Search Results (35)

Data over sound (DoS) is an established technique that has experienced a resurgence in recent years, finding applications in areas such as contactless payments, device pairing, authentication, presence detection, toys, and offline data transfer. This study introduces CardiaWhisper, a system that extends the DoS concept to the medical domain by using a medical data-over-sound (MDoS) framework. CardiaWhisper integrates wearable biomedical sensors with home care systems, edge or IoT gateways, and telemedical networks or cloud platforms. Using a transmitter device, vital signs such as ECG (electrocardiogram) signals, PPG (photoplethysmogram) signals, RR (respiratory rate), and ACC (acceleration/movement) are sensed, conditioned, encoded, and acoustically transmitted to a nearby receiver—typically a smartphone, tablet, or other gadget—and can be further relayed to edge and cloud infrastructures. As a case study, this paper presents the real-time transmission and processing of ECG signals. The transmitter integrates an ECG sensing module, an encoder (either a PLL-based FM modulator chip or a microcontroller), and a sound emitter in the form of a standard piezoelectric speaker. The receiver, in the form of a mobile phone, tablet, or desktop computer, captures the acoustic signal via its built-in microphone and executes software routines to decode the data. It then enables a range of control and visualization functions for both local and remote users. Emphasis is placed on describing the system architecture and its key components, as well as the software methodologies used for signal decoding on the receiver side, where several algorithms are implemented using open-source, platform-independent technologies, such as JavaScript, HTML, and CSS. While the main focus is on the transmission of analog data, digital data transmission is also illustrated. The CardiaWhisper system is evaluated across several performance parameters, including functionality, complexity, speed, noise immunity, power consumption, range, and cost-efficiency. Quantitative measurements of the signal-to-noise ratio (SNR) were performed in various realistic indoor scenarios, including different distances, obstacles, and noise environments. Preliminary results are presented, along with a discussion of design challenges, limitations, and feasible applications. Our experience demonstrates that CardiaWhisper provides a low-power, eco-friendly alternative to traditional RF or Bluetooth-based medical wearables in various applications. Full article

Background: T-prolymphocytic leukemia (T-PLL) is a rare lymphoid neoplasm with particularly poor prognosis. Although it is no longer recognized as a distinct entity by the World Health Organization (WHO), B-prolymphocytic leukemia (B-PLL) comprises conditions with unfavorable outcomes. Both diseases most frequently affect patients in the seventh decade of their lives. Allogeneic hematopoietic stem cell transplantation (alloHSCT) significantly improves outcomes for selected PLL cases, as shown by several, mostly retrospective, analyses. Methods: In this article, we provide a review of existing PLL analyses, followed by a summary of cases treated at our center. We describe outcomes of six T-PLL and three B-PLL cases receiving alloHSCT at our institution between 2015 and 2022. Results: Despite a post-transplant 4-year cumulative relapse incidence of 61% in our T-PLL series, the median OS was 78 months, because relapse therapy was remarkably successful. All B-PLL patients are alive and relapse-free, with a median follow-up of 54 (range of 11–74) months. A poor pre-transplant Karnofsky performance status (KPS) (≤ 80%) and an HCT comorbidity index (HCT-CI) of ≥3 were significantly associated with post-transplant mortality. Conclusions: The comparatively favorable outcomes in our case series underline the increasing value of alloHSCT in PLL in the current era, as it offers a prospect of cure in selected patients with otherwise very poor prognosis. Full article

This paper reviews recent developments in highly integrated all-digital frequency synthesizers suitable to deploy in low-power internet-of-things (IoT) applications. This review sets low power consumption as a key criterion for exploring the all-digital frequency synthesizer implemented in CMOS fabrication technology. The alignment with mainstream CMOS technology offers high-density, comprehensive, robust signal processing capability, making it very suitable for all-digital phase-locked loops to harvest that capacity, and it becomes inevitable. This review includes various divider-less low-power frequency synthesizers, including all-digital phase-locked loops (ADPLL), all-digital frequency-locked loops (ADFLL), and hybrid PLLs. This paper also discusses the latest architectural developments for ADPLLs to lead to low-power implementation, such as DTC-assisted TDC, embedded TDC, and various levels of hybridization in ADPLLs. Full article

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma that is usually associated with poor prognosis and short overall survival. Methods: We present a case of a 61-year-old woman presenting with T-PLL and the leukemic cells harboring BCR::ABL1 (BCR—breakpoint cluster region; ABL1—ABL protooncogene 1) fusion transcripts as the result of a variant of t(9;22)(q34;q11) called Philadelphia translocation: t(9;22;18)(q34;q11;q21). Sequencing revealed a rare BCR transcript with an exon 6 breakpoint corresponding to e6a2 transcripts, which has thus far been reported in only 26 cases of leukemias. Results: After 9 months of follow-up, the disease progressed and required treatment. Following alemtuzumab and chemotherapy, a short course of imatinib therapy stabilized the disease for six months, which was followed by progression and the demise of the patient. Conclusions: To the best of our knowledge, this is the first report of a mature T-cell lymphoma with a variant Philadelphia-translocation and a very rare type of BCR::ABL1 transcript. This case highlights the importance of comprehensive genetic testing of malignancies, as abnormal molecular pathways may be uncovered that may be specifically targeted by drugs. Full article

Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of the disease limits the ability to conduct robust clinical trials, making in silico, ex vivo, and in vivo drug screenings essential for designing new therapeutic strategies for T-PLL. We conducted a drug repurposing analysis based on T-PLL gene expression data and identified proteasome inhibitors (PIs) as a promising new class of compounds capable of reversing the T-PLL phenotype. Treatment of ex vivo T-PLL cells with Bortezomib and Carfilzomib, two PI compounds, supported this hypothesis by demonstrating increased apoptosis in leukemic cells. The current lack of a suitable in vitro model for the study of T-PLL prompted us to perform similar experiments in the SUP-T11 cell line, validating its potential by showing an increased apoptotic rate. Taken together, these findings open new avenues for investigating the molecular mechanisms underlying the efficacy of PI in T-PLL and expand the spectrum of potential therapeutic strategies for this highly aggressive disease. Full article

This article reports a 110.2 MHz ultra-low-power phase-locked loop (PLL) for MEMS timing/frequency reference oscillator applications. It utilizes a 6.89 MHz MEMS-based oscillator as an input reference. An ultra-low-power, high-resolution phase-frequency detector (PFD) is utilized to achieve low-noise performance. Eliminating the reset feedback path used in conventional PFDs leads to dead/blind zone-free phase characteristics, which are crucial for low-noise applications within a wide operating frequency range. The PFD operates up to 2.5 GHz and achieves a linear resolution of 100 ps input time difference ($\Delta t_{in}$), without the need for any additional calibration circuits. The linearity of the proposed PFD is tested over a phase difference corresponding to aa $\Delta t_{in}$ ranging from 100 ps to 50 ns. At a 1 V supply voltage, it shows an error of <±1.6% with a resolution of 100 ps and a frequency-normalized power consumption ($P_n$) of 0.106 pW/Hz. The PLL is designed and fabricated using a TSMC 65 nm CMOS process instrument and interfaced with the MEMS-based oscillator. The system reports phase noises of −106.21 dBc/Hz and −135.36 dBc/Hz at 1 kHz and 1 MHz offsets, respectively. It consumes 6.709 $\mathsf{\mu }$W at a 1 V supply and occupies an active CMOS area of 0.1095 mm². Full article

Adenosine is an endogenous molecule that plays a vital role in biological processes. Research indicates that abnormal adenosine levels are associated with a range of diseases. The development of sensors capable of detecting adenosine is pivotal for early diagnosis of disease. For example, elevated adenosine levels are closely associated with the onset and progression of cancer. In this study, we designed a novel DNA biosensor utilizing chaperone copolymer-assisted catalytic hairpin assembly for highly sensitive detection of adenosine. The functional probe comprises streptavidin magnetic beads, an aptamer, and a catalytic chain. In the presence of adenosine, it selectively binds to the aptamer, displacing the catalytic chain into the solution. The cyclic portion of H1 hybridizes with the catalytic strand, while H2 hybridizes with the exposed H1 fragment to form an H1/H2 complex containing a G-quadruplex. Thioflavin T binds specifically to the G-quadruplex, generating a fluorescent signal. As a nucleic acid chaperone, PLL-g-Dex expedites the strand exchange reaction, enhancing the efficiency of catalytic hairpin assembly, thus amplifying the signal and reducing detection time. The optimal detection conditions were determined to be a temperature of 25 °C and a reaction time of 10 min. Demonstrating remarkable sensitivity and selectivity, the sensor achieved a lowest limit of detection of 9.82 nM. Furthermore, it exhibited resilience to interference in complex environments such as serum, presenting an effective approach for rapid and sensitive adenosine detection. Full article

Objectives: This study aimed to determine the impacts of upper and lower limb (UL and LL) spasticity and impairment on spinal alignment in chronic post-stroke patients. Methods: A total of 45 consecutive chronic post-stroke patients, 18 women and 27 men, from 18 to 70 years old who presented post-stroke hemiparesis were recruited in this cross-sectional study. The clinical assessment included the Modified Ashworth Scale (UL-MAS and LL-MAS spasticity), Upper Limb Motricity Index (UL-MI), FAST-UL, and Five Times Sit-to-Stand Test (5T-STS); the Associated Reaction Rating Scale was used to measure associated reactions in the hemiparetic UL, the plumb line distance from the spinous process of C7 on the sagittal (PL-C7s) and frontal plane (Pl-C7f), the kyphosis apex (PL-AK), and the spinous process of L3 (PL-L3). Angular measures of spinal alignment were measured by a Bunnell scoliometer™ (angle of trunk rotation—ATR) and a gravity-dependent inclinometer (inclination at C7-T1 and T12-L1). Results: In chronic post-stroke patients, there was found to be an association between the 5T-STS and PL-C7f (β = 0.41, p = 0.05) and the angle of inclination at T12-L1 (β = 0.44, p = 0.01). The FAST-UL correlated with PL-C7f (β = −0.41, p = 0.05), while the UL-MI correlated with this last parameter (β = −0.36, p = 0.04) and the ATR (β = −0.31, p = 0.05). The UL-MAS showed correlation with the ATR (β = 0.38, p = 0.01). Conclusions: The results lead to the possibility that, in chronic post-stroke patients, spinal misalignment on the frontal and sagittal plane is associated both with strength impairment and UL spasticity. The improvement or restoration of spinopelvic parameters can take advantage of therapeutic interventions targeted at motor improvement and spasticity reduction of the hemiparetic side. Full article

A fully integrated 24-GHz radar transceiver with one transmitter (TX) and two receivers (RXs) for compact frequency modulated continuous wave (FMCW) radar applications is here presented. The FMCW synthesizer was realized using a fractional-N phase-locked loop (PLL) and programmable chirp generator, which are completely integrated in the proposed transceiver. The measured output phase noise of the synthesizer is −80 dBc/Hz at 100 kHz offset. The TX consists of a three-bit bridged t-type attenuator for gain control, a two-stage drive amplifier (DA) and a one-stage power amplifier (PA). The TX chain provides an output power of 13 dBm while achieving <0.5 dB output power variation within the range of 24 to 24.25 GHz. The RX with a direct conversion I-Q structure is composed of a two-stage low noise amplifier (LNA), I-Q generator, mixer, transimpedance amplifier (TIA), a two-stage biquad band pass filter (BPF), and a differential-to-single (DTS) amplifier. The TIA and the BPF employ a DC offset cancellation (DCOC) circuit to suppress the strong reflection signal and TX-RX leakage. The RX chain exhibits an overall gain of 100 dB. The proposed radar transceiver is fabricated using a 65 nm CMOS technology. The transceiver consumes 220 mW from a 1 V supply voltage and has 4.84 mm² die size including all pads. The prototype FMCW radar is realized with the proposed transceiver and Yagi antenna to verify the radar functionality, such as the distance and angle of targets. Full article

EZH2, a subunit of the polycomb repressive complex 2 (PRC2), is an important methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 is overexpressed in various malignancies. Here, we investigated EZH2 expression and potential signaling molecules that correlate with EZH2 expression in ATLL and other T-cell neoplasms. Immunohistochemical staining (IHC) was performed for EZH2, pERK, MYC, and pSTAT3 on 43 ATLL cases and 104 cases of other T-cell neoplasms. Further IHC studies were conducted for Ki-67, SUZ12, and H3K27me3 on ATLL cases. All ATLL cases showed EZH2 overexpression. In other T-cell neoplasms, a high prevalence of EZH2 overexpression was identified (86%), except for T-PLL (33%). In ATLL, EZH2 overexpression correlated with pERK co-expression (86%), while only a small subset of cases showed MYC (7%) or pSTAT3 (14%) co-expression. In the other T-cell neoplasms, there was a variable, but higher, co-expression of EZH2 with pERK, MYC, and pSTAT3. In ATLL, enhanced EZH2 expression correlated with higher Ki-67 staining, SUZ12 (another PRC2 subunit), and H3K27me3 co-expression. In conclusion, EZH2 is overexpressed in ATLL and is associated with pERK expression. It correlates with an increased proliferation index, indicating an aggressive clinical course. EZH2 also correlates with SUZ12 and H3K27me3 co-expression, suggesting its PRC2-dependent catalytic activity through trimethylation. Additionally, EZH2 is overexpressed in most T-cell neoplasms, suggesting that EZH2 could function as an oncogenic protein in T-cell tumorigenesis. EZH2 and pERK could serve as potential therapeutic targets for treating aggressive ATLL. EZH2 could also be targeted in other T-cell neoplasms. Full article

A low-power and low-jitter 1.2 GHz Integer-N PLL (INPLL) is designed in a 65 nm standard CMOS process. A novel high-gain sampling phase detector (PD), which takes advantage of a transconductance (Gm) cell to boost the gain, is developed to increase the phase detection gain by ~100× compared to the Phase-Frequency Detectors (PFDs) used in conventional PLLs. Using this high detection gain, the noise contribution of the PFD and Charge Pump (CP), reference clock, and dividers on the PLL output is minimized, enabling low output jitter at low power, even when using low-frequency reference clocks. To provide a sufficient frequency locking range, an auxiliary frequency-locked loop (AFLL) is embedded within the INPLL. An integrated Lock Detector (LD) helps detect the INPLL locked state and disables the AFLL to save on power consumption and minimize its impact on the INPLL jitter. The proposed INPLL layout measures 700 µm × 350 µm, consumes 350 µW, and exhibits an integrated phase noise (IPN) of −37 dBc (from 10 kHz to 10 MHz), equivalent to 2.9 ps rms jitter, while keeping the spur level 64 dBc lower, resulting in jitter figure of Merit ($Fo{M}_{jitter}$) ~−236 dB. Full article

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response. Full article

Phase jitter is one of the crucial factors in modern digital electronics, determining the reliability of a design. This paper presents a novel approach to designing a jitter comparison system and methodology for FPGA chips using a Tapped Delay Line (TDL)—commonly used to implement a Time-to-Digital Converter (TDC). The design and its revision utilizing latches replacing some of the flip-flops are presented and discussed, with potential further improvements. A minimal temperature influence is verified and presented. The methodology of automated relative jitter measurements is discussed. Multiple different FPGA clock signal path configurations are measured, and the results are presented. The influence of clock routing is identified as critical when MMCM or PLL modules are omitted. It is demonstrated that with careful resource and routing allocation, the clock signal’s jitter performance does not have to be deteriorated by the absence of jitter filtering blocks. The proposed technique was implemented and verified and relative jitter performance was measured in the AMD/Xilinx Artix 7 35T FPGA platform. Full article

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 (TCL1) overexpression and ATM loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between TCL1 family members and ATM is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review. Full article

As a major component of the plant primary cell wall, structure changes in pectin may affect the formation of the secondary cell wall and lead to serious consequences on plant growth and development. Pectin-modifying enzymes including pectate lyase-like proteins (PLLs) participate in the remodeling of pectin during organogenesis, especially during fruit ripening. In this study, we used Arabidopsis as a model system to identify critical PLL genes that are of particular importance for vascular development. Four PLL genes, named AtPLL15, AtPLL16, AtPLL19, and AtPLL26, were identified for xylem-specific expression. A knock-out T-DNA mutant of AtPLL16 displayed an increased amount of pectin, soluble sugar, and acid-soluble lignin (ASL). Interestingly, the atpll16 mutant exhibited an irregular xylem phenotype, accompanied by disordered xylem ray cells and an absence of interfascicular phloem fibers. The xylem fiber cell walls in the atpll16 mutant were thicker than those of the wild type. On the contrary, AtPLL16 overexpression resulted in expansion of the phloem and a dramatic change in the xylem-to-phloem ratios. Altogether, our data suggest that AtPLL16 as a pectate lyase plays an important role during vascular development in Arabidopsis. Full article