tbuckley/cabot-search huggingface dataset:
Neural mechanism of trigeminal nerve stimulation recovering defensive arousal responses in traumatic brain injury
Authors: Qian Zhang, Haiyun Ma, Lifang Huo, Shaoling Wang, Qian Yang, Zhimin Ye, Jie Cao, Shaoling Wu, Chao Ma, Congping Shang
Journal: Theranostics (2025)

The arousal state is defined as the degree to which an individual is aware of themselves and their surroundings, and is a crucial component of consciousness. Trigeminal nerve stimulation (TNS), a non-invasive clinical neuromodulation technique, has shown potential in aiding the functional recovery of patients with impaired consciousness. Understanding the specific neuronal subpopulations and circuits through which TNS improves arousal states is essential for advancing its clinical application. Methods: A mouse model of traumatic brain injury (TBI) was established using a weight-drop technique to induce neurological dysfunction, and the arousal state was assessed through visual and auditory defensive responses. Techniques such as viral tracing, chemogenetics, patch-clamp recordings, calcium signaling, and neurotransmitter probes were employed to investigate the relevant subpopulations of trigeminal ganglion (TG) neurons and the underlying mechanisms in the central nervous system. Results: Neuronal subgroups involved in TNS therapy at the key peripheral nucleus, the TG, were identified. Two distinct types of neurons were found to contribute differently: The Tac1+TG-locus coeruleus (LC)-superior colliculus (SC) pathway elevated noradrenaline levels in the SC, enhancing receptive field sensitivity recovery in TBI mice; the Piezo2+TG-paraventricular hypothalamic nucleus (PVN)-substantia nigra pars compacta (SNc)-dorsal striatum (DS) pathway initiated dopamine (DA) release in the DS, ameliorating motor disorders in TBI mice. Conclusion: These pathways contribute to the improvement of defensive arousal responses from different perspectives. The findings from this study imply that TNS effectively restores defensive arousal responses to visual and auditory threats in mice suffering from TBI, offering insights that may facilitate the implementation of TNS therapy in clinical settings.
Epigenetic regulation-mediated disorders in dopamine transporter endocytosis: A novel mechanism for the pathogenesis of Parkinson's disease
Authors: Ziqi Liang, Wanqing Liu, Mian Cao, Jiajun Cui, Jinshuai Lan, Yue Ding, Tong Zhang, Zizhao Yang
Journal: Theranostics (2025)

Mechanisms such as DNA methylation, histone modifications, and non-coding RNA regulation may impact the endocytosis of dopamine transporter (DAT) by influencing processes like neuronal survival, thereby contributing to the initiation and progression of Parkinson's Disease (PD). Some small molecule inhibitors or natural bioactive compounds have the potential to modulate epigenetic processes, thereby reversing induced pluripotent stem cells (iPSCs) reprogramming and abnormal differentiation, offering potential therapeutic effects for PD. Although no specific DNA modification enzyme directly regulates DAT endocytosis, enzymes such as DNA methyltransferases (DNMTs) may indirectly influence DAT endocytosis by regulating the expression of genes associated with this process. DNA modifications impact DAT endocytosis by modulating key signaling pathways, including the (protein kinase C) PKC and D2 receptor (D2R) pathways. Key enzymes involved in RNA modifications that influence DAT endocytosis include m6A methyltransferases and other related enzymes. This regulation impacts the synthesis and function of proteins involved in DAT endocytosis, thereby indirectly affecting the process itself. RNA modifications regulate DAT endocytosis through various indirect pathways, as well as histone modifications. Key enzymes influence the expression of genes associated with DAT endocytosis by modulating the chromatin's accessibility and compaction state. These enzymes control the expression of proteins involved in regulating endocytosis, promoting endosome formation, and facilitating recycling processes. Through the modulation exerted by these enzymes, the speed of DAT endocytosis and recycling patterns are indirectly regulated, establishing a crucial epigenetic control point for the regulation of neurotransmitter transport. Based on this understanding, we anticipate that targeting these processes could lead to favorable therapeutic effects for early PD pathogenesis.
CD34<sup>+</sup> PI16<sup>+</sup> fibroblast progenitors aggravate neointimal lesions of allograft arteries via CCL11/CCR3-PI3K/AKT pathway
Authors: Xiaodong Xu, Pengwei Zhu, Han Wang, Kai Chen, Liang Liu, Luping Du, Liujun Jiang, Yanhua Hu, Xuhao Zhou, Bohuan Zhang, Xiangyuan Pu, Xiaosheng Hu, Qingbo Xu, Li Zhang, Weidong Li
Journal: Theranostics (2025)

Rationale: Transplant-accelerated arteriosclerosis is a common complication that limits the long-term survival of organ transplant recipients. While previous studies have indicated the involvement of CD34+ stem/progenitor cells (SPCs) in this process, their heterogeneity and potential adverse effects remains incompletely understood. Methods: To investigate the role of CD34+ SPCs in transplant arteriosclerosis, we used various genetically modified mouse models, including BALB/c, C57BL/6J, CD34-CreERT2, Rosa26-tdTomato, Rosa26-iDTR, CD34-Dre, PI16-CreERT2, and CAG-LSL-RSR-tdTomato-2A-DTR mice. Single-cell RNA sequencing (scRNA-seq), chemokine antibody microarrays, ELISA assays, and immunohistochemistry were employed to identify fibroblast progenitors and their interactions with smooth muscle cells. Furthermore, in vivo and in vitro experiments targeting the CCL11/CCR3-PI3K/AKT signaling pathway were conducted to assess its role in the pathogenesis of transplant arteriosclerosis. Results: Single-cell RNA-seq and genetic lineage tracing revealed a subpopulation of fibroblast progenitors, characterized by high CD34 and PI16 expression, which differentiated into a distinct chemotactic fibroblast subset. Proteomic and scRNA analysis revealed that this CD34+ PI16- subgroup released CCL11 (Eotaxin-1), which promoted intimal hyperplasia through the paracrine activation of smooth muscle cells. Binding of CCL11 to its receptor CCR3 activated the PI3K/AKT signaling pathway in smooth muscle cells, driving their proliferation and migration. In vivo, overexpression of CCL11 promoted neointimal hyperplasia, while neutralizing CCL11 or inhibiting CCR3 alleviated neointimal formation. Conclusions: These findings identified CD34+ PI16+ fibroblast progenitors that differentiate into specific chemotactic fibroblasts, releasing chemokines pivotal for neointima formation, suggesting a therapeutic strategy targeting their chemotactic activity.
Contribution of shotgun metagenomics in the diagnosis of a subcutaneous phaeohyphomycosis caused by <i>Parathyridaria percutanea</i>
Authors: Lorra Monpierre, Cécile Angebault, Camille Hua, Léa Merio, Nicolas Ortonne, Emmanuel Lafont, Franҫoise Foulet, Franҫoise Botterel
Journal: British Journal of Dermatology (2025)

Diagnosis of subcutaneous infection caused by Parathyridaria percutanea, a rare and emerging tropical fungal pathogen identified in an immunocompromised woman using clinical shotgun metagenomic.
Screening for Metabolic Dysfunction–Associated Steatotic Liver Disease–Related Advanced Fibrosis in Diabetology: A Prospective Multicenter Study
Authors: Cyrielle Caussy, Bruno Vergès, Damien Leleu, Laurence Duvillard, Fabien Subtil, Amna Abichou-Klich, Valérie Hervieu, Laurent Milot, Bérénice Ségrestin, Sylvie Bin, Alexia Rouland, Dominique Delaunay, Pierre Morcel, Samy Hadjadj, Claire Primot, Jean-Michel Petit, Sybil Charrière, Philippe Moulin, Massimo Levrero, Bertrand Cariou, Emmanuel Disse
Journal: Diabetes Care (2025)

OBJECTIVE Screening for advanced fibrosis (AF) resulting from metabolic dysfunction–associated steatotic liver disease (MASLD) is recommended in diabetology. This study aimed to compare the performance of noninvasive tests (NITs) with that of two-step algorithms for detecting patients at high risk of AF requiring referral to hepatologists. RESEARCH DESIGN AND METHODS We conducted a planned interim analysis of a prospective multicenter study including participants with type 2 diabetes and/or obesity and MASLD with comprehensive liver assessment comprising blood-based NITs, vibration-controlled transient elastography (VCTE), and two-dimensional shear-wave elastography (2D-SWE). AF risk stratification was determined by a composite criterion of liver biopsy, magnetic resonance elastography, or VCTE ≥12 kPa depending on availability. RESULTS Of 654 patients (87% with type 2 diabetes, 56% male, 74% with obesity), 17.6% had an intermediate/high risk of AF, and 9.3% had a high risk of AF. The area under the empirical receiver operating characteristic curves of NITs for detection of high risk of AF were as follows: Fibrosis-4 (FIB-4) score, 0.78 (95% CI 0.72–0.84); FibroMeter, 0.74 (0.66–0.83); Fibrotest, 0.78 (0.72–0.85); Enhanced Liver Fibrosis (ELF) test, 0.82 (0.76–0.87); and SWE, 0.84 (0.78–0.89). Algorithms with FIB-4 score/VCTE showed good diagnostic performance for referral of patients at intermediate/high risk of AF to specialized care in hepatology. An alternative FIB-4 score/ELF test strategy showed a high negative predictive value (NPV; 88–89%) and a lower positive predictive value (PPV; 39–46%) at a threshold of 9.8. The FIB-4 score/2D-SWE strategy had an NPV of 91% and a PPV of 58–62%. The age-adapted FIB-4 score threshold resulted in lower NPVs and PPVs in all algorithms. CONCLUSIONS The FIB-4 score/VCTE algorithm showed excellent diagnostic performance, demonstrating its applicability for routine screening in diabetology. The ELF test using an adapted low threshold at 9.8 may be used as an alternative to VCTE.
Phosphoproteomics delineates hepatocellular carcinoma subtypes and pinpoints therapeutic targets
Authors: Ze Zhang, Zhenpeng Zhang, Yao Zhang, Yuan Li, Kaixuan Li, Shu Liu, Junning Cao, Yanchang Li, Xuehui Peng, Suzhen Li, Yanan Yin, Songhao Jiang, Tao Zuo, Lei Chang, Zhongwei Xu, Chonghui Li, Jin Ding, Jushan Wu, Wenwen Zhang, Xinxin Wang, Guimin Xia, Shichun Lu, Ping Xu
Journal: Hepatology (2025)

Background &amp; Aims: Only a minority of patients could benefit from systemic therapy owing to the high heterogeneity of HCC. Therefore, a deeper understanding of the pathogenesis of HCC is essential for precision therapy. Genomic and proteomic studies of HCC have enhanced our understanding of HCC. However, phosphoproteomic characterization of HCC remains poorly understood. Approach &amp; Results: We conducted an in-depth analysis of a clinical cohort of HCC using high-coverage phosphoproteomic. Effective therapeutic targets were validated using liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models that correspond to the phosphoproteomic subtypes of HCC. Phosphoproteomic analysis classified HCC into three subtypes, A, B, and C, with increasing malignancy and correlation with clinical features, including patient prognosis, tumor staging, serum alpha fetoprotein (AFP) levels, tumor thrombus, and tumor size. Phosphoproteomic subtyping deeply reflected the biological characteristics and clinical features of HCC patients. The profiles of HCC dysregulated kinase activities inferred from the different phosphoproteomic subtypes, consistently identifying increased kinase activity related to cell proliferation. Subtype-C HCC patients showed the most significant dysregulation, indicating a potential therapeutic target. The corresponding drug, bosutinib, demonstrated efficacy in inhibiting the growth of subtype C tumors in liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models representative of the phosphoproteomic HCC subtypes. Conclusions: Our study provides a comprehensive exploration of the phosphoproteomic landscape of HCC, establishing new subtypes that match clinical features and identifying potential therapeutic targets for the most malignant C subtype.
Wave in Pediatric Type 1 Diabetes Incidence After the Emergence of COVID-19: Peak and Trough Patterns in German Youth—A Population-Based Study From the Prospective Multicenter DPV Registry
Authors: Clemens Kamrath, Alexander J. Eckert, Sarah Lignitz, Nikolas Hillenbrand, Axel Dost, Katharina Warncke, Daniela Klose, Karina Grohmann-Held, Reinhard W. Holl, Joachim Rosenbauer
Journal: Diabetes Care (2025)
Time-dependent reduction of somatic variants in lichen striatus as evidence for the clearance of mutated skin cells
Authors: Byunghyuk Lee, Dong Min Lim, Kihyuk Shin, Hyun Jung Lee, Jungsoo Lee, Hoon-Soo Kim, Byung-Soo Kim, Moon-Bum Kim, Kihun Kim, Won Kyu Kim, Junho Kang, Hyun-Chang Ko, Yun Hak Kim
Journal: Journal of the American Academy of Dermatology (2025)
Language models for data extraction and risk of bias assessment in complementary medicine
Authors: Honghao Lai, Jiayi Liu, Chunyang Bai, Hui Liu, Bei Pan, Xufei Luo, Liangying Hou, Weilong Zhao, Danni Xia, Jinhui Tian, Yaolong Chen, Lu Zhang, Janne Estill, Jie Liu, Xing Liao, Nannan Shi, Xin Sun, Hongcai Shang, Zhaoxiang Bian, Kehu Yang, Luqi Huang, Long Ge, Haodong Li, Ye Wang, Huayu Zhang, Di Zhu, Dongrui Peng, Fan Wang, Yueyan Li, Shilin Tang, Hanxiang Liu, Zeming Li, Zhenhua Yang, Xuan Yu, Yishan Qin
Journal: npj Digital Medicine (2025)

Large language models (LLMs) have the potential to enhance evidence synthesis efficiency and accuracy. This study assessed LLM-only and LLM-assisted methods in data extraction and risk of bias assessment for 107 trials on complementary medicine. Moonshot-v1-128k and Claude-3.5-sonnet achieved high accuracy (≥95%), with LLM-assisted methods performing better (≥97%). LLM-assisted methods significantly reduced processing time (14.7 and 5.9 min vs. 86.9 and 10.4 min for conventional methods). These findings highlight LLMs' potential when integrated with human expertise.
Results of a phase Ib study of olaparib with concomitant radiotherapy in soft-tissue sarcoma: a French sarcoma group study
Authors: P Sargos, M P Sunyach, A Ducassou, C Llacer, D Dinart, A Michot, T Valentin, N Firmin, J Y Blay, P Gillon, C Bellera, A Italiano
Journal: Annals of Oncology (2025)

Radiotherapy is essential for locoregional control in resectable soft-tissue sarcoma (STS) and remains a key strategy for unresectable STS. PARP inhibitors, such as olaparib, may enhance radiosensitivity by targeting DNA damage repair pathways. This multicenter phase 1b trial evaluated the combination of olaparib and radiotherapy in STS of the limbs or trunk wall. Olaparib was administered twice daily at doses of 25, 50, 100, or 150 mg during the dose-escalation phase. Radiotherapy consisted of 50 Gy (25 fractions) for resectable tumors or 59.4 Gy (33 fractions) for unresectable tumors. Radiotherapy was exclusively preoperative for operable patients. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Dose escalation was conducted using the Time-to-Event Continual Reassessment Method (TITE-CRM). Histological response was assessed in surgical cases, and RECIST 1.1 criteria were applied for non-surgical cases. Between October 2016 and April 2021, 41 patients were recruited across five French centers. The RP2D was identified as 100 mg olaparib twice daily. For operable patients, a favorable histological response was observed in 33% of patients, with a local relapse-free survival rate of 90.5% at one year. In contrast, among patients with inoperable tumors, the median progression-free survival was 7.7 months (95% CI: 2.6-28.4), with partial responses achieved in 20% of cases and stable disease in 60%. Grade 3 radiation dermatitis was the most frequent adverse event (34.1%), and two patients experienced grade 5 toxicity (4.8%). The combination of olaparib and radiotherapy is feasible for STS patients but requires stringent selection, avoiding patients with tumors involving critical vascular structures or those at high surgical risk, to minimize severe complications. Further randomized trials are warranted to validate efficacy and safety compared to radiotherapy alone.
Mortality Trends Among Early Adults in the United States, 1999-2023
Authors: Elizabeth Wrigley-Field, Rafeya V. Raquib, Kaitlyn M. Berry, Keeley J. Morris, Andrew C. Stokes
Journal: JAMA Network Open (2025)

This cross-sectional study examines trends in mortality rates among adults aged 25 to 44 years across the pre–COVID-19 pandemic, pandemic, and postpandemic periods.
Adverse Prehospital Events and Outcomes After Traumatic Brain Injury
Authors: Amelia W. Maiga, Hsing-Hua Sylvia Lin, Stephen R. Wisniewski, Joshua B. Brown, Ernest E. Moore, Martin A. Schreiber, Bellal Joseph, Chad T. Wilson, Bryan A. Cotton, Daniel G. Ostermayer, Brian G. Harbrecht, Mayur B. Patel, Jason L. Sperry, Francis X. Guyette, Henry E. Wang
Journal: JAMA Network Open (2025)

Importance While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes. Objective To validate the associations of prehospital hypoxia, hypotension, and hypocarbia with TBI outcomes in a US national trauma network. Design, Setting, and Participants This cohort study examined data from 8 level I trauma centers and their affiliated ground and air emergency medical services (EMS) agencies in the Linking Investigations in Trauma and Emergency Services (LITES) Network from January 1, 2017, to June 30, 2021. Adult patients (aged ≥18 years) with confirmed TBI (head Abbreviated Injury Score [AIS] of 1-6) and Injury Severity Score (ISS) of at least 9 were included. Interfacility transfers and patients who underwent prehospital cardiopulmonary resuscitation were excluded. Data were analyzed between April 20, 2022, and November 27, 2023. Exposures Adverse prehospital TBI events, including hypoxia, hypotension, or hypocarbia. Main Outcomes and Measures The primary outcomes were death in the emergency department (ED), hospital death, and unfavorable discharge disposition. Log-binomial regression models were used to estimate the association between adverse TBI events and outcomes, adjusting for sex, race and ethnicity, age, study site, transport mode, initial Glasgow Coma Scale, ISS, head AIS score, injury mechanism, and multiple trauma. Results The analytic cohort included 14 994 patients (median [IQR] age, 47 [31-64] years; 71% male; median [IQR] head AIS, 3 [2-4]). Patients with adverse TBI events included 12% (1577 of 13 604) with hypoxia, 10% (1426 of 14 842) with hypotension, and 61% (650 of 1068) with hypocarbia among those with advanced airway management. Patient outcomes included 2% (259 of 14 939) who died in the ED, 12% (1764 of 14 623) who died in the hospital, and 25% (3705 of 14 623) with an unfavorable discharge disposition. Hypoxia (adjusted relative risk [ARR], 2.24; 95% CI, 1.69-2.97), hypotension (ARR, 2.05; 95% CI, 1.54-2.72), and hypocarbia (ARR, 7.99; 95% CI, 2.47-25.85) were associated with increased risks of ED death. Each adverse TBI event exposure was also associated with higher risks of hospital death and unfavorable discharge disposition. Conclusions and Relevance In this multicenter cohort study, prehospital hypoxia, hypotension, and hypocarbia were associated with poorer TBI outcomes. These results underscore the importance of optimal oxygenation, ventilation, and perfusion in prehospital TBI care.
Assessing the Gun Violence Archive and Public Police Data as Comprehensive Sources for Gun Violence
Authors: Michael G. Anchan, Jennifer Harris, Sophia Natale-Short, Megan R. Georges, Elizabeth C. Pino
Journal: JAMA Network Open (2025)

This cross-sectional study evaluates how many fatal and nonfatal firearm injuries in the Boston area are captured in the Gun Violence Archive and public police data and what factors are associated with being included in these datasets.
Inequalities at Age of Diagnosis of Severe Mental Illness in England
Authors: Sheena E. Ramsay, Ziyi Cai, David R. Sinclair, Matthew Prina, David P. J. Osborn, Ashley J. Adamson, Eileen Kaner, Emma A. Adams
Journal: JAMA Network Open (2025)

This cohort study evaluates whether socioeconomic factors, including sex, race and ethnicity, material deprivation, and rurality) are associated with the age at which patients are diagnosed with severe mental illness.
Beyond Boundaries in <i>ERBB2</i>-Positive Brain Metastatic Breast Cancer
Authors: Dario Trapani, Carmine Valenza, Giuseppe Curigliano
Journal: JAMA Network Open (2025)

Emanuela Ferraro, MD; Anne S. Reiner, MPH; Rabih Bou Nassif, MD; Umberto Tosi, MD; Samantha Brown, MS; Sabrina Zeller, MD; Chau T. Dang, MD; Andrew D. Seidman, MD; Nelson S. Moss, MD
Adverse Prehospital Events and Traumatic Brain Injury Outcomes
Authors: Ricardo Rendel, Shevonne S. Satahoo, Carl I. Schulman
Journal: JAMA Network Open (2025)

Amelia W. Maiga, MD, MPH; Hsing-Hua Sylvia Lin, MS, PhD; Stephen R. Wisniewski, PhD; Joshua B. Brown, MD, MSc; Ernest E. Moore, MD; Martin A. Schreiber, MD; Bellal Joseph, MD; Chad T. Wilson, MD; Bryan A. Cotton, MD; Daniel G. Ostermayer, MD; Brian G. Harbrecht, MD; Mayur B. Patel, MD, MPH; Jason L. Sperry, MD, MPH; Francis X. Guyette, MD, MPH; Henry E. Wang, MD, MS
Navigating Uncertainty in Digital Health Education
Authors: David M. Liebovitz
Journal: JAMA Network Open (2025)

Josip Car, MD, PhD; Qi Chwen Ong, MBBS; Tatiana Erlikh Fox, MD; Daniel Leightley, PhD; Sandra J. Kemp, PhD; Igor Švab, MD, PhD; Kelvin K. F. Tsoi, PhD; Amir H. Sam, MBBS, PhD; Fiona M. Kent, PhD; Attila J. Hertelendy, PhD; Christopher A. Longhurst, MD, MS; John Powell, MBBChir, PhD; Hossam Hamdy, MBChB, PhD; Huy V.Q. Nguyen, MD, PhD; Sola Aoun Bahous, MD, PhD; Mai Wang, MBBS, PhD; Martin Baumgartner, MSc; Yodi Mahendradhata, MD, PhD; Natasa Popovic, MD, PhD; Andy W. H. Khong, PhD; Charles G. Prober, MD; Rifat Atun, MBBS, MBA; Digital Health Systems Collaborative; Abebe Bekele Zerihun, MD; Akira-Sebastian Poncette, MD; Al Joseph R. Molina, MD; Albano V.L. Ferreira, MD, PhD; Almir Fajkić, MD, PhD; Amit Kaushal, MD, PhD; Andrew J. Farmer, DM; Andrew S. Lane, MBBS, PhD; Andrzej A. Kononowicz, PhD; Aparna V. Bhongir, MD; Barnabas T. Alayande, MBBS; Benard Ayaka Bene, MBBS, MPH; Christian J. Dameff, MD, MS; Cynthia Hallensleben, BSc; David A. Back, MD; Dawan J. Hawezy, MBChB; Dieudonné Steve M. Tulantched, MD; Ekaterina Kldiashvili, PhD; Emmanuel K. Achampong, PhD; Ganesh Ramachandran, MD; Goran Hauser, MD, PhD; Jakob Grove, PhD; Jason P. Y. Cheung, MBBS, MD; John O. Imaralu, MBChB, MD; John O. Sotunsa, MBBS, MPH; Juan P. Bulnes Vides, MD; Katharine S. Lawrence, MD, MPH; Louis Agha-Mir-Salim, MBBS; Luca Saba, MD; Luxia Zhang, MD, MPH; Mahmoud M. A. Elfiky, MD; Markus W. Hesseling, MD; Michelle P. Guppy, MBBS; Mrunal S. Phatak, MBBS, MD; Muna A. A. Al Saadoon, MD, PhD; Nai Ming Lai, MBBS; Niels H. Chavannes, MD, PhD; Oliver Kimberger, MD, MBA; Pedro Povoa, MD, PhD; Poh-Sun Goh, MBBS; Rebecca Grainger, MBChB, PhD; Rishi S. Nannan Panday, MD, PhD; Rowena Forsyth, PhD; Sandro Vento, MD; Sang Yeoup Lee, MD, PhD; Sanjay Kumar Yadav, MCh; Shabbir Syed-Abdul, MD, PhD; Simone Appenzeller, MD, PhD; Spiros Denaxas, PhD; Stephen Ekundayo Garba, MBBS, MTh; Tabea Flügge, DDS; Tomislav Bokun, MD, PhD; Vajira H. W. Dissanayake, MBBS, PhD; Vincent Ho, MBBS, PhD; Yasser A. Obadiel, MD