 in 268 boys. We expect that other neuromuscular disorders and disabilities can also be found with this tool.

Background The U.S. Food and Drug Administration (FDA)’s platform technology designation program aims to streamline the development and approval process for advanced therapy medicinal products and is anticipated to be particularly beneficial for the development of gene therapies for rare and ultra-rare diseases. This is an exploratory interview study of Swiss-based perspectives, including insights from stakeholders in industry, academia, regulation, and reimbursement. The objective of our study is to document Swiss professionals’ views on the US platform designation program and to assess the acceptability and feasibility of a similar program in Europe. Results Participants identified benefits such as reduced redundancy in pre-clinical testing, standardization of manufacturing, and increased predictability of regulatory requirements. Concerns were raised about clinical assessment, commercialization strategies, and global regulatory alignment. Though participants anticipate it to increase innovation in the rare disease area, some raised the possibility that technologies may stagnate around a platform, or that designations may quickly become obsolete due to the speed of technological development. Conclusions The introduction of the platform technology designation program in the US is a step towards increasing treatment options for ultra-rare diseases. While there is potential for platform designation to enable development in this area, its success will depend on addressing the outlined challenges.