The Challenges and Pitfalls of Detecting Sleep Hypopnea Using a Wearable Optical Sensor: Comparative Study.

BACKGROUND Obstructive sleep apnea (OSA) is the most prevalent respiratory sleep disorder occurring in 9% to 38% of the general population. About 90% of patients with suspected OSA remain undiagnosed due to the lack of sleep laboratories or specialists and the high cost of gold-standard in-lab polysomnography diagnosis, leading to a decreased quality of life and increased health care burden in cardio- and cerebrovascular diseases. Wearable sleep trackers like smartwatches and armbands are booming, creating a hope for cost-efficient at-home OSA diagnosis and assessment of treatment (eg, continuous positive airway pressure [CPAP] therapy) effectiveness. However, such wearables are currently still not available and cannot be used to detect sleep hypopnea. Sleep hypopnea is defined by ≥30% drop in breathing and an at least 3% drop in peripheral capillary oxygen saturation (Spo2) measured at the fingertip. Whether the conventional measures of oxygen desaturation (OD) at the fingertip and at the arm or wrist are identical is essentially unknown. OBJECTIVE We aimed to compare event-by-event arm OD (arm_OD) with fingertip OD (finger_OD) in sleep hypopneas during both naïve sleep and CPAP therapy. METHODS Thirty patients with OSA underwent an incremental, stepwise CPAP titration protocol during all-night in-lab video-polysomnography monitoring (ie, 1-h baseline sleep without CPAP followed by stepwise increments of 1 cmH2O pressure per hour starting from 5 to 8 cmH2O depending on the individual). Arm_OD of the left biceps muscle and finger_OD of the left index fingertip in sleep hypopneas were simultaneously measured by frequency-domain near-infrared spectroscopy and video-polysomnography photoplethysmography, respectively. Bland-Altman plots were used to illustrate the agreements between arm_OD and finger_OD during baseline sleep and under CPAP. We used t tests to determine whether these measurements significantly differed. RESULTS In total, 534 obstructive apneas and 2185 hypopneas were recorded. Of the 2185 hypopneas, 668 (30.57%) were collected during baseline sleep and 1517 (69.43%), during CPAP sleep. The mean difference between finger_OD and arm_OD was 2.86% (95% CI 2.67%-3.06%, t667=28.28; P<.001; 95% limits of agreement [LoA] -2.27%, 8.00%) during baseline sleep and 1.83% (95% CI 1.72%-1.94%, t1516=31.99; P<.001; 95% LoA -2.54%, 6.19%) during CPAP. Using the standard criterion of 3% saturation drop, arm_OD only recognized 16.32% (109/668) and 14.90% (226/1517) of hypopneas at baseline and during CPAP, respectively. CONCLUSIONS arm_OD is 2% to 3% lower than standard finger_OD in sleep hypopnea, probably because the measured arm_OD originates physiologically from arterioles, venules, and capillaries; thus, the venous blood adversely affects its value. Our findings demonstrate that the standard criterion of ≥3% OD drop at the arm or wrist is not suitable to define hypopnea because it could provide large false-negative results in diagnosing OSA and assessing CPAP treatment effectiveness

Constructing a Population-Based Research Database from Routine Maternal Screening Records: A Resource for Studying Alloimmunization in Pregnant Women

Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues.Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays.More than one million (1,191,761) births with valid screening information from 1982–2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time.This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions, such as the etiological significance of non-anti-D antibodies

Clinical application value of metagenomic second-generation sequencing technology in hematologic diseases with and without transplantation

IntroductionHematological patients are at risk of infections. It is unknown whether the pathogenic microbial spectrum differs between HSCT and non-HSCT patients, and whether metagenomic next-generation sequencing (mNGS) of peripheral blood can be used as a substitute test specimen such as alveolar lavage.MethodsA retrospective study was conducted to evaluate the clinical application value of mNGS in hematological patients with and without HSCT.ResultsViruses were prevalent pathogens in both non-HSCT (44%) and HSCT (45%) patients, chiefly human cytomegalovirus and Epstein–Barr virus. In non-HSCT patients, Gram-negative bacilli accounted for 33% (predominantly Klebsiella pneumonia), and Gram-positive cocci accounted for 7% (predominantly Enterococcus faecium) of pathogens. However, in HSCT patients, Gram-negative bacilli accounted for 13% (predominantly Stenotrophomonas maltophilia), and Gram-positive cocci accounted for 24% (predominantly Streptococcus pneumonia) of pathogens. Mucor was the most common fungu s in two groups. The positive rate of pathogens by mNGS was 85.82%, higher than conventional detection (20.47%, P &lt; 0.05). Mixed infection accounted for 67.00%, among which the mixed infection of bacteria and virus (25.99%) was the most common. 78 cases had pulmonary infection, the positive rate of traditional laboratory tests was 42.31% (33/78), and of mNGS in peripheral blood was 73.08% (57/78), showing a statistical difference (P = 0.000). The non-HSCT patients had a higher frequency of Klebsiella pneumonia (OR=0.777, 95% CI, 0.697-0.866, P = 0.01) and Torque teno virus (OR=0.883, 95% CI, 0.820-0.950, P = 0.031) infections than HSCT patients, while the rates of Streptococcus pneumonia (OR=12.828, 95% CI, 1.378-119.367, P = 0.016), Candida pseudosmooth (OR=1.100, 95% CI, 0.987-1.225, P = 0.016), human betaherpesvirus 6B (OR=6.345, 95% CI, 1.105-36.437, P = 0.039) and human polyomavirus 1 (OR=1.100, 95% CI, 0.987-1.225, P = 0.016) infections were lower. Leishmania could be detected by mNGS.ConclusionmNGS of peripheral blood can be used as a substitute test method for hematological patients with pulmonary infection, the detection rate of mixed infections by mNGS was high, and mNGS has high clinical recognition rate and sensitivity in pathogen detection, and provides a basis for guiding the anti-infective treatment in hematological diseases with symptoms such as fever

Advances in targeted therapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal malignancy characterized by genetic heterogeneity due to recurrent gene mutations. Treatment with cytotoxic chemotherapy has been the standard of care for more than half of a century. Although much progress has been made toward improving treatment related mortality rate in the past few decades, long term overall survival has stagnated. Exciting developments of gene mutation-targeted therapeutic agents are now changing the landscape in AML treatment. New agents offer more clinical options for patients and also confer a more promising outcome. Since Midostaurin, a FLT3 inhibitor, was first approved by US FDA in 2017 as the first gene mutation-targeted therapeutic agent, an array of new gene mutation-targeted agents are now available for AML treatment. In this review, we will summarize the recent advances in gene mutation-targeted therapies for patients with AML

m5U-GEPred: prediction of RNA 5-methyluridine sites based on sequence-derived and graph embedding features.

5-Methyluridine (m5U) is one of the most common post-transcriptional RNA modifications, which is involved in a variety of important biological processes and disease development. The precise identification of the m5U sites allows for a better understanding of the biological processes of RNA and contributes to the discovery of new RNA functional and therapeutic targets. Here, we present m5U-GEPred, a prediction framework, to combine sequence characteristics and graph embedding-based information for m5U identification. The graph embedding approach was introduced to extract the global information of training data that complemented the local information represented by conventional sequence features, thereby enhancing the prediction performance of m5U identification. m5U-GEPred outperformed the state-of-the-art m5U predictors built on two independent species, with an average AUROC of 0.984 and 0.985 tested on human and yeast transcriptomes, respectively. To further validate the performance of our newly proposed framework, the experimentally validated m5U sites identified from Oxford Nanopore Technology (ONT) were collected as independent testing data, and in this project, m5U-GEPred achieved reasonable prediction performance with ACC of 91.84%. We hope that m5U-GEPred should make a useful computational alternative for m5U identification

Four-Dimensional Computed Tomography-Based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophageal Cancer

Purpose: To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Methods and Materials: The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results: Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Conclusions: Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses. © 2008 Elsevier Inc. All rights reserved

Trimester-and Assay-Specific Thyroid Reference Intervals for Pregnant Women in China

Objective. The guidelines of the American Thyroid Association (ATA) recommend an upper limit reference interval (RI) of thyroid stimulating hormone (TSH) of 2.5 mIU/L in the first trimester of pregnancy and 3.0 mIU/L in subsequent trimesters, but some reported ranges in China are significantly higher. Our study aimed to establish trimester-and assay-specific RIs for thyroid hormones in normal pregnant Chinese women. Methods. In this cross-sectional study, 2540 women with normal pregnancies (first trimester, = 398; second trimester, = 797; third trimester, = 1345) and 237 healthy nonpregnant control subjects were recruited. Serum TSH, free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels were determined by automated chemiluminescence with an Immulite 2000 system (Siemens, Erlangen, Germany). After outliers were excluded, the 2.5-97.5th percentiles were used to define the RIs. Results. The RIs of thyroid function in the first, second, and third trimesters of pregnancy and in nonpregnant controls were 0. .61 pmol/L for FT4, respectively. Conclusion. The trimester-and assay-specific RIs of thyroid function during pregnancy differed between trimesters, which suggests that it is advisable to detect and avoid misclassification of thyroid dysfunction during pregnancy for women in Henan, China

Trimester- and Assay-Specific Thyroid Reference Intervals for Pregnant Women in China

Objective. The guidelines of the American Thyroid Association (ATA) recommend an upper limit reference interval (RI) of thyroid stimulating hormone (TSH) of 2.5 mIU/L in the first trimester of pregnancy and 3.0 mIU/L in subsequent trimesters, but some reported ranges in China are significantly higher. Our study aimed to establish trimester- and assay-specific RIs for thyroid hormones in normal pregnant Chinese women. Methods. In this cross-sectional study, 2540 women with normal pregnancies (first trimester, n=398; second trimester, n=797; third trimester, n=1345) and 237 healthy nonpregnant control subjects were recruited. Serum TSH, free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels were determined by automated chemiluminescence with an Immulite 2000 system (Siemens, Erlangen, Germany). After outliers were excluded, the 2.5–97.5th percentiles were used to define the RIs. Results. The RIs of thyroid function in the first, second, and third trimesters of pregnancy and in nonpregnant controls were 0.07–3.96, 0.27–4.53, 0.48–5.40, and 0.69–5.78 mIU/L for TSH and 9.16–18.12, 8.67–16.21, 7.80–13.90, and 8.24–16.61 pmol/L for FT4, respectively. Conclusion. The trimester- and assay-specific RIs of thyroid function during pregnancy differed between trimesters, which suggests that it is advisable to detect and avoid misclassification of thyroid dysfunction during pregnancy for women in Henan, China