Role of clinical pharmacists in multidisciplinary collaborative management of blood glucose in COVID-19 patients with hyperglycemia.

BACKGROUND: During the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial. OBJECTIVE: To introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia. METHODS: Patients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events. RESULTS: After 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events. CONCLUSIONS: Multidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators.

RegEMR: a natural language processing system to automatically identify premature ovarian decline from Chinese electronic medical records.

BACKGROUND: The ovarian reserve is a reservoir for reproductive potential. In clinical practice, early detection and treatment of premature ovarian decline characterized by abnormal ovarian reserve tests is regarded as a critical measure to prevent infertility. However, the relevant data are typically stored in an unstructured format in a hospital's electronic medical record (EMR) system, and their retrieval requires tedious manual abstraction by domain experts. Computational tools are therefore needed to reduce the workload. METHODS: We presented RegEMR, an artificial intelligence tool composed of a rule-based natural language processing (NLP) extractor and a knowledge-based disease scoring model, to automatize the screening procedure of premature ovarian decline using Chinese reproductive EMRs. We used regular expressions (REs) as a text mining method and explored whether REs automatically synthesized by the genetic programming-based online platform RegexGenerator + + could be as effective as manually formulated REs. We also investigated how the representativeness of the learning corpus affected the performance of machine-generated REs. Additionally, we translated the clinical diagnostic criteria into a programmable disease diagnostic model for disease scoring and risk stratification. Four hundred outpatient medical records were collected from a Chinese fertility center. Manual review served as the gold standard, and fivefold cross-validation was used for evaluation. RESULTS: The overall F-score of manually built REs was 0.9444 (95% CI 0.9373 to 0.9515), with no significant difference (paired t test p > 0.05) compared with machine-generated REs that could be affected by training set sizes and annotation portions. The extractor performed effectively in automatically tracing the dynamic changes in hormone levels (F-score 0.9518-0.9884) and ultrasonographic measures (F-score 0.9472-0.9822). Applying the extracted information to the proposed diagnostic model, the program obtained an accuracy of 0.98 and a sensitivity of 0.93 in risk screening. For each specific disease, the automatic diagnosis in 76% of patients was consistent with that of the clinical diagnosis, and the kappa coefficient was 0.63. CONCLUSION: A Chinese NLP system named RegEMR was developed to automatically identify high risk of early ovarian aging and diagnose related diseases from Chinese reproductive EMRs. We hope that this system can aid EMR-based data collection and clinical decision support in fertility centers.

Risk Factors for Granulocytopenia in Patients with Graves' Disease Receiving Antithyroid Drugs.

Objective: To study the risk factors for granulocytopenia caused by antithyroid drugs. Methods: Patients who were diagnosed with Graves' hyperthyroidism and regularly treated with antithyroid drugs (ATDs) from January 2010 to July 2022 at Nanjing Drum Tower Hospital, aged >18 years, were selected for general information and laboratory tests and divided into two groups according to the occurrence of granulocytopenia. Independent risk factors for the development of granulocytopenia in patients treated with ATDs were analyzed using one-way and multiway logistic regression analyses, and the predictive value of each index was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 818 patients were enrolled, of which 95 developed granulocytopenia. Univariate analysis revealed that sex, white blood cell (WBC) counts, neutrophil-to-lymphocyte ratio (NLR), glutamic-pyruvic transaminase (ALT), aspartate transaminase (AST), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) before medication were risk factors for ATD-induced granulocytopenia (P < 0.05). The abovementioned indicators were taken as independent variables, and multivariate logistic regression analysis showed that female sex, higher ALT levels before medication, and lower NLR and WBC levels were independent risk factors for granulocytopenia using ATDs (P < 0.05). ROC curve analysis showed that sex, NLR, ALT, and WBC count had significant predictive values (P < 0.05), and NLR and WBC count had higher predictive values (AUC = 0.916 and 0.700, respectively). Conclusion: Sex, NLR, ALT, and WBC were the main risk factors for granulocytopenia in patients with ATD.

Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-d]pyrimidine RET Inhibitors.

The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-d]pyrimidine scaffold. The optimization of this pyrrolo[2,3-d]pyrimidine core resulted in compound 1, which demonstrated potent in vitro RET kinase inhibition and robust in vivo efficacy in RET-driven tumor xenografts upon multiday dosing in mice. The administration of 1 was well-tolerated at established efficacious doses (10 and 30 mg/kg, po, qd), and plasma exposure levels indicated a minimal risk of KDR or hERG inhibition in vivo, as evaluated by Miles assay and free plasma concentrations, respectively.

Role of trace elements in anaerobic digestion of food waste: Process stability, recovery from volatile fatty acid inhibition and microbial community dynamics.

Role of trace elements (TEs) in long-term anaerobic digestion of food waste (FW) under fixed and stepwise increasing loads and under early and medium volatile fatty acid (VFA) inhibition was investigated. Digesters under high load suffered VFA inhibition. Mismatch between scarce TEs in FW and essential TEs for sustainable methanogenesis suppressed Methanosaeta causing blocked aceticlastic methanogenesis and shift to CO2 reduction pathway, as indicated by decreased Methanosaeta from above 70.0% to below 42.0% and enriched hydrogenotrophic methanogens (Methanospirillum, Methanoculleus, Methanobacterium) from below 15.0% to above 53.6%. Dual stresses of VFA inhibition and TEs deficiency resulted in recession of syntrophic Bacteria Syntrophomonadaceae. Conversely, digesters with TEs supplementation maintained high activity of Syntrophomonadaceae and ensured predominant aceticlastic methanogenesis and powerful methanogenic community functions. Early and medium VFA inhibition were reversed by TEs supplementation or coupling with pH adjustment by stimulating VFAs degradation via syntrophic metabolism and unclogging acetate conversion via aceticlastic methanogenesis.

Ultrasensitive Surface Plasmon Resonance Biosensor Using Blue Phosphorus-Graphene Architecture.

This study theoretically proposed a novel surface plasmon resonance biosensor by incorporating emerging two dimensional material blue phosphorus and graphene layers with plasmonic gold film. The excellent performances employed for biosensing can be realized by accurately tuning the thickness of gold film and the number of blue phosphorus interlayer. Our proposed plasmonic biosensor architecture designed by phase modulation is much superior to angular modulation, providing 4 orders of magnitude sensitivity enhancement. In addition, the optimized stacked configuration is 42 nm Au film/2-layer blue phosphorus /4-layer graphene, which can produce the sharpest differential phase of 176.7661 degrees and darkest minimum reflectivity as low as 5.3787 × 10-6. For a tiny variation in local refractive index of 0.0012 RIU (RIU, refractive index unit) due to the binding interactions of aromatic biomolecules, our proposed biosensor can provide an ultrahigh detection sensitivity up to 1.4731 × 105 °/RIU, highly promising for performing ultrasensitive biosensing application.

Efficacy and Tolerability of Pyrazolo[1,5-a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma.

RET (REarranged during Transfection) kinase gain-of-function aberrancies have been identified as potential oncogenic drivers in lung adenocarcinoma, along with several other cancer types, prompting the discovery and assessment of selective inhibitors. Internal mining and analysis of relevant kinase data informed the decision to investigate a pyrazolo[1,5-a]pyrimidine scaffold, where subsequent optimization led to the identification of compound WF-47-JS03 (1), a potent RET kinase inhibitor with >500-fold selectivity against KDR (Kinase insert Domain Receptor) in cellular assays. In subsequent mouse in vivo studies, compound 1 demonstrated effective brain penetration and was found to induce strong regression of RET-driven tumor xenografts at a well-tolerated dose (10 mg/kg, po, qd). Higher doses of 1, however, were poorly tolerated in mice, similar to other pyrazolo[1,5-a]pyrimidine compounds at or near the efficacious dose, and indicative of the narrow therapeutic windows seen with this scaffold.

Dynamic behaviors of batch anaerobic systems of food waste for methane production under different organic loads, substrate to inoculum ratios and initial pH.

This study characterized dynamic behaviors of batch anaerobic digesters treating food waste in terms of methane production, organics destruction and process stability under different organic loads (OLs), substrate to inoculum (S/I) ratios [on volatile solid (VS) basis] and initial pH. The results showed that OL, S/I ratio and initial pH significantly affected batch anaerobic process. Methane yield was proved to be inversely proportional to OL and S/I ratio. Digester with lowest OL (5 g VS/L) obtained greatest methane yield (551.4 mL/g VS), highest organics removal (94.1%) and good stability. Enhancing OL to 10 g VS/L was recommended for satisfactory stability and higher volumetric methane productivity. When OL was designated as 10 g VS/L, digester with low S/I ratio (1/2) achieved satisfactory methane yield (539.3 mL/g VS), high organics removal (92.3%) and stable performance. When OL was relatively high (20 g VS/L), adjusting initial pH to 7.5 contributed to stable performance via enhancing buffering capacity against volatile fatty acids (VFA) disturbance. Strong VFA inhibition occurred under high OL (40 g VS/L) or great S/I ratio (2/1) or acidic initial pH (6.5). In this case, acetate was dominant VFA, followed by butyrate. However, when digester was stable, acetate was main VFA, followed by propionate. This study provided practical guidance on process configurations for batch digesters of food waste needed to achieve satisfactory performance and stability.

Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.

Constitutive overexpression and activation of NPM-ALK fusion protein [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival and proliferation of anaplastic large-cell lymphomas (ALCLs). We have identified a highly potent and selective small-molecule ALK inhibitor, NVP-TAE684, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC(50) values between 2 and 10 nM. NVP-TAE684 treatment resulted in a rapid and sustained inhibition of phosphorylation of NPM-ALK and its downstream effectors and subsequent induction of apoptosis and cell cycle arrest. In vivo, NVP-TAE684 suppressed lymphomagenesis in two independent models of ALK-positive ALCL and induced regression of established Karpas-299 lymphomas. NVP-TAE684 also induced down-regulation of CD30 expression, suggesting that CD30 may be used as a biomarker of therapeutic NPM-ALK kinase activity inhibition.