3SAT on an all-to-all-connected CMOS Ising solver chip.

This work solves 3SAT, a classical NP-complete problem, on a CMOS-based Ising hardware chip with all-to-all connectivity. The paper addresses practical issues in going from algorithms to hardware. It considers several degrees of freedom in mapping the 3SAT problem to the chip-using multiple Ising formulations for 3SAT; exploring multiple strategies for decomposing large problems into subproblems that can be accommodated on the Ising chip; and executing a sequence of these subproblems on CMOS hardware to obtain the solution to the larger problem. These are evaluated within a software framework, and the results are used to identify the most promising formulations and decomposition techniques. These best approaches are then mapped to the all-to-all hardware, and the performance of 3SAT is evaluated on the chip. Experimental data shows that the deployed decomposition and mapping strategies impact SAT solution quality: without our methods, the CMOS hardware cannot achieve 3SAT solutions on SATLIB benchmarks. Under the assumption of some hardware improvements, our chip-based 3SAT solver demonstrates a remarkable 250 × acceleration compared to Tabu search in dwave-hybrid on a CPU.

Heart Failure Among Patients with Multiple Myeloma Treated with Carfilzomib-Based Versus Non-Carfilzomib-Based Regimens in the United States by Race.

BACKGROUND: Carfilzomib treatment for multiple myeloma (MM) can increase heart failure risk. Whether this risk differs by race is unknown. PATIENTS AND METHODS: We sought to estimate the incidence rates (IRs) of heart failure hospitalization among mostly 65-years-and-older US patients with MM by race treated with carfilzomib- and non-carfilzomib-based regimens in the real-world using Centers for Medicare & Medicaid Services Medicare Fee-for-Service data, Optum Clinformatics Data Mart, and Humana Research Database. The risk of heart failure hospitalization associated with a carfilzomib-based regimen was evaluated using propensity score matching among Black and White patients receiving second or later lines of therapy. RESULTS: Most patient-episodes (88%) were in persons 65 years or older for the 3 cohorts combined. The IR (95% CI) of heart failure hospitalization was higher for patient-episodes treated with a carfilzomib-based regimen than those with a non-carfilzomib-based regimen for both White (14.5 [12.2-17.0] vs. 10.7 [10.3-11.2] events per person-years) and Black patients (15.8 [10.1-23.5] vs. 12.1 [10.9-13.4] events per person-years) in the Medicare cohort. After propensity score matching, the hazard ratio (95% CI) of increased heart failure hospitalization comparing carfilzomib-based to non-carfilzomib-based regimens for White patients (1.6 [1.3-2.0]) was similar to that of Black patients (1.7 [1.0-2.9]) in the Medicare Database, and in the Humana Database (1.4 [0.8-2.6] and 1.2 [0.4-3.5], respectively). CONCLUSION: Although the IR of heart failure among patients with MM treated with a carfilzomib-based regimen was slightly higher, no evidence suggested the relative risk was different between White and Black patients with MM.

Small RNA sequencing of small extracellular vesicles secreted by umbilical cord mesenchymal stem cells following replicative senescence.

BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSC) are subsets of multipotent stem cells involved in immune modulation, tissue regeneration, and antimicrobial defense. Cellular senescence is associated with the onset of aging-related diseases and small extracellular vesicles (sEVs) are important mediators of senescence and aging. OBJECTIVE: However, little is known about the role and function of microRNAs (miRNAs) carried by UCMSC-derived sEVs. To analyze the expression profiles of miRNAs secreted by senescent UCMSC, small RNA sequencing of the miRNAs within the sEVs was performed in this study. METHODS: UCMSC cultures underwent serial passaging beyond passage number 20 to achieve replicative senescence, which was confirmed by various methods, including increased senescence-associated ß-gal staining and cytokine secretion levels. sEVs derived from non-senescent and senescent UCMSC were isolated and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis. RESULTS: Small RNA sequencing of the miRNAs within the sEVs revealed senescence-associated differences in the miRNA composition, as shown by the upregulation of miR-122-5p and miR-146a-5p, and downregulation of miR-125b-5p and miR-29-3p. In addition, total RNA sequencing analysis showed that PENK, ITGA8, and TSIX were upregulated, whereas AKR1B10, UNC13D, and IL21R were downregulated by replicative senescence in UCMSC. In sEVs, upregulated genes were linked to downregulated miRNAs, and vice versa. In the gene-concept network analysis, five gynecologic terms were retrieved. CONCLUSIONS: The study provides an insight into the cellular characteristics of UCMSC following replicative senescence and emphasizes the importance of monitoring passage numbers of UCMSC for further therapeutic use.

Infection rates following urologic prosthetic revision without replacement of any device components compared to partial or complete device exchange: a single-center retrospective cohort study.

Urologic implant revision carries a higher infection risk than virgin implantation. Historically, exchanging device components at the time of revision was performed to reduce infection risk. We hypothesize that revision without replacement of any parts of the device may not be associated with increased infection risk. A single-center, retrospective cohort study was performed on patients undergoing urologic implant revision from 2000 to 2021. Revisions involving exchange of any/all device components (+CE) were compared to revisions without exchange of any components (-CE). The primary outcome was infection or erosion within 12 weeks of revision. Infection rates were compared using Fischer exact test. Infection-free survival (IFS) was compared with Kaplan-Meier (KM) log-rank test and Cox proportional hazards (CPH) model. 551 revisions were included, including 497 revisions with CE and 54 without CE. Among those with at least 12 weeks follow-up, no difference was seen in infection rates within 12 weeks of revision [-CE 3/39 (7.7%) vs. +CE 10/383 (2.6%)], p = 0.109). In addition, IFS was comparable between groups (log-rank test p = 0.22, HR for -CE 1.65 (0.65-4.21). Revision surgery for IPP or AUS without CE may not present an elevated risk of infection in the properly selected patient.

Humoral and Cellular Immune Responses to Vector, Mix-and-Match, or mRNA Vaccines against SARS-CoV-2 and the Relationship between the Two Immune Responses.

We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.

Identification of large offspring syndrome during pregnancy through ultrasonography and maternal blood transcriptome analyses.

In vitro production (IVP) of embryos in cattle can result in large/abnormal offspring syndrome (LOS/AOS) which is characterized by macrosomia. LOS can cause dystocia and lead to the death of dam and calf. Currently, no test exists to identify LOS pregnancies. We hypothesized that fetal ultrasonography and/or maternal blood markers are useful to identify LOS. Bovine fetuses were generated by artificial insemination (control) or IVP. Fetal ultrasonographies were taken on gestation D55 (D55) and fetal collections performed on D56 or D105 (gestation in cattle ≈ D280). IVP fetuses weighing ≥ 97 percentile of the control weight were considered LOS. Ultrasonography results show that the product of six D55 measurements can be used to identify extreme cases of LOS. To determine whether maternal blood can be used to identify LOS, leukocyte mRNA from 23 females was sequenced. Unsupervised hierarchical clustering grouped the transcriptomes of the two females carrying the two largest LOS fetuses. Comparison of the leukocyte transcriptomes of these two females to the transcriptome of all other females identified several misregulated transcripts on gestation D55 and D105 with LOC783838 and PCDH1 being misregulated at both time-points. Together our data suggest that LOS is identifiable during pregnancy in cattle.

An automated COVID-19 triage pipeline using artificial intelligence based on chest radiographs and clinical data.

While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital's image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.

GeNVoM: Read Mapping Near Non-Volatile Memory.

DNA sequencing is the physical/biochemical process of identifying the location of the four bases (Adenine, Guanine, Cytosine, Thymine) in a DNA strand. As semiconductor technology revolutionized computing, modern DNA sequencing technology (termed Next Generation Sequencing, NGS) revolutionized genomic research. As a result, modern NGS platforms can sequence hundreds of millions of short DNA fragments in parallel. The sequenced DNA fragments, representing the output of NGS platforms, are termed reads. Besides genomic variations, NGS imperfections induce noise in reads. Mapping each read to (the most similar portion of) a reference genome of the same species, i.e., read mapping, is a common critical first step in a diverse set of emerging bioinformatics applications. Mapping represents a search-heavy memory-intensive similarity matching problem, therefore, can greatly benefit from near-memory processing. Intuition suggests using fast associative search enabled by Ternary Content Addressable Memory (TCAM) by construction. However, the excessive energy consumption and lack of support for similarity matching (under NGS and genomic variation induced noise) renders direct application of TCAM infeasible, irrespective of volatility, where only non-volatile TCAM can accommodate the large memory footprint in an area-efficient way. This paper introduces GeNVoM, a scalable, energy-efficient and high-throughput solution. Instead of optimizing an algorithm developed for general-purpose computers or GPUs, GeNVoM rethinks the algorithm and non-volatile TCAM-based accelerator design together from the ground up. Thereby GeNVoM can improve the throughput by up to 3.67×; the energy consumption, by up to 1.36×, when compared to an ASIC baseline, which represents one of the highest-throughput implementations known.

A new allele, HLA-C*08:228, identified by sequence-based typing in a Korean individual.

The new allele C*08:228 showed one nucleotide difference from C*08:01:01 in codon 36 (TTC -> TTG).

Angioedema Secondary to tPA Use in Acute Ischemic Stroke Patient with Hypertension: A Case Report.

INTRODUCTION: A well-documented complication of administering tissue plasminogen activator (tPA) in stroke patients is acute intracranial bleeding. A lesser known but still significant complication is angioedema secondary to tPA administration, which can develop in certain individuals with risk factors such as angiotensin converting enzyme (ACE) inhibitor use and location of the stroke. Knowing the potential for this life-threatening complication and being prepared for its proper management is vital for emergency physicians. CASE REPORT: We report a 53-year-old Black female who presented to the emergency department with sudden onset of slurred speech and a facial droop. She was found to have an acute ischemic stroke and tPA was administered. She subsequently developed angioedema. Retrospectively, the patient was found to have risk factors that are thought to predispose patients to tPA-induced angioedema. CONCLUSION: Risk factors associated with angioedema secondary to tPA administration have been documented in patients taking ACE inhibitors, as well as patients who develop strokes in the frontal lobe. While many cases may be mild, some patients may develop life-threatening angioedema. Although this complication does not necessarily contraindicate tPA use, it is prudent for the emergency physician to be vigilant for its development, prepared for its treatment, and to be diligent in assessing the need for control of the patient's airway.

Acute Thromboembolism from Trauma in a Patient with Abdominal Aortic Aneurysm.

CASE PRESENTATION: A 64-year-old man with a history of a 5.5-centimeter (cm) abdominal aortic aneurysm (AAA) presented to the emergency department (ED) complaining of severe back pain after climbing over a fence and falling a distance of eight feet. Prior to arrival, the prehospital paramedics reported that the patient did not have palpable pulses in either lower extremity. The initial physical examination in the ED was significant for absent dorsalis pedis pulses bilaterally as well as absent posterior tibialis pulses bilaterally and cold, insensate lower extremities. Point-of-care ultrasound identified an approximate 7-cm infrarenal AAA with a mural thrombus present. After receiving several computed tomography (CT) studies including CT head without contrast and CT angiography of the chest, abdomen and pelvis, the patient was diagnosed with acute thrombosis of AAA and associated thromboembolic occlusion of both his right and left distal iliac vessels causing bilateral acute limb ischemia. He immediately received unfractionated heparin and was admitted to the hospital for embolectomy and intra-arterial tissue plasminogen activator. DISCUSSION: Acute thrombosis of AAA and subsequent thromboembolic events are a rare but significant complication that can occur in patients with a history of AAA. Thromboembolic events may occur spontaneously or in the setting of blunt abdominal trauma. Common presenting signs and symptoms include distal limb ischemia and absent femoral pulses. Timely management and recognition of this rare complication is vital as this condition can ultimately result in limb loss or death if not treated in a timely manner. Heparinization after confirmation of non-ruptured AAA as well as vascular surgery, and therapeutic and vascular interventional radiology consultations are key steps that should be taken to decrease patient morbidity and mortality.

Atypical case of Crohn's colitis in a patient with adult-onset Still's disease.

A 65-year-old woman with a background of adult-onset Still's disease (AOSD) presented acutely to a general surgical unit with signs of bowel obstruction and sepsis. A CT scan was indicative of a mesenteric lymphadenopathy suspicious of malignancy. At the time of the surgery, a clinical diagnosis of lymphoma was made given the large number of lymph nodes; however, histological diagnosis was resulted as Crohn's colitis. There is only one other case of AOSD and Crohn's disease in the literature, and there is no clear pathological connection between the two inflammatory conditions. This case highlights the surgical management of an unusual presentation.

Trichoblastic carcinosarcoma in a 34-year-old woman with histopathologic and molecular analysis, including re-demonstration of a CDKN2A p.(R58*) mutation.

Trichoblastic carcinosarcomas are rare, adnexal-type cutaneous carcinosarcomas that are thought to be related histogenetically to trichoblastomas, yet in which both the epithelial and stromal components show features of malignancy. Ten cases have been described in the literature thus far, with a predilection for the head and neck of older males. We present a case of cutaneous carcinosarcoma in sun-damaged skin of a 34-year-old woman showing features of a trichoblastic carcinosarcoma, with histopathologic analysis along with targeted next-generation sequencing of 50 cancer-associated genes. Two pathogenic variants in TP53 were identified, p.(R158C), p.(R273P), along with a likely pathogenic variant CDKN2A, p.(R58*). In particular, it is noted that the CDKN2A p.(R58*) missense mutation has been described in two previous cases of cutaneous carcinosarcomas, including a case of trichoblastic carcinosarcoma.

Wearable Millimeter-Wave Device for Contactless Measurement of Arterial Pulses.

Wearable monitors for measuring vital signs such as blood pressure will greatly impact the medical field. This work presents a millimeter-wave, radar-based system for performing accurate measurements of arterial pulse waveforms without contacting the region that is pulsing. Electromagnetic and radar-system simulation models are utilized to demonstrate the viability and safety of this approach. This is followed by hardware/software implementation and a study on 12 human subjects. Measured radial arterial waveforms exhibit signal strengths that are well above the noise floor of the system and a morphology that would be expected in an arterial pulse. Finally, comparison of the radar-based signals with a reference tonometer indicates a strong correlation between waveforms, as well as similar spectral signatures. The results observed suggest a millimeter-wave based approach for arterial pulse detection is very promising for future applications in pulse wave analysis and pulse transit time measurement for blood pressure tracking.

CorNET: Deep Learning Framework for PPG-Based Heart Rate Estimation and Biometric Identification in Ambulant Environment.

Advancements in wireless sensor network technologies have enabled the proliferation of miniaturized body-worn sensors, capable of long-term pervasive biomedical signal monitoring. Remote cardiovascular monitoring has been one of the beneficiaries of this development, resulting in non-invasive, photoplethysmography (PPG) sensors being used in ambulatory settings. Wrist-worn PPG, although a popular alternative to electrocardiogram, suffers from motion artifacts inherent in daily life. Hence, in this paper, we present a novel deep learning framework (CorNET) to efficiently estimate heart rate (HR) information and perform biometric identification (BId) using only a wrist-worn, single-channel PPG signal collected in ambulant environment. We have formulated a completely personalized data-driven approach, using a four-layer deep neural network. Two convolution neural network layers are used in conjunction with two long short-term memory layers, followed by a dense output layer for modeling the temporal sequence inherent within the pulsatile signal representative of cardiac activity. The final dense layer is customized with respect to the application, functioning as: regression layer-having a single neuron to predict HR; classification layer-two neurons that identify a subject among a group. The proposed network was evaluated on the TROIKA dataset having 22 PPG records collected during various physical activities. We achieve a mean absolute error of 1.47 ± 3.37 beats per minute for HR estimation and an average accuracy of 96% for BId on 20 subjects. CorNET was further evaluated successfully in an ambulant use-case scenario with custom sensors for two subjects.

BioTranslator: Inferring R-Peaks from Ambulatory Wrist-Worn PPG Signal.

Advancements in wireless sensor networks (WSN) technology and miniaturization of wearable sensors have enabled long-term continuous pervasive biomedical signal monitoring. Wrist-worn photoplethysmography (PPG) sensors have gained popularity given their form factor. However the signal quality suffers due to motion artifacts when used in ambulatory settings, making vital parameter estimation a challenging task. In this paper, we present a novel deep learning framework, BioTranslator, for computing the instantaneous heart rate (IHR), using wrist-worn PPG signals collected during physical activity. Using one-dimensional Convolution-Deconvolution Network, we translate a single channel PPG signal to an electrocardiogram(ECG)-like time series signal, from which relevant R-peak information can be inferred enabling IHR measures. The proposed network configuration was evaluated on 12 subjects of the TROIKA dataset, involved in physical activity. The proposed network identifies 92.8% of R-peaks, besides achieving a mean absolute error of 51±6.3ms with respect to reference ECG-derived IHR.

No clinical differences between anteromedial portal and transtibial technique for femoral tunnel positioning in anterior cruciate ligament reconstruction: a prospective randomized, controlled trial.

PURPOSE: The anteromedial (AMP) portal technique was introduced to position the femoral tunnel in anterior cruciate ligament (ACL) reconstruction to more closely replicate the original ACL footprint compared to the transtibial (TT) approach. Few randomized trials have evaluated differences in these techniques with respect to clinical outcomes. The purpose of this study was to determine if there are any differences in clinical outcome between the AMP and TT approaches. METHODS: This is a single-blinded, prospective, randomized controlled trial. Participants were randomized to undergo ACL reconstruction using the AMP or TT approach. The primary outcome measure was the ACL quality of life (ACL-QOL), and secondary outcomes were the IKDC knee assessment, side-to-side difference in anterior-posterior knee laxity (KT-1000) and tunnel orientation (X-ray findings) at preoperative, 3, 6, 12, and 24 months postoperative. Statistical comparisons were performed using a series of t tests for independent groups with equal variance. RESULTS: Ninety-six participants were consented and randomized between 2007 and 2011 with eight excluded postrandomization. Mean (SD) preoperative ACL-QOL was 33 (13) for TT and 36 (17) for AMP and improved significantly (p < 0.001) in both groups to 79 (18) and 78 (18) at 24 months postoperative, respectively. The preoperative median IKDC grade for both groups was C and improved similarly in both groups at 24 months (n.s.). There was no side-to-side difference in knee laxity based on KT-1000 measurements with a mean (SD) 1 (3) mm between affected and unaffected limbs in the TT group compared to 1 (3) mm for the AMP group. A significant difference was found in femoral tunnel orientation with the AMP group at 43° (7) and the TT group 58° (8) in the coronal plane (p < 0.001). CONCLUSION: No differences in clinical outcome were found when comparing AMP to TT in primary ACL reconstruction using a STG graft. This prospective randomized controlled trial suggests surgeons can use either method without significantly compromising clinical outcome. LEVEL OF EVIDENCE: I.

Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage.

Solution-Processed Carbon Nanotube True Random Number Generator.

With the growing adoption of interconnected electronic devices in consumer and industrial applications, there is an increasing demand for robust security protocols when transmitting and receiving sensitive data. Toward this end, hardware true random number generators (TRNGs), commonly used to create encryption keys, offer significant advantages over software pseudorandom number generators. However, the vast network of devices and sensors envisioned for the "Internet of Things" will require small, low-cost, and mechanically flexible TRNGs with low computational complexity. These rigorous constraints position solution-processed semiconducting single-walled carbon nanotubes (SWCNTs) as leading candidates for next-generation security devices. Here, we demonstrate the first TRNG using static random access memory (SRAM) cells based on solution-processed SWCNTs that digitize thermal noise to generate random bits. This bit generation strategy can be readily implemented in hardware with minimal transistor and computational overhead, resulting in an output stream that passes standardized statistical tests for randomness. By using solution-processed semiconducting SWCNTs in a low-power, complementary architecture to achieve TRNG, we demonstrate a promising approach for improving the security of printable and flexible electronics.

Correction: Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection.

[This corrects the article DOI: 10.1371/journal.ppat.1006046.].