Current Status and Future Directions: The Application of Artificial Intelligence/Machine Learning for Precision Medicine.

Technological innovations, such as artificial intelligence (AI) and machine learning (ML), have the potential to expedite the goal of precision medicine, especially when combined with increased capacity for voluminous data from multiple sources and expanded therapeutic modalities; however, they also present several challenges. In this communication, we first discuss the goals of precision medicine, and contextualize the use of AI in precision medicine by showcasing innovative applications (e.g., prediction of tumor growth and overall survival, biomarker identification using biomedical images, and identification of patient population for clinical practice) which were presented during the February 2023 virtual public workshop entitled "Application of Artificial Intelligence and Machine Learning for Precision Medicine," hosted by the US Food and Drug Administration (FDA) and University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI). Next, we put forward challenges brought about by the multidisciplinary nature of AI, particularly highlighting the need for AI to be trustworthy. To address such challenges, we subsequently note practical approaches, viz., differential privacy, synthetic data generation, and federated learning. The proposed strategies - some of which are highlighted presentations from the workshop - are for the protection of personal information and intellectual property. In addition, methods such as the risk-based management approach and the need for an agile regulatory ecosystem are discussed. Finally, we lay out a call for action that includes sharing of data and algorithms, development of regulatory guidance documents, and pooling of expertise from a broad-spectrum of stakeholders to enhance the application of AI in precision medicine.

Endoscopic retrograde cholangiopancreatography using short-type double-balloon enteroscope: Experience in Hong Kong.

OBJECTIVE: To illustrate the efficacy and safety profile of double-balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) using a short enteroscope in patients with surgically altered anatomy. METHODS: A retrospective study was performed to review the endoscopic outcomes of patients undergoing DBE-assisted ERCP for biliary diseases in Tuen Mun and Pok Oi hospitals in Hong Kong SAR, China from December 2015 to December 2020. RESULTS: Altogether 46 DBE-assisted ERCP procedures were performed in 37 patients. The enteroscopic success rate, defined as reaching the papilla or bilioenteric anastomosis, was 95.7% (95% confidence interval [CI] 85.2%-99.5%), which was significantly lower in patients with intact stomach than in those who had a previous gastrectomy (67% vs 100%, P = 0.014). The diagnostic ERCP success rate, defined as performance in an informative cholangiogram, was 84.1% (95% CI 69.9%-93.4%) in cases where it was attempted. Intended biliary therapeutic interventions were successfully performed in 76.1% (95% CI 61.2%-87.4%) of all procedures. Adverse events were reported in six (13.0%) procedures (95% CI 4.9%-26.3%), including the micro-perforation of the intestine in two (4.3%) patients with prior Roux-en-Y gastrectomy, three (6.5%) of acute cholangitis and one (2.2%) of acute pancreatitis. All adverse events were managed successfully using conservative methods except in one case of micro-perforation, which required a laparotomy. CONCLUSIONS: DBE-assisted ERCP using a short enteroscope is a promising technique for managing biliary diseases in patients with surgically altered anatomy. It must be performed to avoid perforation, particularly in patients with a Roux-en-Y reconstruction.

COVID-19: Where are the Nigerian social workers?

The emergence of COVID-19 pandemic has brought untold hardship across the globe. Developed nations have taken relatively commendable actions to quell its impact on livelihood and most have also included social workers in the frontline due to their expertise in working with vulnerable populations. Same cannot be said of developing nations particularly Nigeria who hurriedly copied the measures adopted by the developed nations without carefully considering her peculiarities. Given Nigeria's high poverty rate prior to and even higher during the pandemic as well as the few available resources, it is important that Nigerian social workers should be called upon as frontline workers with regards to the welfare of the vulnerable and the psychosocial well-being of infected persons and their families. Instead, Nigeria has totally ignored the importance of social workers and palliatives have been stolen by those tasked with distribution while the psychosocial well-being of affected persons has been left to fate.

Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine.

BACKGROUND: Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines. METHODS: With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care. RESULTS: High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus CONCLUSION: The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.

Taiwan Government-Guided Strategies Contributed to Combating and Controlling COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is highly contagious, and thus has become an emerging health crisis worldwide. The optimal strategies to prevent the spread of this disease are inconclusive, and therefore, the adopted measurements to combat COVID-19 varies in different countries. In mid-March and late-August 2020, we performed internet searches to collect relevant information, from sources such as the website of the World Health Organization. The epidemiological data of COVID-19 from several countries were collected and we found that Taiwan had a comparably successful story for combating the pandemic. As of mid-March, Taiwan had high rates of diagnostic testing (688.5 tests per million citizens) with a lower infection rate (49 cases, 2.1 cases per million people). As of late-August, there were 488 cases (20 cases per million people). Furthermore, Taiwanese government-guided strategies and hospital data were also reviewed. We summarized some important strategies to combat COVID-19, which include: (1) border control; (2) official media channel and press conferences; (3) name-based rationing system for medical masks; (4) TOCC-based rapid triage, outdoor clinics, and protective sampling devices; and (5) social distancing, delaying the start of new semesters, and religious assembly restriction. In conclusion, Taiwan had lower rates of COVID-19 compared with other countries, and Taiwan government-guided strategies contributed to the control of the disease's spread.

The impact of four processing methods on trypsin-, chymotrypsin- and alpha-amylase inhibitors present in underutilised legumes.

The global trend in increasing plant-based protein diets due to health and ideological reasons, has created an increased demand for food legumes that exceeds current production. To meet this demand, it is timely to reduce relying solely on soybean, and explore the potential of the underutilised legumes that are cultivated regionally. Underutilised legumes are rich in protein, carbohydrates and other nutrients that are essential for consumer. However, relatively little is known about their anti-nutritional properties and processing methods. Anti-nutritional factors (ANFs) such as enzyme inhibitors are prevalent in legumes and may interfere with digestibility and nutrient absorption. Nevertheless, an optimised food processing method will overcome this challenge and warrant a safe inclusion of legume in plant-based protein diets. Hence current study aimed to optimise the food processing methods (soaking, wet heating, autoclaving and freezing) and evaluate their efficiency in eliminating the enzyme inhibitors [trypsin, chymotrypsin (CIA) and α-amylase (AIA) inhibitors] present in seven underutilised legumes. Current study showed that autoclaving at 121 °C for 15 min reduced the AIA in all underutilised legumes tested. The AIA and CIA of bambara groundnut were successfully inactivated by wet heating at 50 °C for 60 min, and by autoclaving at 121 °C for 15 min. While the CIA of chickpea was successfully inactivated by freezing at - 80 °C for 24 h.

Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model.

AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid.

Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA.

New antitubercular agents are needed to combat the spread of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis. The frontline antitubercular drug isoniazid (INH) targets the mycobacterial enoyl-ACP reductase, InhA. Resistance to INH is predominantly through mutations affecting the prodrug-activating enzyme KatG. Here, we report the identification of the diazaborines as a new class of direct InhA inhibitors. The lead compound, AN12855, exhibited in vitro bactericidal activity against replicating bacteria and was active against several drug-resistant clinical isolates. Biophysical and structural investigations revealed that AN12855 binds to and inhibits the substrate-binding site of InhA in a cofactor-independent manner. AN12855 showed good drug exposure after i.v. and oral delivery, with 53% oral bioavailability. Delivered orally, AN12855 exhibited dose-dependent efficacy in both an acute and chronic murine model of tuberculosis infection that was comparable with INH. Combined, AN12855 is a promising candidate for the development of new antitubercular agents.

[Introduction of Clinical Practice Guidelines for Emergency Patients].

A hospital emergency department is unique among medical environments, with risks of medical errors often higher than in other medical units. Previous studies have confirmed that establishing comprehensive clinical practice guidelines in the emergency department reduces medical costs and improves patient safety and satisfaction. Furthermore, having these guidelines positively influences and significantly impacts the work of emergency care professionals. This article addresses the current assessment and treatment of common emergency care, including non-invasive temperature measurements, oxygenated monitoring during procedural sedation and analgesia, postural differences and vital signs monitoring, and difficulties in peripheral vein placement. Further, this article introduces the recommendations of the Emergency Nurses Association on the empirical level and in terms of the clinical application of these practices in order to help emergency staffs develop domestic and local emergency clinical care guidelines in order to reduce the incidence of medical malpractice and improve care quality and patient satisfaction.

Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656).

There is an urgent need to develop new and safer antitubercular agents that possess a novel mode of action. We synthesized and evaluated a novel series of 3-aminomethyl 4-halogen benzoxaboroles as Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase (LeuRS) inhibitors. A number of Mtb LeuRS inhibitors were identified that demonstrated good antitubercular activity with high selectivity over human mitochondrial and cytoplasmic LeuRS. Further evaluation of these Mtb LeuRS inhibitors by in vivo pharmacokinetics (PK) and murine tuberculosis (TB) efficacy models led to the discovery of GSK3036656 (abbreviated as GSK656). This molecule shows potent inhibition of Mtb LeuRS (IC50 = 0.20 µM) and in vitro antitubercular activity (Mtb H37Rv MIC = 0.08 µM). Additionally, it is highly selective for the Mtb LeuRS enzyme with IC50 of >300 µM and 132 µM for human mitochondrial LeuRS and human cytoplasmic LeuRS, respectively. In addition, it exhibits remarkable PK profiles and efficacy against Mtb in mouse TB infection models with superior tolerability over initial leads. This compound has been progressed to clinical development for the treatment of tuberculosis.

Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase.

The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against M. tuberculosis in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against M. tuberculosis Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.

Enhancing growth and non-specific immunity of grass carp and Nile tilapia by incorporating Chinese herbs (Astragalus membranaceus and Lycium barbarum) into food waste based pellets.

The effects of Astragalus membranaceus and Lycium barbarum on the growth performance and non-specific immunity of grass carp and Nile tilapia were studied. Herb extracts of Chinese medicinal herbs (2 g kg-1 or 20 g kg-1) were incorporated into food waste based fish feed pellets. Fish growth and selected non-specific immune parameters of grass carp and Nile tilapia were studied in two separate feeding trials. Both grass carp and Nile tilapia fed diets of feed pellets containing 2 g kg-1Lycium barbarum extract achieved the best relative weight gain, feed conversion ratio, specific growth rate and protein efficiency ratio among all experimental diets. Fish fed with diets containing 2 g kg-1Lycium barbarum also resulted in significantly higher total immunoglobin, bactericidal activity and anti-protease activity; and also a lower mortality when challenged with pathogenic bacteria. On the other hand, both fish species fed with diets containing 20 g kg-1 of Astragalus membranaceus and 20 g kg-1Lycium barbarum, resulted in significantly impaired weight gain. In addition, incorporation of 2 g kg-1Lycium barbarum extract would be a more suitable dose for both fish species, in terms of achieving better feed conversion ratio, specific growth rate, protein digestibility, and improved non-specific immune parameters. Based on this study, it can be concluded that waste based feed pellets incorporated with Chinese medicinal herb extracts have the ability to enhance growth and immunity of fish. Therefore, the use of Chinese medicinal herbs in aquaculture should be encouraged, in order to replace certain antibiotics known to impose environmental and health effects through the discharge of aquaculture effluents.

Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase.

There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum Two 3-aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [(14)C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS.

Recycle food wastes into high quality fish feeds for safe and quality fish production.

The amount of food waste generated from modern societies is increasing, which has imposed a tremendous pressure on its treatment and disposal. Food waste should be treated as a valuable resource rather than waste, and turning it into fish feeds would be a viable alternative. This paper attempts to review the feasibility of using food waste to formulate feed pellets to culture a few freshwater fish species, such as grass carp, grey mullet, and tilapia, under polyculture mode (growing different species in the same pond). These species occupy different ecological niches, with different feeding modes (i.e., herbivorous, filter feeding, etc.), and therefore all the nutrients derived from the food waste could be efficiently recycled within the ecosystem. The problems facing environmental pollution and fish contamination; the past and present situation of inland fish culture (focusing on South China); upgrade of food waste based feed pellets by adding enzymes, vitamin-mineral premix, probiotics (yeast), prebiotics, and Chinese medicinal herbs into feeds; and potential health risks of fish cultivated by food waste based pellets are discussed, citing some local examples. It can be concluded that appropriate portions of different types of food waste could satisfy basic nutritional requirements of lower trophic level fish species such as grass carp and tilapia. Upgrading the fish pellets by adding different supplements mentioned above could further elevated the quality of feeds, leading to higher growth rates, and enhanced immunity of fish. Health risk assessments based on the major environmental contaminants (mercury, PAHs and DDTs) in fish flesh showed that fish fed food waste based pellets are safer for consumption, when compared with those fed commercial feed pellets.

A novel client service quality measuring model and an eHealthcare mitigating approach.

OBJECTIVES: Facing population ageing in Hong Kong, the demand of long-term elderly health care services is increasing. The challenge is to support a good quality service under the constraints faced by recent shortage of nursing and care services professionals without redesigning the work flow operated in the existing elderly health care industries. the existing elderly health care industries. RESULTS: The Total QoS measure based on Finite Capacity Queuing Model is a reliable method and an effective measurement for Quality of services. The value is good for measuring the staffing level and offers a measurement for efficiency enhancement when incorporate new technologies like ICT. The implemented system has improved the Quality of Service by more than 14% and the extra released manpower resource will allow clinical care provider to offer further value added services without actually increasing head count. CONCLUSIONS: We have developed a novel Quality of Service measurement for Clinical Care services based on multi-queue using finite capacity queue model M/M/c/K/n and the measurement is useful for estimating the shortage of staff resource in a caring institution. It is essential for future integration with the existing widely used assessment model to develop reliable measuring limits which allow an effective measurement of public fund used in health care industries.

Food wastes as fish feeds for polyculture of low-trophic-level fish: bioaccumulation and health risk assessments of heavy metals in the cultured fish.

The major purpose of this study was to use different types of food wastes which serve as the major sources of protein to replace the fish meal used in fish feeds to produce quality fish. Two types of food waste-based feed pellets FW A (with cereals) and FW B (with cereals and meat products) and the commercial feed Jinfeng® were used to culture fingerlings of three low-trophic-level fish species: bighead carp, grass carp, and mud carp (in the ratio of 1:3:1) for 1 year period in the Sha Tau Kok Organic Farm in Hong Kong. Heavy metal concentrations in all of the fish species fed with food waste pellets and commercial pellets in Sha Tau Kok fish ponds were all below the local and international maximum permissible levels in food. Health risk assessments indicated that human consumption of the fish fed with food waste feed pellets was safe for the Hong Kong residents. The present results revealed that recycling of food waste for cultivating low-trophic-level fish (mainly herbivores and detritus feeders) is feasible, and at the same time will ease the disposal pressure of food waste, a common problem of densely populated cities like Hong Kong.

Emergency medicine as a specialty in Asia.

Aim: We aim to examine the similarities and differences in areas of EM development, workload, workforce, and capabilities and support in the Asia region. Emerging challenges faced by our EM community are also discussed. Methods: The National Societies for Emergency Medicine of Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand and Turkey participated in the joint Japanese Association of Acute Medicine (JAAM) and Asian Conference of Emergency Medicine (ACEM) Special Symposium held in October 2013 at Tokyo, Japan. The findings are reviewed in this paper. Results: Emergency medicine (EM) has over the years evolved into a distinct and recognized medical discipline requiring a unique set of cognitive, administrative and technical skills for managing all types of patients with acute illness or injury. EM has contributed to healthcare by providing effective, safe, efficient and cost-effective patient care. Integrated systems have developed to allow continuity of emergency care from the community into emergency departments. Structured training curriculum for undergraduates, and specialty training programs for postgraduates are in place to equip trainees with the knowledge and skills required for the unique practice of EM. Conclusion: The practice of EM still varies among the Asian countries. However, as a region, we strive to continue in our efforts to develop the specialty and improve the delivery of EM.

The use of food waste-based diets and Napier grass to culture grass carp: growth performance and contaminants contained in cultured fish.

The present study used commercial feeds, food waste feeds, Napier grass, and mixed feeds (food waste feed to Napier grass ratio, 1:10) to feed grass carp (Ctenopharyngodon idellus). The results indicated that grass carp fed with food waste feeds and mix feeds achieved growth performance (based on specific growth rate and feed conversion ratio) that was similar to commercial feeds (p > 0.05). Concentrations of metalloid/metals in food waste feeds and polycyclic aromatic hydrocarbons (PAHs) in Napier grass were relatively higher than other types of fish feeds (p < 0.05). However, most of the metalloid/metals and PAH levels in fish fed with four types of fish feeds were not significantly different (p > 0.05). These findings show that food waste feeds are suitable for using in the production of fish feed and Napier grass can be served as supplemental feeds for grass carp, and hence reducing the production cost.

Use of food waste as fish feeds: effects of prebiotic fibers (inulin and mannanoligosaccharide) on growth and non-specific immunity of grass carp (Ctenopharyngodon idella).

The effects of inulin and mannanoligosaccharide (MOS) on the growth performance and non-specific immunity of grass carp were studied. Two doses of prebiotic fiber with 0.2 or 2% of the fibers are being mixed into fish feed pellets. Fish growth as well as selected non-specific immune parameters of grass carp were tested in a feeding trial, which lasted for 8 weeks. Fish was fed at 2.5% body mass per day. INU02, INU2, and MOS2 significantly improved relative weight gain, specific growth rate, protein efficiency ratio, and food conversion ratio of grass carp fed with food waste-based diet. In terms of non-specific immune response, grass carp showed significant improvement in all three tested parameters (total serum immunoglobin, bactericidal activity, and anti-protease activity). Adding 2% of inulin (INU2) into food waste diets seemed to be more preferable than other supplemented experimental diets (INU02, MOS02, MOS2), as it could promote growth of grass carp as well as improving the non-specific immune systems of grass carp.