Over the past decade, our understanding of human diseases has rapidly grown from the rise of single-cell spatial biology. While conventional tissue imaging has focused on visualizing morphological features, the development of multiplex tissue imaging from fluorescence-based methods to DNA- and mass cytometry-based methods has allowed visualization of over 60 markers on a single tissue section. The advancement of spatial biology with a single-cell resolution has enabled the visualization of cell-cell interactions and the tissue microenvironment, a crucial part to understanding the mechanisms underlying pathogenesis. Alongside the development of extensive marker panels which can distinguish distinct cell phenotypes, multiplex tissue imaging has facilitated the analysis of high dimensional data to identify novel biomarkers and therapeutic targets, while considering the spatial context of the cellular environment. This mini-review provides an overview of the recent advancements in multiplex imaging technologies and examines how these methods have been used in exploring pathogenesis and biomarker discovery in cancer, autoimmune and infectious diseases.

We aimed to explore the effects of the 60Co-γ irradiated ginseng adventitious root (GAR) with different radiation doses on the hypoglycemic effects of its extract (GARSE) through in vivo and in vitro experiments. The total saponin of GARSE was increased by 4.50% after 5 kGy irradiation, and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was enhanced by 5.10%. At 50 μg/mL, GARSE irradiated by 5 kGy displayed superior protective effects on human glomerular mesangial cells (HMCs) with high glucose damage. After feeding type 1 diabetes mellitus (T1DM) mice with GARSE irradiated by 5 kGy at 500 mg/kg·BW for 4 weeks, the glucose values was decreased by 16.0% compared with the unirradiated. The Keap1/Nrf2/HO-1 pathway was activated and the oxidative stress was attenuated, which further alleviated T1DM.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

BACKGROUND: Inpatient glucose management can be challenging due to evolving factors that influence a patient\'s blood glucose (BG) throughout hospital admission. The purpose of our study was to predict the category of a patient\'s next BG measurement based on electronic medical record (EMR) data.
METHODS: EMR data from 184,361 admissions containing 4,538,418 BG measurements from five hospitals in the Johns Hopkins Health System were collected from patients who were discharged between January 1, 2015 and May 31, 2019. Index BGs used for prediction included the 5th to penultimate BG measurements (N = 2,740,539). The outcome was category of next BG measurement: hypoglycemic (BG  ≤  70 mg/dl), controlled (BG 71-180 mg/dl), or hyperglycemic (BG > 180 mg/dl). A random forest algorithm that included a broad range of clinical covariates predicted the outcome and was validated internally and externally.
RESULTS: In our internal validation test set, 72·8%, 25·7%, and 1·5% of BG measurements occurring after the index BG were controlled, hyperglycemic, and hypoglycemic respectively. The sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·77/0·81, 0·77/0·89, and 0·73/0·91, respectively. On external validation in four hospitals, the ranges of sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·64-0·70/0·80-0·87, 0·75-0·80/0·82-0·84, and 0·76-0·78/0·87-0·90, respectively.
CONCLUSIONS: A machine learning algorithm using EMR data can accurately predict the category of a hospitalized patient\'s next BG measurement. Further studies should determine the effectiveness of integration of this model into the EMR in reducing rates of hypoglycemia and hyperglycemia.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.

UNASSIGNED: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality.
UNASSIGNED: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk.
UNASSIGNED: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015.
UNASSIGNED: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk.
UNASSIGNED: No funding was obtained for this study.

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

UNASSIGNED: We report a case series of 4 patients with type 1 diabetes who used hybrid closed-loop insulin pumps (Medtronic MiniMed 670 G) during hospitalization.
UNASSIGNED: Clinical data and point-of-care glucose values are presented for each patient. Glucose values are shown graphically while in manual mode as well as in auto mode.
UNASSIGNED: The first case was a 30-year-old man admitted for pancreatitis. Mean point-of-care blood glucose was 165.7 mg/dL while in auto mode, without hypoglycemia, compared with 221 mg/dL while in manual mode. The second case was a 28-year-old woman who was admitted for a laparoscopic cholecystectomy. Mean point-of-care blood glucose in auto mode was 131.3 mg/dL, without hypoglycemia, compared with 117.6 mg/dL while in manual mode. The third case was a 46-year-old man admitted to the intensive care unit for influenzal pneumonia. Mean point-of-care blood glucose in auto mode was 159.1 mg/dL without hypoglycemia, compared with 218.5 mg/dL while in manual mode. The fourth case was a 60-year-old man who remained in auto mode throughout his hospitalization except for a period when he removed his pump for an endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. His mean point-of-care blood glucose while in auto mode was 156.8 mg/dL without hypoglycemia.
UNASSIGNED: These case reports support the use of hybrid closed-loop insulin-pump therapy in the inpatient setting to maintain inpatient glycemic targets and avoid hypoglycemia when part of an institution-sanctioned strategy for safe use of insulin pumps that includes point-of-care blood glucose monitoring.

UNASSIGNED: Hybrid closed-loop (HCL) devices can achieve tight glycemic control but are rarely used in pregnancy, which remains an off-label indication. We present a case of a pregnant patient with type 1 diabetes mellitus (T1DM) who used the Medtronic MiniMed 670G HCL system.
UNASSIGNED: MiniMed 670G includes an advanced automode option (HCL therapy), which our patient used from the first trimester to the end of the pregnancy.
UNASSIGNED: An unplanned pregnancy was detected in the T1DM patient, with a glycated hemoglobin level of 8.7 mmol/L (7.1%). The patient started sensor-augmented pump therapy at week 13. Subsequently, she entered automode (HCL) at week 16. The time in range (3.7-7.8 mmol/mol, 63-140 mg/dL) increased from 46.8% to 51.3% after HCL initiation. The glycated hemoglobin level remained close to 48 mmol/mol (6.5%) until the end of the pregnancy. Furthermore, the time under range (<3.7 mmol/mol, <63 mg/dL) remained below the optimal 4% level during the gestation. Finally, a healthy male baby was born at week 37. No safety events were recorded.
UNASSIGNED: This case represents the successful off-label use of HCL during pregnancy in a patient with T1DM.

UNASSIGNED: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a relatively novel class of oral medications for the treatment of type 2 diabetes mellitus (T2DM). Their use has increased recently due to their beneficial renal and cardiovascular outcomes, but they come with the rare risk of diabetic ketoacidosis (DKA) at normal or slightly elevated glucose values, termed euglycemic DKA (euDKA). Recently, carbohydrate-deprived, ketogenic diets have gained popularity due to benefits of weight loss and improved control of T2DM. We describe 2 patients with T2DM who developed euDKA caused by SGLT2 inhibitor use while on a ketogenic diet and provide a review of the literature.
UNASSIGNED: We describe the hospital course, laboratory data, and treatment of 2 patients and provide a literature review.
UNASSIGNED: Both of our patients were found to have normal or mildly elevated serum glucose levels, with an elevated anion gap and ketosis, representative of euDKA. The first patient developed euDKA after only 1 dose of empagliflozin, while the second patient developed euDKA after only 1 week of being on a ketogenic diet while on an SGLT2 inhibitor.
UNASSIGNED: While there have been a few reports of euDKA with SGLT2 inhibitors and ketogenic diets, many physicians prescribing these medications may not be aware of this association. Therefore, they must inform their patients to avoid a ketogenic diet if on an SGLT2 inhibitor. If a patient presents with symptoms of DKA and is eating a carbohydrate-free diet while taking an SGLT2 inhibitor, there should be a low threshold to screen for DKA.