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The key to keep the rising slope of perovskite solar cell performances is to reduce non-radiative losses by minimizing defect density. To this end, a large variety of strategies have been adopted spanning from the use of interfacial layers, surface modifiers, to interface engineering. Although winning concepts have been demonstrated, they result from a mere trial and error approach, which is time consuming and operator-dependent. To face this challenge, in this work, we propose the use of a machine learning approach for an educated and rational material screening with optimal characteristics in terms of surface passivation. In particular, we applied Shapley additive explanation to extract the specific chemical features of the passivator, which directly impact the device parameters, specifically the open circuit voltage (Voc). By monitoring the different material parameters as input, we were able to list the most promising passivators and directly test them in working solar cells. By comparing the device performances with the results of the modeling and with additional optical and morphological characterization, we retrieved the most significant material properties linked to the highest efficiency, which are (i) the presence of chlorine and its strong binding capacity to positively charged defects on perovskite surface, reducing the non-radiative recombination and (ii) an increased flexibility of the molecule, resulting in better coverage of the surface. Finally, we tested the predictive power of the ML algorithm proposing a new passivator, which, implemented in a working device, leads to the predicted high Voc confirming the results of the modeling.

Abstract Background In 2018, our center started a program to offer genetic diagnosis to patients with kidney and liver monogenic rare conditions, potentially eligible for organ transplantation. We exploited a clinical exome sequencing approach, followed by analyses of in silico gene panels tailored to clinical suspicions, obtaining detection rates in line with what reported in literature. However, a percentage of patients remains without a definitive genetic diagnosis. This work aims to evaluate the utility of NGS data re-analysis for those patients with an inconclusive or negative genetic test at the time of first analysis considering that (i) the advance of alignment and variant calling processes progressively improve the detection rate, limiting false positives and false negatives; (ii) gene panels are periodically updated and (iii) variant annotation may change over time. Methods 114 patients, recruited between 2018 and 2020, with an inconclusive or negative NGS report at the time of first analysis, were included in the study. Re-alignment and variant calling of previously generated sequencing raw data were performed using the GenomSys Variant Analyzer software. Results 21 previously not reported potentially causative variants were identified in 20 patients. In most cases (n = 19), causal variants were retrieved out of the re-classification from likely benign to variants of unknown significance (VUS). In one case, the variant was included because of inclusion in the analysis of a newly disease-associated gene, not present in the original gene panel, and in another one due to the improved data alignment process. Whenever possible, variants were validated with Sanger sequencing and family segregation studies. As of now, 16 out of 20 patients have been analyzed and variants confirmed in 8 patients. Specifically, in two pediatric patients, causative variants were de novo mutations while in the others, the variant was present also in other affected relatives. In the remaining patients, variants were present also in non-affected parents, raising questions on their re-classification. Conclusions Overall, these data indicate that periodic and systematic re-analysis of negative or inconclusive NGS data reports can lead to new variant identification or reclassification in a small but significant proportion of cases, with benefits for patients’ management.

Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G>A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment.

Summary: Reconstructive surgery of the medial canthus is among one of the most challenging due to its complex anatomy and aesthetic features. In this area even the slightest deformity or asymmetry is noticeable. Reconstructive surgery of this anatomical region aims to restore the tissue defect ensuring an appropriate aesthetic and functional feature, restoring colour, thickness and consistency of the replaced tissue. Orbicularis oculi myocutaneous flap is an option to reconstruct the medial canthal region; in this paper the authors present their experience with orbicularis oculi myocutaneous flap in 10 patients with medial canthal malignant lesions. The patients’ postoperative period was uneventful, the flaps usually showed some degree of temporary venous congestion during the first days after surgery, and any donor site morbidity was observed: no lid lag, ectropion, ptosis, or other eyelid deformity.This flap offers a similarity in texture, colour, and thickness to the recipient site and a negligible incidence of donor site morbidity, and it can be easily tailored to fit the shape of the soft tissue defect.

Current holographic approaches for neuronal stimulation have limitations in their temporal resolution and the number of targeted neurons. Here, the authors demonstrate an approach for ultra-fast holographic light targeting which, combined with optogenetics, enables sub-millisecond control of sequential neuronal activation and high throughput simultaneous multicell illumination.

Abstract The combination of noradrenergic (reboxetine) plus antimuscarinic (oxybutynin) drugs (reb-oxy) reduced obstructive sleep apnea (OSA) severity but no data are available on its effects on cardiac autonomic modulation. We sought to evaluate the impact of 1-week reb-oxy treatment on cardiovascular autonomic control in OSA patients. OSA patients were randomized to a double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin to a placebo for OSA treatment. Heart rate (HR) variability (HRV), ambulatory blood pressure (BP) monitoring (ABPM) over 24 h baseline and after treatment were performed. Baroreflex sensitivity was tested over beat-to-beat BP recordings. 16 subjects with (median [interquartile range]) age 57 [51–61] years and body mass index 30 [26–36]kg/m2 completed the study. The median nocturnal HR was 65 [60–69] bpm at baseline and increased to 69 [64–77] bpm on reb-oxy vs 66 [59–70] bpm on placebo (p = 0.02). The mean 24 h HR from ABPM was not different among treatment groups. Reb-oxy administration was not associated with any modification in HRV or BP. Reb-oxy increased the baroreflex sensitivity and did not induce orthostatic hypotension. In conclusion, administration of reb-oxy did not induce clinically relevant sympathetic overactivity over 1-week and, together with a reduction in OSA severity, it improved the baroreflex function.

Abstract Purpose Inherited kidney diseases are among the leading causes of kidney failure in children, resulting in increased mortality, high healthcare costs and need for organ transplantation. Next-generation sequencing technologies can help in the diagnosis of rare monogenic conditions, allowing for optimized medical management and therapeutic choices. Methods Clinical exome sequencing (CES) was performed on a cohort of 191 pediatric patients from a single institution, followed by Sanger sequencing to confirm identified variants and for family segregation studies. Results All patients had a clinical diagnosis of kidney disease: the main disease categories were glomerular diseases (32.5%), ciliopathies (20.4%), CAKUT (17.8%), nephrolithiasis (11.5%) and tubular disease (10.5%). 7.3% of patients presented with other conditions. A conclusive genetic test, based on CES and Sanger validation, was obtained in 37.1% of patients. The highest detection rate was obtained for ciliopathies (74.4%), followed by nephrolithiasis (45.5%), tubular diseases (45%), while most glomerular diseases and CAKUT remained undiagnosed. Conclusions Results indicate that genetic testing consistently used in the diagnostic workflow of children with chronic kidney disease can (i) confirm clinical diagnosis, (ii) provide early diagnosis in the case of inherited conditions, (iii) find the genetic cause of previously unrecognized diseases and (iv) tailor transplantation programs.

Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo-electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and the H2AK119-ubiquitin, whereas AEBP2 has an additional scaffolding role. The presence of these cofactors partially overcomes the inhibitory effect that H3K4me3 and H3K36me3 exert on core PRC2 (in the absence of cofactors). Our results support a key role for JARID2 and AEBP2 in the cross-talk between histone modifications and PRC2 activity.

Continuous adaptations of the movement system to changing environments or task demands rely on superposed fractal processes exhibiting power laws, that is, multifractality. The estimators of the multifractal spectrum potentially reflect the adaptive use of perception, cognition, and action. To observe time-specific behavior in multifractal dynamics, a multiscale multifractal analysis based on DFA (MFMS-DFA) has been recently proposed and applied to cardiovascular dynamics. Here we aimed at evaluating whether MFMS-DFA allows identifying multiscale structures in the dynamics of human movements. Thirty-six (12 females) participants pedaled freely, after a metronomic initiation of the cadence at 60 rpm, against a light workload for 10 min: in reference to cycling (C), cycling while playing “Tetris” on a computer, alone (CT) or collaboratively (CTC) with another pedaling participant. Pedal revolution periods (PRP) series were examined with MFMS-DFA and compared to linearized surrogates, which attested to a presence of multifractality at almost all scales. A marked alteration in multifractality when playing Tetris was evidenced at two scales, τ ≈ 16 and τ ≈ 64 s, yet less marked at τ ≈ 16 s when playing collaboratively. Playing Tetris in collaboration attenuated these alterations, especially in the best Tetris players. This observation suggests the high sensitivity to cognitive demand of MFMS-DFA estimators, extending to the assessment of skill/demand interplay from individual behavior. So, by identifying scale-dependent multifractal structures in movement dynamics, MFMS-DFA has obvious potential for examining brain-movement coordinative structures, likely with sufficient sensitivity to find echo in diagnosing disorders and monitoring the progress of diseases that affect cognition and movement control.

Background Pulmonary artery wedge pressure (PAWP) during exercise, as a surrogate for left ventricular (LV) end-diastolic pressure (EDP), is used to diagnose heart failure with preserved ejection fraction (HFpEF). However, LVEDP is the gold standard to assess LV filling, end-diastolic PAWP (PAWPED) is supposed to coincide with LVEDP and mean PAWP throughout the cardiac cycle (PAWPM) better reflects the haemodynamic load imposed on the pulmonary circulation. The objective of the present study was to determine precision and accuracy of PAWP estimates for LVEDP during exercise, as well as the rate of agreement between these measures. Methods 46 individuals underwent simultaneous right and left heart catheterisation, at rest and during exercise, to confirm/exclude HFpEF. We evaluated: linear regression between LVEDP and PAWP, Bland–Altman graphs, and the rate of concordance of dichotomised LVEDP and PAWP ≥ or < diagnostic thresholds for HFpEF. Results At peak exercise, PAWPM and LVEDP, as well as PAWPED and LVEDP, were fairly correlated (R2>0.69, p2 mmHg·L−1·min−1. Conclusions During exercise, PAWP is accurate but not precise for the estimation of LVEDP. Despite a good rate of concordance, these two measures might occasionally disagree.

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking.Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners’ offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed.Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study’s course and findings through regular meetings.Trial registration number NCT05339841.

There is a growing interest in photoplethysmography (PPG) for the continuous monitoring of cardio-respiratory signals by portable instrumentation aimed at the early diagnosis of cardiovascular diseases. In this context, it is conceivable that PPG sensors working at different wavelengths simultaneously can optimize the identification of apneas and the quantification of the associated heart-rate changes or other parameters that depend on the PPG shape (e.g., systematic vascular resistance and pressure), when evaluating the severity of breathing disorders during sleep and in general for health monitoring. Therefore, the objective of this work is to present a novel pulse oximeter that provides synchronous data logging related to three light wavelengths (green, red, and infrared) in transmission mode to optimize both heart rate measurements and a reliable and continuous assessment of oxygen saturation. The transmission mode is considered more robust over motion artifacts than reflection mode, but current pulse oximeters cannot employ green light in transmission mode due to the high absorbance of body tissues at this wavelength. For this reason, our device is based on a Single-Photon Avalanche Diode (SPAD) with very short deadtime (less than 1 ns) to have, at the same time, the single photon sensitivity and high-count rate that allows acquiring all the wavelengths of interest on the same site and in transmission mode. Previous studies have shown that SPAD cameras can be used for measuring the heart rate through remote PPG, but oxygen saturation and heart-rate measures through contact SPAD-based PPG sensors have never been addressed so far. The results of the preliminary validation on six healthy volunteers reflect the expected physiological phenomena, providing rms errors in the Inter Beat Interval estimation smaller than 70 ms (with green light) and a maximum error in the oxygen saturation smaller than 1% during the apneas. Our prototype demonstrates the reliability of SPAD-based devices for continuous long-term monitoring of cardio-respiratory variables as an alternative to photodiodes especially when minimal area and optical power are required.

Background: While vagus nerve stimulation (VNS) has been in use for over two decades, little professional guidance exists to describe dosing and titration of therapy which is the consequence of a limited amount of evidence developed during the pre-market phase of therapy development. Post-market surveillance of dosing practice has revealed significant deviations from dosing and titration guidance offered by professional societies as well as the manufacturer. Objective: This analysis aims to identify a target dose for VNS Therapy in Epilepsy. Methods: Herein, VNS clinical outcomes are linked to the patient-specific dosing parameters for each study visit (n = 1178 patients). A generalized linear mixed model was built to ascertain the relationship between key stimulation parameters (i.e., Output Current, Pulse Width, Signal Frequency, and Duty Cycle) and clinical response, defined as a 50% or greater reduction in seizure frequency from baseline. Other demographic parameters of interest, such as duration of epilepsy and age at implant, were also explored. Results: A population level target output current and duty cycle for VNS therapy for epilepsy was identified as 1.61 mA and 17.1% duty cycle. Patients with shorter duration of epilepsy were identified to have a higher likelihood to respond to VNS therapy (p

Tanzania reported its first COVID-19 case on 16 March 2020. We conducted event-based surveillance of COVID-19 suspect cases among pharmacy clients presenting with respiratory symptoms and influenza-like illness to increase early and rapid detection of COVID-19 cases and mitigate transmission. We conveniently sampled 103 pharmacies from Dar es Salaam, the epicentre for the COVID-19 pandemic in Tanzania at the time. Between 23 April 2020 and 18 May 2020, 67% of the pharmacies (69/103) reported an observed increase in the number of clients presenting with respiratory symptoms and influenza-like illness compared with the 1 month before the COVID-19 outbreak. In the 1-month surveillance period, the participating pharmacies recorded 75 alerts of COVID-19 suspect cases and referred all suspected COVID-19 cases to rapid response teams for additional symptomatic screening and SARS-CoV-2 testing. A key implementation challenge was that some clients identified as COVID-19 suspected cases were hesitant to provide follow-up information for linkage to rapid response teams. Addressing concerns among drug dispensers in the participating pharmacies and informing them of the benefits of the surveillance activity were important implementation components. Our approach demonstrates the overall feasibility of rapidly implementing an event-based surveillance system for an emerging health threat through an existing network of pharmacies within the community. The approach and tools used in this surveillance activity could be adapted in similar settings to detect and generate alerts of disease outbreaks in the community that other surveillance systems may otherwise miss.

The recent advances of quantum biology suggest a potential role in biomedical research. Studies related to electromagnetic fields, proton pumping in mitochondrial respiratory chain, quantum theory of T-cell receptor (TCR)-degeneracy, theories on biophotons, pyrophosphates or tubulin as possible carriers for neural information, and quantum properties of ions and protons, might be useful for understanding mechanisms of some serious immune, cardiovascular, and neural pathologies for which classic biomedical research, based on biochemical approach, is struggling to find new therapeutic strategies. A breakthrough in medical knowledge is therefore needed in order to improve the understanding of the complex interactions among various systems and organs typical of such pathologies. In particular, problems related to immune system over-activation, to the role of autonomic nervous system (ANS) dysfunction in the obstructive sleep apnea (OSA) syndrome, to the clinical consequences of ion channels dysfunction and inherited cardiac diseases, could benefit from the new perspective provided by quantum biology advancement. Overall, quantum biology might provide a promising biophysical theoretic system, on which to base pathophysiology understanding and hopefully therapeutic strategies. With the present work, authors hope to open a constructive and multidisciplinary debate on this important topic.

Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G>A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment. [ABSTRACT FROM AUTHOR]

Carotid-cavernous fistulas (CCFs) are rare intracranial vascular malformations. Among the various classifications available, the most recently proposed highlights the strong correlation between venous drainage pattern and clinical presentation. We present the case of a woman in her 70s with a history of transient palsy of the fourth cranial nerve who presented with subacute cervical myelopathy, which was caused by a CCF with venous drainage into the peribulbar and perimedullary plexus. Given this atypical presentation of CCF and the diagnostic challenges it poses, we conducted a comprehensive PubMed search looking for CCFs presenting with cervical myelopathy and our results confirmed their rarity and allowed us to identify clinical elements that may help clinicians diagnose and manage this potentially treatable condition. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are emerging as a promising field of research in liver disease. EVs are small, membrane-bound vesicles that contain various bioactive molecules, such as proteins, lipids, and nucleic acids and are involved in intercellular communication. They have been implicated in numerous physiological and pathological processes, including immune modulation and tissue repair, which make their use appealing in liver transplantation (LT). This review summarizes the current state of knowledge regarding the role of EVs in LT, including their potential use as biomarkers and therapeutic agents and their role in graft rejection. By providing a comprehensive insight into this emerging topic, this research lays the groundwork for the potential application of EVs in LT.

Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.

Abstract The target of human flight in space has changed from permanence on the International Space Station to missions beyond low earth orbit and the Lunar Gateway for deep space exploration and Missions to Mars. Several conditions affecting space missions had to be considered: for example the effect of weightlessness and radiations on the human body, behavioral health decrements or communication latency, and consumable resupply. Telemedicine and telerobotic applications, robot-assisted surgery with some hints on experimental surgical procedures carried out in previous missions, had to be considered as well. The need for greater crew autonomy in health issues is related to the increasing severity of medical and surgical interventions that could occur in these missions, and the presence of a highly trained surgeon on board would be recommended. A surgical robot could be a valuable aid but only inasfar as it is provided with multiple functions, including the capability to perform certain procedures autonomously. Space missions in deep space or on other planets present new challenges for crew health. Providing a multi-function surgical robot is the new frontier. Research in this field shall be paving the way for the development of new structured plans for human health in space, as well as providing new suggestions for clinical applications on Earth.

Background: Sleep disordered breathing (SDB) may trigger nocturnal cardiac arrhythmias (NCA) in patients with heart failure with reduced ejection fraction (HFrEF). The NCA ancillary study of the ADVENT-HF trial will test whether, in HFrEF-patients with SDB, peak-flow-triggered adaptive servo-ventilation (ASVpf) reduces NCA. To this end, accurate scoring of NCA from polysomnography (PSG) is required. Objective: To develop a method to detect NCA accurately from a single-lead electrocardiogram (ECG) recorded during PSG and assess inter-observer agreement for NCA detection. Methods: Quality assurance of ECG analysis included training of the investigators, development of standardized technical quality, guideline-conforming semi-automated NCA-scoring via Holter-ECG software and implementation of an arrhythmia adjudication committee. To assess inter-observer agreement, the ECG was analysed by two independent investigators and compared for agreement on premature ventricular complexes (PVC) /h, premature atrial complexes/h (PAC) as well as for other NCA in 62 patients from two centers of the ADVENT-HF trial. Results: The intraclass correlation coefficients for PVC/h and PAC/h were excellent: 0.99 (95%- confidence interval [CI]: 0.99–0.99) and 0.99 (95%-CI: 0.97–0.99), respectively. No clinically relevant difference in inter-observer classification of other NCA was found. The detection of non-sustained ventricular tachycardia (18% versus 19%) and atrial fibrillation (10% versus 11%) was similar between the two investigators. No sustained ventricular tachycardia was detected. Conclusion: These findings indicate that our methods are very reliable for scoring NCAs and are adequate to apply for the entire PSG data set of the ADVENT-HF trial.

BackgroundNovel smartwatch-based cuffless blood pressure (BP) measuring devices are coming to market and receive FDA and CE labels. These devices are often insufficiently validated for clinical use. This study aims to investigate a recently CE-cleared smartwatch using cuffless BP measurement in a population with normotensive and hypertensive individuals scheduled for 24-h BP measurement.MethodsPatients that were scheduled for 24-h ambulatory blood pressure monitoring (ABPM) were recruited and received an additional Samsung Galaxy Watch Active 2 smartwatch for simultaneous BP measurement on their opposite arm. After calibration, patients were asked to measure as much as possible in a 24-h period. Manual activation of the smartwatch is necessary to measure the BP. Accuracy was calculated using sensitivity, specificity, positive and negative predictive values and ROC curves. Bland-Altman method and Taffé methods were used for bias and precision assessment. BP variability was calculated using average real variability, standard deviation and coefficient of variation.ResultsForty patients were included. Bland-Altman and Taffé methods demonstrated a proportional bias, in which low systolic BPs are overestimated, and high BPs are underestimated. Diastolic BPs were all overestimated, with increasing bias toward lower BPs. Sensitivity and specificity for detecting systolic and/or diastolic hypertension were 83 and 41%, respectively. ROC curves demonstrate an area under the curve (AUC) of 0.78 for systolic hypertension and of 0.93 for diastolic hypertension. BP variability was systematically higher in the ABPM measurements compared to the smartwatch measurements.ConclusionThis study demonstrates that the BP measurements by the Samsung Galaxy Watch Active 2 show a systematic bias toward a calibration point, overestimating low BPs and underestimating high BPs, when investigated in both normotensive and hypertensive patients. Standards for traditional non-invasive sphygmomanometers are not met, but these standards are not fully applicable to cuffless devices, emphasizing the urgent need for new standards for cuffless devices. The smartwatch-based BP measurement is not yet ready for clinical usage. Future studies are needed to further validate wearable devices, and also to demonstrate new possibilities of non-invasive, high-frequency BP monitoring.

Type 1 diabetes mellitus (T1DM) has an important impact on morbidity and mortality because it may start early in life. Therefore, the early detection of cardiovascular autonomic neuropathy (DCAN) in T1DM patients is important to intervene quickly and prevent further deterioration. Traditional autonomic function tests detect abnormalities in severely symptomatic patients but they are difficult to be standardized, require the patient’s active participation and their sensitivity to the early disease is limited. In comparison, heart rate variability (HRV) is easier to be measured and standardized. Therefore, we aim to find the HRV indexes that better identify DCAN at an early stage in T1DM patients, and evaluate if HRV is a valid alternative to traditional tests. For this aim, we administered the SCOPA-AUT questionnaire on symptoms of autonomic dysfunction as well as deep breathing, Valsalva, handgrip, head-up tilt (HUT), and cold-pressor tests, to 52 T1DM patients and 27 controls. We calculated HRV indexes during supine rest (SUP) and HUT, assessing differences between groups and postures by a linear mixed-effect model for repeated measures. Receiver Operating Characteristic (ROC) analysis quantified how each HRV index and autonomic test distinguishes between patients and controls. We found that the SCOPA-AUT score was slightly but significantly (p < 0.05) greater in patients, indicating an early DCAN. T1DM patients preserved the HRV response to changing posture but in SUP they showed significantly lower standard deviation and vagal indexes of HRV than controls. The area under the ROC curve of these HRV indexes was not lower than 0.68. By contrast, traditional autonomic tests did not differ between groups. Therefore, early DCAN initially causes an impairment of the cardiac vagal control manifest in conditions of elevated vagal tone, as in SUP. Compensatory adjustments of the sympathetic control might explain the unaltered response to traditional autonomic tests. In conclusion, vagal HRV indexes in SUP help to identify early DCAN better than traditional tests, potentially allowing rapid interventions.

Mobile-health solutions based on heart rate variability often require electrocardiogram (ECG) recordings by inexperienced operators or real-time automatic analyses of long-term recordings by wearable devices in free-moving individuals. In this context, it is useful to associate a quality index with the ECG, scoring the adequacy of the recording for heart rate variability to identify noise or arrhythmias. Therefore, this work aims to propose and validate a computational method for assessing the adequacy of single-lead ECGs for heart rate variability analysis that may run in real time on wearable systems with low computational power. The method quantifies the ECG pseudo-periodic structure employing cepstral analysis. The cepstrum (spectrum of log-spectrum) is estimated on a running ECG window of 10 s before and after “liftering” (filtering in the cepstral domain) to remove slower noise components. The ECG periodicity generates a dominant peak in the liftered cepstrum at the “quefrency” of the mean cardiac interval. The Cepstral Quality Index (CQI) is the ratio between the cepstral-peak power and the total power of the unliftered cepstrum. Noises and arrhythmias reduce the relative power of the cepstral peak decreasing CQI. We analyzed a public dataset of 6072 single-lead ECGs manually classified in normal rhythm or inadequate for heart rate variability analysis because of noise or atrial fibrillation, and the CQI = 47% cut-off identified the inadequate recordings with 79% sensitivity and 85% specificity. We showed that the performance is independent of the lead considering a public dataset of 1,000 12-lead recordings with quality classified as “acceptable” or “unacceptable” by visual inspection. Thus, the cepstrum describes the ECG periodic structure effectively and concisely and CQI appears to be a robust score of the adequacy of ECG recording for heart rate variability analysis, evaluable in real-time on wearable devices.

Distribution Entropy (DistEn) has been introduced as an alternative to Sample Entropy (SampEn) to assess the heart rate variability (HRV) on much shorter series without the arbitrary definition of distance thresholds. However, DistEn, considered a measure of cardiovascular complexity, differs substantially from SampEn or Fuzzy Entropy (FuzzyEn), both measures of HRV randomness. This work aims to compare DistEn, SampEn, and FuzzyEn analyzing postural changes (expected to modify the HRV randomness through a sympatho/vagal shift without affecting the cardiovascular complexity) and low-level spinal cord injuries (SCI, whose impaired integrative regulation may alter the system complexity without affecting the HRV spectrum). We recorded RR intervals in able-bodied (AB) and SCI participants in supine and sitting postures, evaluating DistEn, SampEn, and FuzzyEn over 512 beats. The significance of “case” (AB vs. SCI) and “posture” (supine vs. sitting) was assessed by longitudinal analysis. Multiscale DistEn (mDE), SampEn (mSE), and FuzzyEn (mFE) compared postures and cases at each scale between 2 and 20 beats. Unlike SampEn and FuzzyEn, DistEn is affected by the spinal lesion but not by the postural sympatho/vagal shift. The multiscale approach shows differences between AB and SCI sitting participants at the largest mFE scales and between postures in AB participants at the shortest mSE scales. Thus, our results support the hypothesis that DistEn measures cardiovascular complexity while SampEn/FuzzyEn measure HRV randomness, highlighting that together these methods integrate the information each of them provides.

Abstract Background High number of unintended pregnancies—often leading to induced abortions—are reported among female sex workers (FSWs), highlighting a major unmet need for contraception. To better understand barriers to contraceptive use, we explored FSW’s pregnancy perceptions and experiences of unintended pregnancy. We hypothesized that sex work exacerbates barriers to contraceptive use and that FSW’s pregnancy perceptions and experiences of unintended pregnancy influence future commitment to contraceptive use. Methods We conducted in-depth interviews with 11 FSWs (January–June 2019) in Dar es Salaam, Tanzania. We purposively sampled FSWs with a positive pregnancy test from those participating in a HIV vaccine preparedness cohort. We used open ended questions to explore how FSWs make decisions when facing barriers to contraceptive use, dealing with unintended pregnancy and adhering to contraceptive use after experiencing unintended pregnancy. All interviews were conducted in Kiswahili, audio-recorded, transcribed and translated into English. Grounded theory approach was used to analyse transcripts. Open and selective coding was performed using Nvivo software. Results FSWs reported that sex work impedes good contraceptive behaviour because sex workers felt unable to negotiate consistent condom use, avoided health services due to stigma, missed monthly contraceptive supplies because of inconvenient clinic operating hours or skipped contraceptive pills when intoxicated after taking alcohol. FSWs who perceived pregnancy to be a burden terminated the pregnancy because of fear of loss of income during pregnancy or child rearing expenses in case child support was not assured by their partners. FSWs who perceived pregnancy to be a blessing decided to keep the pregnancy because they desired motherhood and hoped that children would bring prosperity. Family planning counselling and availability of contraceptives during postpartum care influenced the initiation of contraception among FSWs. Financial hardships related to childrearing or painful abortion experiences influenced FSWs’ commitment to good contraceptive practices. Conclusion Our results demonstrate that FSWs face barriers to initiating and adhering to contraceptive use because of sex work stigma, inability to negotiate condoms and failure to access medical services at their convenience. Our findings underscore the need to integrate contraceptive services with HIV programs serving FSWs in their areas of work.

Reflecting on this special issue’s critical questions, NSN’s assistant editor Kristen Sun conducts a brief interview with executive editors Kim Tran and Maria Faini about Ethnic Studies today.

Abstract Background Prevalence of HIV infection among people who inject drugs (PWID) has been reported to be higher than that of the general population. The present study aimed to estimate the prevalence of HIV infection and associated risk factors among PWID in Dar es Salaam, Tanzania, following the introduction of a comprehensive HIV intervention package (CHIP) for PWID in the country in 2014. Methods We conducted an integrated bio-behavioral survey (IBBS) among PWID using respondent-driven sampling (RDS) in Dar es Salaam, Tanzania, between October and December 2017. Data on socio-demographic characteristics and risky behaviors were collected through face-to-face interviews. Blood samples were collected and tested for HIV infection. We accounted for weighting in the analyses, and logistic regression was performed to assess risk factors for HIV infection. Results A total of 611 PWID (94.4% males and 5.6% females) with a median age of 34 years (IQR 29–38) were recruited. The overall prevalence of HIV infection was 8.7% (95% CI 6.5–10.9). The prevalence of HIV infections for males and females were 6.8% (95% CI 4.7–8.9%) and 41.2% (95% CI 23.7–58.6%) respectively. Adjusted weighted logistic regression analysis (WLRA) showed that being a female (aOR 19.1; 95% CI 5.9–61.8), injecting drugs for more than 10 years (aOR = 7.32; 95% CI 2.1–25.5) compared to 1 year or less and being 45 years or older (aOR = 34.22; 95% CI 2.4–489.5) compared to being 25 years or younger were associated with increased odds of HIV infection. Use of a sterile needle at last injection decreased odds of HIV infection (aOR = 0.3; 95% CI 0.1–0.8). Conclusions The present study observed a decline in prevalence of HIV infections among PWID in Dar es Salaam (8.7%) compared to a previous estimate of 15.5% from an IBBS conducted in 2013. Despite the decrease, HIV prevalence remains high among PWID compared to the general population, and women are disproportionally affected. The decline may be possibly attributed to the on-going implementation of CHIP for PWID, highlighting the need for strengthening the existing harm reduction interventions by incorporating access to sterile needle/syringe and addressing the layered risks for women.

RtcB enzymes are RNA ligases that play essential roles in tRNA splicing, unfolded protein response, and RNA repair. In metazoa, RtcB functions as part of a five-subunit tRNA ligase complex (tRNA-LC) along with Ddx1, Cgi-99, Fam98B, and Ashwin. The human tRNA-LC or its individual subunits have been implicated in additional cellular processes including microRNA maturation, viral replication, DNA double-strand break repair, and mRNA transport. Here, we present a biochemical analysis of the inter-subunit interactions within the human tRNA-LC along with crystal structures of the catalytic subunit RTCB and the N-terminal domain of CGI-99. We show that the core of the human tRNA-LC is assembled from RTCB and the C-terminal alpha-helical regions of DDX1, CGI-99, and FAM98B, all of which are required for complex integrity. The N-terminal domain of CGI-99 displays structural homology to calponin-homology domains, and CGI-99 and FAM98B associate via their N-terminal domains to form a stable subcomplex. The crystal structure of GMP-bound RTCB reveals divalent metal coordination geometry in the active site, providing insights into its catalytic mechanism. Collectively, these findings shed light on the molecular architecture and mechanism of the human tRNA ligase complex and provide a structural framework for understanding its functions in cellular RNA metabolism.

Introduction: Limited information is available on blood pressure (BP) behavior in workers exposed to chronic intermittent hypoxia (CIH), and even less is known regarding effects of CIH on 24-h ambulatory BP in those affected by arterial hypertension at sea level (SL). The aims of this study were to assess clinic and 24-h ambulatory BP at SL and at high altitude (HA; 3,870 m above SL) in workers exposed to CIH, and to compare BP response to HA exposure between normotensive and hypertensive workers.Methods: Nineteen normotensive and 18 pharmacologically treated hypertensive miners acclimatized to CIH were included, whose work was organized according to a “7 days-on−7 days-off” shift pattern between SL and HA. All measurements were performed on the second and seventh day of their HA shift and after the second day of SL sojourn.Results: Compared to SL, 24-h systolic BP (SBP) and diastolic BP (DBP) increased at HA [+14.7 ± 12.6 mmHg (p < 0.001) and +8.7 ± 7.2 mmHg (p < 0.001), respectively], and SBP nocturnal fall decreased consistently (−4.1 ± 9.8%; p < 0.05) in all participants, with hypertensives showing higher nocturnal DBP than normotensives (p < 0.05) despite the current therapy. Also, heart rate (HR) nocturnal fall tended to be reduced at HA. In addition, the 24-h SBP/DBP hypertension threshold of ≥130/80 mmHg was exceeded by 39% of workers at SL and by 89% at HA. Clinic HR, SBP, and DBP were significantly higher on the second day of work at HA compared with SL, the increase being more pronounced for SBP in hypertensives (p < 0.05) and accompanied by, on average, mild altitude sickness in both groups. These symptoms and the values of all cardiovascular variables decreased on the seventh day at HA (p < 0.05) regardless of CIH exposure duration.Conclusion: Long history of work at HA according to scheduled CIH did not prevent the occurrence of acute cardiovascular changes at HA during the first days of exposure. The BP response to HA tended to be more pronounced in hypertensive than in normotensive workers despite being already treated; the BP changes were more evident for 24-h ambulatory BP. Twenty-four-hour ABP monitoring is a useful tool for an appropriate evaluation of BP in CIH workers.