Toward Unified AI Drug Discovery with Multimodal Knowledge.

Background: In real-world drug discovery, human experts typically grasp molecular knowledge of drugs and proteins from multimodal sources including molecular structures, structured knowledge from knowledge bases, and unstructured knowledge from biomedical literature. Existing multimodal approaches in AI drug discovery integrate either structured or unstructured knowledge independently, which compromises the holistic understanding of biomolecules. Besides, they fail to address the missing modality problem, where multimodal information is missing for novel drugs and proteins. Methods: In this work, we present KEDD, a unified, end-to-end deep learning framework that jointly incorporates both structured and unstructured knowledge for vast AI drug discovery tasks. The framework first incorporates independent representation learning models to extract the underlying characteristics from each modality. Then, it applies a feature fusion technique to calculate the prediction results. To mitigate the missing modality problem, we leverage sparse attention and a modality masking technique to reconstruct the missing features based on top relevant molecules. Results: Benefiting from structured and unstructured knowledge, our framework achieves a deeper understanding of biomolecules. KEDD outperforms state-of-the-art models by an average of 5.2% on drug-target interaction prediction, 2.6% on drug property prediction, 1.2% on drug-drug interaction prediction, and 4.1% on protein-protein interaction prediction. Through qualitative analysis, we reveal KEDD's promising potential in assisting real-world applications. Conclusions: By incorporating biomolecular expertise from multimodal knowledge, KEDD bears promise in accelerating drug discovery.

The Twists and Turns of Diagnosis and Treatment of Pediatric Neuro-Behcet's Disease: A Case Report and Literature Review.

Background: The neurological manifestation of Behcet's disease (BD) is known as Neuro-Behcet's disease (NBD). The lack of a specific diagnostic method for NBD renders the diagnosis and treatment of NBD challenging. Methods and Results: We report a boy aged 11 years and 11 months who underwent right-eye intraocular lens implantation, appendectomy, perianal abscess removal, thalidomide therapy, and infliximab infusions for his Crohn disease. Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) were performed to address the onset of headache during the course of his treatment, and cerebral venous sinus thrombosis was detected. After the diagnosis of NBD, the patient was treated with anticoagulation therapy (nadroparin calcium), low-dose corticosteroids, and an immunosuppressant (cyclophosphamide), and consequently, he recovered. Conclusion: This case report shows that NBD is prone to misdiagnosis and missed diagnosis and should be diagnosed based on clinical manifestations and results from colonoscopy, pathological examination, and MRI or MRV.

Role of community health service programs in navigating the medical ethical slippery slope-a 10-year retrospective study among medical students from southern China.

BACKGROUND: For promoting autonomous learning motivation, the learning effect of community-oriented service is beneficial, because through community participation and service, students can transfer their implicit cognition of ethics into explicit cognition, leading to the cultivation of a sympathetic partnership between the community and medical students. Despite the proven benefits of medical students' community health service (CHS) in Western countries, CHS programs designed for medical students are not well established in mainland China, and their effects on medical students' ethical cognition are largely unknown. This study evaluated the effects of CHS programs on the ethical cognition of medical students. METHODS: A cross-sectional study was conducted on third- and fourth-year medical students and graduates working at Shantou University Medical College by using a self-administered anonymous questionnaire. Through interviews, we applied a thematic approach to analyze the responses of the participating students. The questionnaire adopted in this study was revised based on a review of the literature on medical ethics in medical students and on the CHS environment in China. The reviewed questionnaires included an evaluation questionnaire on cultivating medical ethics in a CHS context, and questionnaires used to explore the cultivation and transformation of medical ethics in medical students during the preclinical period. RESULTS: A total of 361 (54.4%) undergraduate medical students and 302 (45.6%) graduates participated in this survey. Significant differences were observed in self-evaluation of the cognitive development of ethics between those who had participated in CHS programs 1-5 times and those who had participated > 6 times. The successful identification of accepting money from the patients under the table as unethical behavior significantly differed (p = .031) among the graduates but not (p = .567) among the undergraduate students. The participants expressed the positive impact of CHS programs on their self-development. CONCLUSION: CHS programs can be widely applied in medical education in China. This educational strategy, which supports medical professionalism and incorporates humanitarian behavior as a complement to learning, should be encouraged and promoted nationally.

ß-MnO2 /Metal-Organic Framework Derived Nanoporous ZnMn2 O4 Nanorods as Lithium-Ion Battery Anodes with Superior Lithium-Storage Performance.

Nanoporous ZnMn2 O4 nanorods have been successfully synthesized by calcining ß-MnO2 /ZIF-8 precursors (ZIF-8 is a type of metal-organic framework). If measured as an anode material for lithium-ion batteries, the ZnMn2 O4 nanorods exhibit an initial discharge capacity of 1792 mA h g-1 at 200 mA g-1 , and an excellent reversible capacity of 1399.8 mA h g-1 after 150 cycles (78.1 % retention of the initial discharge capacity). Even at 1000 mA g-1 , the reversible capacity is still as high as 998.7 mA h g-1 after 300 cycles. The remarkable lithium-storage performance is attributed to the one-dimensional nanoporous structure. The nanoporous architecture not only allows more lithium ions to be stored, which provides additional interfacial lithium-storage capacity, but also buffers the volume changes, to a certain degree, during the Li+ insertion/extraction process. The results demonstrate that nanoporous ZnMn2 O4 nanorods with superior lithium-storage performance have the potential to be candidates for commercial anode materials in lithium-ion batteries.

Uncommon foreign body in the hypopharynx: A case report.

RATIONALE: Pharyngeal foreign bodies are a common complaint in emergent cases, and sometimes can be lethal. A large variety of foreign bodies may lodge in the pharynx. We present a case of uncommon foreign body in the hypopharynx. PATIENT CONCERNS: A 9-month-old boy presented for an hour of crying associated with having congee. No abnormality was revealed in physical examination or cervicothoracic computed tomography (CT) scan. Flexible laryngoscopy showed a size tag on the posterior hypopharyngeal wall. DIAGNOSES: Foreign body in the hypopharynx. INTERVENTIONS: The foreign body was removed from the hypopharynx. OUTCOMES: The patient was discharged after the removal of the foreign body. LESSONS: Infants with foreign bodies in the hypopharynx may presented with no obvious clinical manifestation. Pharyngeal foreign bodies may be the potential for disastrous consequences. Otolaryngologists should pay attention to these foreign bodies.

Presence of Tablet Remnants of Nevirapine Extended-Release in Stools and Its Impact on Virological Outcome in HIV-1-Infected Patients: A Prospective Cohort Study.

BACKGROUND: Nevirapine extended-release (NVP-XR) taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies. METHODS: Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(t)ide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively) of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded. RESULTS: During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1%) noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002) and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76) on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively), but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06), and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95) when compared with those who did not notice tablet remnants. CONCLUSIONS: The presence of tablet remnants of NVP XR in stools is not uncommon in HIV-1-infected Taiwanese patients receiving NVP XR-based antiretroviral regimens, which does not have an adverse impact on the virological and immunological outcomes.