Clonal dynamics in early human embryogenesis inferred from somatic mutation.

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.

Design of 2-Pyridone Fluorophores for Brighter Emissions at Longer Wavelengths.

The recent discovery of blue fluorophores with high quantum yields based on pyridone structures inspired the development of new low-molecular-weight fluorophores with bright emissions at tunable wavelengths, which are highly attractive for various applications. In this study, we propose a rational design strategy for 2-pyridone-based fluorophores with bright emissions at long wavelengths. With a detailed understanding of the positional substitution effects on each carbon atom of the 2-pyridone core, we developed a bright blue fluorophore (λabs =377 nm; λem =433 nm; ϵ=13,200 M-1 cm-1 ; ϕF =88 %) through C3 -aryl and C4 -ester substitutions followed by cyclization. Furthermore, by applying the intramolecular charge transfer (ICT) principle, we invented a bright green fluorophore through C3 - and C4 -diester and C6 -aryl substitutions. The ICT fluorophore based on the pyridone structure shows large molar absorptivity (ϵ=20,100 M-1 cm-1 ), longer emission wavelength (λem =539 nm), high emission quantum yield (ϕF =74 %), and large Stokes shift (Δv=5720 cm-1 ), which are comparable to those of practical fluorescent probes.

Five-Year Oncologic Outcome and Surgical Completeness of Transoral Robotic Thyroidectomy for Papillary Thyroid Carcinoma: Comparison with Conventional Transcervical Thyroidectomy Using Propensity Score Matching.

OBJECTIVE: This study aimed to evaluate the oncological outcomes and surgical completeness of transoral robotic thyroidectomy (TORT) for papillary thyroid carcinoma (PTC) compared with conventional transcervical thyroidectomy. METHODS: We analyzed 489 patients with PTC who underwent thyroidectomy with or without central neck dissection (CND; 311 conventional thyroidectomy and 178 TORT) between January 2017 and December 2021. Patients with gross invasion of the surrounding structures, revision or completion thyroidectomy, and lateral neck dissection were excluded. Propensity score-matched analysis was performed using eight covariates, including age, sex, extent of thyroidectomy, tumor size, extrathyroidal extension (ETE), radioactive iodine (RAI) ablation, lymphovascular invasion (LVI), and CND. RESULTS: Before propensity score matching (PSM), age, male-to-female ratio, and body mass index were lower in the TORT group. The ratio of total thyroidectomy and CND, tumor size and bilaterality, LVI, and RAI ablation were higher in the conventional group. PSM generated two matched groups of 100 patients each. After PSM, significant differences between the two groups in the baseline analysis disappeared. In the matched samples, the recurrence rate (2% and 0% in the conventional and TORT groups, respectively) and recurrence-free survival curves did not differ between the two groups. The mean thyroid-stimulating hormone (TSH)-stimulated thyroglobulin level in the RAI group and TSH-suppressed thyroglobulin level in the non-RAI group were not different between the two groups. CONCLUSIONS: The 5-year oncologic outcomes and surgical completeness of TORT were comparable with those of conventional thyroidectomy in patients with small, localized, low-risk PTC when performed by experienced surgeons.

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

PURPOSE: The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. METHOD: We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. RESULTS: The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1 month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. CONCLUSION: Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

Spectral Efficiency Improvement Using Bi-Deep Learning Model for IRS-Assisted MU-MISO Communication System.

The intelligent reflecting surface (IRS) is a two-dimensional (2D) surface with a programmable structure and is composed of many arrays. The arrays are used to supervise electromagnetic wave propagation by altering the electric and magnetic properties of the 2D surface. IRS can influentially convert wireless channels to very effectively enhance spectral efficiency (SE) and communication performance in wireless systems. However, proper channel information is necessary to realize the IRS anticipated gains. The conventional technique has been taken into consideration in recent attempts to fix this issue, which is straightforward but not ideal. A deep learning model which is called the long short-term memory (Bi-LSTM) model can tackle this issue due to its good learning capability and it plays a vital role in enhancing SE. Bi-LSTM can collect data from both forward and backward directions simultaneously to provide improved prediction accuracy. Because of the tremendous benefits of the Bi-LSTM model, in this paper, an IRS-assisted Bi-LSTM model-based multi-user multiple input single output downlink system is proposed for SE improvement. A Wiener filter is used to determine the optimal phase of each IRS element. In the simulation results, the proposed system is compared with other DL models and methods for the SE performance evaluation. The model exhibits satisfactory SE performance with a different signal-to-noise ratio compared to other schemes in the online phase.

A Comprehensive Survey on MIMO Visible Light Communication: Current Research, Machine Learning and Future Trends.

Visible light communication (VLC) has contributed new unused spectrum in addition to the traditional radio frequency communication and can play a significant role in wireless communication. The adaptation of VLC technology enhances wireless connectivity both in indoor and outdoor environments. Multiple-input multiple-output (MIMO) communication has been an efficient technique for increasing wireless communications system capacity and performance. With the advantages of MIMO techniques, VLC can achieve an additional degree of freedom. In this paper, we systematically perform a survey of the existing work based on MIMO VLC. We categorize the types of different MIMO techniques, and a brief description is given. Different problem-solving approaches are given in the subsequent sections. In addition, machine learning approaches are also discussed in sufficient detail. Finally, we identify the future study direction for MIMO-based communication in VLC.

Formation of the Tertiary Sulfonamide C(sp3)-N Bond Using Alkyl Boronic Ester via Intramolecular and Intermolecular Copper-Catalyzed Oxidative Cross-Coupling.

A synthetic strategy for the formation of C(sp3)-N bonds, particularly through a copper-catalyzed oxidative cross-coupling, is rare. Herein, we report a novel synthetic approach for the preparation of tertiary sulfonamides via copper-catalyzed intra- and intermolecular oxidative C(sp3)-N cross-coupling reactions. This method allows the utilization of the readily available C(sp3)-based pinacol boronate as a substrate and the tolerance of a wide range of functional groups under mild reaction conditions. The success of this strategy relies on the unprecedented additive effects of silanol and NaIO4.

Risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in papillary thyroid carcinoma.

PURPOSE: Thyroid lobectomy is now preferred over total thyroidectomy to preserve thyroid function and reduce complications in patients with low-risk papillary thyroid carcinoma (PTC). One inevitable consequence of thyroidectomy includes hypothyroidism. This study aimed to evaluate the risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in patients with PTC. METHODS: We retrospectively studied 353 patients with PTC who underwent hemithyroidectomy with or without central neck dissection from January 2012 to January 2019. We excluded patients who had hypo- or hyperthyroidism preoperatively and those who underwent total or subtotal thyroidectomy. We analyzed various risk factors related to postoperative hypothyroidism and thyroid hormone supplementation. RESULTS: Of the patients, 54.7% showed hypothyroidism after hemithyroidectomy (n=193 with n=157, subclinical hypothyroidism; n=36, overt hypothyroidism). Ninety-one percent of postoperative hypothyroidism cases developed within 7 months postoperatively. Eventually, 43.1% (n=152) of patients received levothyroxine after hemithyroidectomy. Preoperative high thyroid-stimulating hormone (TSH) level and low free thyroxine (fT4) level were significantly associated with postoperative hypothyroidism and the need for thyroid hormone supplementation postoperatively. CONCLUSION: Preoperative TSH and fT4 levels are predictive risk factors of hypothyroidism and need for supplementation of levothyroxine after hemithyroidectomy in patients with PTC. Finally, approximately 43% of patients need levothyroxine supplementation after hemithyroidectomy, and individual preoperative counseling is necessary for these patients.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever.

BACKGROUND: Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. METHODS: All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. RESULTS: Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. CONCLUSION: The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

Moving Object Detection Based on Optical Flow Estimation and a Gaussian Mixture Model for Advanced Driver Assistance Systems.

Most approaches for moving object detection (MOD) based on computer vision are limited to stationary camera environments. In advanced driver assistance systems (ADAS), however, ego-motion is added to image frames owing to the use of a moving camera. This results in mixed motion in the image frames and makes it difficult to classify target objects and background. In this paper, we propose an efficient MOD algorithm that can cope with moving camera environments. In addition, we present a hardware design and implementation results for the real-time processing of the proposed algorithm. The proposed moving object detector was designed using hardware description language (HDL) and its real-time performance was evaluated using an FPGA based test system. Experimental results demonstrate that our design achieves better detection performance than existing MOD systems. The proposed moving object detector was implemented with 13.2K logic slices, 104 DSP48s, and 163 BRAM and can support real-time processing of 30 fps at an operating frequency of 200 MHz.