Maternal lineages of mitochondrial DNA (mtDNA) are recognized as important components of intra- and inter-specific biodiversity and help us to disclose the phylogeny and divergence times of many taxa. Species of the genus Capra are canonical mountain dwellers. Among these is the Siberian ibex (Capra sibirica), which is regarded as a relic species whose intra-specific classification has been controversial so far. We collected 54 samples in Xinjiang, China, and analyzed the mtDNA genes to shed light on the intra-specific relationships of the C. sibirica populations and estimate the divergence time. Intriguingly, we found that the mtDNA sequences of C. sibirica split into two main lineages in both phylogenetic and network analyses: the southern lineage, sister to C. falconeri, consisting of samples from India, Ulugqat, and Kagilik in Xinjiang; and the northern lineage further divided into four monophyletic clades A–D corresponding to their geographic origins. Samples from Urumqi, Sawan, and Arturk formed a distinct monophyletic clade C within the northern lineage. The genetic distance between the C. sibirica clades ranges from 3 to 8.6 percent, with values of FST between 0.72 and 0.95, indicating notable genetic differentiation. The split of the genus Capra occurred approximately 6.75 Mya during the late Miocene. The northern lineage diverged around 5.88 Mya, following the divergence of Clades A–D from 3.3 Mya to 1.9 Mya during the late Pliocene and early Pleistocene. The radiation between the southern lineage and C. falconeri occurred at 2.29 Mya during the early Pleistocene. Our results highlight the importance of extensive sampling when relating to genetic studies of alpine mammals and call for further genomic studies to draw definitive conclusions.
Optical coherence tomography angiography (OCTA) has successfully demonstrated its viability for clinical applications in dermatology. Due to the high optical scattering property of skin, extracting high-quality OCTA images from skin tissues requires at least six-repeated scans. While the motion artifacts from the patient and the free hand-held probe can lead to a low-quality OCTA image. Our deep-learning-based scan pipeline enables fast and high-quality OCTA imaging with 0.3-second data acquisition. We utilize a fast scanning protocol with a 60 µm/pixel spatial interval rate and introduce Angiography-Reconstruction-Transformer (ART) for 4× super-resolution of low transverse resolution OCTA images. The ART outperforms state-of-the-art networks in OCTA image super-resolution and provides a lighter network size. ART can restore microvessels while reducing the processing time by 85%, and maintaining improvements in structural similarity and peak-signal-to-noise ratio. This study represents that ART can achieve fast and flexible skin OCTA imaging while maintaining image quality.
The Optical Kerr Effect was investigated for the first time in biological tissues. This nonlinear optical effect was explored in both human brain and avian breast tissues using a time-resolved femtosecond pump-probe Optical Kerr Gate. The Optical Kerr Effect describes the nonlinear change in a material’s refractive index in response to an electric field. It is fundamental to spectral effects that are commonly used in biological science. The tested tissues produced a unique ultrafast (700-800 fs) doubled peaked Kerr signal, which is indicative of temporal interplay between the different components (electronic plasma, and molecular) that make up the Kerr index. Temporal properties varied between samples suggesting that this method could be used as a new diagnostic. Understanding this Kerr behavior can help improve current spectral diagnostic techniques, such as SRS, and potentially create a new Kerr based biopsy method for the detection of diseased tissues, such as cancer and Alzheimer’s.
Introduction Zanubrutinib is a second generation Bruton’s tyrosine kinase inhibitor (BTKi) often used to treat B cell malignancies such as marginal zone lymphoma. BTKis belong to a protein tyrosine kinase family that plays an essential role in the proliferation, differentiation, and survival of B cells. The side effects of BTKis include infection, diarrhea, skin rash, and atrial fibrillation. Invasive fungal infections have been previously described with Ibrutinib (a first generation BTKi) but seldom with second generation BTKis such as zanubrutinib.
Tongue Necrosis as a Manifestation of Immune Dysfunction: A Complex Case of Lupus, Histoplasmosis, and Macrophage Activation SyndromeMadalyn Walsh, MD1, Alick Feng, MD2, Petar Lenart, MD PhD2, Bharat Kumar, MD MME21Department of Internal Medicine, University of Iowa Hospitals & Clinics2Division of Immunology, University of Iowa Hospitals & Clinics
As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyze this corollary discharge phenomenon (agency and ownership), we registered the Event-Related Potentials of forty-two healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership), and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared to the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience), and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.
Chronic limb-threatening ischemia (CLTI) with severe below-the-ankle (BTA) lesions is often difficult to revascularize with endovascular treatment (EVT) and surgical treatment. We present a case of successful limb salvage using percutaneous deep venous arterialization (pDVA) in a patient with CLTI whose BTA lesion reconstruction failed. A 57-year-old man with diabetes mellitus
The occurrence of random mutations can increase the diversity of the genome and promote the evolutionary process of organisms. High efficiency mutagenesis techniques significantly accelerate the evolutionary process. In this work, we describe a targeted in vivo mutagenesis system to significantly increase mutation frequency and generate mutations across all four nucleotides. We constructed different DNA-modifying enzyme-PmCDA1-T7 RNA polymerase fusion proteins, achieved targeted mutagenesis by flanking the target gene with T7 promoters, and tuned the mutation spectra by introducing different DNA-modifying enzymes. With the mutagenesis fusion proteins, the mutation frequency of the target gene could reach 5.13x10-3, and the proportion of non-C→T mutations is 10~11-fold higher than the cytidine-based evolutionary tools. We also demonstrated that our mutagenesis tools could be used to evolve the essential enzyme in the β-carotene biosynthesis process and generate mutations with different types.
Background: The purpose of this article is armed to provide some experience and insight for the clinical treatment of primary mediastinal yolk sac tumor (PMYST) basing on our case report and relevant literature review. Case report and literature review: A 15-year-old boy was diagnosed as PMYST with the volume about 13*12*8cm. The
Mapping fluvial hydromorphology is an important part of defining river habitat. Mapping via field sampling or hydraulic modelling is however time consuming, and mapping hydromorphology directly from remote sensing data may offer an efficient solution. Here we present a system for automated classification of fluvial hydromorphology based on a deep learning classification scheme applied to aerial orthophotos. Using selected rivers in Norway, we show how surface flow patterns (smooth or rippled surfaces versus standing waves) can be classified in imagery using a trained convolutional neural network. We show how integration of these classified surface flow patterns with information on channel gradient, obtained from airborne topographic LiDAR data, can be used to compartmentalize the rivers into hydromorphological units that represent the dominant flow features. Automated classifications were consistent with those produced manually. They were found to be discharge-dependent, showing the temporally dynamic aspect of hydromorphology. The proposed system is quick, flexible, generalizable, and free from researcher-subjectivity. The deep learning approach used here can be customized to provide more detailed information on flow features, such as delineating between standing waves and advective diffusion of air bubbles/foam, to provide a more refined classification of surface flow patterns, and the classification approach can be further advanced by inclusion of additional remote sensing methods that provide further information on hydromorphological features.
A Ka-band low noise amplifier (LNA) is presented that improves the traditional source-degeneration LNA by utilizing broadband transformer matching and gate-drain feedback technology. The proposed LNA achieves an ultra-wideband LNA while maintaining the advantages of high integration and low power consumption of the traditional source-degeneration LNA. In addition, cascade technology is adopted to further improve peak gain. The proposed LNA is implemented in 55nm CMOS process. The simulated results show that the LNA achieves stable gain response in the 21.7-36.5 GHz frequency band, with a peak power gain of 20.8 dB. The minimum noise coefficient is 4.4 dB, and the DC power consumption is 15 mW. The LNA achieves a compact chip area of 0.33 mm 2.
Background Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. Procedure The Children’s Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug reinduction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m 2/dose) was administered orally once daily for 21 consecutive days, first as a single agent (days 1-3) and subsequently combined with reinduction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) followed by an expansion pharmacokinetic (PK) cohort. Results Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose-limiting hematologic toxicity (DLT) occurred at the starting dose of 50 mg/m 2/dose orally for 21 days. No additional DLTs were observed in the dose determination or PK expansion cohorts and overall rates of grade 3/4 non-hematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. Conclusions Palbociclib in combination with reinduction chemotherapy was well tolerated with a RP2D of 50 mg/m 2/day for 21 days. Complete responses were observed among heavily pretreated patients.
A coupled inductor based on dual switches buck-boost converter is proposed in the article, which can be used in renewable energy applications. Wide conversion ratio can be realized by regulating turns ratio of the coupled inductor and the duty cycle. The topology has a quadratic- like voltage gain, and the low voltage stress and current stress. Combing the passive clamping circuit to recover leakage energy, the voltage spikes of power switches are suppressed, improving the efficiency. Moreover, it has the merits of continuous input current and common ground. To demonstrate the superior performances of the presented converter, the principle of operation and steady-state analysis are presented in detail. At last, a 100 W experimental prototype was designed to verify the correctness of the theoretical analysis, with a maximum efficiency of 95.7% in step-up mode and 96.8 % in step-down mode.
This paper proposes a new precharging scheme to reduce the power consumption in dynamic comparator. It basically allows the comparator to perform evaluation after precharging the output nodes to a weaker potential rather than full V DD , which eventually helps in reducing the power consumption of the comparator significantly. Corresponding proposed design also improves the input offset voltage of the comparator. The proposed comparator has been realized in cadence virtuoso environment using the GPDK 45nm CMOS process and results have been extracted using SPECTRE simulator. Proposed comparator achieves an input offset voltage of 0.5 mV, and it consumes an average power of 367 nW while operating at a maximum frequency of 2.5 GHz. Comparison of these results with referred work indicates the that proposed comparator design archives 4.1× better energy efficiency in terms of energy per conversion and 20× better input offset voltage.
Childhood interstitial lung disease (chILD) is a heterogeneous group of diffuse lung diseases (DLD) that can be challenging to diagnose. With relative rarity of individual entities, data are limited on disease prevalence, care patterns, and healthcare utilization. The objective of this study was to evaluate chILD prevalence and review diagnostic and clinical care patterns at our center. A single-center, retrospective cohort study was conducted of patients receiving care at the Children’s Hospital of Philadelphia (CHOP) between January 1, 2019, and December 31, 2021. Through query of selected ICD-10 billing codes relevant for chILD/DLD, a total of 306 patients were identified receiving care during this period. Respiratory symptom onset was documented to have developed before two years of age for 40% of cases. The most common diagnostic categories included those with oncologic disease (21.2%), bronchiolitis obliterans (10.1%), and connective tissue disease (9.5%). Genetic testing was performed in 49% of cases, while 36% underwent lung biopsy. Hospitalization at CHOP had occurred for 80.4% of patients, with 45.1% ever hospitalized in an intensive care unit. One-third of children had required chronic supplemental oxygen. Seven (2.3%) patients died during this three-year period. Collectively, these data demonstrate the scope of chILD and extent of health care utilization at a large volume tertiary care center. This approach to cohort identification and EMR-driven data collection in chILD provides new opportunities for cohort analysis and will inform the feasibility of future studies.